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Sample records for susceptibility locus influencing

  1. Influence of TYK2 in systemic sclerosis susceptibility : a new locus in the IL-12 pathway

    NARCIS (Netherlands)

    López-Isac, Elena; Campillo-Davo, Diana; Bossini-Castillo, Lara; Guerra, Sandra G; Assassi, Shervin; Simeón, Carmen Pilar; Carreira, Patricia; Ortego-Centeno, Norberto; García de la Peña, Paloma; Beretta, Lorenzo; Santaniello, Alessandro; Bellocchi, Chiara; Lunardi, Claudio; Moroncini, Gianluca; Gabrielli, Armando; Riemekasten, Gabriela; Witte, Torsten; Hunzelmann, Nicolas; Kreuter, Alexander; Distler, Jörg Hw; Voskuyl, Alexandre E; de Vries-Bouwstra, Jeska; Herrick, Ariane; Worthington, Jane; Denton, Christopher P; Fonseca, Carmen; Radstake, Timothy Rdj; Mayes, Maureen D; Martín, Javier

    OBJECTIVES: TYK2 is a common genetic risk factor for several autoimmune diseases. This gene encodes a protein kinase involved in interleukin 12 (IL-12) pathway, which is a well-known player in the pathogenesis of systemic sclerosis (SSc). Therefore, we aimed to assess the possible role of this locus

  2. A Quantitative-Trait Locus in the Human Factor XII Gene Influences Both Plasma Factor XII Levels and Susceptibility to Thrombotic Disease

    Science.gov (United States)

    Soria, José Manuel; Almasy, Laura; Souto, Juan Carlos; Bacq, Delphine; Buil, Alfonso; Faure, Alexandra; Martínez-Marchán, Elisabeth; Mateo, José; Borrell, Montserrat; Stone, William; Lathrop, Mark; Fontcuberta, Jordi; Blangero, John

    2002-01-01

    One approach to the identification of genetic loci that influence complex diseases is through the study of quantitative risk factors correlated with disease susceptibility. Factor XII (FXII) plasma levels, a related phenotype correlated with thrombosis, is such a risk factor. We conducted the first genomewide linkage screen to localize genes that influence variation in FXII levels. Two loci were detected: one on chromosome 5 and another on chromosome 10 (LOD scores 4.73 and 3.53, respectively). On chromosome 5, the peak LOD score occurred in the 5q33-5ter region, near the FXII gene. Addition of a 46C/T mutation in the FXII gene increased the multipoint LOD score to 10.21 (P=3.6×10-12). A bivariate linkage analysis of FXII activity and thrombosis further improved the linkage signal (LOD = 11.73) and provided strong evidence that this quantitative-trait locus (QTL) has a pleiotropic effect on the risk of thrombosis (P=.004). Linkage analysis conditional on 46C/T indicated that this mutation alone cannot explain the chromosome 5 signal, implying that other functional sites must exist. These results represent the first direct genetic evidence that a QTL in or near the FXII gene influences both FXII activity and susceptibility to thrombosis and suggest the presence of one or more still unknown functional variants in FXII. PMID:11805911

  3. Inherited coding variants at the CDKN2A locus influence susceptibility to acute lymphoblastic leukaemia in children

    DEFF Research Database (Denmark)

    Xu, Heng; Zhang, Hui; Yang, Wenjian

    2015-01-01

    in CDKN2A associated with the development of ALL at genome-wide significance (rs3731249, P = 9.4 x 10-23, odds ratio = 2.23). Functional studies indicate that this hypomorphic variant results in reduced tumour suppressor function of p16INK4A, increases the susceptibility to leukaemic transformation...

  4. Identification of a Sjögren's syndrome susceptibility locus at OAS1 that influences isoform switching, protein expression, and responsiveness to type I interferons.

    Directory of Open Access Journals (Sweden)

    He Li

    2017-06-01

    Full Text Available Sjögren's syndrome (SS is a common, autoimmune exocrinopathy distinguished by keratoconjunctivitis sicca and xerostomia. Patients frequently develop serious complications including lymphoma, pulmonary dysfunction, neuropathy, vasculitis, and debilitating fatigue. Dysregulation of type I interferon (IFN pathway is a prominent feature of SS and is correlated with increased autoantibody titers and disease severity. To identify genetic determinants of IFN pathway dysregulation in SS, we performed cis-expression quantitative trait locus (eQTL analyses focusing on differentially expressed type I IFN-inducible transcripts identified through a transcriptome profiling study. Multiple cis-eQTLs were associated with transcript levels of 2'-5'-oligoadenylate synthetase 1 (OAS1 peaking at rs10774671 (PeQTL = 6.05 × 10-14. Association of rs10774671 with SS susceptibility was identified and confirmed through meta-analysis of two independent cohorts (Pmeta = 2.59 × 10-9; odds ratio = 0.75; 95% confidence interval = 0.66-0.86. The risk allele of rs10774671 shifts splicing of OAS1 from production of the p46 isoform to multiple alternative transcripts, including p42, p48, and p44. We found that the isoforms were differentially expressed within each genotype in controls and patients with and without autoantibodies. Furthermore, our results showed that the three alternatively spliced isoforms lacked translational response to type I IFN stimulation. The p48 and p44 isoforms also had impaired protein expression governed by the 3' end of the transcripts. The SS risk allele of rs10774671 has been shown by others to be associated with reduced OAS1 enzymatic activity and ability to clear viral infections, as well as reduced responsiveness to IFN treatment. Our results establish OAS1 as a risk locus for SS and support a potential role for defective viral clearance due to altered IFN response as a genetic pathophysiological basis of this complex autoimmune disease.

  5. PHIP - a novel candidate breast cancer susceptibility locus on 6q14.1

    NARCIS (Netherlands)

    Jiao, X. (Xiang); Aravidis, C. (Christos); Marikkannu, R. (Rajeshwari); Rantala, J. (Johanna); Picelli, S. (Simone); Adamovic, T. (Tatjana); Liu, T. (Tao); Maguire, P. (Paula); B. Kremeyer (Barbara); Luo, L. (Liping); von Holst, S. (Susanna); Kontham, V. (Vinaykumar); Thutkawkorapin, J. (Jessada); Margolin, S. (Sara); Du, Q. (Quan); Lundin, J. (Johanna); Michailidou, K. (Kyriaki); Bolla, M.K. (Manjeet K.); Wang, Q. (Qin); Dennis, J. (Joe); Lush, M. (Michael); C.B. Ambrosone (Christine); I.L. Andrulis (Irene); H. Anton-Culver (Hoda); Antonenkova, N.N. (Natalia N.); Arndt, V. (Volker); M.W. Beckmann (Matthias); C. Blomqvist (Carl); W.J. Blot (William); Boeckx, B. (Bram); S.E. Bojesen (Stig); B. Bonnani (Bernardo); J.S. Brand (Judith S.); H. Brauch (Hiltrud); H. Brenner (Hermann); A. Broeks (Annegien); T. Brüning (Thomas); B. Burwinkel (Barbara); Cai, Q. (Qiuyin); J. Chang-Claude (Jenny); NBCS Collaborators, (); Couch, F.J. (Fergus J.); A. Cox (Angela); S.S. Cross (Simon); S.L. Deming-Halverson (Sandra); P. Devilee (Peter); I. dos Santos Silva (Isabel); Dörk, T. (Thilo); M. Eriksson (Mats); P.A. Fasching (Peter); J.D. Figueroa (Jonine); D. Flesch-Janys (Dieter); H. Flyger (Henrik); M. Gabrielson (Marike); M. García-Closas (Montserrat); Giles, G.G. (Graham G.); A. González-Neira (Anna); P. Guénel (Pascal); Q. Guo (Qi); Gündert, M. (Melanie); C.A. Haiman (Christopher); Hallberg, E. (Emily); U. Hamann (Ute); P. harrington (Patricia); M.J. Hooning (Maartje); J.L. Hopper (John); Huang, G. (Guanmengqian); A. Jakubowska (Anna); M. Jones (Michael); M. Kerin (Michael); V-M. Kosma (Veli-Matti); Kristensen, V.N. (Vessela N.); Lambrechts, D. (Diether); L. Le Marchand (Loic); J. Lubinski (Jan); A. Mannermaa (Arto); J.W.M. Martens (John); A. Meindl (Alfons); R.L. Milne (Roger); A.-M. Mulligan (Anna-Marie); S.L. Neuhausen (Susan); H. Nevanlinna (Heli); J. Peto (Julian); K. Pykäs (Katri); P. Radice (Paolo); V. Rhenius (Valerie); E.J. Sawyer (Elinor); M.K. Schmidt (Marjanka); R.K. Schmutzler (Rita); C.M. Seynaeve (Caroline); Shah, M. (Mitul); J. Simard (Jacques); Southey, M.C. (Melissa C.); A.J. Swerdlow (Anthony ); T. Truong (Thérèse); Wendt, C. (Camilla); R. Winqvist (Robert); W. Zheng (Wei); kConFab/AOCS Investigators, (); J. Benítez (Javier); A.M. Dunning (Alison); P.D.P. Pharoah (Paul); D.F. Easton (Douglas); K. Czene (Kamila); P. Hall (Per); A. Lindblom (Annika)

    2017-01-01

    textabstractMost non-BRCA1/2 breast cancer families have no identified genetic cause. We used linkage and haplotype analyses in familial and sporadic breast cancer cases to identify a susceptibility locus on chromosome 6q. Two independent genome-wide linkage analysis studies suggested a 3 Mb locus

  6. PHIP - a novel candidate breast cancer susceptibility locus on 6q14.1

    DEFF Research Database (Denmark)

    Jiao, Xiang; Aravidis, Christos; Marikkannu, Rajeshwari

    2017-01-01

    Most non-BRCA1/2 breast cancer families have no identified genetic cause. We used linkage and haplotype analyses in familial and sporadic breast cancer cases to identify a susceptibility locus on chromosome 6q. Two independent genome-wide linkage analysis studies suggested a 3 Mb locus on chromos...

  7. The genetic and regulatory architecture of ERBB3-type 1 diabetes susceptibility locus

    DEFF Research Database (Denmark)

    Kaur, Simranjeet; Mirza, Aashiq H.; Brorsson, Caroline Anna

    2016-01-01

    -producing INS-1E cells and the genetic and regulatory architecture of the ERBB3 locus to provide insights to how rs2292239 may confer disease susceptibility. rs2292239 strongly correlated with residual β-cell function and metabolic control in children with T1D. ERBB3 locus associated lncRNA (NONHSAG011351...

  8. A canine chromosome 7 locus confers compulsive disorder susceptibility

    National Research Council Canada - National Science Library

    Dodman, N H; Karlsson, E K; Moon-Fanelli, A; Galdzicka, M; Perloski, M; Shuster, L; Lindblad-Toh, K; Ginns, E I

    2010-01-01

    ... pincher CCD with a chromosome 7 locus containing , an attractive candidate.Genome-wide association analyses were performed using DNA from 92 rigorously phenotyped Doberman pinscher FS BS cases and 6...

  9. The Role of Locus of Control in Leader Influence Behavior.

    Science.gov (United States)

    Johnson, Avis L.; And Others

    1984-01-01

    Investigated whether leader's (N=89) locus of control moderated the relationship between perceived leader influence behaviors and certain subordinate (N=245) outcome variables. The results showed that locus of control did significantly moderate the effect of supervisor influence on productivity and subordinate satisfaction with supervision. (JAC)

  10. Male-pattern baldness susceptibility locus at 20p11.

    NARCIS (Netherlands)

    Richards, J.B.; Yuan, X.; Geller, F.; Waterworth, D.; Bataille, V.; Glass, D.; Song, K.; Waeber, G.; Vollenweider, P.; Aben, K.K.H.; Kiemeney, L.A.L.M.; Walters, B.; Soranzo, N.; Thorsteinsdottir, U.; Kong, A.; Rafnar, T.; Deloukas, P.; Sulem, P.; Stefansson, H.; Stefansson, K.; Spector, T.D.; Mooser, V.

    2008-01-01

    We conducted a genome-wide association study for androgenic alopecia in 1,125 men and identified a newly associated locus at chromosome 20p11.22, confirmed in three independent cohorts (n = 1,650; OR = 1.60, P = 1.1 x 10(-14) for rs1160312). The one man in seven who harbors risk alleles at both

  11. Multidimensional Genetic Analysis of Repeated Seizures in the Hybrid Mouse Diversity Panel Reveals a Novel Epileptogenesis Susceptibility Locus

    Directory of Open Access Journals (Sweden)

    Russell J. Ferland

    2017-08-01

    Full Text Available Epilepsy has many causes and comorbidities affecting as many as 4% of people in their lifetime. Both idiopathic and symptomatic epilepsies are highly heritable, but genetic factors are difficult to characterize among humans due to complex disease etiologies. Rodent genetic studies have been critical to the discovery of seizure susceptibility loci, including Kcnj10 mutations identified in both mouse and human cohorts. However, genetic analyses of epilepsy phenotypes in mice to date have been carried out as acute studies in seizure-naive animals or in Mendelian models of epilepsy, while humans with epilepsy have a history of recurrent seizures that also modify brain physiology. We have applied a repeated seizure model to a genetic reference population, following seizure susceptibility over a 36-d period. Initial differences in generalized seizure threshold among the Hybrid Mouse Diversity Panel (HMDP were associated with a well-characterized seizure susceptibility locus found in mice: Seizure susceptibility 1. Remarkably, Szs1 influence diminished as subsequent induced seizures had diminishing latencies in certain HMDP strains. Administration of eight seizures, followed by an incubation period and an induced retest seizure, revealed novel associations within the calmodulin-binding transcription activator 1, Camta1. Using systems genetics, we have identified four candidate genes that are differentially expressed between seizure-sensitive and -resistant strains close to our novel Epileptogenesis susceptibility factor 1 (Esf1 locus that may act individually or as a coordinated response to the neuronal stress of seizures.

  12. Search for a schizophrenia susceptibility locus of human chromosome 22

    Energy Technology Data Exchange (ETDEWEB)

    Coon, H.; Hoff, M.; Holik, J. [Univ. of Utah Medical Center, Salt Lake City, UT (United States)] [and others

    1994-06-15

    We used 10 highly informative DNA polymorphic markers and genetic linkage analysis to examine whether a gene locus predisposing to schizophrenia is located on chromosome 22, in 105 families with schizophrenia and schizoaffective disorder. The LOD score method, including analysis for heterogeneity, provided no conclusive evidence of linkage under a dominant, recessive, or penetrance free model of inheritance. Affected sib-pair analysis was inconclusive. Affected Pedigree Member (APM) analysis gave only suggestive evidence for linkage. Multipoint APM analysis, using 4 adjacent loci including D22S281 and IL2RB, a region of interest from the APM analysis, gave non-significant results for the three different weighting functions. 18 refs., 1 fig., 7 tabs.

  13. 9q31.2-rs865686 as a susceptibility locus for estrogen receptor-positive breast cancer

    DEFF Research Database (Denmark)

    Warren, Helen; Dudbridge, Frank; Fletcher, Olivia

    2012-01-01

    Our recent genome-wide association study identified a novel breast cancer susceptibility locus at 9q31.2 (rs865686).......Our recent genome-wide association study identified a novel breast cancer susceptibility locus at 9q31.2 (rs865686)....

  14. Fine-mapping of the 1p11.2 breast cancer susceptibility locus

    NARCIS (Netherlands)

    Horne, H.N. (Hisani N.); Chung, C.C. (Charles C.); Zhang, H. (Han); Yu, K. (Kai); Prokunina-Olsson, L. (Ludmila); K. Michailidou (Kyriaki); M.K. Bolla (Manjeet K.); Q. Wang (Qing); J. Dennis (Joe); J.L. Hopper (John); M.C. Southey (Melissa); M.K. Schmidt (Marjanka); A. Broeks (Annegien); K.R. Muir (K.); A. Lophatananon (Artitaya); P.A. Fasching (Peter); M.W. Beckmann (Matthias); O. Fletcher (Olivia); Johnson, N. (Nichola); E.J. Sawyer (Elinor); I.P. Tomlinson (Ian); Burwinkel, B. (Barbara); Marme, F. (Frederik); P. Guénel (Pascal); T. Truong (Thérèse); S.E. Bojesen (Stig); H. Flyger (Henrik); J. Benítez (Javier); A. González-Neira (Anna); H. Anton-Culver (Hoda); S.L. Neuhausen (Susan); Brenner, H. (Hermann); V. Arndt (Volker); A. Meindl (Alfons); R.K. Schmutzler (Rita); H. Brauch (Hiltrud); U. Hamann (Ute); H. Nevanlinna (Heli); S. Khan (Sofia); K. Matsuo (Keitaro); H. Iwata (Hiroji); T. Dörk (Thilo); N.V. Bogdanova (Natalia); A. Lindblom (Annika); S. Margolin (Sara); A. Mannermaa (Arto); V-M. Kosma (Veli-Matti); G. Chenevix-Trench (Georgia); A.H. Wu (Anna); Ven Den Berg, D. (David); A. Smeets (Ann); H. Zhao (Hui); J. Chang-Claude (Jenny); A. Rudolph (Anja); P. Radice (Paolo); M. Barile (Monica); F.J. Couch (Fergus); Vachon, C. (Celine); Giles, G.G. (Graham G.); R.L. Milne (Roger); C.A. Haiman (Christopher A.); L. Le Marchand (Loic); M.S. Goldberg (Mark); S.-H. Teo; N.A.M. Taib (Nur Aishah Mohd); V. Kristensen (Vessela); Borresen-Dale, A.-L. (Anne-Lise); W. Zheng (Wei); M. Shrubsole (Martha); R. Winqvist (Robert); A. Jukkola-Vuorinen (Arja); I.L. Andrulis (Irene); J.A. Knight (Julia); P. Devilee (Peter); C.M. Seynaeve (Caroline); M. García-Closas (Montserrat); K. Czene (Kamila); H. Darabi (Hatef); A. Hollestelle (Antoinette); J.W.M. Martens (John); J. Li (Jingmei); W. Lu (Wei); X.-O. Shu (Xiao-Ou); A. Cox (Angela); S.S. Cross (Simon); W.J. Blot (William); Q. Cai (Qiuyin); M. Shah (Mitul); C. Luccarini (Craig); Baynes, C. (Caroline); P. harrington (Patricia); D. Kang (Daehee); J.-Y. Choi (Ji-Yeob); J.M. Hartman (Joost); Chia, K.S. (Kee Seng); M. Kabisch (Maria); D. Torres (Diana); A. Jakubowska (Anna); J. Lubinski (Jan); S. Sangrajrang (Suleeporn); P. Brennan (Paul); S. Slager (Susan); D. Yannoukakos (Drakoulis); C.-Y. Shen (Chen-Yang); M.-F. Hou (Ming-Feng); A.J. Swerdlow (Anthony ); N. Orr (Nick); J. Simard (Jacques); P. Hall (Per); P.D.P. Pharoah (Paul); D.F. Easton (Douglas F.); Chanock, S.J. (Stephen J.); A.M. Dunning (Alison); J.D. Figueroa (Jonine)

    2016-01-01

    textabstractThe Cancer Genetic Markers of Susceptibility genome-wide association study (GWAS) originally identified a single nucleotide polymorphism (SNP) rs11249433 at 1p11.2 associated with breast cancer risk. To fine-map this locus, we genotyped 92 SNPs in a 900kb region (120,505,799-121,481,132)

  15. 19p13.1 Is a triple-negative-specific breast cancer susceptibility locus

    NARCIS (Netherlands)

    K. Stevens (Kristen); Z. Fredericksen (Zachary); C. Vachon (Celine); X. Wang (Xing); S. Margolin (Sara); A. Lindblom (Annika); H. Nevanlinna (Heli); D. Greco (Dario); K. Aittomäki (Kristiina); C. Blomqvist (Carl); J. Chang-Claude (Jenny); A. Vrieling (Alina); D. Flesch-Janys (Dieter); H.-P. Sinn (Hans-Peter); S. Wang-Gohrke (Shan); S. Nickels (Stefan); H. Brauch (Hiltrud); Y-D. Ko (Yon-Dschun); H.-P. Fischer; R.K. Schmutzler (Rita); A. Meindl (Alfons); C.R. Bartram (Claus); S. Schott (Sarah); C. Engel (Christoph); A.K. Godwin (Andrew); J. Weaver (JoEllen); S.S. Pathak; P. Sharma (Pankaj); H. Brenner (Hermann); H. Mul̈ler (Heiko); V. Arndt (Volker); C. Stegmaier (Christa); P. Miron (Penelope); D. Yannoukakos (Drakoulis); A. Stavropoulou (Alexandra); G. Fountzilas (George); H. Gogas (Helen); R. Swann (Ruth); M. Dwek (Miriam); A. Perkins (Annie); R.L. Milne (Roger); J. Benítez (Javier); M.P. Zamora (Pilar); J.I.A. Perez (Jose Ignacio Arias); S.E. Bojesen (Stig); S.F. Nielsen (Sune); B.G. Nordestgaard (Børge); H. Flyger (Henrik); P. Guénel (Pascal); T. Truong (Thérèse); F. Menegaux (Florence); E. Cordina-Duverger (Emilie); B. Burwinkel (Barbara); F. Marme (Federick); A. Schneeweiss (Andreas); C. Sohn (Christof); E.J. Sawyer (Elinor); I.P. Tomlinson (Ian); M. Kerin (Michael); J. Peto (Julian); N. Johnson (Nichola); O. Fletcher (Olivia); I. dos Santos Silva (Isabel); P.A. Fasching (Peter); M.W. Beckmann (Matthias); A. Hartmann; A.B. Ekici (Arif); A. Lophatananon (Artitaya); K.R. Muir (Kenneth); P. Puttawibul (Puttisak); S. Wiangnon (Surapon); M.K. Schmidt (Marjanka); A. Broeks (Annegien); L.M. Braaf (Linde); E.H. Rosenberg (Efraim); J.L. Hopper (John); C. Apicella (Carmel); D.J. Park (Daniel); M.C. Southey (Melissa); A.J. Swerdlow (Anthony ); A. Ashworth (Alan); O. Nicholas (Orr); M. Schoemaker (Minouk); H. Anton-Culver (Hoda); A. Ziogas (Argyrios); L. Bernstein (Leslie); C.C. Dur (Christina Clarke); C-Y. Shen (Chen-Yang); J-C. Yu (Jyh-Cherng); H.-M. Hsu (Huan-Ming); C.-N. Hsiung (Chia-Ni); U. Hamann (Ute); T. Dun̈nebier (Thomas); T. Rud̈iger (Thomas); H.U. Ulmer (Hans); P.D.P. Pharoah (Paul); A.M. Dunning (Alison); M.K. Humphreys (Manjeet); Q. Wang (Qing); A. Cox (Angela); S.S. Cross (Simon); M.W.R. Reed (Malcolm); P. Hall (Per); K. Czene (Kamila); C.B. Ambrosone (Christine); F. Ademuyiwa (Foluso); H. Hwang (Helena); D. Eccles (Diana); M. García-Closas (Montserrat); J.D. Figueroa (Jonine); M.E. Sherman (Mark); J. Lissowska (Jolanta); P. Devilee (Peter); C.M. Seynaeve (Caroline); R.A.E.M. Tollenaar (Rob); M.J. Hooning (Maartje); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); A.M. Mulligan (Anna Marie); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); M. Grip (Mervi); E.M. John (Esther); A. Miron (Alexander); G.G. Alnæs (Grethe); V. Kristensen (Vessela); A.-L. Brøresen-Dale (Anne-Lise); G.G. Giles (Graham); L. Baglietto (Laura); C.A. McLean (Catriona Ann); G. Severi (Gianluca); M. Kosel (Matthew); V.S. Pankratz (Shane); S. Slager (Susan); J.E. Olson (Janet); P. Radice (Paolo); P. Peterlongo (Paolo); S. Manoukian (Siranoush); M. Barile (Monica); D. Lambrechts (Diether); S. Hatse (Sigrid); A.-S. Dieudonné (Anne-Sophie); M.R. Christiaens (Marie Rose); G. Chenevix-Trench (Georgia); J. Beesley (Jonathan); X. Chen (Xiaoqing); A. Mannermaa (Arto); V-M. Kosma (Veli-Matti); J. Hartikainen (Jaana); Y. Soini (Ylermi); D.F. Easton (Douglas); F.J. Couch (Fergus)

    2012-01-01

    textabstractThe 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with the risk of ovarian cancer. Here, we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER),

  16. Identification of DIO2 as a new susceptibility locus for symptomatic osteoarthritis

    NARCIS (Netherlands)

    I. Meulenbelt (Ingrid); J. Min (Josine); S.D. Bos (Steffan); N. Riyazi (Naghmeh); J.J. Houwing-Duistermaat (Jeanine); H.J. van der Wijk; H.M. Kroon (Herman); M. Nakajima; S. Ikegawa (Shiro); A.G. Uitterlinden (André); J.B.J. van Meurs (Joyce); W.M. van der Deure (Wendy); T.J. Visser (Theo); A.B. Seymour (Albert); N. Lakenberg (Nico); R. van der Breggen (Ruud); D. Kremer (Dennis); P. Tikka-Kleemola (Päivi); M. Kloppenburg (Margreet); J. Loughlin (John); P.E. Slagboom (Eline)

    2008-01-01

    textabstractOsteoarthritis [MIM 165720] is a common late-onset articular joint disease for which no pharmaceutical intervention is available to attenuate the cartilage degeneration. To identify a new osteoarthritis susceptibility locus, a genome-wide linkage scan and combined linkage association

  17. PHIP - a novel candidate breast cancer susceptibility locus on 6q14.1

    DEFF Research Database (Denmark)

    Jiao, Xiang; Aravidis, Christos; Marikkannu, Rajeshwari

    2017-01-01

    Most non-BRCA1/2 breast cancer families have no identified genetic cause. We used linkage and haplotype analyses in familial and sporadic breast cancer cases to identify a susceptibility locus on chromosome 6q. Two independent genome-wide linkage analysis studies suggested a 3 Mb locus on chromos...

  18. X Chromosome-wide Association Study Identifies a Susceptibility Locus for Inflammatory Bowel Disease in Koreans.

    Science.gov (United States)

    Lee, Ho-Su; Oh, Hyunjung; Yang, Suk-Kyun; Baek, Jiwon; Jung, Seulgi; Hong, Myunghee; Kim, Kyung Mo; Shin, Hyoung Doo; Kim, Kyung-Jo; Park, Sang Hyoung; Ye, Byong Duk; Han, Buhm; Song, Kyuyoung

    2017-07-01

    Genome-wide association studies of inflammatory bowel disease identified > 200 susceptibility loci only in autosomes. This study aimed to identify inflammatory bowel disease susceptibility loci on the X chromosome. We performed an X chromosome-wide association study in Korean patients with inflammatory bowel disease. We analysed X chromosome data from our recent genome-wide association studies, including 1505 cases [922 Crohn's disease and 583 ulcerative colitis] and 4041 controls during the discovery phase, followed by replication in additional 1989 cases [993 Crohn's disease, 996 ulcerative colitis] and 3491 controls. Sex-related differential effects of single nucleotide polymorphisms on disease were also evaluated. We confirmed a significant association of a previously reported inflammatory bowel disease susceptibility locus at chromosome Xq26.3 [CD40LG-ARHGEF6; odds ratio, 1.22; 95% confidence interval, 1.16-1.28; combined p = 3.79 × 10-15]. This locus accounted for 0.18% and 0.12% of genetic variance in Crohn's disease and ulcerative colitis, respectively, and increased the total autosomal chromosome genetic variance from 6.65% to 6.83% and from 5.47% to 5.59% for Crohn's disease and ulcerative colitis risk, respectively, in the Korean population. Sex-stratified analyses did not reveal sex-related differences in effect sizes. We confirmed the association of rs2427870 at the CD40LG-ARHGEF6 locus with an inflammatory bowel disease through an X chromosome-wide association study in a Korean population. Our data suggest that the CD40LG-ARHGEF6 locus on the X chromosome might play a role in inflammatory bowel disease pathogenesis in the Korean population.

  19. The Influence of Locus of Control on Student Financial Behavior

    Science.gov (United States)

    Britt, Sonya; Cumbie, Julie A.; Bell, Mary M.

    2013-01-01

    Data on psychological influences of financial behaviors has not been well addressed in student populations, which is concerning given the high levels of general and financial stress experienced by college students. The findings of this study indicate that college students with an external locus of control exhibit the worst financial behaviors.…

  20. (PLWHA): influence of social support, self-esteem, health locus

    African Journals Online (AJOL)

    Coping among people living with HIV/AIDS (PLWHA): influence of social support, self-esteem, health locus of control and gender. ... 73) = 5.59, p.05). It is then concluded that management of HIV/AIDS should ...

  1. Influence of organisational climate and locus of control on job ...

    African Journals Online (AJOL)

    This study examined the influence of perceived organisational climate and locus of control on job satisfaction and turnover intentions of commercial bank workers in Benin, Edo State, Nigeria. To determine this, a 2X2 ANOVA was used to analyse the data. Results from a field study of 200 employees of 25 commercial banks ...

  2. Influences of peer relations and locus of control on students ...

    African Journals Online (AJOL)

    Effort to checkmate extravagance and maximize gain is the focus of all organizations more in this period of global financial crisis. There is need therefore to checkmate unnecessary financial spending. This study examines the influence of the variables, peer relations and locus of control, on such spending among University ...

  3. 240 INFLUENCES OF PEER RELATIONS AND LOCUS OF ...

    African Journals Online (AJOL)

    therefore to checkmate unnecessary financial spending. This study examines the influence of the variables, peer relations and locus of control, on such spending among University students. Three hundred (144 males and 156 females) participants were used for the study. Their ages ranged between 20-30 years with mean ...

  4. PHIP - a novel candidate breast cancer susceptibility locus on 6q14.1.

    Science.gov (United States)

    Jiao, Xiang; Aravidis, Christos; Marikkannu, Rajeshwari; Rantala, Johanna; Picelli, Simone; Adamovic, Tatjana; Liu, Tao; Maguire, Paula; Kremeyer, Barbara; Luo, Liping; von Holst, Susanna; Kontham, Vinaykumar; Thutkawkorapin, Jessada; Margolin, Sara; Du, Quan; Lundin, Johanna; Michailidou, Kyriaki; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Lush, Michael; Ambrosone, Christine B; Andrulis, Irene L; Anton-Culver, Hoda; Antonenkova, Natalia N; Arndt, Volker; Beckmann, Matthias W; Blomqvist, Carl; Blot, William; Boeckx, Bram; Bojesen, Stig E; Bonanni, Bernardo; Brand, Judith S; Brauch, Hiltrud; Brenner, Hermann; Broeks, Annegien; Brüning, Thomas; Burwinkel, Barbara; Cai, Qiuyin; Chang-Claude, Jenny; Couch, Fergus J; Cox, Angela; Cross, Simon S; Deming-Halverson, Sandra L; Devilee, Peter; Dos-Santos-Silva, Isabel; Dörk, Thilo; Eriksson, Mikael; Fasching, Peter A; Figueroa, Jonine; Flesch-Janys, Dieter; Flyger, Henrik; Gabrielson, Marike; García-Closas, Montserrat; Giles, Graham G; González-Neira, Anna; Guénel, Pascal; Guo, Qi; Gündert, Melanie; Haiman, Christopher A; Hallberg, Emily; Hamann, Ute; Harrington, Patricia; Hooning, Maartje J; Hopper, John L; Huang, Guanmengqian; Jakubowska, Anna; Jones, Michael E; Kerin, Michael J; Kosma, Veli-Matti; Kristensen, Vessela N; Lambrechts, Diether; Le Marchand, Loic; Lubinski, Jan; Mannermaa, Arto; Martens, John W M; Meindl, Alfons; Milne, Roger L; Mulligan, Anna Marie; Neuhausen, Susan L; Nevanlinna, Heli; Peto, Julian; Pylkäs, Katri; Radice, Paolo; Rhenius, Valerie; Sawyer, Elinor J; Schmidt, Marjanka K; Schmutzler, Rita K; Seynaeve, Caroline; Shah, Mitul; Simard, Jacques; Southey, Melissa C; Swerdlow, Anthony J; Truong, Thérèse; Wendt, Camilla; Winqvist, Robert; Zheng, Wei; Benitez, Javier; Dunning, Alison M; Pharoah, Paul D P; Easton, Douglas F; Czene, Kamila; Hall, Per; Lindblom, Annika

    2017-11-28

    Most non-BRCA1/2 breast cancer families have no identified genetic cause. We used linkage and haplotype analyses in familial and sporadic breast cancer cases to identify a susceptibility locus on chromosome 6q. Two independent genome-wide linkage analysis studies suggested a 3 Mb locus on chromosome 6q and two unrelated Swedish families with a LOD >2 together seemed to share a haplotype in 6q14.1. We hypothesized that this region harbored a rare high-risk founder allele contributing to breast cancer in these two families. Sequencing of DNA and RNA from the two families did not detect any pathogenic mutations. Finally, 29 SNPs in the region were analyzed in 44,214 cases and 43,532 controls from BCAC, and the original haplotypes in the two families were suggested as low-risk alleles for European and Swedish women specifically. There was also some support for one additional independent moderate-risk allele in Swedish familial samples. The results were consistent with our previous findings in familial breast cancer and supported a breast cancer susceptibility locus at 6q14.1 around the PHIP gene.

  5. Possible linkage of a breast cancer-susceptibility locus to the ABO locus: sensitivity of LOD scores to a single new recombinant observation.

    Science.gov (United States)

    Skolnick, M H; Thompson, E A; Bishop, D T; Cannon, L A

    1984-01-01

    We present evidence of a pedigree in which a major gene for breast cancer-susceptibility appears to segregate in a dominant fashion. Linkage analysis suggests that the breast cancer-susceptibility locus in this family may be linked to the ABO locus, which is located on band q34 of chromosome 9. At an early stage in the analysis, a LOD score of 3.0 for zero recombination was obtained for linkage between ABO and the susceptibility locus, but a single recombinant reduced the LOD score to 1.72 at a recombination fraction of 0.06. A final observation of a nonrecombinant brings the LOD score for this pedigree to 1.99 at theta = 0.05. We attempt to put these results in perspective by discussing the sensitivity of the LOD score to the next observation. Examples of the volatility of LOD scores are given. These simple calculations show that tight linkage represents the worst case for the interpretation of a LOD score of 3.0. Finally, we discuss the linkage between the breast cancer-susceptibility locus and the ABO blood group and approaches to confirming or denying this result.

  6. Identification of I kappa BL as the second major histocompatibility complex-linked susceptibility locus for rheumatoid arthritis.

    Science.gov (United States)

    Okamoto, Koichi; Makino, Satoshi; Yoshikawa, Yoko; Takaki, Asumi; Nagatsuka, Yumie; Ota, Masao; Tamiya, Gen; Kimura, Akinori; Bahram, Seiamak; Inoko, Hidetoshi

    2003-02-01

    Rheumatoid arthritis (RA) is a chronic inflammatory joint disease with a complex etiology in which environmental factors within a genetically susceptible host maneuver the innate and adaptive arms of the immune system toward recognition of autoantigens. This ultimately leads to joint destruction and clinical symptomatology. Despite the identification of a number of disease-susceptibility regions across the genome, RA's major genetic linkage remains with the major histocompatibility complex (MHC), which contains not only the key immune-response class I and class II genes but also a host of other loci, some with potential immunological relevance. Inside the MHC itself, the sole consistent RA association is that with HLA-DRB1, although this does not encode all MHC-related susceptibility. Indeed, in a set of Japanese patients with RA and a control group, we previously reported the presence of a second RA-susceptibility gene within the telomeric human leukocyte antigen (HLA) class III region. Using microsatellites, we narrowed the susceptibility region to 70 kb telomeric of the TNF cluster, known to harbor four expressed genes (I kappa BL, ATP6G, BAT1, and MICB). Here, using numerous single-nucleotide polymorphisms (SNPs) and insertion/deletion polymorphisms, we identify the second RA-susceptibility locus within the HLA region, as the T allele of SNP 96452 (T/A), in the promoter region (position -62) of the I kappa BL gene (P=.0062). This -62T/A SNP disrupts the putative binding motif for the transcriptional repressor, delta EF1, and hence may influence the transcription of I kappa BL, homologous to I kappa B alpha, the latter being a known inhibitor of NF kappa B, which is central to innate immunity. Therefore, the MHC may harbor RA genetic determinants affecting the innate and adaptive arms of the immune system.

  7. An Analysis of Leader Locus of Control and Influence Behaviors.

    Science.gov (United States)

    1983-05-01

    Social desirability response .j• bias: Three alternative models . Academy of Management Journal, 1983, 26. Graen, C., & Schiemann, W. Leader -member...among managers . Organizational Behavior and Human Performance, 1973, 1 184-200. Durand, D.E., & Nord, W.R. Perceived leader behavior as a function of...AD-A129 100 A N A NALYSIS OF LEAQER LOCUS OF CONTROL AND INFLUENCE BEHAVIORS U) NEBRASKA UNIV LINCOLN DEPT OF MANAGEMENT UNLSIID A L JOHNSON ET AL

  8. Sequence divergence of Mus spretus and Mus musculus across a skin cancer susceptibility locus

    Science.gov (United States)

    Mahler, Kimberly L; Fleming, Jessica L; Dworkin, Amy M; Gladman, Nicholas; Cho, Hee-Yeon; Mao, Jian-Hua; Balmain, Allan; Toland, Amanda Ewart

    2008-01-01

    Background Mus spretus diverged from Mus musculus over one million years ago. These mice are genetically and phenotypically divergent. Despite the value of utilizing M. musculus and M. spretus for quantitative trait locus (QTL) mapping, relatively little genomic information on M. spretus exists, and most of the available sequence and polymorphic data is for one strain of M. spretus, Spret/Ei. In previous work, we mapped fifteen loci for skin cancer susceptibility using four different M. spretus by M. musculus F1 backcrosses. One locus, skin tumor susceptibility 5 (Skts5) on chromosome 12, shows strong linkage in one cross. Results To identify potential candidate genes for Skts5, we sequenced 65 named and unnamed genes and coding elements mapping to the peak linkage area in outbred spretus, Spret/EiJ, FVB/NJ, and NIH/Ola. We identified polymorphisms in 62 of 65 genes including 122 amino acid substitutions. To look for polymorphisms consistent with the linkage data, we sequenced exons with amino acid polymorphisms in two additional M. spretus strains and one additional M. musculus strain generating 40.1 kb of sequence data. Eight candidate variants were identified that fit with the linkage data. To determine the degree of variation across M. spretus, we conducted phylogenetic analyses. The relatedness of the M. spretus strains at this locus is consistent with the proximity of region of ascertainment of the ancestral mice. Conclusion Our analyses suggest that, if Skts5 on chromosome 12 is representative of other regions in the genome, then published genomic data for Spret/EiJ are likely to be of high utility for genomic studies in other M. spretus strains. PMID:19105829

  9. Sequence divergence of Mus spretus and Mus musculus across a skin cancer susceptibility locus

    Directory of Open Access Journals (Sweden)

    Balmain Allan

    2008-12-01

    Full Text Available Abstract Background Mus spretus diverged from Mus musculus over one million years ago. These mice are genetically and phenotypically divergent. Despite the value of utilizing M. musculus and M. spretus for quantitative trait locus (QTL mapping, relatively little genomic information on M. spretus exists, and most of the available sequence and polymorphic data is for one strain of M. spretus, Spret/Ei. In previous work, we mapped fifteen loci for skin cancer susceptibility using four different M. spretus by M. musculus F1 backcrosses. One locus, skin tumor susceptibility 5 (Skts5 on chromosome 12, shows strong linkage in one cross. Results To identify potential candidate genes for Skts5, we sequenced 65 named and unnamed genes and coding elements mapping to the peak linkage area in outbred spretus, Spret/EiJ, FVB/NJ, and NIH/Ola. We identified polymorphisms in 62 of 65 genes including 122 amino acid substitutions. To look for polymorphisms consistent with the linkage data, we sequenced exons with amino acid polymorphisms in two additional M. spretus strains and one additional M. musculus strain generating 40.1 kb of sequence data. Eight candidate variants were identified that fit with the linkage data. To determine the degree of variation across M. spretus, we conducted phylogenetic analyses. The relatedness of the M. spretus strains at this locus is consistent with the proximity of region of ascertainment of the ancestral mice. Conclusion Our analyses suggest that, if Skts5 on chromosome 12 is representative of other regions in the genome, then published genomic data for Spret/EiJ are likely to be of high utility for genomic studies in other M. spretus strains.

  10. Allele variations in the OCA2 gene (pink-eyed-dilution locus) are associated with genetic susceptibility to melanoma.

    Science.gov (United States)

    Jannot, Anne-Sophie; Meziani, Roubila; Bertrand, Guylene; Gérard, Benedicte; Descamps, Vincent; Archimbaud, Alain; Picard, Catherine; Ollivaud, Laurence; Basset-Seguin, Nicole; Kerob, Delphine; Lanternier, Guy; Lebbe, Celeste; Saiag, P; Crickx, Beatrice; Clerget-Darpoux, Françoise; Grandchamp, Bernard; Soufir, Nadem; Melan-Cohort

    2005-08-01

    The occuloalbinism 2 (OCA2) gene, localized at 15q11, encodes a melanosomal transmembrane protein that is involved in the most common form of human occulo-cutaneous albinism, a human genetic disorder characterized by fair pigmentation and susceptibility to skin cancer. We wondered whether allele variations at this locus could influence susceptibility to malignant melanoma (MM). In all, 10 intragenic single-nucleotide polymorphisms (SNPs) were genotyped in 113 patients with melanomas and in 105 Caucasian control subjects with no personal or family history of skin cancer. By comparing allelic distribution between cases and controls, we show that MM and OCA2 are associated (p value=0.030 after correction for multiple testing). Then, a recently developed strategy, the 'combination test' enabled us to show that a combination formed by two SNPs was most strongly associated to MM, suggesting a possible interaction between intragenic SNPs. In addition, the role of OCA2 on MM risk was also detected using a logistic model taking into account the presence of variants of the melanocortin 1 receptor gene (MC1R, a key pigmentation gene) and all pigmentation characteristics as melanoma risk factors. Our data demonstrate that a second pigmentation gene, in addition to MC1R, is involved in genetic susceptibility to melanoma.

  11. Identification of a shared genetic susceptibility locus for coronary heart disease and periodontitis.

    Directory of Open Access Journals (Sweden)

    Arne S Schaefer

    2009-02-01

    Full Text Available Recent studies indicate a mutual epidemiological relationship between coronary heart disease (CHD and periodontitis. Both diseases are associated with similar risk factors and are characterized by a chronic inflammatory process. In a candidate-gene association study, we identify an association of a genetic susceptibility locus shared by both diseases. We confirm the known association of two neighboring linkage disequilibrium regions on human chromosome 9p21.3 with CHD and show the additional strong association of these loci with the risk of aggressive periodontitis. For the lead SNP of the main associated linkage disequilibrium region, rs1333048, the odds ratio of the autosomal-recessive mode of inheritance is 1.99 (95% confidence interval 1.33-2.94; P = 6.9 x 10(-4 for generalized aggressive periodontitis, and 1.72 (1.06-2.76; P = 2.6 x 10(-2 for localized aggressive periodontitis. The two associated linkage disequilibrium regions map to the sequence of the large antisense noncoding RNA ANRIL, which partly overlaps regulatory and coding sequences of CDKN2A/CDKN2B. A closely located diabetes-associated variant was independent of the CHD and periodontitis risk haplotypes. Our study demonstrates that CHD and periodontitis are genetically related by at least one susceptibility locus, which is possibly involved in ANRIL activity and independent of diabetes associated risk variants within this region. Elucidation of the interplay of ANRIL transcript variants and their involvement in increased susceptibility to the interactive diseases CHD and periodontitis promises new insight into the underlying shared pathogenic mechanisms of these complex common diseases.

  12. Evidence against an X-linked visual loss susceptibility locus in Leber hereditary optic neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Chalmers, R.M.; Davis, M.B.; Sweeney, M.G.; Wood, N.W.; Harding, A.E. [Inst. of Neurology, London (United Kingdom)

    1996-07-01

    Pedigree analysis of British families with Leber hereditary optic neuropathy (LHON) closely fits a model in which a pathogenic mtDNA mutation interacts with an X-linked visual loss susceptibility locus (VLSL). This model predicts that 60% of affected females will show marked skewing of X inactivation. Linkage analysis in British and Italian families with genetically proven LHON has excluded the presence of such a VLSL over 169 cM of the X chromosome both when all families were analyzed together and when only families with the bp 11778 mutation were studied. Further, there was no excess skewing of X inactivation in affected females. There was no evidence for close linkage to three markers in the pseudoautosomal region of the sex chromosomes. The mechanism of incomplete penetrance and male predominance in LHON remains unclear. 27 refs., 1 fig., 3 tabs.

  13. Fine-Mapping of the 1p11.2 Breast Cancer Susceptibility Locus

    Science.gov (United States)

    Horne, Hisani N.; Chung, Charles C.; Zhang, Han; Yu, Kai; Prokunina-Olsson, Ludmila; Michailidou, Kyriaki; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Hopper, John L.; Southey, Melissa C.; Schmidt, Marjanka K.; Broeks, Annegien; Muir, Kenneth; Lophatananon, Artitaya; Fasching, Peter A.; Beckmann, Matthias W.; Fletcher, Olivia; Johnson, Nichola; Sawyer, Elinor J.; Tomlinson, Ian; Burwinkel, Barbara; Marme, Frederik; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E.; Flyger, Henrik; Benitez, Javier; González-Neira, Anna; Anton-Culver, Hoda; Neuhausen, Susan L.; Brenner, Hermann; Arndt, Volker; Meindl, Alfons; Schmutzler, Rita K.; Brauch, Hiltrud; Hamann, Ute; Nevanlinna, Heli; Khan, Sofia; Matsuo, Keitaro; Iwata, Hiroji; Dörk, Thilo; Bogdanova, Natalia V.; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Chenevix-Trench, Georgia; Wu, Anna H.; ven den Berg, David; Smeets, Ann; Zhao, Hui; Chang-Claude, Jenny; Rudolph, Anja; Radice, Paolo; Barile, Monica; Couch, Fergus J.; Vachon, Celine; Giles, Graham G.; Milne, Roger L.; Haiman, Christopher A.; Marchand, Loic Le; Goldberg, Mark S.; Teo, Soo H.; Taib, Nur A. M.; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Zheng, Wei; Shrubsole, Martha; Winqvist, Robert; Jukkola-Vuorinen, Arja; Andrulis, Irene L.; Knight, Julia A.; Devilee, Peter; Seynaeve, Caroline; García-Closas, Montserrat; Czene, Kamila; Darabi, Hatef; Hollestelle, Antoinette; Martens, John W. M.; Li, Jingmei; Lu, Wei; Shu, Xiao-Ou; Cox, Angela; Cross, Simon S.; Blot, William; Cai, Qiuyin; Shah, Mitul; Luccarini, Craig; Baynes, Caroline; Harrington, Patricia; Kang, Daehee; Choi, Ji-Yeob; Hartman, Mikael; Chia, Kee Seng; Kabisch, Maria; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Sangrajrang, Suleeporn; Brennan, Paul; Slager, Susan; Yannoukakos, Drakoulis; Shen, Chen-Yang; Hou, Ming-Feng; Swerdlow, Anthony; Orr, Nick; Simard, Jacques; Hall, Per; Pharoah, Paul D. P.

    2016-01-01

    The Cancer Genetic Markers of Susceptibility genome-wide association study (GWAS) originally identified a single nucleotide polymorphism (SNP) rs11249433 at 1p11.2 associated with breast cancer risk. To fine-map this locus, we genotyped 92 SNPs in a 900kb region (120,505,799–121,481,132) flanking rs11249433 in 45,276 breast cancer cases and 48,998 controls of European, Asian and African ancestry from 50 studies in the Breast Cancer Association Consortium. Genotyping was done using iCOGS, a custom-built array. Due to the complicated nature of the region on chr1p11.2: 120,300,000–120,505,798, that lies near the centromere and contains seven duplicated genomic segments, we restricted analyses to 429 SNPs excluding the duplicated regions (42 genotyped and 387 imputed). Per-allelic associations with breast cancer risk were estimated using logistic regression models adjusting for study and ancestry-specific principal components. The strongest association observed was with the original identified index SNP rs11249433 (minor allele frequency (MAF) 0.402; per-allele odds ratio (OR) = 1.10, 95% confidence interval (CI) 1.08–1.13, P = 1.49 x 10-21). The association for rs11249433 was limited to ER-positive breast cancers (test for heterogeneity P≤8.41 x 10-5). Additional analyses by other tumor characteristics showed stronger associations with moderately/well differentiated tumors and tumors of lobular histology. Although no significant eQTL associations were observed, in silico analyses showed that rs11249433 was located in a region that is likely a weak enhancer/promoter. Fine-mapping analysis of the 1p11.2 breast cancer susceptibility locus confirms this region to be limited to risk to cancers that are ER-positive. PMID:27556229

  14. Fine-Mapping of the 1p11.2 Breast Cancer Susceptibility Locus.

    Directory of Open Access Journals (Sweden)

    Hisani N Horne

    Full Text Available The Cancer Genetic Markers of Susceptibility genome-wide association study (GWAS originally identified a single nucleotide polymorphism (SNP rs11249433 at 1p11.2 associated with breast cancer risk. To fine-map this locus, we genotyped 92 SNPs in a 900kb region (120,505,799-121,481,132 flanking rs11249433 in 45,276 breast cancer cases and 48,998 controls of European, Asian and African ancestry from 50 studies in the Breast Cancer Association Consortium. Genotyping was done using iCOGS, a custom-built array. Due to the complicated nature of the region on chr1p11.2: 120,300,000-120,505,798, that lies near the centromere and contains seven duplicated genomic segments, we restricted analyses to 429 SNPs excluding the duplicated regions (42 genotyped and 387 imputed. Per-allelic associations with breast cancer risk were estimated using logistic regression models adjusting for study and ancestry-specific principal components. The strongest association observed was with the original identified index SNP rs11249433 (minor allele frequency (MAF 0.402; per-allele odds ratio (OR = 1.10, 95% confidence interval (CI 1.08-1.13, P = 1.49 x 10-21. The association for rs11249433 was limited to ER-positive breast cancers (test for heterogeneity P≤8.41 x 10-5. Additional analyses by other tumor characteristics showed stronger associations with moderately/well differentiated tumors and tumors of lobular histology. Although no significant eQTL associations were observed, in silico analyses showed that rs11249433 was located in a region that is likely a weak enhancer/promoter. Fine-mapping analysis of the 1p11.2 breast cancer susceptibility locus confirms this region to be limited to risk to cancers that are ER-positive.

  15. Fine-Mapping of the 1p11.2 Breast Cancer Susceptibility Locus.

    Science.gov (United States)

    Horne, Hisani N; Chung, Charles C; Zhang, Han; Yu, Kai; Prokunina-Olsson, Ludmila; Michailidou, Kyriaki; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Hopper, John L; Southey, Melissa C; Schmidt, Marjanka K; Broeks, Annegien; Muir, Kenneth; Lophatananon, Artitaya; Fasching, Peter A; Beckmann, Matthias W; Fletcher, Olivia; Johnson, Nichola; Sawyer, Elinor J; Tomlinson, Ian; Burwinkel, Barbara; Marme, Frederik; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E; Flyger, Henrik; Benitez, Javier; González-Neira, Anna; Anton-Culver, Hoda; Neuhausen, Susan L; Brenner, Hermann; Arndt, Volker; Meindl, Alfons; Schmutzler, Rita K; Brauch, Hiltrud; Hamann, Ute; Nevanlinna, Heli; Khan, Sofia; Matsuo, Keitaro; Iwata, Hiroji; Dörk, Thilo; Bogdanova, Natalia V; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Chenevix-Trench, Georgia; Wu, Anna H; Ven den Berg, David; Smeets, Ann; Zhao, Hui; Chang-Claude, Jenny; Rudolph, Anja; Radice, Paolo; Barile, Monica; Couch, Fergus J; Vachon, Celine; Giles, Graham G; Milne, Roger L; Haiman, Christopher A; Marchand, Loic Le; Goldberg, Mark S; Teo, Soo H; Taib, Nur A M; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Zheng, Wei; Shrubsole, Martha; Winqvist, Robert; Jukkola-Vuorinen, Arja; Andrulis, Irene L; Knight, Julia A; Devilee, Peter; Seynaeve, Caroline; García-Closas, Montserrat; Czene, Kamila; Darabi, Hatef; Hollestelle, Antoinette; Martens, John W M; Li, Jingmei; Lu, Wei; Shu, Xiao-Ou; Cox, Angela; Cross, Simon S; Blot, William; Cai, Qiuyin; Shah, Mitul; Luccarini, Craig; Baynes, Caroline; Harrington, Patricia; Kang, Daehee; Choi, Ji-Yeob; Hartman, Mikael; Chia, Kee Seng; Kabisch, Maria; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Sangrajrang, Suleeporn; Brennan, Paul; Slager, Susan; Yannoukakos, Drakoulis; Shen, Chen-Yang; Hou, Ming-Feng; Swerdlow, Anthony; Orr, Nick; Simard, Jacques; Hall, Per; Pharoah, Paul D P; Easton, Douglas F; Chanock, Stephen J; Dunning, Alison M; Figueroa, Jonine D

    2016-01-01

    The Cancer Genetic Markers of Susceptibility genome-wide association study (GWAS) originally identified a single nucleotide polymorphism (SNP) rs11249433 at 1p11.2 associated with breast cancer risk. To fine-map this locus, we genotyped 92 SNPs in a 900kb region (120,505,799-121,481,132) flanking rs11249433 in 45,276 breast cancer cases and 48,998 controls of European, Asian and African ancestry from 50 studies in the Breast Cancer Association Consortium. Genotyping was done using iCOGS, a custom-built array. Due to the complicated nature of the region on chr1p11.2: 120,300,000-120,505,798, that lies near the centromere and contains seven duplicated genomic segments, we restricted analyses to 429 SNPs excluding the duplicated regions (42 genotyped and 387 imputed). Per-allelic associations with breast cancer risk were estimated using logistic regression models adjusting for study and ancestry-specific principal components. The strongest association observed was with the original identified index SNP rs11249433 (minor allele frequency (MAF) 0.402; per-allele odds ratio (OR) = 1.10, 95% confidence interval (CI) 1.08-1.13, P = 1.49 x 10-21). The association for rs11249433 was limited to ER-positive breast cancers (test for heterogeneity P≤8.41 x 10-5). Additional analyses by other tumor characteristics showed stronger associations with moderately/well differentiated tumors and tumors of lobular histology. Although no significant eQTL associations were observed, in silico analyses showed that rs11249433 was located in a region that is likely a weak enhancer/promoter. Fine-mapping analysis of the 1p11.2 breast cancer susceptibility locus confirms this region to be limited to risk to cancers that are ER-positive.

  16. Test of linkage between candidate loci and a prostate cancer susceptibility locus in a set of high risk kindreds

    Energy Technology Data Exchange (ETDEWEB)

    Cannon-Albright, L.A.; Neuhausen, S.; Goldgar, D.E. [Univ. of Utah, Salt Lake City, UT (United States)] [and others

    1994-09-01

    Although no prostate cancer susceptibility locus has yet been mapped, candidate loci have been suggested by a series of allele loss studies in prostate tumors. We have used linkage analysis to investigate each locus previously shown to be lost in at least 30 percent of tumors. Seven high risk cases were screened with 31 markers representing loci on 11 chromosome arms to test for cosegregation of the markers and prostate cancer. Age of cancer onset for prostate cancer cases was not considered for ascertainment. A variety of models were utilized in linkage analysis, as well as model-free methods. A subset of Lod scored at {theta}=.01 are shown for a low penetrance affected-only model which assumed a rare dominant susceptibility and allowed sporadic cases. Multiple markers were run for each locus considered. Positive Lod scores >1.0 in specific kindreds are being investigated further and an exclusion map will be presented.

  17. 2q37 as a susceptibility locus for idiopathic basal ganglia calcification (IBGC) in a large South Tyrolean family.

    Science.gov (United States)

    Volpato, Claudia Béu; De Grandi, Alessandro; Buffone, Ebba; Facheris, Maurizio; Gebert, Uwe; Schifferle, Günther; Schönhuber, Rudolf; Hicks, Andrew; Pramstaller, Peter P

    2009-11-01

    Familial idiopathic basal ganglia calcification (FIBGC) is an inherited neurodegenerative disorder characterized by the accumulation of calcium deposits in different brain regions, particularly in the basal ganglia. FIBGC usually follows an autosomal dominant pattern of inheritance. Despite the mapping to chromosome 14q of a susceptibility locus for IBGC (IBCG1) in one family, this locus has been excluded in several others, demonstrating genetic heterogeneity in this disorder. The etiology of this disorder thus remains largely unknown. Using a large extended multigenerational Italian family from South Tyrol with 17 affected in a total of 56 members, we performed a genome-wide linkage analysis in which we were able to exclude linkage to the IBCG1 locus on chromosome 14q and obtain evidence of a novel locus on chromosome 2q37. Electronic supplementary material. The online version of this article (doi:10.1007/s12031-009-9287-3) contains supplementary material, which is available to authorized users.

  18. Assessment of relatedness between neurocan gene as bipolar disorder susceptibility locus and schizophrenia

    Directory of Open Access Journals (Sweden)

    Lilijana Oruč

    2012-11-01

    Full Text Available Large scale genetic association meta-analyses showed that neurocan (NCAN gene polymorphism rs1064395 is susceptibility locus for bipolar disorder. These studies also included patients with bipolar disorder originated from Bosnia and Herzegovina. Followed by theory of shared genetic elements between bipolar disorder and schizophrenia susceptibility, other studies explored several genetic factors with schizophrenia vulnerability as well. In this work, authors investigated the association between previously confirmed bipolar disorder genetic risk factor-neurocan with schizophrenia in a population sample of Bosnia and Herzegovina.Ethical aspects of this research were assessed by Ethics Committee of Clinical Center University of Sarajevo. Blood samples for DNA extraction were taken from the total of 86 patients and healthy individuals who previously signed informed consent. Genotyping for rs 1064395 was done using direct sequencing method. A case-control analysis of common genetic polymorphism within neurocan gene and schizophrenia status in a consecutively sampled patient cohort have been done using Fisher-exact test with odds-ratio calculation. No statistically significant allele and genotype association with disease status was found (p>0.05.Our finding supports the fact that large-scale genetic association studies approach need to be employed when detecting the variants with small additive effect in phenotypes with complex ethiology.

  19. Evidence for a susceptibility locus for manic-depressive disorder in Xq26

    Energy Technology Data Exchange (ETDEWEB)

    Pekkarinen, P.; Bredbacka, P.E.; Terwilliger, J. [National Public Health Institute, Helsinki (Finland)] [and others

    1994-09-01

    Manic-depression (MD) is a severe psychiatric disorder affecting 1% of the population. Several linkage studies have provided evidence for a susceptibility locus for MD in chromosome Xq27-28. However, validity of these findings have remained unclear for several reasons: linkage has been suggested to two distinct chromosomal regions (F9 and CB-G6PD) separated by 30 cM, linkage has been found in only few of the pedigrees analyzed and ascertainment bias have probably been introduced when using classical markers like CB. The aim of our study was to analyze several markers expanding both of these regions in one extended Finnish pedigree with 13 affected individuals (bipolar or schizoaffective disorder) and without male-to-male transmission. Together 27 polymorphic X chromosomal markers were studied, 22 of them in Xq25-q28. Linkage analyses were carried out using a dominant model, 0.005 disease gene frequency, age-dependent penetrance with a maximum penetrance of 0.80 and low phenocopy rate. Two-point linkage analyses resulted in clearly negative lod scores (<-2) to almost all markers outside the chromosomal region of Xq26. Three markers DXS458, GABRA3 and G6PD, gave uninformative lod scores but respective chromosomal areas could be excluded by other markers in the vicinity. Opposite to this, several markers on Xq26 resulted in positive lod scores. A maximum lod score of 3.4 was obtained with the marker AFM205wd2 at {theta}=0.0. This marker is located about 7 cM centromeric to F9. When all published linkage data on Xq26-q28 was reanalyzed no evidence for locus heterogeneity emerged suggesting a more general significance of this DNA region in the predisposition to manic-depressive disorder.

  20. Trans-Ancestral Studies Fine Map the SLE-Susceptibility Locus TNFSF4

    Science.gov (United States)

    Manku, Harinder; Langefeld, Carl D.; Guerra, Sandra G.; Malik, Talat H.; Alarcon-Riquelme, Marta; Anaya, Juan-Manuel; Bae, Sang-Cheol; Boackle, Susan A.; Brown, Elizabeth E.; Criswell, Lindsey A.; Freedman, Barry I.; Gaffney, Patrick M.; Gregersen, Peter A.; Guthridge, Joel M.; Han, Sang-Hoon; Harley, John B.; Jacob, Chaim O.; James, Judith A.; Kamen, Diane L.; Kaufman, Kenneth M.; Kelly, Jennifer A.; Martin, Javier; Merrill, Joan T.; Moser, Kathy L.; Niewold, Timothy B.; Park, So-Yeon; Pons-Estel, Bernardo A.; Sawalha, Amr H.; Scofield, R. Hal; Shen, Nan; Stevens, Anne M.; Sun, Celi; Gilkeson, Gary S.; Edberg, Jeff C.; Kimberly, Robert P.; Nath, Swapan K.; Tsao, Betty P.; Vyse, Tim J.

    2013-01-01

    We previously established an 80 kb haplotype upstream of TNFSF4 as a susceptibility locus in the autoimmune disease SLE. SLE-associated alleles at this locus are associated with inflammatory disorders, including atherosclerosis and ischaemic stroke. In Europeans, the TNFSF4 causal variants have remained elusive due to strong linkage disequilibrium exhibited by alleles spanning the region. Using a trans-ancestral approach to fine-map the locus, utilising 17,900 SLE and control subjects including Amerindian/Hispanics (1348 cases, 717 controls), African-Americans (AA) (1529, 2048) and better powered cohorts of Europeans and East Asians, we find strong association of risk alleles in all ethnicities; the AA association replicates in African-American Gullah (152,122). The best evidence of association comes from two adjacent markers: rs2205960-T (P = 1.71×10−34, OR = 1.43[1.26–1.60]) and rs1234317-T (P = 1.16×10−28, OR = 1.38[1.24–1.54]). Inference of fine-scale recombination rates for all populations tested finds the 80 kb risk and non-risk haplotypes in all except African-Americans. In this population the decay of recombination equates to an 11 kb risk haplotype, anchored in the 5′ region proximal to TNFSF4 and tagged by rs2205960-T after 1000 Genomes phase 1 (v3) imputation. Conditional regression analyses delineate the 5′ risk signal to rs2205960-T and the independent non-risk signal to rs1234314-C. Our case-only and SLE-control cohorts demonstrate robust association of rs2205960-T with autoantibody production. The rs2205960-T is predicted to form part of a decameric motif which binds NF-κBp65 with increased affinity compared to rs2205960-G. ChIP-seq data also indicate NF-κB interaction with the DNA sequence at this position in LCL cells. Our research suggests association of rs2205960-T with SLE across multiple groups and an independent non-risk signal at rs1234314-C. rs2205960-T is associated with autoantibody production and

  1. Trans-ancestral studies fine map the SLE-susceptibility locus TNFSF4.

    Directory of Open Access Journals (Sweden)

    Harinder Manku

    Full Text Available We previously established an 80 kb haplotype upstream of TNFSF4 as a susceptibility locus in the autoimmune disease SLE. SLE-associated alleles at this locus are associated with inflammatory disorders, including atherosclerosis and ischaemic stroke. In Europeans, the TNFSF4 causal variants have remained elusive due to strong linkage disequilibrium exhibited by alleles spanning the region. Using a trans-ancestral approach to fine-map the locus, utilising 17,900 SLE and control subjects including Amerindian/Hispanics (1348 cases, 717 controls, African-Americans (AA (1529, 2048 and better powered cohorts of Europeans and East Asians, we find strong association of risk alleles in all ethnicities; the AA association replicates in African-American Gullah (152,122. The best evidence of association comes from two adjacent markers: rs2205960-T (P=1.71 × 10(-34 , OR=1.43[1.26-1.60] and rs1234317-T (P=1.16 × 10(-28 , OR=1.38[1.24-1.54]. Inference of fine-scale recombination rates for all populations tested finds the 80 kb risk and non-risk haplotypes in all except African-Americans. In this population the decay of recombination equates to an 11 kb risk haplotype, anchored in the 5' region proximal to TNFSF4 and tagged by rs2205960-T after 1000 Genomes phase 1 (v3 imputation. Conditional regression analyses delineate the 5' risk signal to rs2205960-T and the independent non-risk signal to rs1234314-C. Our case-only and SLE-control cohorts demonstrate robust association of rs2205960-T with autoantibody production. The rs2205960-T is predicted to form part of a decameric motif which binds NF-κBp65 with increased affinity compared to rs2205960-G. ChIP-seq data also indicate NF-κB interaction with the DNA sequence at this position in LCL cells. Our research suggests association of rs2205960-T with SLE across multiple groups and an independent non-risk signal at rs1234314-C. rs2205960-T is associated with autoantibody production and lymphopenia. Our data

  2. Susceptibility to peer pressure, self-esteem, and health locus of control as correlates of adolescent substance abuse.

    Science.gov (United States)

    Dielman, T E; Campanelli, P C; Shope, J T; Butchart, A T

    1987-01-01

    As part of a school-based alcohol misuse prevention study, questionnaires were administered to 2,589 fifth and sixth grade students to determine levels of use of alcohol, marijuana, and cigarettes, intentions to use these substances, and problems resulting from alcohol misuse. The questionnaire also included 45 items concerning susceptibility to peer pressure, self-esteem, and health locus of control. These 45 items were factor analyzed separately for two groups formed by random assignment. Six factors were identified which were both internally consistent and replicable, and indices were constructed. The indices measuring susceptibility to peer pressure, self-esteem, and internal health locus of control were significantly and negatively correlated with most of the substance use, misuse, and intention items, and an external health locus of control index was not significantly related to most of the substance use, misuse, and intention items. The "Susceptibility to Peer Pressure" index correlated more highly with the adolescent substance use, misuse, and intention items than the self-esteem or the health locus of control indices, and it had the highest alpha coefficient. Implications for the design of school-based substance abuse prevention programs are discussed.

  3. Testicular germ cell tumor susceptibility associated with the UCK2 locus on chromosome 1q23.

    Science.gov (United States)

    Schumacher, Fredrick R; Wang, Zhaoming; Skotheim, Rolf I; Koster, Roelof; Chung, Charles C; Hildebrandt, Michelle A T; Kratz, Christian P; Bakken, Anne C; Bishop, D Timothy; Cook, Michael B; Erickson, R Loren; Fosså, Sophie D; Greene, Mark H; Jacobs, Kevin B; Kanetsky, Peter A; Kolonel, Laurence N; Loud, Jennifer T; Korde, Larissa A; Le Marchand, Loic; Lewinger, Juan Pablo; Lothe, Ragnhild A; Pike, Malcolm C; Rahman, Nazneen; Rubertone, Mark V; Schwartz, Stephen M; Siegmund, Kimberly D; Skinner, Eila C; Turnbull, Clare; Van Den Berg, David J; Wu, Xifeng; Yeager, Meredith; Nathanson, Katherine L; Chanock, Stephen J; Cortessis, Victoria K; McGlynn, Katherine A

    2013-07-01

    Genome-wide association studies (GWASs) have identified multiple common genetic variants associated with an increased risk of testicular germ cell tumors (TGCTs). A previous GWAS reported a possible TGCT susceptibility locus on chromosome 1q23 in the UCK2 gene, but failed to reach genome-wide significance following replication. We interrogated this region by conducting a meta-analysis of two independent GWASs including a total of 940 TGCT cases and 1559 controls for 122 single-nucleotide polymorphisms (SNPs) on chromosome 1q23 and followed up the most significant SNPs in an additional 2202 TGCT cases and 2386 controls from four case-control studies. We observed genome-wide significant associations for several UCK2 markers, the most significant of which was for rs3790665 (PCombined = 6.0 × 10(-9)). Additional support is provided from an independent familial study of TGCT where a significant over-transmission for rs3790665 with TGCT risk was observed (PFBAT = 2.3 × 10(-3)). Here, we provide substantial evidence for the association between UCK2 genetic variation and TGCT risk.

  4. Fine-Mapping of the 1p11.2 Breast Cancer Susceptibility Locus

    DEFF Research Database (Denmark)

    Horne, Hisani N; Chung, Charles C; Zhang, Han

    2016-01-01

    -specific principal components. The strongest association observed was with the original identified index SNP rs11249433 (minor allele frequency (MAF) 0.402; per-allele odds ratio (OR) = 1.10, 95% confidence interval (CI) 1.08-1.13, P = 1.49 x 10-21). The association for rs11249433 was limited to ER-positive breast......The Cancer Genetic Markers of Susceptibility genome-wide association study (GWAS) originally identified a single nucleotide polymorphism (SNP) rs11249433 at 1p11.2 associated with breast cancer risk. To fine-map this locus, we genotyped 92 SNPs in a 900kb region (120,505,799-121,481,132) flanking...... rs11249433 in 45,276 breast cancer cases and 48,998 controls of European, Asian and African ancestry from 50 studies in the Breast Cancer Association Consortium. Genotyping was done using iCOGS, a custom-built array. Due to the complicated nature of the region on chr1p11.2: 120...

  5. Adolescent Susceptibility to Peer Influence in Sexual Situations

    National Research Council Canada - National Science Library

    Widman, Laura; Choukas-Bradley, Sophia; Helms, Sarah W; Prinstein, Mitchell J

    2016-01-01

    ...; however, not all youth are equally susceptible to these peer influence effects. Understanding individual differences in susceptibility to peer influence is critical to identifying adolescents at risk for negative health outcomes...

  6. Heterogeneous Responses to Antioxidants in Noradrenergic Neurons of the Locus Coeruleus Indicate Differing Susceptibility to Free Radical Content

    Science.gov (United States)

    de Oliveira, Ramatis B.; Gravina, Fernanda S.; Lim, Rebecca; Brichta, Alan M.; Callister, Robert J.; van Helden, Dirk F.

    2012-01-01

    The present study investigated the effects of the antioxidants trolox and dithiothreitol (DTT) on mouse Locus coeruleus (LC) neurons. Electrophysiological measurement of action potential discharge and whole cell current responses in the presence of each antioxidant suggested that there are three neuronal subpopulations within the LC. In current clamp experiments, most neurons (55%; 6/11) did not respond to the antioxidants. The remaining neurons exhibited either hyperpolarization and decreased firing rate (27%; 3/11) or depolarization and increased firing rate (18%; 2/11). Calcium and JC-1 imaging demonstrated that these effects did not change intracellular Ca2+ concentration but may influence mitochondrial function as both antioxidant treatments modulated mitochondrial membrane potential. These suggest that the antioxidant-sensitive subpopulations of LC neurons may be more susceptible to oxidative stress (e.g., due to ATP depletion and/or overactivation of Ca2+-dependent pathways). Indeed it may be that this subpopulation of LC neurons is preferentially destroyed in neurological pathologies such as Parkinson's disease. If this is the case, there may be a protective role for antioxidant therapies. PMID:22577493

  7. Speech sound disorder influenced by a locus in 15q14 region.

    Science.gov (United States)

    Stein, Catherine M; Millard, Christopher; Kluge, Amy; Miscimarra, Lara E; Cartier, Kevin C; Freebairn, Lisa A; Hansen, Amy J; Shriberg, Lawrence D; Taylor, H Gerry; Lewis, Barbara A; Iyengar, Sudha K

    2006-11-01

    Despite a growing body of evidence indicating that speech sound disorder (SSD) has an underlying genetic etiology, researchers have not yet identified specific genes predisposing to this condition. The speech and language deficits associated with SSD are shared with several other disorders, including dyslexia, autism, Prader-Willi Syndrome (PWS), and Angelman's Syndrome (AS), raising the possibility of gene sharing. Furthermore, we previously demonstrated that dyslexia and SSD share genetic susceptibility loci. The present study assesses the hypothesis that SSD also shares susceptibility loci with autism and PWS. To test this hypothesis, we examined linkage between SSD phenotypes and microsatellite markers on the chromosome 15q14-21 region, which has been associated with autism, PWS/AS, and dyslexia. Using SSD as the phenotype, we replicated linkage to the 15q14 region (P=0.004). Further modeling revealed that this locus influenced oral-motor function, articulation and phonological memory, and that linkage at D15S118 was potentially influenced by a parent-of-origin effect (LOD score increase from 0.97 to 2.17, P=0.0633). These results suggest shared genetic determinants in this chromosomal region for SSD, autism, and PWS/AS.

  8. Linkage Analysis in Autoimmune Addison's Disease: NFATC1 as a Potential Novel Susceptibility Locus.

    Directory of Open Access Journals (Sweden)

    Anna L Mitchell

    Full Text Available Autoimmune Addison's disease (AAD is a rare, highly heritable autoimmune endocrinopathy. It is possible that there may be some highly penetrant variants which confer disease susceptibility that have yet to be discovered.DNA samples from 23 multiplex AAD pedigrees from the UK and Norway (50 cases, 67 controls were genotyped on the Affymetrix SNP 6.0 array. Linkage analysis was performed using Merlin. EMMAX was used to carry out a genome-wide association analysis comparing the familial AAD cases to 2706 UK WTCCC controls. To explore some of the linkage findings further, a replication study was performed by genotyping 64 SNPs in two of the four linked regions (chromosomes 7 and 18, on the Sequenom iPlex platform in three European AAD case-control cohorts (1097 cases, 1117 controls. The data were analysed using a meta-analysis approach.In a parametric analysis, applying a rare dominant model, loci on chromosomes 7, 9 and 18 had LOD scores >2.8. In a non-parametric analysis, a locus corresponding to the HLA region on chromosome 6, known to be associated with AAD, had a LOD score >3.0. In the genome-wide association analysis, a SNP cluster on chromosome 2 and a pair of SNPs on chromosome 6 were associated with AAD (P <5x10-7. A meta-analysis of the replication study data demonstrated that three chromosome 18 SNPs were associated with AAD, including a non-synonymous variant in the NFATC1 gene.This linkage study has implicated a number of novel chromosomal regions in the pathogenesis of AAD in multiplex AAD families and adds further support to the role of HLA in AAD. The genome-wide association analysis has also identified a region of interest on chromosome 2. A replication study has demonstrated that the NFATC1 gene is worthy of future investigation, however each of the regions identified require further, systematic analysis.

  9. Further evidence for the existence of major susceptibility of nasopharyngeal carcinoma in the region near HLA-A locus in Southern Chinese

    National Research Council Canada - National Science Library

    Zhao, Manli; Cai, Hongbing; Li, Xin; Zheng, Hang; Yang, Xuexi; Fang, Weiyi; Zhang, Longcheng; Wei, Ganguan; Li, Ming; Yao, Kaitai

    2012-01-01

    .... Human leukocyte antigen (HLA) complex, specially the region near HLA-A locus, was regarded as a major candidate region bearing NPC genetic susceptibility loci in many previous studies including two recent genome-wide association (GWA) studies...

  10. Analysis of positional candidate genes in the AAA1 susceptibility locus for abdominal aortic aneurysms on chromosome 19

    Directory of Open Access Journals (Sweden)

    Ferrell Robert E

    2011-01-01

    Full Text Available Abstract Background Abdominal aortic aneurysm (AAA is a complex disorder with multiple genetic risk factors. Using affected relative pair linkage analysis, we previously identified an AAA susceptibility locus on chromosome 19q13. This locus has been designated as the AAA1 susceptibility locus in the Online Mendelian Inheritance in Man (OMIM database. Methods Nine candidate genes were selected from the AAA1 locus based on their function, as well as mRNA expression levels in the aorta. A sample of 394 cases and 419 controls was genotyped for 41 SNPs located in or around the selected nine candidate genes using the Illumina GoldenGate platform. Single marker and haplotype analyses were performed. Three genes (CEBPG, PEPD and CD22 were selected for DNA sequencing based on the association study results, and exonic regions were analyzed. Immunohistochemical staining of aortic tissue sections from AAA and control individuals was carried out for the CD22 and PEPD proteins with specific antibodies. Results Several SNPs were nominally associated with AAA (p CEBPG, peptidase D (PEPD, and CD22. Haplotype analysis found a nominally associated 5-SNP haplotype in the CEBPG/PEPD locus, as well as a nominally associated 2-SNP haplotype in the CD22 locus. DNA sequencing of the coding regions revealed no variation in CEBPG. Seven sequence variants were identified in PEPD, including three not present in the NCBI SNP (dbSNP database. Sequencing of all 14 exons of CD22 identified 20 sequence variants, five of which were in the coding region and six were in the 3'-untranslated region. Five variants were not present in dbSNP. Immunohistochemical staining for CD22 revealed protein expression in lymphocytes present in the aneurysmal aortic wall only and no detectable expression in control aorta. PEPD protein was expressed in fibroblasts and myofibroblasts in the media-adventitia border in both aneurysmal and non-aneurysmal tissue samples. Conclusions Association testing

  11. Identification of the tyrosine-protein phosphatase non-receptor type 2 as a rheumatoid arthritis susceptibility locus in europeans.

    Directory of Open Access Journals (Sweden)

    Joanna E Cobb

    Full Text Available OBJECTIVES: Genome-wide association studies have facilitated the identification of over 30 susceptibility loci for rheumatoid arthritis (RA. However, evidence for a number of potential susceptibility genes have not so far reached genome-wide significance in studies of Caucasian RA. METHODS: A cohort of 4286 RA patients from across Europe and 5642 population matched controls were genotyped for 25 SNPs, then combined in a meta-analysis with previously published data. RESULTS: Significant evidence of association was detected for nine SNPs within the European samples. When meta-analysed with previously published data, 21 SNPs were associated with RA susceptibility. Although SNPs in the PTPN2 gene were previously reported to be associated with RA in both Japanese and European populations, we show genome-wide evidence for a different SNP within this gene associated with RA susceptibility in an independent European population (rs7234029, P = 4.4×10(-9. CONCLUSIONS: This study provides further genome-wide evidence for the association of the PTPN2 locus (encoding the T cell protein tyrosine phosphastase with Caucasian RA susceptibility. This finding adds to the growing evidence for PTPN2 being a pan-autoimmune susceptibility gene.

  12. Identification of the Tyrosine-Protein Phosphatase Non-Receptor Type 2 as a Rheumatoid Arthritis Susceptibility Locus in Europeans

    Science.gov (United States)

    Cobb, Joanna E.; Plant, Darren; Flynn, Edward; Tadjeddine, Meriem; Dieudé, Philippe; Cornélis, François; Ärlestig, Lisbeth; Dahlqvist, Solbritt Rantapää; Goulielmos, George; Boumpas, Dimitrios T.; Sidiropoulos, Prodromos; Krintel, Sophine B.; Ørnbjerg, Lykke M.; Hetland, Merete L.; Klareskog, Lars; Haeupl, Thomas; Filer, Andrew; Buckley, Christopher D.; Raza, Karim; Witte, Torsten; Schmidt, Reinhold E.; FitzGerald, Oliver; Veale, Douglas; Eyre, Stephen; Worthington, Jane

    2013-01-01

    Objectives Genome-wide association studies have facilitated the identification of over 30 susceptibility loci for rheumatoid arthritis (RA). However, evidence for a number of potential susceptibility genes have not so far reached genome-wide significance in studies of Caucasian RA. Methods A cohort of 4286 RA patients from across Europe and 5642 population matched controls were genotyped for 25 SNPs, then combined in a meta-analysis with previously published data. Results Significant evidence of association was detected for nine SNPs within the European samples. When meta-analysed with previously published data, 21 SNPs were associated with RA susceptibility. Although SNPs in the PTPN2 gene were previously reported to be associated with RA in both Japanese and European populations, we show genome-wide evidence for a different SNP within this gene associated with RA susceptibility in an independent European population (rs7234029, P = 4.4×10−9). Conclusions This study provides further genome-wide evidence for the association of the PTPN2 locus (encoding the T cell protein tyrosine phosphastase) with Caucasian RA susceptibility. This finding adds to the growing evidence for PTPN2 being a pan-autoimmune susceptibility gene. PMID:23840476

  13. Plasminogen alleles influence susceptibility to invasive aspergillosis.

    Directory of Open Access Journals (Sweden)

    Aimee K Zaas

    2008-06-01

    Full Text Available Invasive aspergillosis (IA is a common and life-threatening infection in immunocompromised individuals. A number of environmental and epidemiologic risk factors for developing IA have been identified. However, genetic factors that affect risk for developing IA have not been clearly identified. We report that host genetic differences influence outcome following establishment of pulmonary aspergillosis in an exogenously immune suppressed mouse model. Computational haplotype-based genetic analysis indicated that genetic variation within the biologically plausible positional candidate gene plasminogen (Plg; Gene ID 18855 correlated with murine outcome. There was a single nonsynonymous coding change (Gly110Ser where the minor allele was found in all of the susceptible strains, but not in the resistant strains. A nonsynonymous single nucleotide polymorphism (Asp472Asn was also identified in the human homolog (PLG; Gene ID 5340. An association study within a cohort of 236 allogeneic hematopoietic stem cell transplant (HSCT recipients revealed that alleles at this SNP significantly affected the risk of developing IA after HSCT. Furthermore, we demonstrated that plasminogen directly binds to Aspergillus fumigatus. We propose that genetic variation within the plasminogen pathway influences the pathogenesis of this invasive fungal infection.

  14. Influence of Locus Control on Real and Perceived Relationships ...

    African Journals Online (AJOL)

    They included the Nowicki-Strickland Internal – External Locus of Control Scale for children by Nowicki and Strickland (1973) and Emotional – Social Loneliness Inventory by Vincenzi and Grabosky, (1987). A cross sectional survey design was used while regression analysis and multivariate statistics were used in data ...

  15. Confirmation of a dyslexia susceptibility locus on chromosome 1p34-p36 in a set of 100 Canadian families.

    Science.gov (United States)

    Tzenova, Jordana; Kaplan, Bonnie J; Petryshen, Tracey L; Field, L Leigh

    2004-05-15

    Dyslexia is a common and genetically complex trait that manifests primarily as a reading disability independent of general intelligence and educational opportunity. Strong evidence for a dyslexia susceptibility locus on chromosome 1p34-p36 (near marker D1S199) was recently reported, and an earlier study found suggestive evidence for linkage to the same region. We tested for the presence of a dyslexia gene in this region in a sample of 100 Canadian families using both qualitative and quantitative definitions of the phenotype. Using a qualitative definition of dyslexia (affected, unaffected, or uncertain), the largest multipoint Genehunter Maximum LOD-Score (MLS) in 100 core nuclear families was 3.65 at D1S507, distal to D1S199. Quantitative trait locus (QTL) linkage analysis was performed for four measures of dyslexia (phonological awareness, phonological coding, spelling, and rapid automatized naming speed) employing the variance components approach implemented in Genehunter. Using a model with QTL additive and dominance variance and polygenic additive variance, the multipoint LOD scores maximized proximal to D1S199 (between D1S552 and D1S1622), with peaks of 4.01 for spelling and 1.65 for phonological coding (corresponding LOD scores under 1 degree of freedom were 3.30 and 1.13, respectively). In conclusion, our study confirms and strengthens recent findings of a dyslexia susceptibility gene on chromosome 1p34-p36 (now designated DYX8). Copyright 2003 Wiley-Liss, Inc.

  16. Novel susceptibility locus at 22q11 for diabetic nephropathy in type 1 diabetes

    DEFF Research Database (Denmark)

    Wessman, Maija; Forsblom, Carol; Kaunisto, Mari A

    2011-01-01

    Diabetic nephropathy (DN) affects about 30% of patients with type 1 diabetes (T1D) and contributes to serious morbidity and mortality. So far only the 3q21-q25 region has repeatedly been indicated as a susceptibility region for DN. The aim of this study was to search for new DN susceptibility loc...

  17. Analysis of human chromosome 21 for a locus conferring susceptibility to Hirschsprung Disease

    Energy Technology Data Exchange (ETDEWEB)

    Bolk, S.; Duggan, D.J.; Chakravarti, A. [Case Western Reserve Univ., Cleveland, OH (United States)

    1994-09-01

    It has been estimated that approximately 5% of patients diagnosed with Hirschsprung disease (HSCR), or aganglionic megacolon, have trisomy 21. Since the incidence of Hirschsprung disease is 1/5000 live births and the incidence of trisomy 21 is approximately 1/1000 live births, the observed occurrence of HSCR in trisomy 21 is fifty times higher than expected. We propose that at least one locus on chromosome 21 predisposes to HSCR. Although at fifty times elevated risk, only 1% of Down Syndrome cases have HSCR. Thus additional genes or genetic events are necessary for HSCR to manifest in patients with trisomy 21. Based on segregation analysis, Badner et al. postulated that recessive genes may be responsible for up to 80% of HSCR. We postulate that at least one such gene is on chromosome 21 and increased homozygosity for common recessive HSCR mutations may be one cause for the elevated risk of HSCR in cases of trisomy 21. To map such a chromosome 21 locus, we are searching for segments of human chromosome 21 which are identical by descent from the parent in whom non-disjunction occurred. These segments will arise either from meiosis I (followed by a crossover between the centromere and the locus) or from meiosis II (followed by no crossovers). Nine nuclear families with a proband diagnosed with HSCR and Down Syndrome have been genotyped for 18 microsatellite markers spanning human chromosome 21q. In all nine cases analyzed thus far, trisomy 21 resulted from maternal non-disjunction at meiosis I. At this point no single IBD region is apparent. Therefore, additional families are being ascertained and additional markers at high density are being genotyped to map the HSCR locus.

  18. The 12p13.33/RAD52 locus and genetic susceptibility to squamous cell cancers of upper aerodigestive tract.

    Directory of Open Access Journals (Sweden)

    Manon Delahaye-Sourdeix

    Full Text Available Genetic variants located within the 12p13.33/RAD52 locus have been associated with lung squamous cell carcinoma (LUSC. Here, within 5,947 UADT cancers and 7,789 controls from 9 different studies, we found rs10849605, a common intronic variant in RAD52, to be also associated with upper aerodigestive tract (UADT squamous cell carcinoma cases (OR = 1.09, 95% CI: 1.04-1.15, p = 6x10(-4. We additionally identified rs10849605 as a RAD52 cis-eQTL inUADT(p = 1x10(-3 and LUSC (p = 9x10(-4 tumours, with the UADT/LUSC risk allele correlated with increased RAD52 expression levels. The 12p13.33 locus, encompassing rs10849605/RAD52, was identified as a significant somatic focal copy number amplification in UADT(n = 374, q-value = 0.075 and LUSC (n = 464, q-value = 0.007 tumors and correlated with higher RAD52 tumor expression levels (p = 6x10(-48 and p = 3x10(-29 in UADT and LUSC, respectively. In combination, these results implicate increased RAD52 expression in both genetic susceptibility and tumorigenesis of UADT and LUSC tumors.

  19. Evidence for chromosome 2p16.3 polycystic ovary syndrome susceptibility locus in affected women of European ancestry.

    Science.gov (United States)

    Mutharasan, Priscilla; Galdones, Eugene; Peñalver Bernabé, Beatriz; Garcia, Obed A; Jafari, Nadereh; Shea, Lonnie D; Woodruff, Teresa K; Legro, Richard S; Dunaif, Andrea; Urbanek, Margrit

    2013-01-01

    A previous genome-wide association study in Chinese women with polycystic ovary syndrome (PCOS) identified a region on chromosome 2p16.3 encoding the LH/choriogonadotropin receptor (LHCGR) and FSH receptor (FSHR) genes as a reproducible PCOS susceptibility locus. The objective of the study was to determine the role of the LHCGR and/or FSHR gene in the etiology of PCOS in women of European ancestry. This was a genetic association study in a European ancestry cohort of women with PCOS. The study was conducted at an academic medical center. Participants in the study included 905 women with PCOS diagnosed by National Institutes of Health criteria and 956 control women. We genotyped 94 haplotype-tagging single-nucleotide polymorphisms and two coding single-nucleotide polymorphisms mapping to the coding region of LHCGR and FSHR plus 20 kb upstream and downstream of the genes and test for association in the case control cohort and for association with nine quantitative traits in the women with PCOS. We found strong evidence for an association of PCOS with rs7562215 (P = 0.0037) and rs10495960 (P = 0.0046). Although the marker with the strongest association in the Chinese PCOS genome-wide association study (rs13405728) was not informative in the European populations, we identified and genotyped three markers (rs35960650, rs2956355, and rs7562879) within 5 kb of rs13405728. Of these, rs7562879 was nominally associated with PCOS (P = 0.020). The strongest evidence for association mapping to FSHR was observed with rs1922476 (P = 0.0053). Furthermore, markers with the FSHR gene region were associated with FSH levels in women with PCOS. Fine mapping of the chromosome 2p16.3 Chinese PCOS susceptibility locus in a European ancestry cohort provides evidence for association with two independent loci and PCOS. The gene products LHCGR and FSHR therefore are likely to be important in the etiology of PCOS, regardless of ethnicity.

  20. acetyltransferases: Influence on Lung Cancer Susceptibility

    African Journals Online (AJOL)

    Lung cancer remains a major health challenge in the world. It is the commonest cause of cancer mortality in men, it has been suggested that genetic susceptibility may contribute to the major risk factor, with increasing prevalence of smoking. Lung cancer has reached epidemic proportions in India. Recently indoor air ...

  1. 11q13 is a Susceptibility Locus for Hormone Receptor Positive Breast Cancer

    DEFF Research Database (Denmark)

    Lambrechts, Diether; Truong, Therese; Justenhoven, Christina

    2012-01-01

    A recent two-stage genome-wide association study (GWAS) identified five novel breast cancer susceptibility loci on chromosomes 9, 10 and 11. To provide more reliable estimates of the relative risk associated with these loci and investigate possible heterogeneity by subtype of breast cancer, we ge...

  2. Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease

    NARCIS (Netherlands)

    Khor, Chiea Chuen; Davila, Sonia; Breunis, Willemijn B.; Lee, Yi-Ching; Shimizu, Chisato; Wright, Victoria J.; Yeung, Rae S. M.; Tan, Dennis E. K.; Sim, Kar Seng; Wang, Jie Jin; Wong, Tien Yin; Pang, Junxiong; Mitchell, Paul; Cimaz, Rolando; Dahdah, Nagib; Cheung, Yiu-Fai; Huang, Guo-Ying; Yang, Wanling; Park, In-Sook; Lee, Jong-Keuk; Wu, Jer-Yuarn; Levin, Michael; Burns, Jane C.; Burgner, David; Kuijpers, Taco W.; Hibberd, Martin L.; Lau, Yu-Lung; Zhang, Jing; Ma, Xiao-Jing; Liu, Fang; Wu, Lin; Yoo, Jeong-Jin; Hong, Soo-Jong; Kim, Kwi-Joo; Kim, Jae-Jung; Park, Young-Mi; Mi Hong, Young; Sohn, Sejung; Young Jang, Gi; Ha, Kee-Soo; Nam, Hyo-Kyoung; Byeon, Jung-Hye; Weon Yun, Sin; Ki Han, Myung; Lee, Kyung-Yil; Hwang, Ja-Young; Rhim, Jung-Woo; Seob Song, Min; Lee, Hyoung-Doo; Kim, Dong Soo; Lee, Jae-Moo; Chang, Jeng-Sheng; Tsai, Fuu-Jen; Liang, Chi-Di; Chen, Ming-Ren; Chi, Hsin; Chiu, Nan-Chang; Huang, Fu-Yuan; Chang, Luan-Yin; Huang, Li-Min; Kuo, Ho-Chang; Huang, Kao-Pin; Lee, Meng-Luen; Hwang, Betau; Huang, Yhu-Chering; Lee, Pi-Chang; Odam, Miranda; Christiansen, Frank T.; Witt, Campbell; Goldwater, Paul; Curtis, Nigel; Palasanthiran, Pamela; Ziegler, John; Nissen, Michael; Nourse, Clare; Kuipers, Irene M.; Ottenkamp, Jaap J.; Geissler, Judy; Biezeveld, Maarten; Tacke, Carline; Filippini, Luc; Brogan, Paul; Klein, Nigel; Shah, Vanita; Dillon, Michael; Booy, Robert; Shingadia, Delane; Bose, Anu; Mukasa, Thomas; Tulloh, Robert; Michie, Colin; Newburger, Jane W.; Baker, Annette L.; Rowley, Anne H.; Shulman, Stanford T.; Mason, Wilbert; Takahashi, Masato; Melish, Marian E.; Tremoulet, Adriana H.; Viswanathan, Ananth; Rochtchina, Elena; Attia, John; Scott, Rodney; Holliday, Elizabeth; Harrap, Stephen

    2011-01-01

    Kawasaki disease is a systemic vasculitis of unknown etiology, with clinical observations suggesting a substantial genetic contribution to disease susceptibility. We conducted a genome-wide association study and replication analysis in 2,173 individuals with Kawasaki disease and 9,383 controls from

  3. Association study of nicotinic acetylcholine receptor genes identifies a novel lung cancer susceptibility locus near CHRNA1 in African-Americans.

    Science.gov (United States)

    Walsh, Kyle M; Amos, Christopher I; Wenzlaff, Angela S; Gorlov, Ivan P; Sison, Jennette D; Wu, Xifeng; Spitz, Margaret R; Hansen, Helen M; Lu, Emily Y; Wei, Chongjuan; Zhang, Huifeng; Chen, Wei; Lloyd, Stacy M; Frazier, Marsha L; Bracci, Paige M; Seldin, Michael F; Wrensch, Margaret R; Schwartz, Ann G; Wiencke, John K

    2012-11-01

    Studies in European and East Asian populations have identified lung cancer susceptibility loci in nicotinic acetylcholine receptor (nAChR) genes on chromosome 15q25.1 which also appear to influence smoking behaviors. We sought to determine if genetic variation in nAChR genes influences lung cancer susceptibly in African-Americans, and evaluated the association of these cancer susceptibility loci with smoking behavior. A total of 1308 African-Americans with lung cancer and 1241 African-American controls from three centers were genotyped for 378 single nucleotide polymorphisms (SNPs) spanning the sixteen human nAChR genes. Associations between SNPs and the risk of lung cancer were estimated using logistic regression, adjusted for relevant covariates. Seven SNPs in three nAChR genes were significantly associated with lung cancer at a strict Bonferroni-corrected level, including a novel association on chromosome 2 near the promoter of CHRNA1 (rs3755486: OR = 1.40, 95% CI = 1.18-1.67, P = 1.0 x 10-4). Association analysis of an additional 305 imputed SNPs on 2q31.1 supported this association. Publicly available expression data demonstrated that the rs3755486 risk allele correlates with increased CHRNA1 gene expression. Additional SNP associations were observed on 15q25.1 in genes previously associated with lung cancer, including a missense variant in CHRNA5 (rs16969968: OR = 1.60, 95% CI = 1.27-2.01, P = 5.9 x 10-5). Risk alleles on 15q25.1 also correlated with an increased number of cigarettes smoked per day among the controls. These findings identify a novel lung cancer risk locus on 2q31.1 which correlates with CHRNA1 expression and replicate previous associations on 15q25.1 in African-Americans.

  4. Locus of Peer Influence: Social Crowd and Best Friend.

    Science.gov (United States)

    Urberg, Kathryn A.

    1992-01-01

    The relative influence of best friends and social crowds of 324 older adolescents (eleventh graders) on cigarette smoking was examined to determine influences as a function of sex, conformity, and friendship mutuality. Best friends, rather than social crowd, appeared to be the major influence in this group. (SLD)

  5. Adolescents' Susceptibility to Maternal and Peer Influence

    OpenAIRE

    Thomas, April Gile

    2017-01-01

    Adolescence is a time of heightened risk taking and vulnerability to social influence. Research has demonstrated the effects of social influence on adolescents’ risk taking; however, most research has focused on the effects of peer influence, with less known about the direct effects of parental influence on adolescent risk. The present study uses an experimental design to examine the effect of indirect and direct maternal and peer influence on adolescents’ risk taking on two behavioral tasks....

  6. The CTRB1/2 locus affects diabetes susceptibility and treatment via the incretin pathway

    DEFF Research Database (Denmark)

    't Hart, Leen M; Fritsche, Andreas; Nijpels, Giel

    2013-01-01

    locus, also associated with an absolute 0.51±0.16% (5.6±1.7 mmol/mol) lower A1C response to DPP-4 inhibitor treatment in G allele carriers but there was no effect on GLP-1 RA treatment in type 2 diabetes patients (n=527). Furthermore, in pancreatic tissue we show that rs7202877 acts as expression......The incretin hormone glucagon-like-peptide 1 (GLP-1) promotes glucose homeostasis and enhances beta-cell function. GLP-1 receptor agonists (GLP-1 RA) and dipeptidyl peptidase-4 (DPP-4) inhibitors, which inhibit the physiological inactivation of endogenous GLP-1, are used for the treatment of type 2...... in the regulation of the incretin pathway, development of diabetes and response to DPP-4 inhibitor treatment....

  7. Multiple signals at the extended 8p23 locus are associated with susceptibility to systemic lupus erythematosus.

    Science.gov (United States)

    Demirci, F Yesim; Wang, Xingbin; Morris, David L; Feingold, Eleanor; Bernatsky, Sasha; Pineau, Christian; Clarke, Ann; Ramsey-Goldman, Rosalind; Manzi, Susan; Vyse, Timothy J; Kamboh, M I

    2017-06-01

    A major systemic lupus erythematosus (SLE) susceptibility locus lies within a common inversion polymorphism region (encompassing 3.8 - 4.5  Mb) located at 8p23. Initially implicated genes included FAM167A-BLK and XKR6, of which BLK received major attention due to its known role in B-cell biology. Recently, additional SLE risk carried in non-inverted background was also reported. In this case -control study, we further investigated the 'extended' 8p23 locus (~ 4  Mb) where we observed multiple SLE signals and assessed these signals for their relation to the inversion affecting this region. The study involved a North American discovery data set (~ 1200  subjects) and a replication data set (> 10 000  subjects) comprising European-descent individuals. Meta-analysis of 8p23 SNPs, with p data sets, identified 51 genome-wide significant SNPs (p signals (XKR6-FAM167A-BLK subregion), our results also revealed two 'new' SLE signals, including SGK223-CLDN23-MFHAS1 (6.06 × 10-9 ≤ meta p ≤ 4.88 × 10-8) and CTSB (meta p = 4.87 × 10-8) subregions that are located > 2 Mb upstream and ~ 0.3  Mb downstream from previously reported signals. Functional assessment of relevant SNPs indicated putative cis-effects on the expression of various genes at 8p23. Additional analyses in discovery sample, where the inversion genotypes were inferred, replicated the association of non-inverted status with SLE risk and suggested that a number of SLE risk alleles are predominantly carried in non-inverted background. Our results implicate multiple (known+novel) SLE signals/genes at the extended 8p23 locus, beyond previously reported signals/genes, and suggest that this broad locus contributes to SLE risk through the effects of multiple genes/pathways. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  8. 9q31.2-rs865686 as a susceptibility locus for estrogen receptor-positive breast cancer: Evidence from the Breast Cancer Association Consortium

    NARCIS (Netherlands)

    H. Warren (Helen); F. Dudbridge (Frank); O. Fletcher (Olivia); N. Orr (Nick); N. Johnson (Nichola); J.L. Hopper (John); C. Apicella (Carmel); M.C. Southey (Melissa); M. Mahmoodi (Maryam); M.K. Schmidt (Marjanka); A. Broeks (Annegien); S. Cornelissen (Sten); L.M. Braaf (Linde); K.R. Muir (Kenneth); A. Lophatananon (Artitaya); A. Chaiwerawattana (Arkom); S. Wiangnon (Surapon); P.A. Fasching (Peter); M.W. Beckmann (Matthias); A.B. Ekici (Arif); R. Schulz-Wendtland (Rüdiger); E.J. Sawyer (Elinor); I.P. Tomlinson (Ian); M. Kerin (Michael); B. Burwinkel (Barbara); F. Marme (Federick); A. Schneeweiss (Andreas); C. Sohn (Christof); P. Guénel (Pascal); T. Truong (Thérèse); P. Laurent-Puig (Pierre); C. Mulot (Claire); S.E. Bojesen (Stig); S.F. Nielsen (Sune); H. Flyger (Henrik); B.G. Nordestgaard (Børge); R.L. Milne (Roger); J. Benítez (Javier); J.I. Arias Pérez (José Ignacio); M.P. Zamora (Pilar); H. Anton-Culver (Hoda); A. Ziogas (Argyrios); L. Bernstein (Leslie); C.C. Dur (Christina Clarke); H. Brenner (Hermann); H. Müller (Heike); V. Arndt (Volker); A. Langheinz (Anne); A. Meindl (Alfons); M. Golatta (Michael); C.R. Bartram (Claus); R.K. Schmutzler (Rita); H. Brauch (Hiltrud); C. Justenhoven (Christina); T. Brüning (Thomas); J. Chang-Claude (Jenny); S. Wang-Gohrke (Shan); U. Eilber (Ursula); T. Dörk (Thilo); P. Schürmann (Peter); M. Bremer (Michael); P. Hillemanns (Peter); H. Nevanlinna (Heli); T.A. Muranen (Taru); K. Aittomäki (Kristiina); C. Blomqvist (Carl); N.V. Bogdanova (Natalia); N.N. Antonenkova (Natalia); Y.I. Rogov (Yuri); M. Bermisheva (Marina); D. Prokofyeva (Darya); G. Zinnatullina (Guzel); E.K. Khusnutdinova (Elza); A. Lindblom (Annika); S. Margolin (Sara); A. Mannermaa (Arto); V-M. Kosma (Veli-Matti); J. Hartikainen (Jaana); V. Kataja (Vesa); G. Chenevix-Trench (Georgia); J. Beesley (Jonathan); X. Chen (Xiaoqing); D. Lambrechts (Diether); A. Smeets (Ann); R. Paridaens (Robert); C. Weltens (Caroline); D. Flesch-Janys (Dieter); K. Buck (Katharina); T.W. Behrens (Timothy); P. Peterlongo (Paolo); L. Bernard (Loris); S. Manoukian (Siranoush); P. Radice (Paolo); F.J. Couch (Fergus); C. Vachon (Celine); X. Wang (Xing); J.E. Olson (Janet); G.G. Giles (Graham); L. Baglietto (Laura); C.A. McLean (Cariona); G. Severi (Gianluca); E.M. John (Esther); A. Miron (Alexander); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); M. Grip (Mervi); I.L. Andrulis (Irene); J.A. Knight (Julia); A.M. Mulligan (Anna Marie); N. Weerasooriya (Nayana); P. Devilee (Peter); R.A.E.M. Tollenaar (Rob); J.W.M. Martens (John); C.M. Seynaeve (Caroline); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); A. Jager (Agnes); M.M.A. Tilanus-Linthorst (Madeleine); P. Hall (Per); K. Czene (Kamila); J. Liu (Jianjun); J. Li (Jingmei); A. Cox (Angela); S.S. Cross (Simon); I.W. Brock (Ian); M.W.R. Reed (Malcolm); P.D.P. Pharoah (Paul); F. Blows (Fiona); A.M. Dunning (Alison); M. Ghoussaini (Maya); A. Ashworth (Alan); A.J. Swerdlow (Anthony ); M. Jones (Marta); M. Schoemaker (Minouk); D.F. Easton (Douglas); M.K. Humphreys (Manjeet); Q. Wang (Qing); J. Peto (Julian); I. dos Santos Silva (Isabel)

    2012-01-01

    textabstractBackground: Our recent genome-wide association study identified a novel breast cancer susceptibility locus at 9q31.2 (rs865686). Methods: To further investigate the rs865686-breast cancer association, we conducted a replication study within the Breast Cancer Association Consortium, which

  9. Sex-specific effects of naturally occurring variants in the dopamine receptor D2 locus on insulin secretion and Type 2 diabetes susceptibility

    DEFF Research Database (Denmark)

    Guigas, B; de Leeuw van Weenen, J E; van Leeuwen, N

    2014-01-01

    AIMS: Modulation of dopamine receptor D2 (DRD2) activity affects insulin secretion in both rodents and isolated pancreatic β-cells. We hypothesized that single nucleotide polymorphisms in the DRD2/ANKK1 locus may affect susceptibility to Type 2 diabetes in humans. METHODS: Four potentially...

  10. Physical Confirmation and Comparative Genomics of the Rat Mammary carcinoma susceptibility 3 Quantitative Trait Locus

    Directory of Open Access Journals (Sweden)

    Saasha Le

    2017-06-01

    Full Text Available Human breast and rat mammary cancer susceptibility are complex phenotypes where complete sets of risk associated loci remain to be identified for both species. We tested multiple congenic rat strains to physically confirm and positionally map rat Mammary carcinoma susceptibility 3 (Mcs3—a mammary cancer resistance allele previously predicted at Rattus norvegicus chromosome 1 (RNO1. The mammary cancer susceptible Wistar Furth (WF strain was the recipient, and the mammary cancer resistant Copenhagen (Cop strain was the RNO1-segment donor for congenics. Inbred WF females averaged 6.3 carcinogen-induced mammary carcinomas per rat. Two WF.Cop congenic strains averaged 2.8 and 3.4 mammary carcinomas per rat, which confirmed Mcs3 as an independently acting allele. Two other WF.Cop congenic strains averaged 6.6 and 8.1 mammary carcinomas per rat, and, thus, did not contain Mcs3. Rat Mcs3 was delimited to 27.8 Mb of RNO1 from rs8149408 to rs105131702 (RNO1:143700228-171517317 of RGSC 6.0/rn6. Human genetic variants with p values for association to breast cancer risk below 10−7 had not been reported for Mcs3 orthologous loci; however, human variants located in Mcs3-orthologous regions with potential association to risk (10−7 < p < 10−3 were listed in some population-based studies. Further, rat Mcs3 contains sequence orthologous to human 11q13/14—a region frequently amplified in female breast cancer. We conclude that Mcs3 is an independently acting mammary carcinoma resistance allele. Human population-based, genome-targeted association studies interrogating Mcs3 orthologous loci may yield novel breast cancer risk associated variants and genes.

  11. Adolescent Susceptibility to Peer Influence in Sexual Situations

    Science.gov (United States)

    Widman, Laura; Choukas-Bradley, Sophia; Helms, Sarah W.; Prinstein, Mitchell J.

    2016-01-01

    Purpose One consistent predictor of adolescents’ engagement in sexual risk behavior is their belief that peers are engaging in similar behavior; however, not all youth are equally susceptible to these peer influence effects. Understanding individual differences in susceptibility to peer influence is critical to identifying adolescents at risk for negative health outcomes. The purpose of this project was to identify predictors of susceptibility to peer influence using a novel performance-based measure of sexual risk-taking. Methods Participants were 300 early adolescents (Mage=12.6; 53% female; 44% Caucasian) who completed 1) a pretest assessment of demographics, sexual attitudes, and hypothetical scenarios measuring the likelihood of engaging in sexual risk behavior, and 2) a subsequent experimental procedure that simulated an internet chat room in which youth believed they were communicating with peers regarding these same hypothetical scenarios. In reality, these “peers” were computer-programmed e-confederates. Changes in responses to the sexual scenarios in the private pretest versus during the public chat room provided a performance-based measure of peer influence susceptibility. Results In total, 78% of youth provided more risky responses in the chat room than in pretest. The most robust predictor of this change was gender, with boys significantly more susceptible to peer influence than girls. Significant interactions also were noted, with greater susceptibility among boys with later pubertal development and African American boys. Conclusion Results confirm that not all youth are equally susceptible to peer influence. Consistent with sexual script theory, boys evidence greater susceptibility to social pressure regarding sexual behavior than girls. PMID:26794431

  12. Adolescent Susceptibility to Peer Influence in Sexual Situations.

    Science.gov (United States)

    Widman, Laura; Choukas-Bradley, Sophia; Helms, Sarah W; Prinstein, Mitchell J

    2016-03-01

    One consistent predictor of adolescents' engagement in sexual risk behavior is their belief that peers are engaging in similar behavior; however, not all youth are equally susceptible to these peer influence effects. Understanding individual differences in susceptibility to peer influence is critical to identifying adolescents at risk for negative health outcomes. The purpose of this project was to identify predictors of susceptibility to peer influence using a novel performance-based measure of sexual risk taking. Participants were 300 early adolescents (Mage = 12.6 years; 53% female; 44% Caucasian) who completed (1) a pretest assessment of demographics, sexual attitudes, and hypothetical scenarios measuring the likelihood of engaging in sexual risk behavior and (2) a subsequent experimental procedure that simulated an Internet chat room in which youth believed that they were communicating with peers regarding these same hypothetical scenarios. In reality, these "peers" were computer-programmed e-confederates. Changes in responses to the sexual scenarios in the private pretest versus during the public chat room provided a performance-based measure of peer influence susceptibility. In total, 78% of youth provided more risky responses in the chat room than those in pretest. The most robust predictor of this change was gender, with boys significantly more susceptible to peer influence than girls. Significant interactions also were noted, with greater susceptibility among boys with later pubertal development and African-American boys. Results confirm that not all youth are equally susceptible to peer influence. Consistent with sexual script theory, boys evidence greater susceptibility to social pressure regarding sexual behavior than girls. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  13. Clinical outcomes for Early Childhood Caries (ECC): the influence of health locus of control.

    Science.gov (United States)

    Chase, I; Berkowitz, R J; Proskin, H M; Weinstein, P; Billings, R

    2004-06-01

    To assess the relationship between clinical outcomes for children treated for ECC and health locus of control. The study cohort consisted of 79 children (42 males, 37 females) treated for ECC; age range was 2.3-7.3 years (mean 4.2 years) at the time of entry into the study. A questionnaire [developed by DeVellis et al., 1993] was administered to each child's parent(s) on the day of dental surgery. This questionnaire examined the expectation that healthcare outcomes in children are influenced by one of the following loci of control: Professional, Parent, Child, Media, Fate and Divine. The cohort was evaluated for new caries lesions at 6 months post dental surgery. Relapse was defined as the presence of new smooth surface caries lesions. For each locus, the scores for the Relapse versus Non-relapse groups (returning patients) and the scores for the returning versus non-returning patients were compared using t-tests. 57 children (72%) returned for follow-up and 21 of these 57 (37%) relapsed. No statistically significant difference for Relapse versus Non-relapse groups was indicated with respect to the scores for any locus parameter (p values ranged from 0.35 to 0.95). Returning parents (N=57) versus non- returning parents (N=22) exhibited statistically significant differences with respect to the Parent, Divine and Fate loci. Returning parents exhibited higher scores on the Parent locus (p=0.0392) and lower scores on the Fate (p=0.0024) and Divine (p=0.0031) loci. 1). The relapse rate (37%) was high and rapid for children treated for ECC; 2). no meaningful difference existed between the Relapse versus Non-relapse groups with respect to each health locus of control parameter; 3). parents who returned for follow-up care appeared to have an internal health locus of control while those who did not return had an external locus.

  14. Two-stage genome-wide association study identifies a novel susceptibility locus associated with melanoma.

    Science.gov (United States)

    Ransohoff, Katherine J; Wu, Wenting; Cho, Hyunje G; Chahal, Harvind C; Lin, Yuan; Dai, Hong-Ji; Amos, Christopher I; Lee, Jeffrey E; Tang, Jean Y; Hinds, David A; Han, Jiali; Wei, Qingyi; Sarin, Kavita Y

    2017-03-14

    Genome-wide association studies have identified 21 susceptibility loci associated with melanoma. These loci implicate genes affecting pigmentation, nevus count, telomere maintenance, and DNA repair in melanoma risk. Here, we report the results of a two-stage genome-wide association study of melanoma. The stage 1 discovery phase consisted of 4,842 self-reported melanoma cases and 286,565 controls of European ancestry from the 23andMe research cohort and the stage 2 replication phase consisted of 1,804 melanoma cases and 1,026 controls from the University of Texas M.D. Anderson Cancer Center. We performed a combined meta-analysis totaling 6,628 melanoma cases and 287,591 controls. Our study replicates 20 of 21 previously known melanoma-loci and confirms the association of the telomerase reverse transcriptase, TERT, with melanoma susceptibility at genome-wide significance. In addition, we uncover a novel polymorphism, rs187843643 (OR = 1.96; 95% CI = [1.54, 2.48]; P = 3.53 x 10-8), associated with melanoma. The SNP rs187842643 lies within a noncoding RNA 177kb downstream of BASP1 (brain associated protein-1). We find that BASP1 expression is suppressed in melanoma as compared with benign nevi, providing additional evidence for a putative role in melanoma pathogenesis.

  15. A Locus at 5q33.3 Confers Resistance to Tuberculosis in Highly Susceptible Individuals

    Science.gov (United States)

    Sobota, Rafal S.; Stein, Catherine M.; Kodaman, Nuri; Scheinfeldt, Laura B.; Maro, Isaac; Wieland-Alter, Wendy; Igo, Robert P.; Magohe, Albert; Malone, LaShaunda L.; Chervenak, Keith; Hall, Noemi B.; Modongo, Chawangwa; Zetola, Nicola; Matee, Mecky; Joloba, Moses; Froment, Alain; Nyambo, Thomas B.; Moore, Jason H.; Scott, William K.; Lahey, Timothy; Boom, W. Henry; von Reyn, C. Fordham; Tishkoff, Sarah A.; Sirugo, Giorgio; Williams, Scott M.

    2016-01-01

    Immunosuppression resulting from HIV infection increases the risk of progression to active tuberculosis (TB) both in individuals newly exposed to Mycobacterium tuberculosis (MTB) and in those with latent infections. We hypothesized that HIV-positive individuals who do not develop TB, despite living in areas where it is hyperendemic, provide a model of natural resistance. We performed a genome-wide association study of TB resistance by using 581 HIV-positive Ugandans and Tanzanians enrolled in prospective cohort studies of TB; 267 of these individuals developed active TB, and 314 did not. A common variant, rs4921437 at 5q33.3, was significantly associated with TB (odds ratio = 0.37, p = 2.11 × 10−8). This variant lies within a genomic region that includes IL12B and is embedded in an H3K27Ac histone mark. The locus also displays consistent patterns of linkage disequilibrium across African populations and has signals of strong selection in populations from equatorial Africa. Along with prior studies demonstrating that therapy with IL-12 (the cytokine encoded in part by IL12B, associated with longer survival following MTB infection in mice deficient in CD4 T cells), our results suggest that this pathway might be an excellent target for the development of new modalities for treating TB, especially for HIV-positive individuals. Our results also indicate that studying extreme disease resistance in the face of extensive exposure can increase the power to detect associations in complex infectious disease. PMID:26942285

  16. Genetic and environmental influences on the relationship between flow proneness, locus of control and behavioral inhibition.

    Directory of Open Access Journals (Sweden)

    Miriam A Mosing

    Full Text Available Flow is a psychological state of high but subjectively effortless attention that typically occurs during active performance of challenging tasks and is accompanied by a sense of automaticity, high control, low self-awareness, and enjoyment. Flow proneness is associated with traits and behaviors related to low neuroticism such as emotional stability, conscientiousness, active coping, self-esteem and life satisfaction. Little is known about the genetic architecture of flow proneness, behavioral inhibition and locus of control--traits also associated with neuroticism--and their interrelation. Here, we hypothesized that individuals low in behavioral inhibition and with an internal locus of control would be more likely to experience flow and explored the genetic and environmental architecture of the relationship between the three variables. Behavioral inhibition and locus of control was measured in a large population sample of 3,375 full twin pairs and 4,527 single twins, about 26% of whom also scored the flow proneness questionnaire. Findings revealed significant but relatively low correlations between the three traits and moderate heritability estimates of .41, .45, and .30 for flow proneness, behavioral inhibition, and locus of control, respectively, with some indication of non-additive genetic influences. For behavioral inhibition we found significant sex differences in heritability, with females showing a higher estimate including significant non-additive genetic influences, while in males the entire heritability was due to additive genetic variance. We also found a mainly genetically mediated relationship between the three traits, suggesting that individuals who are genetically predisposed to experience flow, show less behavioral inhibition (less anxious and feel that they are in control of their own destiny (internal locus of control. We discuss that some of the genes underlying this relationship may include those influencing the function of

  17. Replication of GWAS Coding SNPs Implicates MMEL1 as a Potential Susceptibility Locus among Saudi Arabian Celiac Disease Patients

    Directory of Open Access Journals (Sweden)

    Omar I. Saadah

    2015-01-01

    Full Text Available Celiac disease (CD, a gluten intolerance disorder, was implicated to have 57 genetic susceptibility loci for Europeans but not for culturally and geographically distinct ethnic populations like Saudi Arabian CD patients. Therefore, we genotyped Saudi CD patients and healthy controls for three polymorphisms, that is, Phe196Ser in IRAK1, Trp262Arg in SH2B3, and Met518Thr in MMEL1 genes. Single locus analysis identified that carriers of the 518 Thr/Thr (MMEL1 genotype conferred a 1.6-fold increased disease risk compared to the noncarriers (OR = 2.6; 95% CI: 1.22–5.54; P<0.01. This significance persisted even under allelic (OR = 1.55; 95% CI: 1.05–2.28; P=0.02 and additive (OR = 0.35; 95% CI: 0.17–0.71; P=0.03 genetic models. However, frequencies for Trp262Arg (SH2B3 and Phe196Ser (IRAK1 polymorphisms were not significantly different between patients and controls. The overall best MDR model included Met518Thr and Trp262Arg polymorphisms, with a maximal testing accuracy of 64.1% and a maximal cross-validation consistency of 10 out of 10 (P=0.0156. Allelic distribution of the 518 Thr/Thr polymorphism in MMEL1 primarily suggests its independent and synergistic contribution towards CD susceptibility among Saudi patients. Lack of significant association of IRAK and SH2B3 gene polymorphisms in Saudi patients but their association in European groups suggests the genetic heterogeneity of CD.

  18. An X chromosome association scan of the Norfolk Island genetic isolate provides evidence for a novel migraine susceptibility locus at Xq12.

    Directory of Open Access Journals (Sweden)

    Bridget H Maher

    Full Text Available Migraine is a common and debilitating neurovascular disorder with a complex envirogenomic aetiology. Numerous studies have demonstrated a preponderance of women affected with migraine and previous pedigree linkage studies in our laboratory have identified susceptibility loci on chromosome Xq24-Xq28. In this study we have used the genetic isolate of Norfolk Island to further analyse the X chromosome for migraine susceptibility loci.An association approach was employed to analyse 14,124 SNPs spanning the entire X chromosome. Genotype data from 288 individuals comprising a large core-pedigree, of which 76 were affected with migraine, were analysed. Although no SNP reached chromosome-wide significance (empirical α = 1 × 10(-5 ranking by P-value revealed two primary clusters of SNPs in the top 25. A 10 SNP cluster represents a novel migraine susceptibility locus at Xq12 whilst a 11 SNP cluster represents a previously identified migraine susceptibility locus at Xq27. The strongest association at Xq12 was seen for rs599958 (OR = 1.75, P = 8.92 × 10(-4, whilst at Xq27 the strongest association was for rs6525667 (OR = 1.53, P = 1.65 × 10(-4. Further analysis of SNPs at these loci was performed in 5,122 migraineurs from the Women's Genome Health Study and provided additional evidence for association at the novel Xq12 locus (P<0.05.Overall, this study provides evidence for a novel migraine susceptibility locus on Xq12. The strongest effect SNP (rs102834, joint P = 1.63 × 10(-5 is located within the 5'UTR of the HEPH gene, which is involved in iron homeostasis in the brain and may represent a novel pathway for involvement in migraine pathogenesis.

  19. Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31

    Science.gov (United States)

    Permuth-Wey, Jennifer; Lawrenson, Kate; Shen, Howard C.; Velkova, Aneliya; Tyrer, Jonathan P.; Chen, Zhihua; Lin, Hui-Yi; Chen, Y. Ann; Tsai, Ya-Yu; Qu, Xiaotao; Ramus, Susan J.; Karevan, Rod; Lee, Janet; Lee, Nathan; Larson, Melissa C.; Aben, Katja K.; Anton-Culver, Hoda; Antonenkova, Natalia; Antoniou, Antonis; Armasu, Sebastian M.; Bacot, François; Baglietto, Laura; Bandera, Elisa V.; Barnholtz-Sloan, Jill; Beckmann, Matthias W.; Birrer, Michael J.; Bloom, Greg; Bogdanova, Natalia; Brinton, Louise A.; Brooks-Wilson, Angela; Brown, Robert; Butzow, Ralf; Cai, Qiuyin; Campbell, Ian; Chang-Claude, Jenny; Chanock, Stephen; Chenevix-Trench, Georgia; Cheng, Jin Q.; Cicek, Mine S.; Coetzee, Gerhard A.; Cook, Linda S.; Couch, Fergus J.; Cramer, Daniel W.; Cunningham, Julie M.; Dansonka-Mieszkowska, Agnieszka; Despierre, Evelyn; Doherty, Jennifer A; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Easton, Douglas F; Eccles, Diana; Edwards, Robert; Ekici, Arif B.; Fasching, Peter A.; Fenstermacher, David A.; Flanagan, James M.; Garcia-Closas, Montserrat; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind M.; Gonzalez-Bosquet, Jesus; Goodman, Marc T.; Gore, Martin; Górski, Bohdan; Gronwald, Jacek; Hall, Per; Halle, Mari K.; Harter, Philipp; Heitz, Florian; Hillemanns, Peter; Hoatlin, Maureen; Høgdall, Claus K.; Høgdall, Estrid; Hosono, Satoyo; Jakubowska, Anna; Jensen, Allan; Jim, Heather; Kalli, Kimberly R.; Karlan, Beth Y.; Kaye, Stanley B.; Kelemen, Linda E.; Kiemeney, Lambertus A.; Kikkawa, Fumitaka; Konecny, Gottfried E.; Krakstad, Camilla; Kjaer, Susanne Krüger; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Lancaster, Johnathan M.; Le, Nhu D.; Leminen, Arto; Levine, Douglas A.; Liang, Dong; Lim, Boon Kiong; Lin, Jie; Lissowska, Jolanta; Lu, Karen H.; Lubiński, Jan; Lurie, Galina; Massuger, Leon F.A.G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B.; Nakanishi, Toru; Narod, Steven A.; Nedergaard, Lotte; Ness, Roberta B.; Nevanlinna, Heli; Nickels, Stefan; Noushmehr, Houtan; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Paul, James; Pearce, Celeste L; Pejovic, Tanja; Pelttari, Liisa M.; Pike, Malcolm C.; Poole, Elizabeth M.; Raska, Paola; Renner, Stefan P.; Risch, Harvey A.; Rodriguez-Rodriguez, Lorna; Rossing, Mary Anne; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schwaab, Ira; Severi, Gianluca; Shridhar, Vijayalakshmi; Shu, Xiao-Ou; Shvetsov, Yurii B.; Sieh, Weiva; Song, Honglin; Southey, Melissa C.; Spiewankiewicz, Beata; Stram, Daniel; Sutphen, Rebecca; Teo, Soo-Hwang; Terry, Kathryn L.; Tessier, Daniel C.; Thompson, Pamela J.; Tworoger, Shelley S.; van Altena, Anne M.; Vergote, Ignace; Vierkant, Robert A.; Vincent, Daniel; Vitonis, Allison F.; Wang-Gohrke, Shan; Weber, Rachel Palmieri; Wentzensen, Nicolas; Whittemore, Alice S.; Wik, Elisabeth; Wilkens, Lynne R.; Winterhoff, Boris; Woo, Yin Ling; Wu, Anna H.; Xiang, Yong-Bing; Yang, Hannah P.; Zheng, Wei; Ziogas, Argyrios; Zulkifli, Famida; Phelan, Catherine M.; Iversen, Edwin; Schildkraut, Joellen M.; Berchuck, Andrew; Fridley, Brooke L.; Goode, Ellen L.; Pharoah, Paul D. P.; Monteiro, Alvaro N.A.; Sellers, Thomas A.; Gayther, Simon A.

    2013-01-01

    Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3′ untranslated region at putative microRNA (miRNA) binding sites represent functional targets that influence EOC susceptibility. Here, we evaluate the association between 767 miRNA binding site single nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174 EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative Oncological Gene-environment Study. We identify several miRSNPs associated with invasive serous EOC risk (OR=1.12, P=10−8) mapping to an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion (P=10−10). Variation at 17q21.31 associates with neurological diseases, and our collaboration is the first to report an association with EOC susceptibility. An integrated molecular analysis in this region provides evidence for ARHGAP27 and PLEKHM1 as candidate EOC susceptibility genes. PMID:23535648

  20. Evidence against an X-linked locus close to DXS7 determining visual loss susceptibility in British and Italian families with Leber hereditary optic neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Sweeney, M.G.; Davis, M.B.; Lashwood, A.; Brockington, M.; Harding, A.E. (Institute of Neurology, Queen Square, London (United Kingdom)); Toscano, A. (Clinica Neurologica, Messina (Italy))

    1992-10-01

    Leber hereditary optic neuropathy (LHON) is associated with mutations of mtDNA, but two features of LHON pedigrees are not explicable solely on the basis of mitochondrial inheritance. There is a large excess of affected males, and not all males at risk develop the disease. These observations could be explained by the existence of an X-linked visual loss susceptibility gene. This hypothesis was supported by linkage studies in Finland, placing the susceptibility locus at DXS7, with a maximum lod score of 2.48 at a recombination fraction of 0. Linkage studies in 1 Italian and 12 British families with LHON, analyzed either together or separately depending on the associated mtDNA mutation, have excluded the presence of such a locus from an interval of about 30 cM around DXS7 in these kindreds, with a total lod score of -26.51 at a recombination fraction of 0. 17 refs., 2 figs., 1 tab.

  1. Comparative study of genetic influence on the susceptibility of exotic ...

    African Journals Online (AJOL)

    Comparative study of genetic influence on the susceptibility of exotic cockerels, pullets and broilers to infectious bursal disease virus. ... The clinical signs were severe depression, diarrhoea, anorexia, prostration followed by death. Mortality was 92%, 78% and 6% for cockerels, pullets and broilers, respectively, within 3 days ...

  2. Temperament Alters Susceptibility to Negative Peer Influence in Early Adolescence

    Science.gov (United States)

    Mrug, Sylvie; Madan, Anjana; Windle, Michael

    2012-01-01

    The role of deviant peers in adolescent antisocial behavior has been well documented, but less is known about individual differences in susceptibility to negative peer influence. This study examined whether specific temperament dimensions moderate the prospective relationship between peer deviance and delinquent behavior in early adolescence.…

  3. A genome-wide search for linkage to asthma phenotypes in the genetics of asthma international network families: evidence for a major susceptibility locus on chromosome 2p.

    Science.gov (United States)

    Pillai, Sreekumar G; Chiano, Mathias N; White, Nicola J; Speer, Marcy; Barnes, Kathleen C; Carlsen, Karin; Gerritsen, Jorrit; Helms, Peter; Lenney, Warren; Silverman, Michael; Sly, Peter; Sundy, John; Tsanakas, John; von Berg, Andrea; Whyte, Moira; Varsani, Shela; Skelding, Paul; Hauser, Michael; Vance, Jeffery; Pericak-Vance, Margaret; Burns, Daniel K; Middleton, Lefkos T; Brewster, Shyama R; Anderson, Wayne H; Riley, John H

    2006-03-01

    Asthma is a complex disease and the intricate interplay between genetic and environmental factors underlies the overall phenotype of the disease. Families with at least two siblings with asthma were collected from Europe, Australia and the US. A genome scan using a set of 364 families with a panel of 396 microsatellite markers was conducted. Nonparametric linkage analyses were conducted for asthma and three asthma-related phenotypes: bronchial hyper-reactivity (BHR), strict definition of asthma and atopic asthma. Nine chromosomal regions with LOD scores greater than 1.5 were identified (chromosomes 1q, 2p, 3q, 4p, 4q, 6q, 12q, 20p and 21). Linkage refinement analysis was performed for three BHR loci by genotyping single nucleotide polymorphisms at an average marker density of 1 cM. The LOD scores increased to 3.07 at chromosome 4p and 4.58 at chromosome 2p, while the chromosome 6p locus did not refine. The LOD score at the chromosome 2p locus is highly significant on a genome-wide basis. The refined locus covers a region with a physical size of 12.2 Mb. Taken together, these results provide evidence for a major asthma susceptibility locus on chromosome 2p.

  4. Ancestry-shift refinement mapping of the C6orf97-ESR1 breast cancer susceptibility locus.

    Directory of Open Access Journals (Sweden)

    Simon N Stacey

    2010-07-01

    Full Text Available We used an approach that we term ancestry-shift refinement mapping to investigate an association, originally discovered in a GWAS of a Chinese population, between rs2046210[T] and breast cancer susceptibility. The locus is on 6q25.1 in proximity to the C6orf97 and estrogen receptor alpha (ESR1 genes. We identified a panel of SNPs that are correlated with rs2046210 in Chinese, but not necessarily so in other ancestral populations, and genotyped them in breast cancer case:control samples of Asian, European, and African origin, a total of 10,176 cases and 13,286 controls. We found that rs2046210[T] does not confer substantial risk of breast cancer in Europeans and Africans (OR = 1.04, P = 0.099, and OR = 0.98, P = 0.77, respectively. Rather, in those ancestries, an association signal arises from a group of less common SNPs typified by rs9397435. The rs9397435[G] allele was found to confer risk of breast cancer in European (OR = 1.15, P = 1.2 x 10(-3, African (OR = 1.35, P = 0.014, and Asian (OR = 1.23, P = 2.9 x 10(-4 population samples. Combined over all ancestries, the OR was 1.19 (P = 3.9 x 10(-7, was without significant heterogeneity between ancestries (P(het = 0.36 and the SNP fully accounted for the association signal in each ancestry. Haplotypes bearing rs9397435[G] are well tagged by rs2046210[T] only in Asians. The rs9397435[G] allele showed associations with both estrogen receptor positive and estrogen receptor negative breast cancer. Using early-draft data from the 1,000 Genomes project, we found that the risk allele of a novel SNP (rs77275268, which is closely correlated with rs9397435, disrupts a partially methylated CpG sequence within a known CTCF binding site. These studies demonstrate that shifting the analysis among ancestral populations can provide valuable resolution in association mapping.

  5. C4BPB/C4BPA is a new susceptibility locus for venous thrombosis with unknown protein S-independent mechanism: results from genome-wide association and gene expression analyses followed by case-control studies.

    Science.gov (United States)

    Buil, Alfonso; Trégouët, David-Alexandre; Souto, Juan Carlos; Saut, Noémie; Germain, Marine; Rotival, Maxime; Tiret, Laurence; Cambien, Françcois; Lathrop, Mark; Zeller, Tanja; Alessi, Marie-Christine; Rodriguez de Cordoba, Santiago; Münzel, Thomas; Wild, Philipp; Fontcuberta, Jordi; Gagnon, France; Emmerich, Joseph; Almasy, Laura; Blankenberg, Stefan; Soria, José-Manuel; Morange, Pierre-Emmanuel

    2010-06-10

    Through its binding with protein S (PS), a key element of the coagulation/fibrinolysis cascade, the C4b-binding protein (C4BP) has been hypothesized to be involved in the susceptibility to venous thrombosis (VT). To identify genetic factors that may influence the plasma levels of the 3 C4BP existing isoforms, alpha(7)beta(1), alpha(6)beta(1), and alpha(7)beta(0), we conducted a genome-wide association study by analyzing 283 437 single nucleotide polymorphisms (SNPs) in the Genetic Analysis of Idiopathic Thrombophilia (GAIT) study composed of 352 persons. Three SNPs at the C4BPB/C4BPA locus were found genome-wide significantly associated with alpha(7)beta(0) levels. One of these SNPs was further found to explain approximately 11% of the variability of mRNA C4BPA expression in the Gutenberg Heart Study composed of 1490 persons, with no effect on C4BPB mRNA expression. The allele associated with increased alpha(7)beta(0) plasma levels and increased C4BPA expression was further found associated with increased risk of VT (odds ratio [OR] = 1.24 [1.03-1.53]) in 2 independent case-control studies (MARseille THrombosis Association study [MARTHA] and FActeurs de RIsque et de récidives de la maladie thromboembolique VEineuse [FARIVE]) gathering 1706 cases and 1379 controls. This SNP was not associated with free PS or total PS. In conclusion, we observed strong evidence that the C4BPB/C4BPA locus is a new susceptibility locus for VT through a PS-independent mechanism that remains to be elucidated.

  6. Network Analysis of Human Genes Influencing Susceptibility to Mycobacterial Infections.

    Directory of Open Access Journals (Sweden)

    Ettie M Lipner

    Full Text Available Tuberculosis and nontuberculous mycobacterial infections constitute a high burden of pulmonary disease in humans, resulting in over 1.5 million deaths per year. Building on the premise that genetic factors influence the instance, progression, and defense of infectious disease, we undertook a systems biology approach to investigate relationships among genetic factors that may play a role in increased susceptibility or control of mycobacterial infections. We combined literature and database mining with network analysis and pathway enrichment analysis to examine genes, pathways, and networks, involved in the human response to Mycobacterium tuberculosis and nontuberculous mycobacterial infections. This approach allowed us to examine functional relationships among reported genes, and to identify novel genes and enriched pathways that may play a role in mycobacterial susceptibility or control. Our findings suggest that the primary pathways and genes influencing mycobacterial infection control involve an interplay between innate and adaptive immune proteins and pathways. Signaling pathways involved in autoimmune disease were significantly enriched as revealed in our networks. Mycobacterial disease susceptibility networks were also examined within the context of gene-chemical relationships, in order to identify putative drugs and nutrients with potential beneficial immunomodulatory or anti-mycobacterial effects.

  7. Family-based analysis using a dense single-nucleotide polymorphism-based map defines genetic variation at PSORS1, the major psoriasis-susceptibility locus.

    Science.gov (United States)

    Veal, Colin D; Capon, Francesca; Allen, Michael H; Heath, Emma K; Evans, Julie C; Jones, Andrew; Patel, Shanta; Burden, David; Tillman, David; Barker, Jonathan N W N; Trembath, Richard C

    2002-09-01

    Psoriasis is a common skin disorder of multifactorial origin. Genomewide scans for disease susceptibility have repeatedly demonstrated the existence of a major locus, PSORS1 (psoriasis susceptibility 1), contained within the major histocompatibility complex (MHC), on chromosome 6p21. Subsequent refinement studies have highlighted linkage disequilibrium (LD) with psoriasis, along a 150-kb segment that includes at least three candidate genes (encoding human leukocyte antigen-C [HLA-C], alpha-helix-coiled-coil-rod homologue, and corneodesmosin), each of which has been shown to harbor disease-associated alleles. However, the boundaries of the minimal PSORS1 region remain poorly defined. Moreover, interpretations of allelic association with psoriasis are compounded by limited insight of LD conservation within MHC class I interval. To address these issues, we have pursued a high-resolution genetic characterization of the PSORS1 locus. We resequenced genomic segments along a 220-kb region at chromosome 6p21 and identified a total of 119 high-frequency SNPs. Using 59 SNPs (18 coding and 41 noncoding SNPs) whose position was representative of the overall marker distribution, we genotyped a data set of 171 independently ascertained parent-affected offspring trios. Family-based association analysis of this cohort highlighted two SNPs (n.7 and n.9) respectively lying 7 and 4 kb proximal to HLA-C. These markers generated highly significant evidence of disease association (Prisk haplotype. These data demonstrate the power of SNP haplotype-based association analyses and provide high-resolution dissection of genetic variation across the PSORS1 interval, the major susceptibility locus for psoriasis.

  8. Genome wide high density SNP-based linkage analysis of childhood absence epilepsy identifies a susceptibility locus on chromosome 3p23-p14

    DEFF Research Database (Denmark)

    Chioza, Barry A; Aicardi, Jean; Aschauer, Harald

    2009-01-01

    Childhood absence epilepsy (CAE) is an idiopathic generalised epilepsy (IGE) characterised by typical absence seizures manifested by transitory loss of awareness with 2.5-4 Hz spike-wave complexes on ictal EEG. A genetic component to the aetiology is well recognised but the mechanism of inheritance.......1.1 and a susceptibility locus was identified on chromosome 3p23-p14 (Z(mean)=3.9, palpha=0.7). The linked region harbours the functional candidate genes TRAK1 and CACNA2D2. Fine-mapping using a tagSNP approach demonstrated disease association with variants in TRAK1....

  9. Susceptibility and Influence in Social Media Word-of-Mouth

    DEFF Research Database (Denmark)

    Claussen, Jörg; Engelstätter, Benjamin; Ward, Michael R.

    Peer influence through word-of-mouth (WOM) plays an important role in many information systems but identification of causal effects is challenging. We identify causal WOM effects in the empirical setting of game adoption in a social network for gamers by exploiting differences in individuals...... and receiver side. We find that users with the most influence on others tend to be better gamers, have larger social networks, but spend less time playing. Interestingly, these are also the users who are least susceptible to WOM effects.......’ networks. Friends of friends do not directly influence a focal user, so we use their characteristics to instrument for behavior of the focal user’s friends. We go beyond demonstrating a large and highly significant WOM effect and also assess moderating factors of the strength of the effect on the sender...

  10. Validation of genome-wide intervertebral disk calcification associations in Dachshund and further investigation of the chromosome 12 susceptibility locus

    DEFF Research Database (Denmark)

    Ryt-Hansen, Mette Egesborg; Scheibye-Alsing, Karsten; Karlskov-Mortensen, Peter

    2012-01-01

    Herniation of the intervertebral disk is a common cause of neurological dysfunction in the dog, particularly in the Dachshund. Using the Illumina CanineHD BeadChip, we have previously identified a major locus on canine chromosome 12 nucleotide positions 36,750,205-38,524,449 that strongly......(s) are most likely to be found between nucleotide 36,750,205-37,494,845 as this region explains the highest proportion of variance in the dataset. Finally, we develop a risk prediction model for wire-haired Dachshunds. We validated the association of the chromosome 12 locus with disk calcification...

  11. A Clostridium difficile Cell Wall Glycopolymer Locus Influences Bacterial Shape, Polysaccharide Production and Virulence.

    Directory of Open Access Journals (Sweden)

    Michele Chu

    2016-10-01

    Full Text Available Clostridium difficile is a diarrheagenic pathogen associated with significant mortality and morbidity. While its glucosylating toxins are primary virulence determinants, there is increasing appreciation of important roles for non-toxin factors in C. difficile pathogenesis. Cell wall glycopolymers (CWGs influence the virulence of various pathogens. Five C. difficile CWGs, including PSII, have been structurally characterized, but their biosynthesis and significance in C. difficile infection is unknown. We explored the contribution of a conserved CWG locus to C. difficile cell-surface integrity and virulence. Attempts at disrupting multiple genes in the locus, including one encoding a predicted CWG exporter mviN, were unsuccessful, suggesting essentiality of the respective gene products. However, antisense RNA-mediated mviN downregulation resulted in slight morphology defects, retarded growth, and decreased surface PSII deposition. Two other genes, lcpA and lcpB, with putative roles in CWG anchoring, could be disrupted by insertional inactivation. lcpA- and lcpB- mutants had distinct phenotypes, implying non-redundant roles for the respective proteins. The lcpB- mutant was defective in surface PSII deposition and shedding, and exhibited a remodeled cell surface characterized by elongated and helical morphology, aberrantly-localized cell septae, and an altered surface-anchored protein profile. Both lcpA- and lcpB- strains also displayed heightened virulence in a hamster model of C. difficile disease. We propose that gene products of the C. difficile CWG locus are essential, that they direct the production/assembly of key antigenic surface polysaccharides, and thereby have complex roles in virulence.

  12. Early-life environment influencing susceptibility to cytomegalovirus infection

    DEFF Research Database (Denmark)

    Mortensen, Laust Hvas; Maier, A B; Slagbom, P E

    2012-01-01

    genetically informative cohorts. From the Leiden Longevity Study (LLS) we selected long-lived sib-pairs (n=844) and their middle-aged offspring and the offspring's partners (n=1452). From the Longitudinal Study of Aging Danish Twins (LSADT) 604 (302 pairs) same-sex monozygotic (MZ) and dizygotic (DZ) twins...... number for partners was 71% (Penvironment accounts for the similarity within twin pairs. Our findings suggest that susceptibility to CMV infection......--even under continuous within-partnership exposure--appears to be more strongly influenced by early-life environment than by genetic factors and adult environment....

  13. Genotyping of TRIM5 locus in northern pig-tailed macaques (Macaca leonina, a primate species susceptible to Human Immunodeficiency Virus type 1 infection

    Directory of Open Access Journals (Sweden)

    Jiang Xue-Long

    2009-06-01

    Full Text Available Abstract Background The pig-tailed macaques are the only Old World monkeys known to be susceptible to human immunodeficiency virus type 1 (HIV-1 infection. We have previously reported that the TRIM5-Cyclophilin A (TRIMCyp fusion in pig-tailed macaques (Macaca nemestrina is dysfunctional in restricting HIV-1, which may explain why pig-tailed macaques are susceptible to HIV-1 infection. Similar results have also been reported by other groups. However, according to the current primate taxonomy, the previously reported M. nemestrina are further classified into three species, which all belong to the Macaca spp. This calls for the need to look into the previous studies in more details. Results The local species Northern pig-tailed macaque (M. leonina was analyzed for the correlation of TRIM5 structure and HIV-1 infection. Eleven M. leonina animals were analyzed, and all of them were found to possess TRIM5-CypA fusion at the TRIM5 locus. The transcripts encoding the dysfunctional TRIM5-CypA should result from the G-to-T mutation in the 3'-splicing site of intron 6. Polymorphism in the putative TRIMCyp recognition domain was observed. The peripheral blood mononuclear cells (PBMCs of M. leonina were susceptible to HIV-1 infection. Consistent with the previous results, expression of the M. leonina TRIMCyp in HeLa-T4 cells rendered the cells resistant to HIV-2ROD but not to SIVmac239 infection. Conclusion The susceptibility of M. leonina to HIV-1 infection is due to the dysfunctional TRIM5-CypA fusion in the TRIM5 locus. This finding should broaden our perspective in developing better HIV/AIDS non-human primate animal models.

  14. Familial migraine: Exclusion of the susceptibility gene from the reported locus of familial hemiplegic migraine on 19p

    Energy Technology Data Exchange (ETDEWEB)

    Hovatta, I.; Peltonen, L. [National Public Health Institute, Helsinki (Finland); Kallela, M.; Faerkkilae, M. [Helsinki Univ. Central Hospital (Finland)

    1994-10-01

    Genetic isolates are highly useful in analyses of the molecular background of complex diseases since the enrichment of a limited number of predisposing genes can be predicted in representative families or in specific geographical regions. It has been suggested that the pathophysiology and etiology of familial hemiplegic migraine (FHM) and typical migraine with aura are most probably the same. Recent assignment of FHM locus to chromosome 19p in two French families makes it now possible to test this hypothesis. We report here linkage data on four families with multiple cases of migraine disorder originating from the genetically isolated population of Finland. We were interested to discover whether the migraine in these families would also show linkage to the markers on 19p. We could exclude a region of 50 cM, flanking the reported FHM locus, as a site of migraine locus in our four families. It seems evident that locus heterogeneity exists between different diagnostic classes of migraine spectrum of diseases and also between different ethnic groups. 10 refs., 2 figs., 1 tab.

  15. Selection Role on Configuration of Resistance / Susceptibility Degree to Scrapie and on Genetic Diversity at PrP Locus in the Botosani Karakul Sheep Breed

    Directory of Open Access Journals (Sweden)

    Gheorghe Hrinca

    2017-05-01

    Full Text Available The molecular-genetic profiles from the determinant locus of scrapie have been described in the Botosani Karakul breed. Sheep belonged to two farm types: elite farm from Research and Development Station for Sheep and Goat Breeding, Popauti-Botosani and several production farms of some private farmers. The two farm types differ between them by selective specificities; in the farm elite the selection pressure is stronger and the selection criteria applied to sheep have been more accuracy than in the production farms. Sheep genotyping at the PrP locus was achieved by the Real-Time PCR method. By framing the individuals in risk classes concerning the prion disease, there were identified significant differences between the two farm types in terms of resistance / susceptibility to scrapie of sheep. The elite farm population is significantly advantaged as regards the molecular-genetic endowment at the PrP locus and low probability converting of the PrPc normal protein in the PrPSc pathogenic isomorph compared to the population of production farms. The reasons for the different associations of prion genotypes with morbid phenomenon intensity in the two farm types must be sought exclusively in the characteristics of selection systems applied to the animals in each farm type. From the standpoint of informational statistics, there is a high degree of genetic similarity at the PrP locus between the two populations. Contrary to expectations, the genetic diversity of prion structures is more developed in the elite farm than in the production farms. The knowing importance of prion profiles was revealed  in pursuit of genetic and veterinary prophylaxis of the sheep populations.

  16. Identification of the tyrosine-protein phosphatase non-receptor type 2 as a rheumatoid arthritis susceptibility locus in europeans

    DEFF Research Database (Denmark)

    Cobb, Joanna E; Plant, Darren; Flynn, Edward

    2013-01-01

    Genome-wide association studies have facilitated the identification of over 30 susceptibility loci for rheumatoid arthritis (RA). However, evidence for a number of potential susceptibility genes have not so far reached genome-wide significance in studies of Caucasian RA....

  17. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

    DEFF Research Database (Denmark)

    Lawrenson, Kate; Kar, Siddhartha; McCue, Karen

    2016-01-01

    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10(-20)), ER...

  18. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

    DEFF Research Database (Denmark)

    Lawrenson, Kate; Kar, Siddhartha; McCue, Karen

    2016-01-01

    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10(-20)), ER-n...

  19. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

    NARCIS (Netherlands)

    K. Lawrenson (Kate); S. Kar (Siddhartha); K. McCue (Karen); Kuchenbaeker, K. (Karoline); K. Michailidou (Kyriaki); J.P. Tyrer (Jonathan); J. Beesley (Jonathan); S.J. Ramus (Susan); Li, Q. (Qiyuan); Delgado, M.K. (Melissa K.); J.M. Lee (Janet M.); K. Aittomäki (Kristiina); I.L. Andrulis (Irene); H. Anton-Culver (Hoda); Arndt, V. (Volker); B.K. Arun (Banu); B. Arver (Brita Wasteson); E.V. Bandera (Elisa); M. Barile (Monica); Barkardottir, R.B. (Rosa B.); D. Barrowdale (Daniel); M.W. Beckmann (Matthias); J. Benítez (Javier); A. Berchuck (Andrew); M. Bisogna (Maria); L. Bjorge (Line); C. Blomqvist (Carl); W.J. Blot (William); N.V. Bogdanova (Natalia); Bojesen, A. (Anders); S.E. Bojesen (Stig); M.K. Bolla (Manjeet K.); B. Bonnani (Bernardo); A.-L. Borresen-Dale (Anne-Lise); H. Brauch (Hiltrud); P. Brennan (Paul); H. Brenner (Hermann); F. Bruinsma (Fiona); J. Brunet (Joan); S.A.B.S. Buhari (Shaik Ahmad Bin Syed); B. Burwinkel (Barbara); R. Butzow (Ralf); S.S. Buys (Saundra); Q. Cai (Qiuyin); T. Caldes (Trinidad); I. Campbell (Ian); Canniotto, R. (Rikki); J. Chang-Claude (Jenny); Chiquette, J. (Jocelyne); Choi, J.-Y. (Ji-Yeob); K.B.M. Claes (Kathleen B.M.); L.S. Cook (Linda S.); A. Cox (Angela); D.W. Cramer (Daniel); S.S. Cross (Simon); C. Cybulski (Cezary); K. Czene (Kamila); M.B. Daly (Mary B.); F. Damiola (Francesca); A. Dansonka-Mieszkowska (Agnieszka); H. Darabi (Hatef); J. Dennis (Joe); P. Devilee (Peter); O. Díez (Orland); J.A. Doherty (Jennifer A.); S.M. Domchek (Susan); C.M. Dorfling (Cecilia); T. Dörk (Thilo); M. Dumont (Martine); H. Ehrencrona (Hans); B. Ejlertsen (Bent); S.D. Ellis (Steve); C.W. Engel (Christoph); E. Lee (Eunjung); Evans, D.G. (D. Gareth); P.A. Fasching (Peter); L. Feliubadaló (L.); J.D. Figueroa (Jonine); D. Flesch-Janys (Dieter); O. Fletcher (Olivia); H. Flyger (Henrik); L. Foretova (Lenka); F. Fostira (Florentia); W.D. Foulkes (William); B.L. Fridley (Brooke); E. Friedman (Eitan); D. Frost (Debra); Gambino, G. (Gaetana); P.A. Ganz (Patricia A.); J. Garber (Judy); M. García-Closas (Montserrat); A. Gentry-Maharaj (Aleksandra); M. Ghoussaini (Maya); G.G. Giles (Graham); R. Glasspool (Rosalind); A.K. Godwin (Andrew K.); M.S. Goldberg (Mark); D. Goldgar (David); A. González-Neira (Anna); E.L. Goode (Ellen); M.T. Goodman (Marc); M.H. Greene (Mark H.); J. Gronwald (Jacek); P. Guénel (Pascal); C.A. Haiman (Christopher A.); P. Hall (Per); Hallberg, E. (Emily); U. Hamann (Ute); T.V.O. Hansen (Thomas); P. harrington (Patricia); J.M. Hartman (Joost); N. Hassan (Norhashimah); S. Healey (Sue); P.U. Heitz; J. Herzog (Josef); E. Høgdall (Estrid); C.K. Høgdall (Claus); F.B.L. Hogervorst (Frans); A. Hollestelle (Antoinette); J.L. Hopper (John); P.J. Hulick (Peter); T. Huzarski (Tomasz); E.N. Imyanitov (Evgeny); C. Isaacs (Claudine); H. Ito (Hidemi); A. Jakubowska (Anna); R. Janavicius (Ramunas); A. Jensen (Allan); E.M. John (Esther); Johnson, N. (Nichola); M. Kabisch (Maria); D. Kang (Daehee); M.K. Kapuscinski (Miroslav K.); Karlan, B.Y. (Beth Y.); S. Khan (Sofia); L.A.L.M. Kiemeney (Bart); M. Kjaer (Michael); J.A. Knight (Julia); I. Konstantopoulou (I.); V-M. Kosma (Veli-Matti); V. Kristensen (Vessela); J. Kupryjanczyk (Jolanta); A. Kwong (Ava); M. de La Hoya (Miguel); Y. Laitman (Yael); Lambrechts, D. (Diether); N.D. Le (Nhu D.); K. De Leeneer (Kim); K.J. Lester (Kathryn); D.A. Levine (Douglas); J. Li (Jingmei); A. Lindblom (Annika); J. Long (Jirong); A. Lophatananon (Artitaya); J.T. Loud (Jennifer); K.H. Lu (Karen); J. Lubinski (Jan); A. Mannermaa (Arto); S. Manoukian (Siranoush); L. Le Marchand (Loic); S. Margolin (Sara); F. Marme (Frederick); L.F. Massuger (Leon); K. Matsuo (Keitaro); S. Mazoyer (Sylvie); L. McGuffog (Lesley); C.A. McLean (Catriona Ann); I. McNeish (Iain); A. Meindl (Alfons); U. Menon (Usha); Mensenkamp, A.R. (Arjen R.); R.L. Milne (Roger); M. Montagna (Marco); K.B. Moysich (Kirsten); K.R. Muir (K.); A.-M. Mulligan (Anna-Marie); K.L. Nathanson (Katherine); R.B. Ness (Roberta); S.L. Neuhausen (Susan); H. Nevanlinna (Heli); S. Nord (Silje); R.L. Nussbaum (Robert L.); K. Odunsi (Kunle); K. Offit (Kenneth); E. Olah; O.I. Olopade (Olufunmilayo I.); J.E. Olson (Janet); C. Olswold (Curtis); D.M. O'Malley (David M.); I. Orlow (Irene); N. Orr (Nick); A. Osorio (Ana); Park, S.K. (Sue Kyung); C.L. Pearce (Celeste); T. Pejovic (Tanja); P. Peterlongo (Paolo); G. Pfeiler (Georg); C. Phelan (Catherine); E.M. Poole (Elizabeth); K. Pykäs (Katri); P. Radice (Paolo); J. Rantala (Johanna); M.U. Rashid (Muhammad); G. Rennert (Gad); V. Rhenius (Valerie); K. Rhiem (Kerstin); H. Risch (Harvey); G.C. Rodriguez (Gustavo); M.A. Rossing (Mary Anne); Rudolph, A. (Anja); H.B. Salvesen (Helga); Sangrajrang, S. (Suleeporn); Sawyer, E.J. (Elinor J.); J.M. Schildkraut (Joellen); M.K. Schmidt (Marjanka); R.K. Schmutzler (Rita); T.A. Sellers (Thomas A.); C.M. Seynaeve (Caroline); Shah, M. (Mitul); C.-Y. Shen (Chen-Yang); X.-O. Shu (Xiao-Ou); W. Sieh (Weiva); C.F. Singer (Christian); O. Sinilnikova (Olga); S. Slager (Susan); H. Song (Honglin); Soucy, P. (Penny); M.C. Southey (Melissa); M. Stenmark-Askmalm (Marie); D. Stoppa-Lyonnet (Dominique); C. Sutter (Christian); A.J. Swerdlow (Anthony ); Tchatchou, S. (Sandrine); P.J. Teixeira; S.-H. Teo; K.L. Terry (Kathryn); M.B. Terry (Mary Beth); M. Thomassen (Mads); M.G. Tibiletti (Maria Grazia); L. Tihomirova (Laima); S. Tognazzo (Silvia); A.E. Toland (Amanda); I.P. Tomlinson (Ian); D. Torres (Diana); T. Truong (Thérèse); C.-C. Tseng (Chiu-Chen); N. Tung (Nadine); Tworoger, S.S. (Shelley S.); C. Vachon (Celine); Van Den Ouweland, A.M.W. (Ans M.W.); Van Doorn, H.C. (Helena C.); E.J. van Rensburg (Elizabeth); L.J. van 't Veer (Laura); A. Vanderstichele (Adriaan); I. Vergote (Ignace); J. Vijai (Joseph); Wang, Q. (Qin); S. Wang-Gohrke (Shan); J.N. Weitzel (Jeffrey); N. Wentzensen (N.); A.S. Whittemore (Alice); H. Wildiers (Hans); R. Winqvist (Robert); A.H. Wu (Anna); Yannoukakos, D. (Drakoulis); S.-Y. Yoon (Sook-Yee); J-C. Yu (Jyh-Cherng); W. Zheng (Wei); Y. Zheng (Ying); Khanna, K.K. (Kum Kum); J. Simard (Jacques); A.N.A. Monteiro (Alvaro N.); J.D. French (Juliet); F.J. Couch (Fergus); M. Freedman (Matthew); D.F. Easton (Douglas F.); A.M. Dunning (Alison); P.D.P. Pharoah (Paul); S.L. Edwards (Stacey); G. Chenevix-Trench (Georgia); A.C. Antoniou (Antonis C.); S.A. Gayther (Simon); D. Bowtell (David); A. DeFazio (Anna); P. Webb (Penny); M.-A. Collonge-Rame; Damette, A. (Alexandre); E. Barouk-Simonet (Emmanuelle); F. Bonnet (Françoise); V. Bubien (Virginie); N. Sevenet (Nicolas); M. Longy (Michel); P. Berthet (Pascaline); D. Vaur (Dominique); L. Castera (Laurent); S.F. Ferrer; Y.-J. Bignon (Yves-Jean); N. Uhrhammer (Nancy); F. Coron (Fanny); L. Faivre (Laurence); Baurand, A. (Amandine); Jacquot, C. (Caroline); Bertolone, G. (Geoffrey); Lizard, S. (Sarab); D. Leroux (Dominique); H. Dreyfus (Hélène); C. Rebischung (Christine); Peysselon, M. (Magalie); J.-P. Peyrat; J. Fournier (Joëlle); F. Révillion (Françoise); C. Adenis (Claude); L. Vénat-Bouvet (Laurence); M. Léone (Mélanie); N. Boutry-Kryza (N.); A. Calender (Alain); S. Giraud (Sophie); C. Verny-Pierre (Carole); C. Lasset (Christine); V. Bonadona (Valérie); Barjhoux, L. (Laure); H. Sobol (Hagay); V. Bourdon (Violaine); Noguchi, T. (Tetsuro); A. Remenieras (Audrey); I. Coupier (Isabelle); P. Pujol (Pascal); J. Sokolowska (Johanna); M. Bronner (Myriam); C.D. Delnatte (Capucine); Bézieau, S. (Stéphane); Mari, V. (Véronique); M. Gauthier-Villars (Marion); B. Buecher (Bruno); E. Rouleau (Etienne); L. Golmard (Lisa); V. Moncoutier (Virginie); M. Belotti (Muriel); A. de Pauw (Antoine); Elan, C. (Camille); Fourme, E. (Emmanuelle); Birot, A.-M. (Anne-Marie); Saule, C. (Claire); Laurent, M. (Maïté); C. Houdayer (Claude); F. Lesueur (Fabienne); N. Mebirouk (Noura); F. Coulet (Florence); C. Colas (Chrystelle); F. Soubrier; Warcoin, M. (Mathilde); F. Prieur (Fabienne); M. Lebrun (Marine); C. Kientz (Caroline); D.W. Muller (Danièle); J.P. Fricker (Jean Pierre); C. Toulas (Christine); R. Guimbaud (Rosine); L. Gladieff (Laurence); V. Feillel (Viviane); I. Mortemousque (Isabelle); B. Bressac-de Paillerets (Brigitte); O. Caron (Olivier); M. Guillaud-Bataille (Marine); H. Gregory (Helen); Z. Miedzybrodzka (Zosia); P.J. Morrison (Patrick); A. Donaldson (Alan); M.T. Rogers (Mark); M.J. Kennedy (John); M.E. Porteous (Mary); A. Brady (A.); J. Barwell (Julian); Foo, C. (Claire); F. Lalloo (Fiona); L. Side (Lucy); J. Eason (Jacqueline); Henderson, A. (Alex); L.J. Walker (Lisa); J. Cook (Jackie); Snape, K. (Katie); A. Murray (Alexandra); E. McCann (Emma); M.A. Rookus (Matti); F.E. van Leeuwen (F.); L. van der Kolk (Lizet); M.K. Schmidt (Marjanka); N.S. Russell (Nicola); J.L. de Lange (J.); Wijnands, R.; J.M. Collée; M.J. Hooning (Maartje); Seynaeve, C.; C.H.M. van Deurzen (Carolien); A.I.M. Obdeijn (Inge-Marie); C.J. van Asperen (Christi); R.A.E.M. Tollenaar (Rob); T.C.T.E.F. van Cronenburg; C.M. Kets; M.G.E.M. Ausems (Margreet); C. van der Pol (Carmen); T.A.M. van Os (Theo); Q. Waisfisz (Quinten); E.J. Meijers-Heijboer (Hanne); E.B. Gómez García (Encarna); J.C. Oosterwijk (Jan); M.J. Mourits; G.H. de Bock (Geertruida); H. Vasen (Hans); Siesling, S.; Verloop, J.; L.I.H. Overbeek (Lucy); S.B. Fox (Stephen); J. Kirk (Judy); G.J. Lindeman; M. Price (Melanie)

    2016-01-01

    textabstractA locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 ×

  20. Analysis of HLA and disease susceptibility: Chromosome 6 genes and sex influence long-QT phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Weitkamp, L.R.; Moss, A.J.; Hall, W.J.; Robinson, J.L.; Guttormsen, S.A. [Univ. of Rochester School of Medicine and Dentistry, NY (United States); Lewis, R.A. [Pennsylvania State Univ., University Park, PA (United States); MacCluer, J.W. [Southwest Foundation for Biomedical Research, San Antonio, TX (United States); Schwartz, P.J. [Univ. of Pavia (Italy); Locati, E.H. [Univ. of Milan (Italy); Tzivoni, D. [Shaare Zedek Medical Center, Jerusalem (Israel)

    1994-12-01

    The long-QT (LQT) syndrome is a genetically complex disorder that is characterized by syncope and fatal ventricular arrhythmias. LQT syndrome, as defined by a prolonged electrocardiographic QT interval, has a higher incidence in females than in males and does not exhibit Mendelian transmission patterns in all families. Among those families that are nearly consistent with Mendelian transmission, linkage between a locus for LQT syndrome and the H-ras-1 locus on the short arm of chromosome 11 has been reported in some families but not in others. Earlier analyses suggesting that LQT syndrome might be caused by a gene in the HLA region of chromosome 6 were not confirmed by standard linkage analyses. Here, we present an analysis of HLA haplotype sharing among affected pedigree members, showing an excess of haplotype sharing in a previously published Japanese pedigree and possibly also in 15 families of European descent. The haplotypes shared by affected individuals derive from both affected and unaffected parents. In an analysis of independent (unrelated) HLA haplotypes, we also found a nonrandom distribution of HLA-DR genes in LQT syndrome patients compared with controls, suggesting an association between the LQT phenotype and specific HLA-DR genes. Our data indicate that DR2 has a protective effect and, particularly in males, that DR7 may increase susceptibility to the LQT syndrome. Thus, LQT syndrome may be influenced by genes on chromosomes 11 and 6, possibly with a sex-specific effect. These results provide a model for an effect of HLA-region genes inherited from either parent on the expression of an illness that may be determined principally by alleles at loci not linked to HLA.

  1. Genome-wide linkage study suggests a susceptibility locus for isolated bilateral microtia on 4p15.32-4p16.2.

    Directory of Open Access Journals (Sweden)

    Xin Li

    Full Text Available Microtia is a congenital deformity where the external ear is underdeveloped. Genetic investigations have identified many susceptibility genes of microtia-related syndromes. However, no causal genes were reported for isolated microtia, the main form of microtia. We conducted a genome-wide linkage analysis on a 5-generation Chinese pedigree with isolated bilateral microtia. We identified a suggestive linkage locus on 4p15.32-4p16.2 with parametric LOD score of 2.70 and nonparametric linkage score (Zmean of 12.28 (simulated occurrence per genome scan equal to 0.46 and 0.47, respectively. Haplotype reconstruction analysis of the 4p15.32-4p16.2 region further confined the linkage signal to a 10-Mb segment located between rs12505562 and rs12649803 (9.65-30.24 cM; 5.54-15.58 Mb. Various human organ developmental genes reside in this 10-Mb susceptibility region, such as EVC, EVC2, SLC2A9, NKX3-2, and HMX1. The coding regions of three genes, EVC known for cartilage development and NKX3-2, HMX1 involved in microtia, were selected for sequencing with 5 individuals from the pedigree. Of the 38 identified sequence variants, none segregates along with the disease phenotype. Other genes or DNA sequences of the 10-Mb region warrant for further investigation. In conclusion, we report a susceptibility locus of isolated microtia, and this finding will encourage future studies on the genetic basis of ear deformity.

  2. Family-based association analysis confirms the role of the chromosome 9q21.32 locus in the susceptibility of diabetic nephropathy.

    Directory of Open Access Journals (Sweden)

    Marcus G Pezzolesi

    Full Text Available A genome-wide association scan of type 1 diabetic patients from the GoKinD collections previously identified four novel diabetic nephropathy susceptibility loci that have subsequently been shown to be associated with diabetic nephropathy in unrelated patients with type 2 diabetes. To expand these findings, we examined whether single nucleotide polymorphisms (SNPs at these susceptibility loci were associated with diabetic nephropathy in patients from the Joslin Study of Genetics of Nephropathy in Type 2 Diabetes Family Collection. Six SNPs across the four loci identified in the GoKinD collections and 7 haplotype tagging SNPs, were genotyped in 66 extended families of European ancestry. Pedigrees from this collection contained an average of 18.5 members, including 2 to 14 members with type 2 diabetes. Among diabetic family members, the 9q21.32 locus approached statistical significance with advanced diabetic nephropathy (P = 0.037 [adjusted P = 0.222]. When we expanded our definition of diabetic nephropathy to include individuals with high microalbuminuria, the strength of this association improved significantly (P = 1.42×10(-3 [adjusted P = 0.009]. This same locus also trended toward statistical significance with variation in urinary albumin excretion in family members with type 2 diabetes (P = 0.032 [adjusted P = 0.192] and in analyses expanded to include all relatives (P = 0.019 [adjusted P = 0.114]. These data increase support that SNPs identified in the GoKinD collections on chromosome 9q21.32 are true diabetic nephropathy susceptibility loci.

  3. Neural responses to exclusion predict susceptibility to social influence.

    Science.gov (United States)

    Falk, Emily B; Cascio, Christopher N; O'Donnell, Matthew Brook; Carp, Joshua; Tinney, Francis J; Bingham, C Raymond; Shope, Jean T; Ouimet, Marie Claude; Pradhan, Anuj K; Simons-Morton, Bruce G

    2014-05-01

    Social influence is prominent across the lifespan, but sensitivity to influence is especially high during adolescence and is often associated with increased risk taking. Such risk taking can have dire consequences. For example, in American adolescents, traffic-related crashes are leading causes of nonfatal injury and death. Neural measures may be especially useful in understanding the basic mechanisms of adolescents' vulnerability to peer influence. We examined neural responses to social exclusion as potential predictors of risk taking in the presence of peers in recently licensed adolescent drivers. Risk taking was assessed in a driving simulator session occurring approximately 1 week after the neuroimaging session. Increased activity in neural systems associated with the distress of social exclusion and mentalizing during an exclusion episode predicted increased risk taking in the presence of a peer (controlling for solo risk behavior) during a driving simulator session outside the neuroimaging laboratory 1 week later. These neural measures predicted risky driving behavior above and beyond self-reports of susceptibility to peer pressure and distress during exclusion. These results address the neural bases of social influence and risk taking; contribute to our understanding of social and emotional function in the adolescent brain; and link neural activity in specific, hypothesized, regions to risk-relevant outcomes beyond the neuroimaging laboratory. Results of this investigation are discussed in terms of the mechanisms underlying risk taking in adolescents and the public health implications for adolescent driving. Copyright © 2014 Society for Adolescent Health and Medicine. All rights reserved.

  4. DRD4 and susceptibility to peer influence on alcohol use from adolescence to adulthood

    National Research Council Canada - National Science Library

    Mrug, Sylvie; Windle, Michael

    2014-01-01

    The long allele of DRD4 is associated with greater susceptibility to peer influences on alcohol use in young adulthood, but it is unclear whether this increased susceptibility extends to other developmental periods...

  5. Identification of IκBL as the Second Major Histocompatibility Complex–Linked Susceptibility Locus for Rheumatoid Arthritis

    OpenAIRE

    Okamoto, Koichi; Makino, Satoshi; Yoshikawa, Yoko; Takaki, Asumi; Nagatsuka, Yumie; Ota, Masao; Tamiya, Gen; Kimura, Akinori; Bahram, Seiamak; Inoko, Hidetoshi

    2002-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory joint disease with a complex etiology in which environmental factors within a genetically susceptible host maneuver the innate and adaptive arms of the immune system toward recognition of autoantigens. This ultimately leads to joint destruction and clinical symptomatology. Despite the identification of a number of disease-susceptibility regions across the genome, RA’s major genetic linkage remains with the major histocompatibility complex (M...

  6. Influence of health locus of control on recovery of function in recently hospitalized frail older adults.

    Science.gov (United States)

    Milte, Catherine M; Luszcz, Mary A; Ratcliffe, Julie; Masters, Stacey; Crotty, Maria

    2015-03-01

    To investigate the influence of health locus of control on physical function, quality of life, depression and satisfaction with care transition in a sample of older adults after a hospital admission. A total of 230 older adults referred for transition care after a hospital admission (mean length of stay 25.7 days, SD 17.2) were recruited into a randomized controlled intervention trial investigating the effect of specialized coaching compared with usual care. Older adults completed the multidimensional health locus of control (MHLC) survey at baseline. Self-rated quality of life, depression and physical function were assessed at baseline and 12 months using the EuroQol five-dimension, Geriatric Depression Scale (GDS) and Modified Barthel Index (MBI), respectively. Results from hierarchical multiple regression analysis in 136 participants (70 usual care and 66 specialized care) with complete data showed that higher scores on the MHLC internal subscale were related to better quality of life, and better physical function in the usual care group at 12 months, but not depression or transition process satisfaction at 3 months. No relationships between MHLC subscales and outcome measures were observed in the specialized care group, where the coaching intervention might have precluded any relationship observed. A stronger sense of personal control over health was associated with better maintenance of quality of life and physical function at 12 months in older adults undergoing usual care transition after acute hospitalization. Modification of control beliefs has the potential to promote resilience and impact on health outcomes in older adults during care transitions. © 2014 Japan Geriatrics Society.

  7. A genome-wide association study identifies a novel susceptibility locus for renal cell carcinoma on 12p11.23

    Science.gov (United States)

    Wu, Xifeng; Scelo, Ghislaine; Purdue, Mark P.; Rothman, Nathaniel; Johansson, Mattias; Ye, Yuanqing; Wang, Zhaoming; Zelenika, Diana; Moore, Lee E.; Wood, Christopher G.; Prokhortchouk, Egor; Gaborieau, Valerie; Jacobs, Kevin B.; Chow, Wong-Ho; Toro, Jorge R.; Zaridze, David; Lin, Jie; Lubinski, Jan; Trubicka, Joanna; Szeszenia-Dabrowska, Neonilia; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Mates, Dana; Jinga, Viorel; Bencko, Vladimir; Slamova, Alena; Holcatova, Ivana; Navratilova, Marie; Janout, Vladimir; Boffetta, Paolo; Colt, Joanne S.; Davis, Faith G.; Schwartz, Kendra L.; Banks, Rosamonde E.; Selby, Peter J.; Harnden, Patricia; Berg, Christine D.; Hsing, Ann W.; Grubb, Robert L.; Boeing, Heiner; Vineis, Paolo; Clavel-Chapelon, Françoise; Palli, Domenico; Tumino, Rosario; Krogh, Vittorio; Panico, Salvatore; Duell, Eric J.; Quirós, José Ramón; Sanchez, Maria-José; Navarro, Carmen; Ardanaz, Eva; Dorronsoro, Miren; Khaw, Kay-Tee; Allen, Naomi E.; Bueno-de-Mesquita, H. Bas; Peeters, Petra H.M.; Trichopoulos, Dimitrios; Linseisen, Jakob; Ljungberg, Börje; Overvad, Kim; Tjønneland, Anne; Romieu, Isabelle; Riboli, Elio; Stevens, Victoria L; Thun, Michael J; Diver, W. Ryan; Gapstur, Susan M.; Pharoah, Paul D.; Easton, Douglas F.; Albanes, Demetrius; Virtamo, Jarmo; Vatten, Lars; Hveem, Kristian; Fletcher, Tony; Koppova, Kvetoslava; Cussenot, Olivier; Cancel-Tassin, Geraldine; Benhamou, Simone; Hildebrandt, Michelle A.; Pu, Xia; Foglio, Mario; Lechner, Doris; Hutchinson, Amy; Yeager, Meredith; Fraumeni, Joseph F.; Lathrop, Mark; Skryabin, Konstantin G.; McKay, James D.; Gu, Jian; Brennan, Paul; Chanock, Stephen J.

    2012-01-01

    Renal cell carcinoma (RCC) is the most lethal urologic cancer. Only two common susceptibility loci for RCC have been confirmed to date. To identify additional RCC common susceptibility loci, we conducted an independent genome-wide association study (GWAS). We analyzed 533 191 single nucleotide polymorphisms (SNPs) for association with RCC in 894 cases and 1516 controls of European descent recruited from MD Anderson Cancer Center in the primary scan, and validated the top 500 SNPs in silico in 3772 cases and 8505 controls of European descent involved in the only published GWAS of RCC. We identified two common variants in linkage disequilibrium, rs718314 and rs1049380 (r2 = 0.64, D ′ = 0.84), in the inositol 1,4,5-triphosphate receptor, type 2 (ITPR2) gene on 12p11.23 as novel susceptibility loci for RCC (P = 8.89 × 10−10 and P = 6.07 × 10−9, respectively, in meta-analysis) with an allelic odds ratio of 1.19 [95% confidence interval (CI): 1.13–1.26] for rs718314 and 1.18 (95% CI: 1.12–1.25) for rs1049380. It has been recently identified that rs718314 in ITPR2 is associated with waist–hip ratio (WHR) phenotype. To our knowledge, this is the first genetic locus associated with both cancer risk and WHR. PMID:22010048

  8. Nutritional influences on cognitive function: mechanisms of susceptibility.

    Science.gov (United States)

    Leigh Gibson, E; Green, Michael W

    2002-06-01

    The impact of nutritional variation, within populations not overtly malnourished, on cognitive function and arousal is considered. The emphasis is on susceptibility to acute effects of meals and glucose loads, and chronic effects of dieting, on mental performance, and effects of cholesterol and vitamin levels on cognitive impairment. New developments in understanding dietary influences on neurohormonal systems, and their implications for cognition and affect, allow reinterpretation of both earlier and recent findings. Evidence for a detrimental effect of omitting a meal on cognitive performance remains equivocal: from the outset, idiosyncrasy has prevailed. Yet, for young and nutritionally vulnerable children, breakfast is more likely to benefit than hinder performance. For nutrient composition, despite inconsistencies, some cautious predictions can be made. Acutely, carbohydrate-rich-protein-poor meals can be sedating and anxiolytic; by comparison, protein-rich meals may be arousing, improving reaction time but also increasing unfocused vigilance. Fat-rich meals can lead to a decline in alertness, especially where they differ from habitual fat intake. These acute effects may vary with time of day and nutritional status. Chronically, protein-rich diets have been associated with decreased positive and increased negative affect relative to carbohydrate-rich diets. Probable mechanisms include diet-induced changes in monoamine, especially serotoninergic neurotransmitter activity, and functioning of the hypothalamic pituitary adrenal axis. Effects are interpreted in the context of individual traits and susceptibility to challenging, even stressful, tests of performance. Preoccupation with dieting may impair cognition by interfering with working memory capacity, independently of nutritional status. The change in cognitive performance after administration of glucose, and other foods, may depend on the level of sympathetic activation, glucocorticoid secretion, and

  9. Validation of genome-wide intervertebral disc calcification associations in Dachshund and further investigation of the chromosome 12 susceptibility locus

    Directory of Open Access Journals (Sweden)

    Mette Sloth eMogensen

    2012-11-01

    Full Text Available Herniation of the intervertebral disc is a common cause of neurological dysfunction in the dog, particularly in the Dachshund. Using the Illumina CanineHD BeadChip, we have previously identified a major locus on canine chromosome 12 nucleotide positions 36,750,205-38,524,449 that strongly associates with intervertebral disc calcification in Danish wire-haired Dachshunds. In this study, targeted resequencing identified two synonymous variants in MB21D1 and one in the 5’-untranslated region of KCNQ5 that associates with intervertebral disc calcification in an independent sample of wire-haired Dachshunds. Haploview identified seven linkage disequilibrium blocks across the disease associated region. The effect of haplotype windows on disc calcification shows that all haplotype windows are significantly associated with disc calcification. However, our predictions imply that the causal variant(s are most likely to be found between nucleotide 36,750,205-37,494,845 as this region explains the highest proportion of variance in the dataset. Finally, we develop a risk prediction model for wire-haired Dachshunds.We validated the association of the chromosome 12 locus with disc calcification in an independent sample of wire-haired Dachshunds and identify potential risk variants. Additionally, we estimated haplotype effects and set up a model for prediction of disc calcifications in wire-haired dachshunds based on genotype data. This genetic prediction model may prove useful in selection of breeding animals in future breeding programs

  10. A real-time PCR assay for direct characterization of the Neisseria gonorrhoeae GyrA 91 locus associated with ciprofloxacin susceptibility.

    Science.gov (United States)

    Buckley, Cameron; Trembizki, Ella; Donovan, Basil; Chen, Marcus; Freeman, Kevin; Guy, Rebecca; Kundu, Ratan; Lahra, Monica M; Regan, David G; Smith, Helen; Whiley, David M

    2016-02-01

    The objective of this study was to develop a real-time PCR method for specific detection of the gonococcal GyrA amino acid 91 locus directly in clinical samples so as to predict Neisseria gonorrhoeae ciprofloxacin susceptibility. The real-time PCR assay, GyrA91-PCR, was designed using two probes, one for detection of the WT S91 sequence and the other for detection of the S91F alteration. The performance of the assay was initially assessed using characterized N. gonorrhoeae isolates (n = 70), a panel of commensal Neisseria and Moraxella species (n = 55 isolates) and clinical samples providing negative results by a commercial N. gonorrhoeae nucleic acid amplification test (NAAT) method (n = 171). The GyrA91-PCR was then applied directly to N. gonorrhoeae NAAT-positive clinical samples (n = 210) from the year 2014 for which corresponding N. gonorrhoeae isolates with susceptibility results were also available. The GyrA91-PCR accurately characterized the GyrA 91 locus of all 70 N. gonorrhoeae isolates (sensitivity = 100%, 95% CI = 94.9%-100%), whereas all non-gonococcal isolates and N. gonorrhoeae NAAT-negative clinical samples gave negative results by the GyrA91-PCR (specificity = 100%, 95% CI = 98.4%-100%). When applied to the 210 N. gonorrhoeae NAAT-positive clinical samples, the GyrA91-PCR successfully characterized 195 samples (92.9%, 95% CI = 88.5%-95.9%). When compared with the corresponding bacterial culture results, positivity by the GyrA91-PCR WT probe correctly predicted N. gonorrhoeae susceptibility to ciprofloxacin in 161 of 162 (99.4%, 95% CI = 96.6%-99.9%) samples. The use of a PCR assay for detection of mutation in gyrA applied directly to clinical samples can predict ciprofloxacin susceptibility in N. gonorrhoeae. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24.

    NARCIS (Netherlands)

    Birnbaum, S.; Ludwig, K.U.; Reutter, H.; Herms, S.; Steffens, M.; Rubini, M.; Baluardo, C.; Ferrian, M.; Almeida de Assis, N.; Alblas, M.A.; Barth, S.; Freudenberg, J.; Lauster, C.; Schmidt, G; Scheer, M.; Braumann, B.; Berge, S.J.; Reich, R.H.; Schiefke, F.; Hemprich, A.; Potzsch, S.; Steegers-Theunissen, R.P.M.; Potzsch, B.; Moebus, S.; Horsthemke, B.; Kramer, F.J.; Wienker, T.F.; Mossey, P.A.; Propping, P.; Cichon, S.; Hoffmann, P.; Knapp, M.; Nothen, Markus; Mangold, E.

    2009-01-01

    We conducted a genome-wide association study involving 224 cases and 383 controls of Central European origin to identify susceptibility loci for nonsyndromic cleft lip with or without cleft palate (NSCL/P). A 640-kb region at chromosome 8q24.21 was found to contain multiple markers with highly

  12. Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24

    NARCIS (Netherlands)

    Birnbaum, Stefanie; Ludwig, Kerstin U.; Reutter, Heiko; Herms, Stefan; Steffens, Michael; Rubini, Michele; Baluardo, Carlotta; Ferrian, Melissa; de Assis, Nilma Almeida; Alblas, Margrieta A.; Barth, Sandra; Freudenberg, Jan; Lauster, Carola; Schmidt, Guel; Scheer, Martin; Braumann, Bert; Berge, Stefaan J.; Reich, Rudolf H.; Schiefke, Franziska; Hemprich, Alexander; Poetzsch, Simone; Steegers-Theunissen, Regine P.; Poetzsch, Bernd; Moebus, Susanne; Horsthemke, Bernhard; Kramer, Franz-Josef; Wienker, Thomas F.; Mossey, Peter A.; Propping, Peter; Cichon, Sven; Hoffmann, Per; Knapp, Michael; Noethen, Markus M.; Mangold, Elisabeth

    We conducted a genome-wide association study involving 224 cases and 383 controls of Central European origin to identify susceptibility loci for nonsyndromic cleft lip with or without cleft palate (NSCL/P). A 640-kb region at chromosome 8q24.21 was found to contain multiple markers with highly

  13. A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel susceptibility locus

    NARCIS (Netherlands)

    Cozen, W.; Timofeeva, M.N.; Li, D.; Diepstra, A.; Hazelett, D.; Delahaye-Sourdeix, M.; Edlund, C.K.; Franke, L.; Rostgaard, K.; Berg, D.J. Van Den; Cortessis, V.K.; Smedby, K.E.; Glaser, S.L.; Westra, H.J.; Robison, L.L.; Mack, T.M.; Ghesquieres, H.; Hwang, A.E.; Nieters, A.; Sanjose, S. de; Lightfoot, T.; Becker, N.; Maynadie, M.; Foretova, L.; Roman, E.; Benavente, Y.; Rand, K.A.; Nathwani, B.N.; Glimelius, B.; Staines, A.; Boffetta, P.; Link, B.K.; Kiemeney, B.; Ansell, S.M.; Bhatia, S.; Strong, L.C.; Galan, P.; Vatten, L.; Habermann, T.M.; Duell, E.J.; Lake, A.; Veenstra, R.N.; Visser, L de; Liu, Y.; Urayama, K.Y.; Montgomery, D.; Gaborieau, V.; Weiss, L.M.; Byrnes, G.; Lathrop, M.; Cocco, P.; Best, T.; Skol, A.D.; Adami, H.O.; Melbye, M.; Cerhan, J.R.; Gallagher, A.; Taylor, G.M.; Slager, S.L.; Brennan, P.; Coetzee, G.A.; Conti, D.V.; Onel, K.; Jarrett, R.F.; Hjalgrim, H.; Berg, A. van den; McKay, J.D.

    2014-01-01

    Recent genome-wide association studies (GWAS) of Hodgkin lymphoma (HL) have identified associations with genetic variation at both HLA and non-HLA loci; however, much of heritable HL susceptibility remains unexplained. Here we perform a meta-analysis of three HL GWAS totaling 1,816 cases and 7,877

  14. A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel susceptibility locus

    NARCIS (Netherlands)

    Cozen, W.; Timofeeva, M. N.; Li, D.; Diepstra, A.; Hazelett, D.; Delahaye-Sourdeix, M.; Edlund, C. K.; Franke, L.; Rostgaard, K.; Van Den Berg, D. J.; Cortessis, V. K.; Smedby, K. E.; Glaser, S. L.; Westra, H. -J.; Robison, L. L.; Mack, T. M.; Ghesquieres, H.; Hwang, A. E.; Nieters, A.; de Sanjose, S.; Lightfoot, T.; Becker, N.; Maynadie, M.; Foretova, L.; Roman, E.; Benavente, Y.; Rand, K. A.; Nathwani, B. N.; Glimelius, B.; Staines, A.; Boffetta, P.; Link, B. K.; Kiemeney, L.; Ansell, S. M.; Bhatia, S.; Strong, L. C.; Galan, P.; Vatten, L.; Habermann, T. M.; Duell, E. J.; Lake, A.; Veenstra, R. N.; Visser, Lydia; Liu, Y.; Urayama, K. Y.; Montgomery, D.; Gaborieau, V.; Weiss, L. M.; Byrnes, G.; Lathrop, M.; Cocco, P.; Best, T.; Skol, A. D.; Adami, H. -O.; Melbye, M.; Cerhan, J. R.; Gallagher, A.; Taylor, G. M.; Slager, S. L.; Brennan, P.; Coetzee, G. A.; Conti, D. V.; Onel, K.; Jarrett, R. F.; Hjalgrim, H.; van den Berg, A.; Mckay, J. D.

    Recent genome-wide association studies (GWAS) of Hodgkin lymphoma (HL) have identified associations with genetic variation at both HLA and non-HLA loci; however, much of heritable HL susceptibility remains unexplained. Here we perform a meta-analysis of three HL GWAS totaling 1,816 cases and 7,877

  15. A locus on chromosome 2 influences the development of acute graft-versus-host disease in a murine model.

    Science.gov (United States)

    Harper, J M; Slayback, D L; Dobkins, J A; Allen, R D

    1999-06-01

    Despite contemporary typing procedures for bone marrow transplantation (BMT), graft-versus-host disease (GVHD) continues to be a major complication of transplants performed between MHC-matched donors and recipients. Although GVHD can be alleviated by T cell depletion, this procedure increases the risk of graft failure and leukemic relapse and therefore is not a solution to the GVHD problem. The high degree of variation in the intensity of GVHD observed in different patients suggests that multiple non-MHC genetic factors influence GVHD severity. We hypothesize that, in addition to minor histocompatibility antigen disparities, polymorphisms in genes encoding immunologic effector molecules may be important factors influencing GVHD development. This study aims to explore this hypothesis by identifying non-MHC genes that influence the outcome of BMT in a murine model. In this model, B10.D2 donor leukocytes cause acute GVHD in (C57BL/6xDBA/2)F1 (B6D2F1) recipients, whereas DBA/2 donor leukocytes do not. To date, a locus on chromosome 1 has been identified as influencing the severity of GVHD in this model. Our current study shows that a locus on chromosome 2 acts independently of the chromosome 1 locus to also influence GVHD severity in this model. The region of chromosome 2 implicated in our study contains genes encoding beta2-microglobulin, the minor histocompatibility antigen H-3 and the pro-inflammatory cytokine IL-1.

  16. Influence of a quantitative trait locus on mouse chromosome 19 to the light-adapted electroretinogram.

    Science.gov (United States)

    Reynolds, Alison L; Danciger, Michael; Farrar, G Jane; Humphries, Peter; Kenna, Paul F

    2008-09-01

    Both implicit time and amplitude of the cone-mediated electroretinographic (ERG) b-wave differ significantly between the C57BL/6JOlaHsd and 129S2/SvHsd inbred mouse strains. The purpose of this work was to undertake a quantitative genetics study to localize the gene or genes involved. Implicit time and amplitude of the a- and b-waves of the single-flash and flicker cone-mediated ERG were recorded as the quantitative traits in reciprocal backcrossed populations. A genome-wide scan was performed with 106 polymorphic markers. Map Manager (release QTXb20) was used to analyze the data and make phenotype-genotype correlations. A quantitative trait locus (QTL) of major effect in controlling variation in both implicit time and amplitude of the cone-mediated ERG localized to the middle of chromosome 19. Mapping of a QTL influencing both implicit time and b-wave amplitude of the light-adapted ERG represents an initial step toward identifying the gene(s) responsible for this phenotypic variation.

  17. Trans-ethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A.

    Science.gov (United States)

    Wang, Hansong; Burnett, Terrilea; Kono, Suminori; Haiman, Christopher A; Iwasaki, Motoki; Wilkens, Lynne R; Loo, Lenora W M; Van Den Berg, David; Kolonel, Laurence N; Henderson, Brian E; Keku, Temitope O; Sandler, Robert S; Signorello, Lisa B; Blot, William J; Newcomb, Polly A; Pande, Mala; Amos, Christopher I; West, Dee W; Bézieau, Stéphane; Berndt, Sonja I; Zanke, Brent W; Hsu, Li; Lindor, Noralane M; Haile, Robert W; Hopper, John L; Jenkins, Mark A; Gallinger, Steven; Casey, Graham; Stenzel, Stephanie L; Schumacher, Fredrick R; Peters, Ulrike; Gruber, Stephen B; Tsugane, Shoichiro; Stram, Daniel O; Le Marchand, Loïc

    2014-08-08

    The genetic basis of sporadic colorectal cancer (CRC) is not well explained by known risk polymorphisms. Here we perform a meta-analysis of two genome-wide association studies in 2,627 cases and 3,797 controls of Japanese ancestry and 1,894 cases and 4,703 controls of African ancestry, to identify genetic variants that contribute to CRC susceptibility. We replicate genome-wide statistically significant associations (Pvalue of association mapping in diverse populations.

  18. Sterile DJH rearrangements reveal that distance between gene segments on the human Ig H chain locus influences their ability to rearrange

    DEFF Research Database (Denmark)

    Hansen, Tina Østergaard; Lange, Anders Blaabjerg; Barington, Torben

    2015-01-01

    Rearrangement of the Ig locus occurs in two steps. First, a JH gene is rearranged to a D gene followed by a VH gene rearranging to the DJH rearrangement. By next generation sequencing, we analyzed 9969 unique DJH rearrangements and 5919 unique VHDJH rearrangements obtained from peripheral blood B...... frequently than JH locus distal D genes, whereas VH locus proximal D genes were observed more frequently in nonproductive VHDJH rearrangements. We further demonstrate that the distance between VH, D, and JH gene segments influence their ability to rearrange within the human Ig locus....

  19. The influence of message appeal, environmental hyperopia, and environmental locus of control on green policy communication

    National Research Council Canada - National Science Library

    Lee, Yu-Kang

    2013-01-01

      In this paper, the author examined the message appeal in green policy communication by clarifying the moderating roles of environmental hyperopia and individual differences in environmental locus of control...

  20. A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13.

    Science.gov (United States)

    Cho, Michael H; Castaldi, Peter J; Wan, Emily S; Siedlinski, Mateusz; Hersh, Craig P; Demeo, Dawn L; Himes, Blanca E; Sylvia, Jody S; Klanderman, Barbara J; Ziniti, John P; Lange, Christoph; Litonjua, Augusto A; Sparrow, David; Regan, Elizabeth A; Make, Barry J; Hokanson, John E; Murray, Tanda; Hetmanski, Jacqueline B; Pillai, Sreekumar G; Kong, Xiangyang; Anderson, Wayne H; Tal-Singer, Ruth; Lomas, David A; Coxson, Harvey O; Edwards, Lisa D; MacNee, William; Vestbo, Jørgen; Yates, Julie C; Agusti, Alvar; Calverley, Peter M A; Celli, Bartolome; Crim, Courtney; Rennard, Stephen; Wouters, Emiel; Bakke, Per; Gulsvik, Amund; Crapo, James D; Beaty, Terri H; Silverman, Edwin K

    2012-02-15

    The genetic risk factors for chronic obstructive pulmonary disease (COPD) are still largely unknown. To date, genome-wide association studies (GWASs) of limited size have identified several novel risk loci for COPD at CHRNA3/CHRNA5/IREB2, HHIP and FAM13A; additional loci may be identified through larger studies. We performed a GWAS using a total of 3499 cases and 1922 control subjects from four cohorts: the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); the Normative Aging Study (NAS) and National Emphysema Treatment Trial (NETT); Bergen, Norway (GenKOLS); and the COPDGene study. Genotyping was performed on Illumina platforms with additional markers imputed using 1000 Genomes data; results were summarized using fixed-effect meta-analysis. We identified a new genome-wide significant locus on chromosome 19q13 (rs7937, OR = 0.74, P = 2.9 × 10(-9)). Genotyping this single nucleotide polymorphism (SNP) and another nearby SNP in linkage disequilibrium (rs2604894) in 2859 subjects from the family-based International COPD Genetics Network study (ICGN) demonstrated supportive evidence for association for COPD (P = 0.28 and 0.11 for rs7937 and rs2604894), pre-bronchodilator FEV(1) (P = 0.08 and 0.04) and severe (GOLD 3&4) COPD (P = 0.09 and 0.017). This region includes RAB4B, EGLN2, MIA and CYP2A6, and has previously been identified in association with cigarette smoking behavior.

  1. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast–ovarian cancer susceptibility locus

    Science.gov (United States)

    Lawrenson, Kate; Kar, Siddhartha; McCue, Karen; Kuchenbaeker, Karoline; Michailidou, Kyriaki; Tyrer, Jonathan; Beesley, Jonathan; Ramus, Susan J.; Li, Qiyuan; Delgado, Melissa K.; Lee, Janet M.; Aittomäki, Kristiina; Andrulis, Irene L.; Anton-Culver, Hoda; Arndt, Volker; Arun, Banu K.; Arver, Brita; Bandera, Elisa V.; Barile, Monica; Barkardottir, Rosa B.; Barrowdale, Daniel; Beckmann, Matthias W.; Benitez, Javier; Berchuck, Andrew; Bisogna, Maria; Bjorge, Line; Blomqvist, Carl; Blot, William; Bogdanova, Natalia; Bojesen, Anders; Bojesen, Stig E.; Bolla, Manjeet K.; Bonanni, Bernardo; Børresen-Dale, Anne-Lise; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Bruinsma, Fiona; Brunet, Joan; Buhari, Shaik Ahmad; Burwinkel, Barbara; Butzow, Ralf; Buys, Saundra S.; Cai, Qiuyin; Caldes, Trinidad; Campbell, Ian; Canniotto, Rikki; Chang-Claude, Jenny; Chiquette, Jocelyne; Choi, Ji-Yeob; Claes, Kathleen B. M.; Collonge-Rame, Marie- Agnès; Damette, Alexandre; Barouk-Simonet, Emmanuelle; Bonnet, Françoise; Bubien, Virginie; Sevenet, Nicolas; Longy, Michel; Berthet, Pascaline; Vaur, Dominique; Castera, Laurent; Ferrer, Sandra Fert; Bignon, Yves-Jean; Uhrhammer, Nancy; Coron, Fanny; Faivre, Laurence; Baurand, Amandine; Jacquot, Caroline; Bertolone, Geoffrey; Lizard, Sarab; Leroux, Dominique; Dreyfus, Hélène; Rebischung, Christine; Peysselon, Magalie; Peyrat, Jean-Philippe; Fournier, Joëlle; Révillion, Françoise; Adenis, Claude; Vénat-Bouvet, Laurence; Léone, Mélanie; Boutry-Kryza, Nadia; Calender, Alain; Giraud, Sophie; Verny-Pierre, Carole; Lasset, Christine; Bonadona, Valérie; Barjhoux, Laure; Sobol, Hagay; Bourdon, Violaine; Noguchi, Tetsuro; Remenieras, Audrey; Coupier, Isabelle; Pujol, Pascal; Sokolowska, Johanna; Bronner, Myriam; Delnatte, Capucine; Bézieau, Stéphane; Mari, Véronique; Gauthier-Villars, Marion; Buecher, Bruno; Rouleau, Etienne; Golmard, Lisa; Moncoutier, Virginie; Belotti, Muriel; de Pauw, Antoine; Elan, Camille; Fourme, Emmanuelle; Birot, Anne-Marie; Saule, Claire; Laurent, Maïté; Houdayer, Claude; Lesueur, Fabienne; Mebirouk, Noura; Coulet, Florence; Colas, Chrystelle; Soubrier, Florent; Warcoin, Mathilde; Prieur, Fabienne; Lebrun, Marine; Kientz, Caroline; Muller, Danièle; Fricker, Jean-Pierre; Toulas, Christine; Guimbaud, Rosine; Gladieff, Laurence; Feillel, Viviane; Mortemousque, Isabelle; Bressac-de-Paillerets, Brigitte; Caron, Olivier; Guillaud-Bataille, Marine; Cook, Linda S.; Cox, Angela; Cramer, Daniel W.; Cross, Simon S.; Cybulski, Cezary; Czene, Kamila; Daly, Mary B.; Damiola, Francesca; Dansonka-Mieszkowska, Agnieszka; Darabi, Hatef; Dennis, Joe; Devilee, Peter; Diez, Orland; Doherty, Jennifer A.; Domchek, Susan M.; Dorfling, Cecilia M.; Dörk, Thilo; Dumont, Martine; Ehrencrona, Hans; Ejlertsen, Bent; Ellis, Steve; Gregory, Helen; Miedzybrodzka, Zosia; Morrison, Patrick J.; Donaldson, Alan; Rogers, Mark T.; Kennedy, M. John; Porteous, Mary E.; Brady, Angela; Barwell, Julian; Foo, Claire; Lalloo, Fiona; Side, Lucy E.; Eason, Jacqueline; Henderson, Alex; Walker, Lisa; Cook, Jackie; Snape, Katie; Murray, Alex; McCann, Emma; Engel, Christoph; Lee, Eunjung; Evans, D. Gareth; Fasching, Peter A.; Feliubadalo, Lidia; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Foretova, Lenka; Fostira, Florentia; Foulkes, William D.; Fridley, Brooke L.; Friedman, Eitan; Frost, Debra; Gambino, Gaetana; Ganz, Patricia A.; Garber, Judy; García-Closas, Montserrat; Gentry-Maharaj, Aleksandra; Ghoussaini, Maya; Giles, Graham G.; Glasspool, Rosalind; Godwin, Andrew K.; Goldberg, Mark S.; Goldgar, David E.; González-Neira, Anna; Goode, Ellen L.; Goodman, Marc T.; Greene, Mark H.; Gronwald, Jacek; Guénel, Pascal; Haiman, Christopher A.; Hall, Per; Hallberg, Emily; Hamann, Ute; Hansen, Thomas V. O.; Harrington, Patricia A.; Hartman, Mikael; Hassan, Norhashimah; Healey, Sue; Rookus, M. A.; van Leeuwen, F. E.; van der Kolk, L. E.; Schmidt, M. K.; Russell, N. S.; de Lange, J. L.; Wijnands, R.; Collée, J. M.; Hooning, M. J.; Seynaeve, C.; van Deurzen, C. H. M.; Obdeijn, I. M.; van Asperen, C. J.; Tollenaar, R. A. E. M.; van Cronenburg, T. C. T. E. F.; Kets, C. M.; Ausems, M. G. E. M.; van der Pol, C. C.; van Os, T. A. M.; Waisfisz, Q.; Meijers-Heijboer, H. E. J.; Gómez-Garcia, E. B.; Oosterwijk, J. C.; Mourits, M. J.; de Bock, G. H.; Vasen, H. F.; Siesling, S.; Verloop, J.; Overbeek, L. I. H.; Heitz, Florian; Herzog, Josef; Høgdall, Estrid; Høgdall, Claus K.; Hogervorst, Frans B. L.; Hollestelle, Antoinette; Hopper, John L.; Hulick, Peter J.; Huzarski, Tomasz; Imyanitov, Evgeny N.; Fox, Stephen; Kirk, Judy; Lindeman, Geoff; Price, Melanie; Bowtell, David; deFazio, Anna; Webb, Penny; Isaacs, Claudine; Ito, Hidemi; Jakubowska, Anna; Janavicius, Ramunas; Jensen, Allan; John, Esther M.; Johnson, Nichola; Kabisch, Maria; Kang, Daehee; Kapuscinski, Miroslav; Karlan, Beth Y.; Khan, Sofia; Kiemeney, Lambertus A.; Kjaer, Susanne Kruger; Knight, Julia A.; Konstantopoulou, Irene; Kosma, Veli-Matti; Kristensen, Vessela; Kupryjanczyk, Jolanta; Kwong, Ava; de la Hoya, Miguel; Laitman, Yael; Lambrechts, Diether; Le, Nhu; De Leeneer, Kim; Lester, Jenny; Levine, Douglas A.; Li, Jingmei; Lindblom, Annika; Long, Jirong; Lophatananon, Artitaya; Loud, Jennifer T.; Lu, Karen; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Le Marchand, Loic; Margolin, Sara; Marme, Frederik; Massuger, Leon F. A. G.; Matsuo, Keitaro; Mazoyer, Sylvie; McGuffog, Lesley; McLean, Catriona; McNeish, Iain; Meindl, Alfons; Menon, Usha; Mensenkamp, Arjen R.; Milne, Roger L.; Montagna, Marco; Moysich, Kirsten B.; Muir, Kenneth; Mulligan, Anna Marie; Nathanson, Katherine L.; Ness, Roberta B.; Neuhausen, Susan L.; Nevanlinna, Heli; Nord, Silje; Nussbaum, Robert L.; Odunsi, Kunle; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I.; Olson, Janet E.; Olswold, Curtis; O'Malley, David; Orlow, Irene; Orr, Nick; Osorio, Ana; Park, Sue Kyung; Pearce, Celeste L.; Pejovic, Tanja; Peterlongo, Paolo; Pfeiler, Georg; Phelan, Catherine M.; Poole, Elizabeth M.; Pylkäs, Katri; Radice, Paolo; Rantala, Johanna; Rashid, Muhammad Usman; Rennert, Gad; Rhenius, Valerie; Rhiem, Kerstin; Risch, Harvey A.; Rodriguez, Gus; Rossing, Mary Anne; Rudolph, Anja; Salvesen, Helga B.; Sangrajrang, Suleeporn; Sawyer, Elinor J.; Schildkraut, Joellen M.; Schmidt, Marjanka K.; Schmutzler, Rita K.; Sellers, Thomas A.; Seynaeve, Caroline; Shah, Mitul; Shen, Chen-Yang; Shu, Xiao-Ou; Sieh, Weiva; Singer, Christian F.; Sinilnikova, Olga M.; Slager, Susan; Song, Honglin; Soucy, Penny; Southey, Melissa C.; Stenmark-Askmalm, Marie; Stoppa-Lyonnet, Dominique; Sutter, Christian; Swerdlow, Anthony; Tchatchou, Sandrine; Teixeira, Manuel R.; Teo, Soo H.; Terry, Kathryn L.; Terry, Mary Beth; Thomassen, Mads; Tibiletti, Maria Grazia; Tihomirova, Laima; Tognazzo, Silvia; Toland, Amanda Ewart; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Tseng, Chiu-chen; Tung, Nadine; Tworoger, Shelley S.; Vachon, Celine; van den Ouweland, Ans M. W.; van Doorn, Helena C.; van Rensburg, Elizabeth J.; Van't Veer, Laura J.; Vanderstichele, Adriaan; Vergote, Ignace; Vijai, Joseph; Wang, Qin; Wang-Gohrke, Shan; Weitzel, Jeffrey N.; Wentzensen, Nicolas; Whittemore, Alice S.; Wildiers, Hans; Winqvist, Robert; Wu, Anna H.; Yannoukakos, Drakoulis; Yoon, Sook-Yee; Yu, Jyh-Cherng; Zheng, Wei; Zheng, Ying; Khanna, Kum Kum; Simard, Jacques; Monteiro, Alvaro N.; French, Juliet D.; Couch, Fergus J.; Freedman, Matthew L.; Easton, Douglas F.; Dunning, Alison M.; Pharoah, Paul D.; Edwards, Stacey L.; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Gayther, Simon A.

    2016-01-01

    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10−20), ER-negative BC (P=1.1 × 10−13), BRCA1-associated BC (P=7.7 × 10−16) and triple negative BC (P-diff=2 × 10−5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10−3) and ABHD8 (P<2 × 10−3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk. PMID:27601076

  2. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus.

    Science.gov (United States)

    Lawrenson, Kate; Kar, Siddhartha; McCue, Karen; Kuchenbaeker, Karoline; Michailidou, Kyriaki; Tyrer, Jonathan; Beesley, Jonathan; Ramus, Susan J; Li, Qiyuan; Delgado, Melissa K; Lee, Janet M; Aittomäki, Kristiina; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Arun, Banu K; Arver, Brita; Bandera, Elisa V; Barile, Monica; Barkardottir, Rosa B; Barrowdale, Daniel; Beckmann, Matthias W; Benitez, Javier; Berchuck, Andrew; Bisogna, Maria; Bjorge, Line; Blomqvist, Carl; Blot, William; Bogdanova, Natalia; Bojesen, Anders; Bojesen, Stig E; Bolla, Manjeet K; Bonanni, Bernardo; Børresen-Dale, Anne-Lise; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Bruinsma, Fiona; Brunet, Joan; Buhari, Shaik Ahmad; Burwinkel, Barbara; Butzow, Ralf; Buys, Saundra S; Cai, Qiuyin; Caldes, Trinidad; Campbell, Ian; Canniotto, Rikki; Chang-Claude, Jenny; Chiquette, Jocelyne; Choi, Ji-Yeob; Claes, Kathleen B M; Cook, Linda S; Cox, Angela; Cramer, Daniel W; Cross, Simon S; Cybulski, Cezary; Czene, Kamila; Daly, Mary B; Damiola, Francesca; Dansonka-Mieszkowska, Agnieszka; Darabi, Hatef; Dennis, Joe; Devilee, Peter; Diez, Orland; Doherty, Jennifer A; Domchek, Susan M; Dorfling, Cecilia M; Dörk, Thilo; Dumont, Martine; Ehrencrona, Hans; Ejlertsen, Bent; Ellis, Steve; Engel, Christoph; Lee, Eunjung; Evans, D Gareth; Fasching, Peter A; Feliubadalo, Lidia; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Foretova, Lenka; Fostira, Florentia; Foulkes, William D; Fridley, Brooke L; Friedman, Eitan; Frost, Debra; Gambino, Gaetana; Ganz, Patricia A; Garber, Judy; García-Closas, Montserrat; Gentry-Maharaj, Aleksandra; Ghoussaini, Maya; Giles, Graham G; Glasspool, Rosalind; Godwin, Andrew K; Goldberg, Mark S; Goldgar, David E; González-Neira, Anna; Goode, Ellen L; Goodman, Marc T; Greene, Mark H; Gronwald, Jacek; Guénel, Pascal; Haiman, Christopher A; Hall, Per; Hallberg, Emily; Hamann, Ute; Hansen, Thomas V O; Harrington, Patricia A; Hartman, Mikael; Hassan, Norhashimah; Healey, Sue; Heitz, Florian; Herzog, Josef; Høgdall, Estrid; Høgdall, Claus K; Hogervorst, Frans B L; Hollestelle, Antoinette; Hopper, John L; Hulick, Peter J; Huzarski, Tomasz; Imyanitov, Evgeny N; Isaacs, Claudine; Ito, Hidemi; Jakubowska, Anna; Janavicius, Ramunas; Jensen, Allan; John, Esther M; Johnson, Nichola; Kabisch, Maria; Kang, Daehee; Kapuscinski, Miroslav; Karlan, Beth Y; Khan, Sofia; Kiemeney, Lambertus A; Kjaer, Susanne Kruger; Knight, Julia A; Konstantopoulou, Irene; Kosma, Veli-Matti; Kristensen, Vessela; Kupryjanczyk, Jolanta; Kwong, Ava; de la Hoya, Miguel; Laitman, Yael; Lambrechts, Diether; Le, Nhu; De Leeneer, Kim; Lester, Jenny; Levine, Douglas A; Li, Jingmei; Lindblom, Annika; Long, Jirong; Lophatananon, Artitaya; Loud, Jennifer T; Lu, Karen; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Le Marchand, Loic; Margolin, Sara; Marme, Frederik; Massuger, Leon F A G; Matsuo, Keitaro; Mazoyer, Sylvie; McGuffog, Lesley; McLean, Catriona; McNeish, Iain; Meindl, Alfons; Menon, Usha; Mensenkamp, Arjen R; Milne, Roger L; Montagna, Marco; Moysich, Kirsten B; Muir, Kenneth; Mulligan, Anna Marie; Nathanson, Katherine L; Ness, Roberta B; Neuhausen, Susan L; Nevanlinna, Heli; Nord, Silje; Nussbaum, Robert L; Odunsi, Kunle; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I; Olson, Janet E; Olswold, Curtis; O'Malley, David; Orlow, Irene; Orr, Nick; Osorio, Ana; Park, Sue Kyung; Pearce, Celeste L; Pejovic, Tanja; Peterlongo, Paolo; Pfeiler, Georg; Phelan, Catherine M; Poole, Elizabeth M; Pylkäs, Katri; Radice, Paolo; Rantala, Johanna; Rashid, Muhammad Usman; Rennert, Gad; Rhenius, Valerie; Rhiem, Kerstin; Risch, Harvey A; Rodriguez, Gus; Rossing, Mary Anne; Rudolph, Anja; Salvesen, Helga B; Sangrajrang, Suleeporn; Sawyer, Elinor J; Schildkraut, Joellen M; Schmidt, Marjanka K; Schmutzler, Rita K; Sellers, Thomas A; Seynaeve, Caroline; Shah, Mitul; Shen, Chen-Yang; Shu, Xiao-Ou; Sieh, Weiva; Singer, Christian F; Sinilnikova, Olga M; Slager, Susan; Song, Honglin; Soucy, Penny; Southey, Melissa C; Stenmark-Askmalm, Marie; Stoppa-Lyonnet, Dominique; Sutter, Christian; Swerdlow, Anthony; Tchatchou, Sandrine; Teixeira, Manuel R; Teo, Soo H; Terry, Kathryn L; Terry, Mary Beth; Thomassen, Mads; Tibiletti, Maria Grazia; Tihomirova, Laima; Tognazzo, Silvia; Toland, Amanda Ewart; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Tseng, Chiu-Chen; Tung, Nadine; Tworoger, Shelley S; Vachon, Celine; van den Ouweland, Ans M W; van Doorn, Helena C; van Rensburg, Elizabeth J; Van't Veer, Laura J; Vanderstichele, Adriaan; Vergote, Ignace; Vijai, Joseph; Wang, Qin; Wang-Gohrke, Shan; Weitzel, Jeffrey N; Wentzensen, Nicolas; Whittemore, Alice S; Wildiers, Hans; Winqvist, Robert; Wu, Anna H; Yannoukakos, Drakoulis; Yoon, Sook-Yee; Yu, Jyh-Cherng; Zheng, Wei; Zheng, Ying; Khanna, Kum Kum; Simard, Jacques; Monteiro, Alvaro N; French, Juliet D; Couch, Fergus J; Freedman, Matthew L; Easton, Douglas F; Dunning, Alison M; Pharoah, Paul D; Edwards, Stacey L; Chenevix-Trench, Georgia; Antoniou, Antonis C; Gayther, Simon A

    2016-09-07

    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10(-20)), ER-negative BC (P=1.1 × 10(-13)), BRCA1-associated BC (P=7.7 × 10(-16)) and triple negative BC (P-diff=2 × 10(-5)). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10(-3)) and ABHD8 (P<2 × 10(-3)). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3'-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.

  3. Integrated genetic and epigenetic analysis identifies haplotype-specific methylation in the FTO type 2 diabetes and obesity susceptibility locus.

    Directory of Open Access Journals (Sweden)

    Christopher G Bell

    Full Text Available Recent multi-dimensional approaches to the study of complex disease have revealed powerful insights into how genetic and epigenetic factors may underlie their aetiopathogenesis. We examined genotype-epigenotype interactions in the context of Type 2 Diabetes (T2D, focussing on known regions of genomic susceptibility. We assayed DNA methylation in 60 females, stratified according to disease susceptibility haplotype using previously identified association loci. CpG methylation was assessed using methylated DNA immunoprecipitation on a targeted array (MeDIP-chip and absolute methylation values were estimated using a Bayesian algorithm (BATMAN. Absolute methylation levels were quantified across LD blocks, and we identified increased DNA methylation on the FTO obesity susceptibility haplotype, tagged by the rs8050136 risk allele A (p = 9.40×10(-4, permutation p = 1.0×10(-3. Further analysis across the 46 kb LD block using sliding windows localised the most significant difference to be within a 7.7 kb region (p = 1.13×10(-7. Sequence level analysis, followed by pyrosequencing validation, revealed that the methylation difference was driven by the co-ordinated phase of CpG-creating SNPs across the risk haplotype. This 7.7 kb region of haplotype-specific methylation (HSM, encapsulates a Highly Conserved Non-Coding Element (HCNE that has previously been validated as a long-range enhancer, supported by the histone H3K4me1 enhancer signature. This study demonstrates that integration of Genome-Wide Association (GWA SNP and epigenomic DNA methylation data can identify potential novel genotype-epigenotype interactions within disease-associated loci, thus providing a novel route to aid unravelling common complex diseases.

  4. Trans-ethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A

    OpenAIRE

    Wang, Hansong; Burnett, Terrilea; Kono, Suminori; Haiman, Christopher A.; Iwasaki, Motoki; Wilkens, Lynne R.; Lenora W M Loo; Berg, David Van Den; Laurence N Kolonel; Henderson, Brian E.; Keku, Temitope O; Sandler, Robert S.; Signorello, Lisa B.; Blot, William J.; Newcomb, Polly A.

    2014-01-01

    The genetic basis of sporadic colorectal cancer (CRC) is not well explained by known risk polymorphisms. Here we perform a meta-analysis of two genome-wide association studies in 2,627 cases and 3,797 controls of Japanese ancestry and 1,894 cases and 4,703 controls of African ancestry, to identify genetic variants that contribute to CRC susceptibility. We replicate genome-wide statistically significant associations (P < 5×10−8) in 16,823 cases and 18,211 controls of European ancestry. This st...

  5. Identification of a susceptibility locus for severe adolescent idiopathic scoliosis on chromosome 17q24.3.

    Directory of Open Access Journals (Sweden)

    Atsushi Miyake

    Full Text Available Adolescent idiopathic scoliosis (AIS is the most common spinal deformity, affecting around 2% of adolescents worldwide. Genetic factors play an important role in its etiology. Using a genome-wide association study (GWAS, we recently identified novel AIS susceptibility loci on chromosomes 10q24.31 and 6q24.1. To identify more AIS susceptibility loci relating to its severity and progression, we performed GWAS by limiting the case subjects to those with severe AIS. Through a two-stage association study using a total of ∼12,000 Japanese subjects, we identified a common variant, rs12946942 that showed a significant association with severe AIS in the recessive model (P=4.00 × 10(-8, odds ratio [OR]=2.05. Its association was replicated in a Chinese population (combined P=6.43 × 10(-12, OR = 2.21. rs12946942 is on chromosome 17q24.3 near the genes SOX9 and KCNJ2, which when mutated cause scoliosis phenotypes. Our findings will offer new insight into the etiology and progression of AIS.

  6. Meiotic drive influences the outcome of sexually antagonistic selection at a linked locus.

    Science.gov (United States)

    Patten, M M

    2014-11-01

    Most meiotic drivers, such as the t-haplotype in Mus and the segregation distorter (SD) in Drosophila, act in a sex-specific manner, gaining a transmission advantage through one sex although suffering only the fitness costs associated with the driver in the other. Their inheritance is thus more likely through one of the two sexes, a property they share with sexually antagonistic alleles. Previous theory has shown that pairs of linked loci segregating for sexually antagonistic alleles are more likely to remain polymorphic and that linkage disequilibrium accrues between them. I probe this similarity between drive and sexual antagonism and examine the evolution of chromosomes experiencing these selection pressures simultaneously. Reminiscent of previous theory, I find that: the opportunity for polymorphism increases for a sexually antagonistic locus that is physically linked to a driving locus; the opportunity for polymorphism at a driving locus also increases when linked to a sexually antagonistic locus; and stable linkage disequilibrium accompanies any polymorphic equilibrium. Additionally, I find that drive at a linked locus favours the fixation of sexually antagonistic alleles that benefit the sex in which drive occurs. Further, I show that under certain conditions reduced recombination between these two loci is selectively favoured. These theoretical results provide clear, testable predictions about the nature of sexually antagonistic variation on driving chromosomes and have implications for the evolution of genomic architecture. © 2014 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  7. Ordered subset linkage analysis supports a susceptibility locus for age-related macular degeneration on chromosome 16p12

    Directory of Open Access Journals (Sweden)

    Weeks Daniel E

    2004-07-01

    Full Text Available Abstract Background Age-related macular degeneration (AMD is a complex disorder that is responsible for the majority of central vision loss in older adults living in developed countries. Phenotypic and genetic heterogeneity complicate the analysis of genome-wide scans for AMD susceptibility loci. The ordered subset analysis (OSA method is an approach for reducing heterogeneity, increasing statistical power for detecting linkage, and helping to define the most informative data set for follow-up analysis. OSA assesses the linkage evidence in subsets of potentially more homogeneous families by rank-ordering family-specific lod scores with respect to trait-associated covariates or phenotypic features. Here, we present results of incorporating five continuous covariates into our genome-wide linkage analysis of 389 microsatellite markers in 62 multiplex families: Body mass index (BMI, systolic (SBP and diastolic (DBP blood pressure, intraocular pressure (IOP, and pack-years of cigarette smoking. Chromosome-wide significance of increases in nonparametric multipoint lod scores in covariate-defined subsets relative to the overall sample was assessed by permutation. Results Using a correction for testing multiple covariates, statistically significant lod score increases were observed for two chromosomal regions: 14q13 with a lod score of 3.2 in 28 families with average IOP ≤ 15.5 (p = 0.002, and 6q14 with a lod score of 1.6 in eight families with average BMI ≥ 30.1 (p = 0.0004. On chromosome 16p12, nominally significant lod score increases (p ≤ 0.05, up to a lod score of 2.9 in 32 families, were observed with several covariate orderings. While less significant, this was the only region where linkage evidence was associated with multiple clinically meaningful covariates and the only nominally significant finding when analysis was restricted to advanced forms of AMD. Families with linkage to 16p12 had higher averages of SBP, IOP and BMI and were

  8. Allergic rhinitis - a total genome-scan for susceptibility genes suggests a locus on chromosome 4q24-q27

    DEFF Research Database (Denmark)

    Haagerup, A; Bjerke, T; Schøitz, P O

    2001-01-01

    definition of both clinical allergic rhinitis and confirmed specific allergy were chosen. Thirty-three affected sib-pair families qualified for the scan that was undertaken using 446 microsatellite markers. Non-parametric linkage results were obtained from MAPMAKER/SIBS computer program. The study revealed...... one major candidate region on chromosome 4q24-q27 (LOD=2.83) and eight minor candidate regions 2q12-q33, 3q13, 4p15-q12, 5q13-q15, 6p24-p23, 12p13, 22q13, and Xp21 (LOD=1.04-1.63) likely to contain susceptibility genes for allergic rhinitis. Our findings did not support a previous report of linkage...... of allergic rhinitis to chromosome 12q14-q24 but they added positive evidence to the asthma and atopy candidate regions 2q33 and 6p23. Further identification of the specific genes involved in allergic rhinitis will give opportunities for improved diagnosis and treatment....

  9. Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21

    Science.gov (United States)

    Adoue, Véronique; Michailidou, Kyriaki; Canisius, Sander; Lemaçon, Audrey; Droit, Arnaud; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Baynes, Caroline; Blomqvist, Carl; Bogdanova, Natalia V.; Bojesen, Stig E.; Bolla, Manjeet K.; Bonanni, Bernardo; Borresen-Dale, Anne-Lise; Brand, Judith S.; Brauch, Hiltrud; Brenner, Hermann; Broeks, Annegien; Burwinkel, Barbara; Chang-Claude, Jenny; Couch, Fergus J.; Cox, Angela; Cross, Simon S.; Czene, Kamila; Darabi, Hatef; Dennis, Joe; Devilee, Peter; Dörk, Thilo; Dos-Santos-Silva, Isabel; Eriksson, Mikael; Fasching, Peter A.; Figueroa, Jonine; Flyger, Henrik; García-Closas, Montserrat; Giles, Graham G.; Goldberg, Mark S.; González-Neira, Anna; Grenaker-Alnæs, Grethe; Guénel, Pascal; Haeberle, Lothar; Haiman, Christopher A.; Hamann, Ute; Hallberg, Emily; Hooning, Maartje J.; Hopper, John L.; Jakubowska, Anna; Jones, Michael; Kabisch, Maria; Kataja, Vesa; Lambrechts, Diether; Marchand, Loic Le; Lindblom, Annika; Lubinski, Jan; Mannermaa, Arto; Maranian, Mel; Margolin, Sara; Marme, Frederik; Milne, Roger L.; Neuhausen, Susan L.; Nevanlinna, Heli; Neven, Patrick; Olswold, Curtis; Peto, Julian; Plaseska-Karanfilska, Dijana; Pylkäs, Katri; Radice, Paolo; Rudolph, Anja; Sawyer, Elinor J.; Schmidt, Marjanka K.; Shu, Xiao-Ou; Southey, Melissa C.; Swerdlow, Anthony; Tollenaar, Rob A.E.M.; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Vachon, Celine; Van Den Ouweland, Ans M. W.; Wang, Qin; Winqvist, Robert; Investigators, kConFab/AOCS; Zheng, Wei; Benitez, Javier; Chenevix-Trench, Georgia; Dunning, Alison M.; Pharoah, Paul D. P.; Kristensen, Vessela; Hall, Per; Easton, Douglas F.; Pastinen, Tomi; Nord, Silje; Simard, Jacques

    2016-01-01

    There are significant inter-individual differences in the levels of gene expression. Through modulation of gene expression, cis-acting variants represent an important source of phenotypic variation. Consequently, cis-regulatory SNPs associated with differential allelic expression are functional candidates for further investigation as disease-causing variants. To investigate whether common variants associated with differential allelic expression were involved in breast cancer susceptibility, a list of genes was established on the basis of their involvement in cancer related pathways and/or mechanisms. Thereafter, using data from a genome-wide map of allelic expression associated SNPs, 313 genetic variants were selected and their association with breast cancer risk was then evaluated in 46,451 breast cancer cases and 42,599 controls of European ancestry ascertained from 41 studies participating in the Breast Cancer Association Consortium. The associations were evaluated with overall breast cancer risk and with estrogen receptor negative and positive disease. One novel breast cancer susceptibility locus on 4q21 (rs11099601) was identified (OR = 1.05, P = 5.6x10-6). rs11099601 lies in a 135 kb linkage disequilibrium block containing several genes, including, HELQ, encoding the protein HEL308 a DNA dependant ATPase and DNA Helicase involved in DNA repair, MRPS18C encoding the Mitochondrial Ribosomal Protein S18C and FAM175A (ABRAXAS), encoding a BRCA1 BRCT domain-interacting protein involved in DNA damage response and double-strand break (DSB) repair. Expression QTL analysis in breast cancer tissue showed rs11099601 to be associated with HELQ (P = 8.28x10-14), MRPS18C (P = 1.94x10-27) and FAM175A (P = 3.83x10-3), explaining about 20%, 14% and 1%, respectively of the variance inexpression of these genes in breast carcinomas. PMID:27792995

  10. Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21.

    Science.gov (United States)

    Hamdi, Yosr; Soucy, Penny; Adoue, Véronique; Michailidou, Kyriaki; Canisius, Sander; Lemaçon, Audrey; Droit, Arnaud; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Baynes, Caroline; Blomqvist, Carl; Bogdanova, Natalia V; Bojesen, Stig E; Bolla, Manjeet K; Bonanni, Bernardo; Borresen-Dale, Anne-Lise; Brand, Judith S; Brauch, Hiltrud; Brenner, Hermann; Broeks, Annegien; Burwinkel, Barbara; Chang-Claude, Jenny; Couch, Fergus J; Cox, Angela; Cross, Simon S; Czene, Kamila; Darabi, Hatef; Dennis, Joe; Devilee, Peter; Dörk, Thilo; Dos-Santos-Silva, Isabel; Eriksson, Mikael; Fasching, Peter A; Figueroa, Jonine; Flyger, Henrik; García-Closas, Montserrat; Giles, Graham G; Goldberg, Mark S; González-Neira, Anna; Grenaker-Alnæs, Grethe; Guénel, Pascal; Haeberle, Lothar; Haiman, Christopher A; Hamann, Ute; Hallberg, Emily; Hooning, Maartje J; Hopper, John L; Jakubowska, Anna; Jones, Michael; Kabisch, Maria; Kataja, Vesa; Lambrechts, Diether; Le Marchand, Loic; Lindblom, Annika; Lubinski, Jan; Mannermaa, Arto; Maranian, Mel; Margolin, Sara; Marme, Frederik; Milne, Roger L; Neuhausen, Susan L; Nevanlinna, Heli; Neven, Patrick; Olswold, Curtis; Peto, Julian; Plaseska-Karanfilska, Dijana; Pylkäs, Katri; Radice, Paolo; Rudolph, Anja; Sawyer, Elinor J; Schmidt, Marjanka K; Shu, Xiao-Ou; Southey, Melissa C; Swerdlow, Anthony; Tollenaar, Rob A E M; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Vachon, Celine; Van Den Ouweland, Ans M W; Wang, Qin; Winqvist, Robert; Zheng, Wei; Benitez, Javier; Chenevix-Trench, Georgia; Dunning, Alison M; Pharoah, Paul D P; Kristensen, Vessela; Hall, Per; Easton, Douglas F; Pastinen, Tomi; Nord, Silje; Simard, Jacques

    2016-12-06

    There are significant inter-individual differences in the levels of gene expression. Through modulation of gene expression, cis-acting variants represent an important source of phenotypic variation. Consequently, cis-regulatory SNPs associated with differential allelic expression are functional candidates for further investigation as disease-causing variants. To investigate whether common variants associated with differential allelic expression were involved in breast cancer susceptibility, a list of genes was established on the basis of their involvement in cancer related pathways and/or mechanisms. Thereafter, using data from a genome-wide map of allelic expression associated SNPs, 313 genetic variants were selected and their association with breast cancer risk was then evaluated in 46,451 breast cancer cases and 42,599 controls of European ancestry ascertained from 41 studies participating in the Breast Cancer Association Consortium. The associations were evaluated with overall breast cancer risk and with estrogen receptor negative and positive disease. One novel breast cancer susceptibility locus on 4q21 (rs11099601) was identified (OR = 1.05, P = 5.6x10-6). rs11099601 lies in a 135 kb linkage disequilibrium block containing several genes, including, HELQ, encoding the protein HEL308 a DNA dependant ATPase and DNA Helicase involved in DNA repair, MRPS18C encoding the Mitochondrial Ribosomal Protein S18C and FAM175A (ABRAXAS), encoding a BRCA1 BRCT domain-interacting protein involved in DNA damage response and double-strand break (DSB) repair. Expression QTL analysis in breast cancer tissue showed rs11099601 to be associated with HELQ (P = 8.28x10-14), MRPS18C (P = 1.94x10-27) and FAM175A (P = 3.83x10-3), explaining about 20%, 14% and 1%, respectively of the variance inexpression of these genes in breast carcinomas.

  11. Parenting Styles Influence on Locus of Control, Self-Efficacy and Academic Adjustment in College Students

    Science.gov (United States)

    Mills, Kimberly Tracey

    2010-01-01

    The purpose of this study was to investigate the relationship between perceived parenting style, locus of control, self-efficacy, and student outcome (i.e. academic performance, GPA) in a sample of college students. The relationship among gender and ethnicity were also examined across these variables. There were 100 participants in this study,…

  12. A New Susceptibility Locus for Myocardial Infarction, Hypertension, Type 2 Diabetes Mellitus, and Dyslipidemia on Chromosome 12q24

    Directory of Open Access Journals (Sweden)

    Salma M. Wakil

    2014-01-01

    Full Text Available We examined the role of hepatic nuclear factor-1 alpha (HNF1a gene polymorphism on coronary artery disease (CAD traits in 4631 Saudi angiographed individuals (2419 CAD versus 2212 controls using TaqMan assay on ABI Prism 7900HT sequence detection system. Following adjustment for confounders, the rs2259820_CC (1.19 (1.01–1.42; P=0.041, rs2464196_TT (1.19 (1.00–1.40; P=0.045, and rs2259816_T (1.13 (1.01–1.26; P=0.031 were associated with MI. The rs2259820_T (1.14 (1.03–1.26; P=0.011 and rs2464196_C (1.12 (1.02–1.24; P=0.024 were associated with type 2 diabetes mellitus (T2DM, while the rs2393791_T (1.14 (1.01–1.28; P=0.032, rs7310409_G (1.16 (1.03–1.30; P=0.013, and rs2464196_AG+GG (1.25 (1.05–1.49; P=0.012 were implicated in hypertension. Hypertriglyceridemia was linked to the rs2393791_T (1.14 (1.02–1.27; P=0.018, rs7310409_G (1.12 (1.01–1.25; P=0.031, rs1169310_G (1.15 (1.04–1.28; P=0.010, and rs1169313_CT+TT (1.24 (1.06–1.45; P=0.008 and high low density lipoprotein-cholesterol levels were associated with rs2259820_T (1.23 (1.07–1.41; P=0.004, rs2464196_T (1.22 (1.06–1.39; P=0.004, and rs2259816_T (1.18 (1.02–1.36; P=0.023. A 7-mer haplotype CATATAC (χ2=7.50; P=0.0062, constructed from the studied SNPs, was associated with MI, and CATATA implicated in T2DM (χ2=3.94; P=0.047. Hypertriglyceridemia was linked to TGCGGG (χ2=4.26; P=0.039, and obesity to ACGGGT (χ2=5.04; P=0.025. Our results suggest that the HNF1a is a common susceptibility gene for MI, T2DM, hypertension, and dyslipidemia.

  13. 9q31.2-rs865686 as a Susceptibility Locus for Estrogen Receptor-Positive Breast Cancer: Evidence from the Breast Cancer Association Consortium

    Science.gov (United States)

    Warren, Helen; Dudbridge, Frank; Fletcher, Olivia; Orr, Nick; Johnson, Nichola; Hopper, John L.; Apicella, Carmel; Southey, Melissa C.; Mahmoodi, Maryam; Schmidt, Marjanka K.; Broeks, Annegien; Cornelissen, Sten; Braaf, Linda M.; Muir, Kenneth R.; Lophatananon, Artitaya; Chaiwerawattana, Arkom; Wiangnon, Surapon; Fasching, Peter A.; Beckmann, Matthias W.; Ekici, Arif B.; Schulz-Wendtland, Ruediger; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael; Burwinkel, Barbara; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Mulot, Claire; Bojesen, Stig E; Nielsen, Sune F.; Flyger, Henrik; Nordestgaard, Børge G; Milne, Roger L.; Benítez, Javier; Arias-Pérez, José-Ignacio; Zamora, M. Pilar; Anton-Culver, Hoda; Ziogas, Argyrios; Bernstein, Leslie; Dur, Christina Clarke; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Langheinz, Anne; Meindl, Alfons; Golatta, Michael; Bartram, Claus R.; Schmutzler, Rita K.; Brauch, Hiltrud; Justenhoven, Christina; Brüning, Thomas; Chang-Claude, Jenny; Wang-Gohrke, Shan; Eilber, Ursula; Dörk, Thilo; Schürmann, Peter; Bremer, Michael; Hillemanns, Peter; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Bogdanova, Natalia; Antonenkova, Natalia; Rogov, Yuriy; Bermisheva, Marina; Prokofyeva, Darya; Zinnatullina, Guzel; Khusnutdinova, Elza; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.; Kataja, Vesa; Chenevix-Trench, Georgia; Beesley, Jonathan; Chen, Xiaoqing; Lambrechts, Diether; Smeets, Ann; Paridaens, Robert; Weltens, Caroline; Flesch-Janys, Dieter; Buck, Katharina; Behrens, Sabine; Peterlongo, Paolo; Bernard, Loris; Manoukian, Siranoush; Radice, Paolo; Couch, Fergus J.; Vachon, Celine; Wang, Xianshu; Olson, Janet; Giles, Graham; Baglietto, Laura; McLean, Cariona A.; Severi, Gianluca; John, Esther M.; Miron, Alexander; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Andrulis, Irene L.; Knight, Julia A.; Mulligan, Anna Marie; Weerasooriya, Nayana; Devilee, Peter; Tollenaar, Robert A.E.M.; Martens, John W.M.; Seynaeve, Caroline M.; Hooning, Maartje J.; Hollestelle, Antoinette; Jager, Agnes; Tilanus-Linthorst, Madeleine M.A.; Hall, Per; Czene, Kamila; Liu, Jianjun; Li, Jingmei; Cox, Angela; Cross, Simon S.; Brock, Ian W.; Reed, Malcolm W.R.; Pharoah, Paul; Blows, Fiona M.; Dunning, Alison M.; Ghoussaini, Maya; Ashworth, Alan; Swerdlow, Anthony; Jones, Michael; Schoemaker, Minouk; Easton, Douglas F.; Humphreys, Manjeet; Wang, Qin; Peto, Julian; dos-Santos-Silva, Isabel

    2013-01-01

    Background Our recent genome-wide association study identified a novel breast cancer susceptibility locus at 9q31.2 (rs865686). Methods To further investigate the rs865686–breast cancer association, we conducted a replication study within the Breast Cancer Association Consortium, which comprises 37 case–control studies (48,394 cases, 50,836 controls). Results This replication study provides additional strong evidence of an inverse association between rs865686 and breast cancer risk [study-adjusted per G-allele OR, 0.90; 95% confidence interval (CI), 0.88; 0.91, P = 2.01 × 10–29] among women of European ancestry. There were ethnic differences in the estimated minor (G)-allele frequency among controls [0.09, 0.30, and 0.38 among, respectively, Asians, Eastern Europeans, and other Europeans; P for heterogeneity (Phet) = 1.3 × 10–143], but no evidence of ethnic differences in per allele OR (Phet = 0.43). rs865686 was associated with estrogen receptor–positive (ER+) disease (per G-allele OR, 0.89; 95% CI, 0.86–0.91; P = 3.13 × 10–22) but less strongly, if at all, with ER-negative (ER–) disease (OR, 0.98; 95% CI, 0.94–1.02; P = 0.26; Phet = 1.16 × 10–6), with no evidence of independent heterogeneity by progesterone receptor or HER2 status. The strength of the breast cancer association decreased with increasing age at diagnosis, with case-only analysis showing a trend in the number of copies of the G allele with increasing age at diagnosis (P for linear trend = 0.0095), but only among women with ER+ tumors. Conclusions This study is the first to show that rs865686 is a susceptibility marker for ER+ breast cancer. Impact The findings further support the view that genetic susceptibility varies according to tumor subtype. PMID:22859399

  14. Influence of age of mice on the susceptibility to murine ...

    African Journals Online (AJOL)

    Intensity of human schistosomiasis infection increases with age, a peak being attained at early puberty. Hormones could be involved in the age-related changes in susceptibility to schistosomiasis. Male BALB/c mice were infected with Schistosoma mansoni either before or after puberty and worm numbers, cellular immune ...

  15. CDKN2B expression and subcutaneous adipose tissue expandability: Possible influence of the 9p21 atherosclerosis locus

    Energy Technology Data Exchange (ETDEWEB)

    Svensson, Per-Arne; Wahlstrand, Björn; Olsson, Maja [Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg (Sweden); Froguel, Philippe; Falchi, Mario [Department of Genomics of Common Disease, School of Public Health, Imperial College London (United Kingdom); Bergman, Richard N. [Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA (United States); McTernan, Philip G. [Division of Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry (United Kingdom); Hedner, Thomas; Carlsson, Lena M.S. [Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg (Sweden); Jacobson, Peter, E-mail: peter.jacobson@medfak.gu.se [Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg (Sweden)

    2014-04-18

    Highlights: • The tumor suppressor gene CDKN2B is highly expressed in human adipose tissue. • Risk alleles at the 9p21 locus modify CDKN2B expression in a BMI-dependent fashion. • There is an inverse relationship between expression of CDKN2B and adipogenic genes. • CDKN2B expression influences to postprandial triacylglycerol clearance. • CDKN2B expression in adipose tissue is linked to markers of hepatic steatosis. - Abstract: Risk alleles within a gene desert at the 9p21 locus constitute the most prevalent genetic determinant of cardiovascular disease. Previous research has demonstrated that 9p21 risk variants influence gene expression in vascular tissues, yet the biological mechanisms by which this would mediate atherosclerosis merits further investigation. To investigate possible influences of this locus on other tissues, we explored expression patterns of 9p21-regulated genes in a panel of multiple human tissues and found that the tumor suppressor CDKN2B was highly expressed in subcutaneous adipose tissue (SAT). CDKN2B expression was regulated by obesity status, and this effect was stronger in carriers of 9p21 risk alleles. Covariation between expression of CDKN2B and genes implemented in adipogenesis was consistent with an inhibitory effect of CDKN2B on SAT proliferation. Moreover, studies of postprandial triacylglycerol clearance indicated that CDKN2B is involved in down-regulation of SAT fatty acid trafficking. CDKN2B expression in SAT correlated with indicators of ectopic fat accumulation, including markers of hepatic steatosis. Among genes regulated by 9p21 risk variants, CDKN2B appears to play a significant role in the regulation of SAT expandability, which is a strong determinant of lipotoxicity and therefore might contribute to the development of atherosclerosis.

  16. Genome-wide association study implicates chromosome 9q21.31 as a susceptibility locus for asthma in mexican children.

    Directory of Open Access Journals (Sweden)

    Dana B Hancock

    2009-08-01

    Full Text Available Many candidate genes have been studied for asthma, but replication has varied. Novel candidate genes have been identified for various complex diseases using genome-wide association studies (GWASs. We conducted a GWAS in 492 Mexican children with asthma, predominantly atopic by skin prick test, and their parents using the Illumina HumanHap 550 K BeadChip to identify novel genetic variation for childhood asthma. The 520,767 autosomal single nucleotide polymorphisms (SNPs passing quality control were tested for association with childhood asthma using log-linear regression with a log-additive risk model. Eleven of the most significantly associated GWAS SNPs were tested for replication in an independent study of 177 Mexican case-parent trios with childhood-onset asthma and atopy using log-linear analysis. The chromosome 9q21.31 SNP rs2378383 (p = 7.10x10(-6 in the GWAS, located upstream of transducin-like enhancer of split 4 (TLE4, gave a p-value of 0.03 and the same direction and magnitude of association in the replication study (combined p = 6.79x10(-7. Ancestry analysis on chromosome 9q supported an inverse association between the rs2378383 minor allele (G and childhood asthma. This work identifies chromosome 9q21.31 as a novel susceptibility locus for childhood asthma in Mexicans. Further, analysis of genome-wide expression data in 51 human tissues from the Novartis Research Foundation showed that median GWAS significance levels for SNPs in genes expressed in the lung differed most significantly from genes not expressed in the lung when compared to 50 other tissues, supporting the biological plausibility of our overall GWAS findings and the multigenic etiology of childhood asthma.

  17. Genome-wide association study implicates chromosome 9q21.31 as a susceptibility locus for asthma in mexican children.

    Science.gov (United States)

    Hancock, Dana B; Romieu, Isabelle; Shi, Min; Sienra-Monge, Juan-Jose; Wu, Hao; Chiu, Grace Y; Li, Huiling; del Rio-Navarro, Blanca Estela; Willis-Owen, Saffron A G; Willis-Owens, Saffron A G; Weiss, Scott T; Raby, Benjamin A; Gao, Hong; Eng, Celeste; Chapela, Rocio; Burchard, Esteban G; Tang, Hua; Sullivan, Patrick F; London, Stephanie J

    2009-08-01

    Many candidate genes have been studied for asthma, but replication has varied. Novel candidate genes have been identified for various complex diseases using genome-wide association studies (GWASs). We conducted a GWAS in 492 Mexican children with asthma, predominantly atopic by skin prick test, and their parents using the Illumina HumanHap 550 K BeadChip to identify novel genetic variation for childhood asthma. The 520,767 autosomal single nucleotide polymorphisms (SNPs) passing quality control were tested for association with childhood asthma using log-linear regression with a log-additive risk model. Eleven of the most significantly associated GWAS SNPs were tested for replication in an independent study of 177 Mexican case-parent trios with childhood-onset asthma and atopy using log-linear analysis. The chromosome 9q21.31 SNP rs2378383 (p = 7.10x10(-6) in the GWAS), located upstream of transducin-like enhancer of split 4 (TLE4), gave a p-value of 0.03 and the same direction and magnitude of association in the replication study (combined p = 6.79x10(-7)). Ancestry analysis on chromosome 9q supported an inverse association between the rs2378383 minor allele (G) and childhood asthma. This work identifies chromosome 9q21.31 as a novel susceptibility locus for childhood asthma in Mexicans. Further, analysis of genome-wide expression data in 51 human tissues from the Novartis Research Foundation showed that median GWAS significance levels for SNPs in genes expressed in the lung differed most significantly from genes not expressed in the lung when compared to 50 other tissues, supporting the biological plausibility of our overall GWAS findings and the multigenic etiology of childhood asthma.

  18. DNA repair in the c-myc proto-oncogene locus: Possible involvement in susceptibility or resistance to plasmacytoma induction in BALB/c mice

    Energy Technology Data Exchange (ETDEWEB)

    Beecham, E.J.; Mushinski, J.F.; Shacter, E.; Potter, M.; Bohr, V.A. (Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, MD (USA))

    1991-06-01

    This report describes an unexpected difference in the efficiency of removal of UV-induced DNA damage in the c-myc locus in splenic B lymphoblasts from two inbred strains of mice. In cells from plasmacytoma-resistant DBA/2N mice, 35% of UV-induced damage in the regulatory and 5{prime} flank of c-myc is removed by 12 h. However, in cells from plasmacytoma-susceptible BALB/cAn mice, damage is not removed from this region. In the protein-encoding region and 3{prime} flank of c-myc as well as in two dihydrofolate reductase gene fragments, UV damage is repaired with similar efficiency in B lymphoblasts from both strains of mice. Furthermore, in the protein-encoding portion and 3{prime} flank of c-myc, damage is selectively removed from only the transcribed strand. No repair is detected in the nontranscribed strand. In contrast, DNA repair in the 5{prime} flank of c-myc is not strand specific; in DNA from DBA/2N cells, UV damage is rapidly removed from both the transcribed and nontranscribed strands. In BALB/cAn cells no repair was detected in either strand in the 5'flank, consistent with the results with double-stranded, nick-translated probes to this region of c-myc. In addition to the repair studies, we have detected post-UV-damage formation: in most of the genes studied, we find that additional T4 endonuclease-sensitive sites are formed in the DNA 2 h after irradiation. Our findings provide new insights into the details of gene-specific and strand-specific DNA repair and suggest that there may be close links between DNA repair and B-cell neoplastic development.

  19. CDKN2B expression and subcutaneous adipose tissue expandability: possible influence of the 9p21 atherosclerosis locus.

    Science.gov (United States)

    Svensson, Per-Arne; Wahlstrand, Björn; Olsson, Maja; Froguel, Philippe; Falchi, Mario; Bergman, Richard N; McTernan, Philip G; Hedner, Thomas; Carlsson, Lena M S; Jacobson, Peter

    2014-04-18

    Risk alleles within a gene desert at the 9p21 locus constitute the most prevalent genetic determinant of cardiovascular disease. Previous research has demonstrated that 9p21 risk variants influence gene expression in vascular tissues, yet the biological mechanisms by which this would mediate atherosclerosis merits further investigation. To investigate possible influences of this locus on other tissues, we explored expression patterns of 9p21-regulated genes in a panel of multiple human tissues and found that the tumor suppressor CDKN2B was highly expressed in subcutaneous adipose tissue (SAT). CDKN2B expression was regulated by obesity status, and this effect was stronger in carriers of 9p21 risk alleles. Covariation between expression of CDKN2B and genes implemented in adipogenesis was consistent with an inhibitory effect of CDKN2B on SAT proliferation. Moreover, studies of postprandial triacylglycerol clearance indicated that CDKN2B is involved in down-regulation of SAT fatty acid trafficking. CDKN2B expression in SAT correlated with indicators of ectopic fat accumulation, including markers of hepatic steatosis. Among genes regulated by 9p21 risk variants, CDKN2B appears to play a significant role in the regulation of SAT expandability, which is a strong determinant of lipotoxicity and therefore might contribute to the development of atherosclerosis. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  20. An Evolutionary Perspective on Family Studies: Differential Susceptibility to Environmental Influences.

    Science.gov (United States)

    Hartman, Sarah; Belsky, Jay

    2016-12-01

    An evolutionary perspective of human development provides the basis for the differential-susceptibility hypothesis which stipulates that individuals should differ in their susceptibility to environmental influences, with some being more affected than others by both positive and negative developmental experiences and environmental exposures. This paper reviews evidence consistent with this claim while revealing that temperamental and genetic characteristics play a role in distinguishing more and less susceptible individuals. The differential-susceptibility framework under consideration is contrasted to the traditional diathesis-stress view that "vulnerability" traits predispose some to being disproportionately affected by (only) adverse experiences. We raise several issues stimulated by the literature that need to be clarified in further research. Lastly, we suggest that therapy may differ in its effects depending on an individual's susceptibility. © 2015 Family Process Institute.

  1. Susceptibility to Classmates' Influence on Delinquency during Early Adolescence

    Science.gov (United States)

    Müller, Christoph M.; Hofmann, Verena; Arm, Sybille

    2017-01-01

    Early adolescents vary in their susceptibility to peer influence on delinquency. However, it is still less clear which factors explain this variation and how these factors relate to each other. In this study, 10 factors that may moderate peer influence were investigated. A sample of 868 participants was followed across six occasions from seventh…

  2. Susceptibility of volcanic ash-influenced soil in northern Idaho to mechanical compaction

    Science.gov (United States)

    Deborah S. Page-Dumroese

    1993-01-01

    Timber harvesting and mechanical site preparation can reduce site productivity if they excessively disturb or compact the soil. Volcanic ash-influenced soils with low undisturbed bulk densities and rock content are particularly susceptible. This study evaluates the effects of harvesting and site preparation on changes in the bulk density of ash-influenced forest soils...

  3. Change of antibiotic susceptibility testing guidelines from CLSI to EUCAST: Influence on cumulative hospital antibiograms

    OpenAIRE

    Aline Wolfensberger; Hugo Sax; Rainer Weber; Reinhard Zbinden; Kuster, Stefan P.; Michael Hombach

    2013-01-01

    OBJECTIVE: We studied whether the change in antibiotic susceptibility testing (AST) guidelines from CLSI to EUCAST influenced cumulative antibiograms in a tertiary care hospital in Switzerland. METHODS: Antibiotic susceptibilities of non-duplicate isolates collected within a one-year period before (period A) and after (period B) changing AST interpretation from CLSI 2009 to EUCAST 1.3 (2011) guidelines were analysed. In addition, period B isolates were reinterpreted according to the CLSI 2009...

  4. Does gender influence susceptibility and consequences of acquired epilepsies?

    Science.gov (United States)

    Perucca, Piero; Camfield, Peter; Camfield, Carol

    2014-12-01

    Gender differences in the incidence and clinical course of acquired and "cryptogenic" epilepsy are reviewed based on a literature search. We emphasized incidence and population-based studies because they are best suited to assess the effect of gender on susceptibility and clinical evolution of these epilepsies and may control for potential confounding factors. However, such studies were only available for a few acquired etiologies. These included tumor, prenatal and perinatal brain insults, cerebrovascular disease, infection, trauma, neurodegenerative disease, and autoimmune disorders. None of these acquired causes has been consistently shown to affect women or men to a greater or lesser degree, although some of the literature is contradictory or inadequate. There is almost no literature that addresses the effect of gender on the clinical course of epilepsy associated with these acquired causes. In addition, most studies of acquired causes do not take into account the incidence of the cause in the population with or without associated epilepsy. In children, "cryptogenic" epilepsy (non-syndromic and without causative MRI lesion) does not appear to have a gender preference and gender does not seem to affect the likelihood of remission. As further population-based studies of the etiology and clinical course of epilepsy are undertaken, it may be worthwhile to more specifically define the role of gender. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Experimentally measured susceptibility to peer influence and adolescent sexual behavior trajectories: A preliminary study.

    Science.gov (United States)

    Choukas-Bradley, Sophia; Giletta, Matteo; Widman, Laura; Cohen, Geoffrey L; Prinstein, Mitchell J

    2014-09-01

    A performance-based measure of peer influence susceptibility was examined as a moderator of the longitudinal association between peer norms and trajectories of adolescents' number of sexual intercourse partners. Seventy-one 9th grade adolescents (52% female) participated in an experimental "chat room" paradigm involving "e-confederates" who endorsed sexual risk behaviors. Changes in participants' responses to risk scenarios before versus during the "chat room" were used as a performance-based measure of peer influence susceptibility. Participants reported their perceptions of popular peers' number of sexual intercourse partners at baseline and self-reported their number of sexual intercourse partners at baseline and 6, 12, and 18 months later. Susceptibility was examined as a moderator of the longitudinal association between perceptions of popular peers' number of sexual intercourse partners and trajectories of adolescents' own numbers of partners. High perceptions of the number of popular peers' sexual intercourse partners combined with high peer influence susceptibility predicted steeper longitudinal trajectories of adolescents' number of partners. Results provide novel preliminary evidence regarding the importance of peer influence susceptibility in adolescents' development of sexual behaviors.

  6. Experimentally-Measured Susceptibility to Peer Influence and Adolescent Sexual Behavior Trajectories: A Preliminary Study

    Science.gov (United States)

    Choukas-Bradley, Sophia; Giletta, Matteo; Widman, Laura; Cohen, Geoffrey L.; Prinstein, Mitchell J.

    2014-01-01

    A performance-based measure of peer influence susceptibility was examined as a moderator of the longitudinal association between peer norms and trajectories of adolescents' number of sexual intercourse partners. Seventy-one 9th grade adolescents (52% female) participated in an experimental “chat room” paradigm involving “e-confederates” who endorsed sexual risk behaviors. Changes in participants' responses to risk scenarios before versus during the “chat room” were used as a performance-based measure of peer influence susceptibility. Participants reported their perceptions of popular peers' number of sexual intercourse partner sat baseline, and self-reported their number of sexual intercourse partners at baseline and 6, 12, and 18 months later. Susceptibility was examined as a moderator of the longitudinal association between perceptions of popular peers' number of sexual intercourse partners and trajectories of adolescents' own numbers of partners. High perceptions of the number of popular peers' sexual intercourse partners combined with high peer influence susceptibility predicted steeper longitudinal trajectories of adolescents' number of partners. Results provide novel preliminary evidence regarding the importance of peer influence susceptibility in adolescents' development of sexual behaviors. PMID:24999763

  7. Variants in SKP1, PROB1, and IL17B genes at keratoconus 5q31.1-q35.3 susceptibility locus identified by whole-exome sequencing.

    Science.gov (United States)

    Karolak, Justyna A; Gambin, Tomasz; Pitarque, Jose A; Molinari, Andrea; Jhangiani, Shalini; Stankiewicz, Pawel; Lupski, James R; Gajecka, Marzena

    2016-01-01

    Keratoconus (KTCN) is a protrusion and thinning of the cornea, resulting in impairment of visual function. The extreme genetic heterogeneity makes it difficult to discover factors unambiguously influencing the KTCN phenotype. In this study, we used whole-exome sequencing (WES) and Sanger sequencing to reduce the number of candidate genes at the 5q31.1-q35.3 locus and to prioritize other potentially relevant variants in an Ecuadorian family with KTCN. We applied WES in two affected KTCN individuals from the Ecuadorian family that showed a suggestive linkage between the KTCN phenotype and the 5q31.1-q35.3 locus. Putative variants identified by WES were further evaluated in this family using Sanger sequencing. Exome capture discovered a total of 173 rare (minor allele frequency G in SKP1, c.671G>A in PROB1, and c.527G>A in IL17B in the 5q31.1-q35.3 linkage region, and c.850G>A in HKDC1 in the 10q22 locus completely segregated with the phenotype in the studied KTCN family. We demonstrate that a combination of various techniques significantly narrowed the studied genomic region and reduced the list of the putative exonic variants. Moreover, since this locus overlapped two other chromosomal regions previously recognized in distinct KTCN studies, our findings suggest that this 5q31.1-q35.3 locus might be linked with KTCN.

  8. Transformations in Kenyan Science Teachers' Locus of Control: The Influence of Contextualized Science and Emancipated Student Learning

    Science.gov (United States)

    Anderson, D.; Nashon, S.; Namazzi, E.; Okemwa, P.; Ombogo, P.; Ooko, S.; Beru, F.

    2015-11-01

    This study investigated Kenyan science teachers' pedagogical transformations, which manifested as they enacted and experienced a reformed contextualized science curriculum in which students' learning experiences were critical catalysts of teacher change. Twelve high school teachers voluntarily participated in the study and were interviewed about their pedagogical transformations following their enactment of a reformed contextualized science curriculum. The outcomes demonstrated that students' emancipated behaviours, learning and performance, qualitatively influenced teacher change and pedagogical reform. Specifically, changes in students, as a result of the ways the science curriculum was implemented, resulted in epiphanies and dilemmas for teachers who subsequently resolved to surrender their tightly held pedagogical control (locus of control) for the betterment of the learning environment and their sense of professional satisfaction.

  9. Genome wide association identifies common variants at the SERPINA6/SERPINA1 locus influencing plasma cortisol and corticosteroid binding globulin.

    Directory of Open Access Journals (Sweden)

    Jennifer L Bolton

    2014-07-01

    Full Text Available Variation in plasma levels of cortisol, an essential hormone in the stress response, is associated in population-based studies with cardio-metabolic, inflammatory and neuro-cognitive traits and diseases. Heritability of plasma cortisol is estimated at 30-60% but no common genetic contribution has been identified. The CORtisol NETwork (CORNET consortium undertook genome wide association meta-analysis for plasma cortisol in 12,597 Caucasian participants, replicated in 2,795 participants. The results indicate that <1% of variance in plasma cortisol is accounted for by genetic variation in a single region of chromosome 14. This locus spans SERPINA6, encoding corticosteroid binding globulin (CBG, the major cortisol-binding protein in plasma, and SERPINA1, encoding α1-antitrypsin (which inhibits cleavage of the reactive centre loop that releases cortisol from CBG. Three partially independent signals were identified within the region, represented by common SNPs; detailed biochemical investigation in a nested sub-cohort showed all these SNPs were associated with variation in total cortisol binding activity in plasma, but some variants influenced total CBG concentrations while the top hit (rs12589136 influenced the immunoreactivity of the reactive centre loop of CBG. Exome chip and 1000 Genomes imputation analysis of this locus in the CROATIA-Korcula cohort identified missense mutations in SERPINA6 and SERPINA1 that did not account for the effects of common variants. These findings reveal a novel common genetic source of variation in binding of cortisol by CBG, and reinforce the key role of CBG in determining plasma cortisol levels. In turn this genetic variation may contribute to cortisol-associated degenerative diseases.

  10. Obesity, externality, and susceptibility to social influence: an integrated analysis.

    Science.gov (United States)

    Herman, C P; Olmsted, M P; Polivy, J

    1983-10-01

    A pilot study indicated that overweight subjects are more likely to order a particular dessert in a restaurant when the waitress provides an appetizing description of that dessert and encourages the diner to order it; subjects who were not overweight were much less affected by the waitress's behavior. This effect may be interpreted in terms of the greater "externality' of overweight persons (i.e., their greater reactivity to salient food cues); alternatively, it may be seen as evidence for greater compliance by deviant (overweight) individuals. The present study examined these alternatives by separating the perceptual-cues component of the waitress's behavior from the social-influence component in a replication of the pilot study. The results indicated that both the externality and compliance interpretations were tenable. The authors suggest that these two mechanisms may be seen as facets of a more general concern on the part of overweight people to secure behavioral guidance from the external environment, physical or social.

  11. Susceptibility to and impact of interpersonal influence in an investment context

    NARCIS (Netherlands)

    Hoffmann, A. O. I.; Broekhuizen, T. L. J.

    2009-01-01

    This paper demonstrates the relevance of consumers' susceptibility to interpersonal influence (CSII) in an investment context. In Study 1, a survey of individual investors, investment-related knowledge, psycho-social risks, and social needs emerge as antecedents that explain investors'

  12. Affiliation with Antisocial Peers, Susceptibility to Peer Influence, and Antisocial Behavior during the Transition to Adulthood

    Science.gov (United States)

    Monahan, Kathryn C.; Steinberg, Laurence; Cauffman, Elizabeth

    2009-01-01

    Developmental theories suggest that affiliation with deviant peers and susceptibility to peer influence are important contributors to adolescent delinquency, but it is unclear how these variables impact antisocial behavior during the transition to adulthood, a period when most delinquent individuals decline in antisocial behavior. Using data from…

  13. Influence of the IL6 Gene in Susceptibility to Systemic Sclerosis

    NARCIS (Netherlands)

    Cenit, M.C.; Simeon, C.P.; Vonk, M.C.; Callejas-Rubio, J.L.; Espinosa, G.; Carreira, P.; Blanco, F.J.; Narvaez, J.; Tolosa, C.; Roman-Ivorra, J.A.; Gomez-Garcia, I.; Garcia-Hernandez, F.J.; Gallego, M.; Garcia-Portales, R.; Egurbide, M.V.; Fonollosa, V.; Garcia de la Pena, P.; Lopez-Longo, F.J.; Gonzalez-Gay, M.A.; The Spanish Scleroderma, G.; Hesselstrand, R.; Riemekasten, G.; Witte, T.; Voskuyl, A.E.; Schuerwegh, A.J.; Madhok, R.; Fonseca, C.; Denton, C.; Nordin, A.; Palm, O.; Laar, J.M. van; Hunzelmann, N.; Distler, J.H.; Kreuter, A.; Herrick, A.; Worthington, J.; Koeleman, B.P.; Radstake, T.R.D.J.; Martin, J.

    2012-01-01

    OBJECTIVE: Systemic sclerosis (SSc) is a genetically complex autoimmune disease; the genetic component has not been fully defined. Interleukin 6 (IL-6) plays a crucial role in immunity and fibrosis, both key aspects of SSc. We investigated the influence of IL6 gene in the susceptibility and

  14. Variation at the serotonin transporter gene influences susceptibility to bipolar affective puerperal psychosis.

    Science.gov (United States)

    Coyle, N; Jones, I; Robertson, E; Lendon, C; Craddock, N

    2000-10-28

    Up to half of parous females with bipolar disorder (manic depression) develop an episode of severe psychiatric disturbance, usually called puerperal psychosis, within a few days of giving birth. We report significant evidence (p<0.003) that variation at the serotonin transporter gene exerts a substantial (odds ratio=4) and important (population attributable fraction=69%) influence on susceptibility to such episodes.

  15. Experimentally Measured Susceptibility to Peer Influence and Adolescent Sexual Behavior Trajectories: A Preliminary Study

    Science.gov (United States)

    Choukas-Bradley, Sophia; Giletta, Matteo; Widman, Laura; Cohen, Geoffrey L.; Prinstein, Mitchell J.

    2014-01-01

    A performance-based measure of peer influence susceptibility was examined as a moderator of the longitudinal association between peer norms and trajectories of adolescents' number of sexual intercourse partners. Seventy-one 9th grade adolescents (52% female) participated in an experimental "chat room" paradigm involving…

  16. Being in "Bad" Company: Power Dependence and Status in Adolescent Susceptibility to Peer Influence

    Science.gov (United States)

    Vargas, Robert

    2011-01-01

    Theories of susceptibility to peer influence have centered on the idea that lower status adolescents are likely to adopt the behaviors of high status adolescents. While status is important, social exchange theorists have shown the value of analyzing exchange relations between actors to understand differences in power. To build on status-based…

  17. Experimentally measured susceptibility to peer influence and adolescent sexual behavior trajectories : A preliminary study

    NARCIS (Netherlands)

    Choukas-Bradley, S.; Giletta, M.; Widman, L.; Cohen, G.L.; Prinstein, M.J.

    2014-01-01

    A performance-based measure of peer influence susceptibility was examined as a moderator of the longitudinal association between peer norms and trajectories of adolescents' number of sexual intercourse partners. Seventy-one 9th grade adolescents (52% female) participated in an experimental "chat

  18. Change of antibiotic susceptibility testing guidelines from CLSI to EUCAST: influence on cumulative hospital antibiograms.

    Science.gov (United States)

    Wolfensberger, Aline; Sax, Hugo; Weber, Rainer; Zbinden, Reinhard; Kuster, Stefan P; Hombach, Michael

    2013-01-01

    We studied whether the change in antibiotic susceptibility testing (AST) guidelines from CLSI to EUCAST influenced cumulative antibiograms in a tertiary care hospital in Switzerland. Antibiotic susceptibilities of non-duplicate isolates collected within a one-year period before (period A) and after (period B) changing AST interpretation from CLSI 2009 to EUCAST 1.3 (2011) guidelines were analysed. In addition, period B isolates were reinterpreted according to the CLSI 2009, CLSI 2013 and EUCAST 3.1 (2013) guidelines. The majority of species/drug combinations showed no differences in susceptibility rates comparing periods A and B. However, in some gram-negative bacilli, decreased susceptibility rates were observed when comparing CLSI 2009 with EUCAST 1.3 within period B: Escherichia coli / cefepime, 95.8% (CLSI 2009) vs. 93.1% (EUCAST 1.3), P=0.005; Enterobacter cloacae / cefepime, 97.0 (CLSI 2009) vs. 90.5% (EUCAST 1.3), P=0.012; Pseudomonas aeruginosa / meropenem, 88.1% (CLSI 2009) vs. 78.3% (EUCAST 1.3), P=0.002. These differences were still evident when comparing susceptibility rates according to the CLSI 2013 guideline with EUCAST 3.1 guideline. For P. aeruginosa and imipenem, a trend towards a lower antibiotic susceptibility rate in ICUs compared to general wards turned into a significant difference after the change to EUCAST: 87.9% vs. 79.8%, P=0.08 (CLSI 2009) and 86.3% vs. 76.8%, P=0.048 (EUCAST 1.3). The change of AST guidelines from CLSI to EUCAST led to a clinically relevant decrease of susceptibility rates in cumulative antibiograms for defined species/drug combinations, particularly in those with considerable differences in clinical susceptibility breakpoints between the two guidelines.

  19. Sequence variation and genetic evolution at the human F12 locus: mapping quantitative trait nucleotides that influence FXII plasma levels.

    Science.gov (United States)

    Calafell, Francesc; Almasy, Laura; Sabater-Lleal, Maria; Buil, Alfonso; Mordillo, Carolina; Ramírez-Soriano, Anna; Sikora, Martin; Souto, Juan Carlos; Blangero, John; Fontcuberta, Jordi; Soria, José Manuel

    2010-02-01

    The level of Factor XII (FXII) is an important phenotype that exhibits a high genetic component and is associated with thrombotic disease. In a genome-wide linkage scan, we demonstrated that the F12 gene represents a quantitative trait locus (QTL) that influences FXII levels. The current study investigated the genetic architecture of the F12 gene to locate polymorphism(s) responsible for the variation of FXII levels. Re-sequencing of the F12 gene in 40 unrelated individuals (selected from the tails of normal distribution of FXII levels) identified 26 polymorphisms which were genotyped in 398 individuals belonging to 21 families from the GAIT Project. By a measured genotype association analysis, eight of 26 SNPs showed significant P-values less than 10(-5) (after multiple test correction) with FXII levels. In addition, the Bayesian Quantitative Trait Nucleotide method, which infers those polymorphisms most likely to have a direct influence on the trait under study, provided evidence that only rs1801020 variation accounted for the variance attributed to this QTL. Moreover, we have analyzed the evolutionary processes that produced the variation in F12 gene and concluded that is evolutionarily neutral and that the T allele of the rs1801020 appeared approximately 100 000 years ago and spread to most human populations rising to high frequencies by genetic drift. Our study provides a template for future genetic studies of human quantitative traits, as we move beyond QTL localization to the polymorphisms responsible for the variation of important biomedical phenotypes.

  20. Genome wide association identifies common variants at the SERPINA6/SERPINA1 locus influencing plasma cortisol and corticosteroid binding globulin.

    Science.gov (United States)

    Bolton, Jennifer L; Hayward, Caroline; Direk, Nese; Lewis, John G; Hammond, Geoffrey L; Hill, Lesley A; Anderson, Anna; Huffman, Jennifer; Wilson, James F; Campbell, Harry; Rudan, Igor; Wright, Alan; Hastie, Nicholas; Wild, Sarah H; Velders, Fleur P; Hofman, Albert; Uitterlinden, Andre G; Lahti, Jari; Räikkönen, Katri; Kajantie, Eero; Widen, Elisabeth; Palotie, Aarno; Eriksson, Johan G; Kaakinen, Marika; Järvelin, Marjo-Riitta; Timpson, Nicholas J; Davey Smith, George; Ring, Susan M; Evans, David M; St Pourcain, Beate; Tanaka, Toshiko; Milaneschi, Yuri; Bandinelli, Stefania; Ferrucci, Luigi; van der Harst, Pim; Rosmalen, Judith G M; Bakker, Stephen J L; Verweij, Niek; Dullaart, Robin P F; Mahajan, Anubha; Lindgren, Cecilia M; Morris, Andrew; Lind, Lars; Ingelsson, Erik; Anderson, Laura N; Pennell, Craig E; Lye, Stephen J; Matthews, Stephen G; Eriksson, Joel; Mellstrom, Dan; Ohlsson, Claes; Price, Jackie F; Strachan, Mark W J; Reynolds, Rebecca M; Tiemeier, Henning; Walker, Brian R

    2014-07-01

    Variation in plasma levels of cortisol, an essential hormone in the stress response, is associated in population-based studies with cardio-metabolic, inflammatory and neuro-cognitive traits and diseases. Heritability of plasma cortisol is estimated at 30-60% but no common genetic contribution has been identified. The CORtisol NETwork (CORNET) consortium undertook genome wide association meta-analysis for plasma cortisol in 12,597 Caucasian participants, replicated in 2,795 participants. The results indicate that SERPINA1, encoding α1-antitrypsin (which inhibits cleavage of the reactive centre loop that releases cortisol from CBG). Three partially independent signals were identified within the region, represented by common SNPs; detailed biochemical investigation in a nested sub-cohort showed all these SNPs were associated with variation in total cortisol binding activity in plasma, but some variants influenced total CBG concentrations while the top hit (rs12589136) influenced the immunoreactivity of the reactive centre loop of CBG. Exome chip and 1000 Genomes imputation analysis of this locus in the CROATIA-Korcula cohort identified missense mutations in SERPINA6 and SERPINA1 that did not account for the effects of common variants. These findings reveal a novel common genetic source of variation in binding of cortisol by CBG, and reinforce the key role of CBG in determining plasma cortisol levels. In turn this genetic variation may contribute to cortisol-associated degenerative diseases.

  1. Influence of health locus of control and fear of hypoglycaemia on glycaemic control and treatment satisfaction in people with Type 1 diabetes on insulin pump therapy.

    Science.gov (United States)

    Indelicato, L; Mariano, V; Galasso, S; Boscari, F; Cipponeri, E; Negri, C; Frigo, A; Avogaro, A; Bonora, E; Trombetta, M; Bruttomesso, D

    2017-05-01

    To assess the influence of health locus of control and fear of hypoglycaemia on metabolic control and treatment satisfaction in people with Type 1 diabetes mellitus on continuous subcutaneous insulin infusion. People with Type 1 diabetes on continuous subcutaneous insulin infusion for at least 1 year, sub-classified as an 'acceptable glucose control' group [HbA1c ≤ 58 mmol/mol (7.5%)] and a 'suboptimum glucose control' group [HbA1c > 58 mmol/mol (7.5%)], were consecutively enrolled in a multicentre cross-sectional study. Questionnaires were administered to assess health locus of control [Multidimensional Health Locus of Control (MHLC) scale, with internal and external subscales], fear of hypoglycaemia [Hypoglycaemia Fear Survey II (HFS-II)] and treatment satisfaction [Diabetes Treatment Satisfaction Questionnaire (DTSQ)]. We enrolled 214 participants (mean ± sd age 43.4 ± 12.1 years). The suboptimum glucose control group (n = 127) had lower mean ± sd internal MHLC and DTSQ scores than the acceptable glucose control group (19.6 ± 5.2 vs 21.0 ± 5.0, P = 0.04 and 28.8 ± 4.8 vs 30.9 ± 4.5, P Type 1 diabetes receiving continuous subcutaneous insulin infusion, high internal locus represents the most important locus of control pattern for achieving good metabolic control. © 2017 Diabetes UK.

  2. Brief report: personality correlates of susceptibility to peer influence in adolescence.

    Science.gov (United States)

    Stautz, Kaidy; Cooper, Andrew

    2014-06-01

    Adolescents show a heightened susceptibility to peer influence compared to adults. Individual differences in this susceptibility exist, yet there has been little effort to link these with broader personality processes. Reward sensitivity and impulsive behaviour are also heightened in adolescence and could affect the tendency to be influenced by peers. This study examined associations between self-reported resistance to peer influence, facets of reward sensitivity and impulsivity, and subjective social status in a sample of 269 British sixth form students (mean age 16.79). Multiple regression analyses showed that negative and positive urgency were significantly negatively associated with resistance to peer influence. The relationship between negative urgency and resistance was moderated by subjective social status, such that individuals reporting low status showed a stronger negative relationship. Results suggest that a susceptibility to peer influence is linked with a tendency to act impulsively when in heightened emotional states. Adolescents high in negative urgency who feel lower in their social hierarchy may be particularly vulnerable. Copyright © 2014 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  3. Degree of host susceptibility in the initial disease outbreak influences subsequent epidemic spread

    Science.gov (United States)

    Severns, Paul M.; Estep, Laura K.; Sackett, Kathryn E.; Mundt, Christopher C.

    2014-01-01

    Summary Disease epidemics typically begin as an outbreak of a relatively small, spatially explicit population of infected individuals (focus), in which disease prevalence increases and rapidly spreads into the uninfected, at-risk population. Studies of epidemic spread typically address factors influencing disease spread through the at-risk population, but the initial outbreak may strongly influence spread of the subsequent epidemic.We initiated wheat stripe rust Puccinia striiformis f. sp. tritici epidemics to assess the influence of the focus on final disease prevalence when the degree of disease susceptibility differed between the at-risk and focus populations.When the focus/at-risk plantings consisted of partially genetic resistant and susceptible cultivars, final disease prevalence was statistically indistinguishable from epidemics produced by the focus cultivar in monoculture. In these experimental epidemics, disease prevalence was not influenced by the transition into an at-risk population that differed in disease susceptibility. Instead, the focus appeared to exert a dominant influence on the subsequent epidemic.Final disease prevalence was not consistently attributable to either the focus or the at-risk population when focus/at-risk populations were planted in a factorial set-up with a mixture (~28% susceptible and 72% resistant) and susceptible individuals. In these experimental epidemics, spatial heterogeneity in disease susceptibility within the at-risk population appeared to counter the dominant influence of the focus.Cessation of spore production from the focus (through fungicide/glyphosate application) after 1.3 generations of stripe rust spread did not reduce final disease prevalence, indicating that the focus influence on disease spread is established early in the epidemic.Synthesis and applications. Our experiments indicated that outbreak conditions can be highly influential on epidemic spread, even when disease resistance in the at-risk population

  4. Influence of heavy episodic drinking on the relation between men's locus of control and aggression toward intimate partners.

    Science.gov (United States)

    Gallagher, Kathryn E; Parrott, Dominic J

    2010-03-01

    This study examined the interactive effects of locus of control and heavy episodic drinking on men's physical assault and sexual coercion against intimate partners. Participants were 151 heterosexual drinking men who completed self-report measures of locus of control, alcohol consumption during the past 12 months, and intimate-partner aggression during the past 12 months. An internal locus of control was associated with a lower frequency of physical assault and sexual coercion toward intimate partners among men who reported lower quantities of alcohol consumption. However, data suggested that the protective qualities of an internal locus of control for both forms of partner aggression diminished among men who reported higher quantities of alcohol consumption. These results support alcohol myopia theory and extend this theory by suggesting how alcohol consumption may affect the relation between locus of control and different forms of intimate-partner aggression toward women.

  5. Linkage analysis in a large Swedish family supports the presence of a susceptibility locus for adenoma and colorectal cancer on chromosome 9q22.32-31.1

    DEFF Research Database (Denmark)

    Skoglund, J; Djureinovic, T; Zhou, X-L

    2006-01-01

    BACKGROUND: The best known hereditary colorectal cancer syndromes, familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC), constitute about 2% of all colorectal cancers, and there are at least as many non-FAP, non-HNPCC cases where the family history suggests...... previously been investigated but following the identification of adenomas in several previously unaffected family members, these subjects were now considered to be gene carriers. RESULTS: In the present study, we found linkage of adenoma and colorectal cancer to chromosome 9q22.32-31.1 with a multipoint LOD...... a dominantly inherited colorectal cancer risk. Recently, a locus on chromosome 9q22.2-31.2 was identified by linkage analysis in sib pairs with colorectal cancer or adenoma. METHODS: Linkage analysis for the suggested locus on chromosome 9 was carried out in an extended Swedish family. This family had...

  6. Market segmentation based on consumers’ susceptibility to reference group types of influence: Multivariance analysis

    Directory of Open Access Journals (Sweden)

    Mirela Mihić

    2006-12-01

    Full Text Available In this paper we begin with McGuire’s concept of influenceability, according to which individuals differ based on their susceptibility to social influence. The theoretical part explains three types of influence by reference groups and presents previous results relevant to the issue of this paper. The second part of the paper presents the methodology and research results. The aim of this research is to identify different types of reference group influence by using multivariance techniques, and determine whether they can serve as a basis for consumer market segmentation. The research was conducted on a sample of 250 respondents in the Split-Dalmatia County. Keeping in mind the issues and goals of the research, two hypotheses were set. Five factors – influence types were identified by using the factor analysis (normative influence, value-expressive or identificational influence, environment informative influence, salesperson’s informative influence, and comparison to environment and clothing conformity, and were then been used as basic segmentation variables. Cluster analysis singled out three segments: subject to identification or value-expressive influence, subject to information influence and non-subject to influence. To describe them better, demographic variables were employed, i.e. “relation-comparison and interaction with others” variables as well as personal indicators. The research results confirmed both starting hypotheses. The results attained suggest that consumers from particular segments require different communication strategies, based on which, each segment was supported by corresponding recommendations.

  7. Sequence variants at the myostatin gene locus influence the body composition of Thoroughbred horses.

    Science.gov (United States)

    Tozaki, Teruaki; Sato, Fumio; Hill, Emmeline W; Miyake, Takeshi; Endo, Yoshiro; Kakoi, Hironaga; Gawahara, Hitoshi; Hirota, Kei-ichi; Nakano, Yasuko; Nambo, Yasuo; Kurosawa, Masahiko

    2011-12-01

    Myostatin is a member of the transforming growth factor-β family with a key role in inhibition of muscle growth by negative regulation of both myoblast proliferation and differentiation. Recently, a genomic region on ECA18, which includes the MSTN gene, was identified as a candidate region influencing racing performance in Thoroughbreds. In this study, four SNPs on ECA18, g.65809482T>C, g.65868604G>T, g.66493737C>T, and g.66539967A>G, were genotyped in 91 Thoroughbred horses-in-training to evaluate the association between genotype and body composition traits, including body weight, withers height, chest circumference, cannon circumference, and body weight/withers height. Of these, statistically differences in body weight and body weight/withers height were associated with specific genotypes in males. Specifically, body weight/withers height showed statistically significant differences depending on genotype at g.658604G>T, g.66493737C>T, and g.66539967A>G (PT, had the highest value (3.17 ± 0.05 kg·cm(-1)) for body weight/withers height in March, while those with a genotype associated with suitability for long-distance racing, T/T, had the lowest (2.99 ± 0.03 kg·cm(-1)). In females, the trends in the association of body weight/withers height with genotypes were similar to those observed in males. As the SNPs are not believed to be linked to coding variants in MSTN, these results suggest that regulation of MSTN gene expression influences skeletal muscle mass and hence racing performance, particularly optimum race distance, in Thoroughbred horses.

  8. Influence of tobacco marketing and exposure to smokers on adolescent susceptibility to smoking.

    Science.gov (United States)

    Evans, N; Farkas, A; Gilpin, E; Berry, C; Pierce, J P

    1995-10-18

    Today the uptake of smoking is primarily an adolescent pursuit. Awareness of tobacco advertising and promotion is high, and evidence suggests that it plays a role in adolescent smoking uptake. We evaluated the influence of tobacco advertising and promotion and exposure to smokers on never-smoking adolescents' susceptibility to smoking. We used data on 3536 adolescent never smokers (those who had never even puffed on a cigarette) from the 1993 California Tobacco Survey. That survey questioned adolescents about smoking history and inclinations. For this analysis, we defined as susceptible to smoking those never smokers who said on the survey that they could not rule out independently deciding to try a cigarette soon or smoking one offered by a friend. Also for this analysis, we devised two indices: 1) a 5-point index of an individual's receptivity to tobacco advertising as determined by the number of positive responses to five survey items (recognition of advertising messages, having a favorite advertisement, naming a brand he/she might buy, owning a tobacco-related promotional item, and willingness to use a tobacco-related promotional item) and 2) an index classifying an individual's reported exposure to family and peer smoking into one of four levels. Using logistic regression, we assessed the independent importance of our indices in predicting susceptibility to smoking after adjustment for sociodemographic variables, including age, sex, and race/ethnicity, and for perceived school performance. Tests of statistical significance were two-sided. Receptivity to tobacco advertising and exposure to smokers were independently associated with susceptibility to smoking, but the relationship appeared stronger for receptivity to advertising. Adolescents exposed to family members and peers (n = 489) who smoked were 1.89 (95% confidence interval [CI] = 1.30-2.74) times as likely to be susceptible, whereas adolescents who scored 4 or more on the Index of Receptivity to Tobacco

  9. Alcohol Locus of Control.

    Science.gov (United States)

    Johnson, Patrick B.; Reszka, Diane

    Research has shown that differences in perceived control can influence drinking behavior and alcoholic rehabilitation. This study examined the viability of an alcohol-specific locus of control scale. Undergraduate students (41 male and 40 female) completed a demographic questionnaire assessing age, sex, ethnicity, and drinking frequency; Rotter's…

  10. Campylobacter multi-locus sequence types and antimicrobial susceptibility of broiler cecal isolates: a two year study of 143 commercial flocks

    Science.gov (United States)

    The objective of this study was to assess genetic diversity and antimicrobial susceptibility of Campylobacter jejuni and coli recovered from broiler ceca at slaughter. Ceca from one broiler were collected from the evisceration line in a commercial processing plant, once or twice weekly for two year...

  11. Genotype versus phenotype: conflicting results in mapping a lung tumor susceptibility locus to the G7c recombination interval in the mouse MHC class III region

    NARCIS (Netherlands)

    van Kooij, M.; de Groot, K.; van Vugt, H.; Aten, J.; Snoek, M.

    2001-01-01

    Susceptibility to chemically induced lung tumorigenesis has previously been mapped to a genomic interval of 27 kb in the MHC class III region of the mouse using two H2 (a/b) intra- H2 recombinants, B10.A(1R) and B10.A(2R). Three genes are located within this interval, G7e (encoding a viral envelope

  12. Influence of traditional Chinese medicine constitution type on the susceptibility of hypertensive cases to intracerebral haemorrhage.

    Science.gov (United States)

    Han, Shu-hui; Zheng, Jian-ming; Li, Kang-zeng; Liu, You-rong; Ye, Ming-yan

    2014-12-01

    To explore the influence of Chinese medicine constitution type on the susceptibility of hypertensive patients to intracerebral haemorrhage. Primary hypertensive patients were studied and divided into the hypertension and the hypertensive intracerebral haemorrhage groups, depending on whether or not the patients had intracerebral haemorrhage. The demographic characteristics, physiological characteristics, living habits, biochemical tests, other chronic diseases, Chinese medicine constitution type, etc. were collected and compared between the two groups. The neurological deficit in the hypertensive intracerebral haemorrhage group was also compared among the different constitution types. A total of 304 patients participated in this investigation, including 213 cases in the hypertension group and 91 cases in the hypertensive intracerebral haemorrhage group. The percentages of dampness-heat and qi-depression types in the intracerebral haemorrhage group were greater than those with the same types in the hypertension group (20.9% vs 6.1%, 22.0% vs 8.0%; Ptype were different between genders in both groups. In addition, there were more male cases (14/20) with qi-depression type and more female cases (7/8) with phlegm-dampness type in the hypertensive intracerebral haemorrhage group than those with the same types (3/17 and 9/34, respectively) in the hypertension group (Ptypes had greater levels of blood lipids in the intracerebral haemorrhage group than those with the same types in the hypertension group (Ptype presented with a more severe neurological deficit than those with the other types (Ptype might have an impact on the susceptibility of hypertensive patients to have an intracerebral haemorrhage. The heat-dampness and qi-depression types might lead to greater susceptibility than the other types. In addition, the patient's gender and blood lipids might also influence the susceptibility along with the constitution type.

  13. Accurate and Practical Identification of 20 Fusarium Species by Seven-Locus Sequence Analysis and Reverse Line Blot Hybridization, and an In Vitro Antifungal Susceptibility Study▿†

    Science.gov (United States)

    Wang, He; Xiao, Meng; Kong, Fanrong; Chen, Sharon; Dou, Hong-Tao; Sorrell, Tania; Li, Ruo-Yu; Xu, Ying-Chun

    2011-01-01

    Eleven reference and 25 clinical isolates of Fusarium were subject to multilocus DNA sequence analysis to determine the species and haplotypes of the fusarial isolates from Beijing and Shandong, China. Seven loci were analyzed: the translation elongation factor 1 alpha gene (EF-1α); the nuclear rRNA internal transcribed spacer (ITS), large subunit (LSU), and intergenic spacer (IGS) regions; the second largest subunit of the RNA polymerase gene (RPB2); the calmodulin gene (CAM); and the mitochondrial small subunit (mtSSU) rRNA gene. We also evaluated an IGS-targeted PCR/reverse line blot (RLB) assay for species/haplotype identification of Fusarium. Twenty Fusarium species and seven species complexes were identified. Of 25 clinical isolates (10 species), the Gibberella (Fusarium) fujikuroi species complex was the commonest (40%) and was followed by the Fusarium solani species complex (FSSC) (36%) and the F. incarnatum-F. equiseti species complex (12%). Six FSSC isolates were identified to the species level as FSSC-3+4, and three as FSSC-5. Twenty-nine IGS, 27 EF-1α, 26 RPB2, 24 CAM, 18 ITS, 19 LSU, and 18 mtSSU haplotypes were identified; 29 were unique, and haplotypes for 24 clinical strains were novel. By parsimony informative character analysis, the IGS locus was the most phylogenetically informative, and the rRNA gene regions were the least. Results by RLB were concordant with multilocus sequence analysis for all isolates. Amphotericin B was the most active drug against all species. Voriconazole MICs were high (>8 μg/ml) for 15 (42%) isolates, including FSSC. Analysis of larger numbers of isolates is required to determine the clinical utility of the seven-locus sequence analysis and RLB assay in species classification of fusaria. PMID:21389150

  14. DRD4 and susceptibility to peer influence on alcohol use from adolescence to adulthood.

    Science.gov (United States)

    Mrug, Sylvie; Windle, Michael

    2014-12-01

    The long allele of DRD4 is associated with greater susceptibility to peer influences on alcohol use in young adulthood, but it is unclear whether this increased susceptibility extends to other developmental periods. This study examined the interactive effects of DRD4 polymorphism and friends' alcohol use from adolescence to adulthood. Participants (N = 340; 59% female; 98% White) reported on their own and their friends' alcohol use at four time points between mean ages 17 and 33. Autoregressive cross-lagged models evaluated reciprocal relationships between friends' alcohol use and participants' own alcohol use and frequency of heavy drinking over time. Multigroup modeling tested differences in model paths and covariances across high vs. low risk DRD4 polymorphisms. Alcohol use at age 33 was predicted by previous friends' alcohol use and correlated with current friends' alcohol use only for carriers of the DRD4 long allele. Regardless of DRD4 genotype, friends' alcohol use at age 17 predicted greater alcohol use and more frequent heavy drinking at age 23. Alcohol use and/or heavy drinking predicted greater friends' alcohol use at later time points for both genotype groups across adolescence and adulthood. The long allele of DRD4 is associated with increased susceptibility to peer influences on alcohol use in young adulthood, but not earlier in development. Adults with the long allele of DRD4 may benefit from interventions educating them about this risk and equipping them with strategies to reduce affiliations with and influence of drinking friends. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Identification of a breast cancer susceptibility locus at 4q31.22 using a genome-wide association study paradigm.

    Directory of Open Access Journals (Sweden)

    Yadav Sapkota

    Full Text Available More than 40 single nucleotide polymorphisms (SNPs for breast cancer susceptibility were identified by genome-wide association studies (GWASs. However, additional SNPs likely contribute to breast cancer susceptibility and overall genetic risk, prompting this investigation for additional variants. Six putative breast cancer susceptibility SNPs identified in a two-stage GWAS that we reported earlier were replicated in a follow-up stage 3 study using an independent set of breast cancer cases and controls from Canada, with an overall cumulative sample size of 7,219 subjects across all three stages. The study design also encompassed the 11 variants from GWASs previously reported by various consortia between the years 2007-2009 to (i enable comparisons of effect sizes, and (ii identify putative prognostic variants across studies. All SNP associations reported with breast cancer were also adjusted for body mass index (BMI. We report a strong association with 4q31.22-rs1429142 (combined per allele odds ratio and 95% confidence interval = 1.28 [1.17-1.41] and P combined = 1.5×10(-7, when adjusted for BMI. Ten of the 11 breast cancer susceptibility loci reported by consortia also showed associations in our predominantly Caucasian study population, and the associations were independent of BMI; four FGFR2 SNPs and TNRC9-rs3803662 were among the most notable associations. Since the original report by Garcia-Closas et al. 2008, this is the second study to confirm the association of 8q24.21-rs13281615 with breast cancer outcomes.

  16. PTPN22 is associated with susceptibility to psoriatic arthritis but not psoriasis: evidence for a further PsA-specific risk locus.

    LENUS (Irish Health Repository)

    Bowes, John

    2015-04-28

    Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis; it has a higher estimated genetic component than psoriasis alone, however most genetic susceptibility loci identified for PsA to date are also shared with psoriasis. Here we attempt to validate novel single nucleotide polymorphisms selected from our recent PsA Immunochip study and determine specificity to PsA.

  17. Multi-stage genome-wide association study identifies new susceptibility locus for testicular germ cell tumour on chromosome 3q25

    DEFF Research Database (Denmark)

    Litchfield, Kevin; Sultana, Razvan; Renwick, Anthony

    2015-01-01

    Recent genome-wide association studies (GWAS) and subsequent meta-analyses have identified over 25 SNPs at 18 loci, together accounting for >15% of the genetic susceptibility to testicular germ cell tumour (TGCT). To identify further common SNPs associated with TGCT, here we report a three-stage ......) demonstrating association with TGCT [per-allele odds ratio (OR) = 1.16, 95% confidence interval (CI) = 1.06-1.27; P = 1.2 × 10(-9)]....

  18. Infection Susceptibility in Gastric Intrinsic Factor (Vitamin B12-Defective Mice Is Subject to Maternal Influences

    Directory of Open Access Journals (Sweden)

    Lynda Mottram

    2016-06-01

    Full Text Available Mice harboring a mutation in the gene encoding gastric intrinsic factor (Gif, a protein essential for the absorption of vitamin B12/cobalamin (Cbl, have potential as a model to explore the role of vitamins in infection. The levels of Cbl in the blood of Giftm1a/tm1a mutant mice were influenced by the maternal genotype, with offspring born to heterozygous (high Cbl, F1 mothers exhibiting a significantly higher serum Cbl level than those born to homozygous (low Cbl, F2 equivalents. Low Cbl levels correlated with susceptibility to an infectious challenge with Salmonella enterica serovar Typhimurium or Citrobacter rodentium, and this susceptibility phenotype was moderated by Cbl administration. Transcriptional and metabolic profiling revealed that Cbl deficient mice exhibited a bioenergetic shift similar to a metabolic phenomenon commonly found in cancerous cells under hypoxic conditions known as the Warburg effect, with this metabolic effect being exacerbated further by infection. Our findings demonstrate a role for Cbl in bacterial infection, with potential general relevance to dietary deficiency and infection susceptibility.

  19. Influence of penicillin/amoxicillin non-susceptibility on the activity of third-generation cephalosporins against Streptococcus pneumoniae.

    Science.gov (United States)

    Fenoll, A; Giménez, M J; Robledo, O; Aguilar, L; Tarragó, D; Granizo, J J; Martín-Herrero, J E

    2008-01-01

    To study the influence of penicillin/amoxicillin non-susceptibility on the activity of third-generation cephalosporins, 430 consecutive penicillin non-susceptible Streptococcus pneumoniae 2007 isolates received in the Spanish Reference Pneumococcal Laboratory were tested. For comparative purposes, 625 penicillin-susceptible 2007 isolates were also tested. Susceptibility was determined by agar dilution using Mueller-Hinton agar supplemented with 5% sheep blood. Penicillin-susceptible strains were susceptible to amoxicillin, cefotaxime and ceftriaxone, 99.8% to cefpodoxime and 99.5% to cefdinir, and were inhibited by 0.12 microg/ml of cefditoren and 4 microg/ml of cefixime. Penicillin-intermediate strains were susceptible to cefotaxime and ceftriaxone, with <50% susceptibility to cefdinir and cefpodoxime. The MIC(50) and MIC(90) values of cefditoren were 0.25 microg/ml and 0.5 microg/ml, respectively, whereas cefixime exhibited only marginal activity (MIC(90)=16 microg/ml). Penicillin-resistant strains were resistant to cefdinir and cefpodoxime, with 74.8% and 94.1% susceptibility to cefotaxime and ceftriaxone, respectively. Cefditoren MIC(50)/MIC(90) (0.5/1 microg/ml) were lower than cefotaxime and ceftriaxone. Among amoxicillin non-susceptible strains, susceptibility to cefdinir and cefpodoxime was <10%, and susceptibility to cefotaxime decreased from 87.9% in the intermediate category to 63.0% in the resistant group. Cefditoren MIC(50)/MIC(90) (0.5/1 microg/ml) were lower than cefotaxime. In conclusion, the activity of cefixime, cefdinir and cefpodoxime was highly affected by penicillin/amoxicillin non-susceptibility, while parenteral third-generation cephalosporins exhibited higher intrinsic activity (MIC(90)=1 microg/ml for penicillin-resistant and 2 microg/ml for amoxicillin-resistant strains). Cefditoren exhibited one-dilution lower MIC(90) values for these strains, even against those of the most troublesome serotypes.

  20. The influence of fisher knowledge on the susceptibility of reef fish aggregations to fishing.

    Directory of Open Access Journals (Sweden)

    Jan Robinson

    Full Text Available Reef fishes that exhibit predictable aggregating behaviour are often considered vulnerable to overexploitation. However, fisher knowledge of this behaviour is often heterogeneous and, coupled with socioeconomic factors that constrain demand for or access to aggregated fish, will influence susceptibility to fishing. At two case study locations in Papua New Guinea, Ahus and Karkar islands, we conducted interview-based surveys to examine how local context influenced heterogeneity in knowledge of fish aggregations. We then explored the role of fisher knowledge in conferring susceptibility to fishing relative to socioeconomic drivers of fishing effort. Local heterogeneity in knowledge of aggregating behaviour differed between our case studies. At Ahus, variable access rights among fishers and genders to the main habitats were sources of heterogeneity in knowledge. By contrast, knowledge was more homogenous at Karkar and the sole source of variation was gear type. Differences between locations in the susceptibility of aggregations to fishing depended primarily on socioeconomic drivers of fishing effort rather than catchability. While Ahus fishers were knowledgeable of fish aggregations and used more selective gears, Karkar fishers were less constrained by tenure in their access to aggregation habitat. However, fishing effort was greater at Ahus and likely related to high dependency on fishing, greater access to provincial capital markets than Karkar and a weakening of customary management. Moreover, highly efficient fishing techniques have emerged at Ahus to exploit the non-reproductive aggregating behaviour of target species. Understanding how knowledge is structured within fishing communities and its relation to socioeconomic drivers of fishing effort is important if customary practices for conservation, such as tambu areas, are to be supported. The findings of this study call for a holistic approach to assessing the risks posed to reef fish

  1. Silicosis and its progress influenced by genetic variation on TNF-alpha locus- 308, TNF-alpha and IL-10 cytokine on cement factory workers in Indonesia.

    Science.gov (United States)

    Kurniawidjaja, L Meily

    2014-02-01

    This study aimed to assess the association of Tumor Necrosis Factor (TNF-alpha) Locus-308 variant, TNF-alpha and Interleukin (IL-10) Cytokine with the risk of silicosis and its progress in Indonesian cement factory workers, There is an urgent need to explore the determining factors other than exposure since silicosis is chronic progressive and life threatening but remains found, though much industrial hygiene effort has been made. This study population was 6,069 workers registered during 31 December 1990 to 31 December 2003. First, prospective study with Nested Case Control design was conducted on 336 workers in 2003, ten years later the progression of silicosis was assessed in 2013. The result showed proportion of the genetic variation on TNF-alpha on Locus -308 in Indonesia was significantly (p = 0.02) higher on silicosis (13.45%) than nonsilicosis (5.45%) but lower than silicosis in Africa and US miners, since susceptibility loci might vary in different ethnic groups. The sign and symptoms remained as simple silicosis after ten years; The TNF-alpha:IL-10 ratio > 1 was a risk factor in silicosis; the ratio of TNF-alpha:IL-10 > 1 caused a rapid decline of lung function compare to ratio silicosis in Indonesia cement factory. Its role is indirect, but through mechanism of controlling the blood Cytokine level ratio of TNF-alpha toward IL-10.

  2. Genome-wide association study using a high-density SNP-array and case-control design identifies a novel essential hypertension susceptibility locus in the promoter region of eNOS

    Science.gov (United States)

    Salvi, Erika; Kutalik, Zoltán; Glorioso, Nicola; Benaglio, Paola; Frau, Francesca; Kuznetsova, Tatiana; Arima, Hisatomi; Hoggart, Clive; Tichet, Jean; Nikitin, Yury P.; Conti, Costanza; Seidlerova, Jitka; Tikhonoff, Valérie; Stolarz-Skrzypek, Katarzyna; Johnson, Toby; Devos, Nabila; Zagato, Laura; Guarrera, Simonetta; Zaninello, Roberta; Calabria, Andrea; Stancanelli, Benedetta; Troffa, Chiara; Thijs, Lutgarde; Rizzi, Federica; Simonova, Galina; Lupoli, Sara; Argiolas, Giuseppe; Braga, Daniele; D’Alessio, Maria C.; Ortu, Maria F.; Ricceri, Fulvio; Mercurio, Maurizio; Descombes, Patrick; Marconi, Maurizio; Chalmers, John; Harrap, Stephen; Filipovsky, Jan; Bochud, Murielle; Iacoviello, Licia; Ellis, Justine; Stanton, Alice V.; Laan, Maris; Padmanabhan, Sandosh; Dominiczak, Anna F.; Samani, Nilesh J.; Melander, Olle; Jeunemaitre, Xavier; Manunta, Paolo; Shabo, Amnon; Vineis, Paolo; Cappuccio, Francesco P.; Caulfield, Mark J.; Matullo, Giuseppe; Rivolta, Carlo; Munroe, Patricia B.; Barlassina, Cristina; Staessen, Jan A; Beckmann, Jacques S.; Cusi, Daniele

    2012-01-01

    Essential hypertension is a multi-factorial disorder and is the main risk factor for renal and cardiovascular complications. The research on the genetics of hypertension has been frustrated by the small predictive value of the discovered genetic variants. The HYPERGENES Project investigated associations between genetic variants and essential hypertension pursuing a two-stage study by recruiting cases and controls from extensively characterized cohorts recruited over many years in different European regions. The discovery phase consisted of 1,865 cases and 1,750 controls genotyped with 1M Illumina array. Best hits were followed up in a validation panel of 1,385 cases and 1,246 controls that were genotyped with a custom array of 14,055 markers. We identified a new hypertension susceptibility locus (rs3918226) in the promoter region of the endothelial nitric oxide synthase (eNOS) gene (odds ratio 1.54; 95% CI 1.37-1.73; combined p=2.58·10−13). A meta-analysis, using other in-silico/de novo genotyping data for a total of 21714 subjects, resulted in an overall odds ratio of 1.34 (95% CI 1.25-1.44, p=1.032·10−14). The quantitative analysis on a population-based sample revealed an effect size of 1.91 (95% CI 0.16-3.66) for systolic and 1.40 (95% CI 0.25-2.55) for diastolic blood pressure. We identified in-silico a potential binding site for ETS transcription-factors directly next to rs3918226, suggesting a potential modulation of eNOS expression. Biological evidence links eNOS with hypertension, as it is a critical mediator of cardiovascular homeostasis and blood pressure control via vascular tone regulation. This finding supports the hypothesis that there may be a causal genetic variation at this locus. PMID:22184326

  3. Cross-disease Meta-analysis of Genome-wide Association Studies for Systemic Sclerosis and Rheumatoid Arthritis Reveals IRF4 as a New Common Susceptibility Locus

    Science.gov (United States)

    López-Isac, Elena; Martín, Jose-Ezequiel; Assassi, Shervin; Simeón, Carmen P; Carreira, Patricia; Ortego-Centeno, Norberto; Freire, Mayka; Beltrán, Emma; Narváez, Javier; Alegre-Sancho, Juan J; Fernández-Gutiérrez, Benjamín; Balsa, Alejandro; Ortiz, Ana M; González-Gay, Miguel A; Beretta, Lorenzo; Santaniello, Alessandro; Bellocchi, Chiara; Lunardi, Claudio; Moroncini, Gianluca; Gabrielli, Armando; Witte, Torsten; Hunzelmann, Nicolas; Distler, Jörg HW; Riekemasten, Gabriella; van der Helm-van Mil, Annete H; de Vries-Bouwstra, Jeska; Magro-Checa, Cesar; Voskuyl, Alexandre E; Vonk, Madelon C; Molberg, Øyvind; Merriman, Tony; Hesselstrand, Roger; Nordin, Annika; Padyukov, Leonid; Herrick, Ariane; Eyre, Steve; Koeleman, Bobby PC; Denton, Christopher P; Fonseca, Carmen; Radstake, Timothy RDJ; Worthington, Jane; Mayes, Maureen D; Martín, Javier

    2017-01-01

    Objectives Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that share clinical and immunological characteristics. To date, several shared SSc-RA loci have been identified independently. In this study, we aimed to systematically search for new common SSc-RA loci through an inter-disease meta-GWAS strategy. Methods We performed a meta-analysis combining GWAS datasets of SSc and RA using a strategy that allowed identification of loci with both same-direction and opposing-direction allelic effects. The top single-nucleotide polymorphisms (SNPs) were followed-up in independent SSc and RA case-control cohorts. This allowed us to increase the sample size to a total of 8,830 SSc patients, 16,870 RA patients and 43,393 controls. Results The cross-disease meta-analysis of the GWAS datasets identified several loci with nominal association signals (P-value < 5 × 10-6), which also showed evidence of association in the disease-specific GWAS scan. These loci included several genomic regions not previously reported as shared loci, besides risk factors associated with both diseases in previous studies. The follow-up of the putatively new SSc-RA loci identified IRF4 as a shared risk factor for these two diseases (Pcombined = 3.29 × 10-12). In addition, the analysis of the biological relevance of the known SSc-RA shared loci pointed to the type I interferon and the interleukin 12 signaling pathways as the main common etiopathogenic factors. Conclusions Our study has identified a novel shared locus, IRF4, for SSc and RA and highlighted the usefulness of cross-disease GWAS meta-analysis in the identification of common risk loci. PMID:27111665

  4. The Influence of Green Viral Communications on Green Purchase Intentions: The Mediating Role of Consumers’ Susceptibility to Interpersonal Influences

    Directory of Open Access Journals (Sweden)

    Sheng-Hsiung Chang

    2015-04-01

    Full Text Available This paper aims to incorporate the diffusion of innovation theory and conformity theory to explain consumers’ green purchase intentions. To this end, a conceptual model has been proposed and subjected to empirical verification with the use of a survey method. Using a sample of Taiwanese consumers who had the actual purchase experience of green detergents, this study employed structural equation modeling to verify the hypothesis proposed. The empirical results suggested that green viral communication was positively related to normative interpersonal influence, informational interpersonal influence and green purchase intention. Informational interpersonal influence also had a positive impact on green purchase intention. However, the relationship between consumer’s normative interpersonal influence and green purchase intention was not supported. Thus, this study concludes that green marketers must strengthen their green viral communications skills to enhance consumers’ purchase intentions. In addition, this study also contributes to the literature by stating that consumers’ susceptibility to informational interpersonal relationships is an important mediator in the green viral communication and green purchase intentions relationship. This study discusses implications of the findings and research limitations at the end of the paper.

  5. Identification and functional characterization of G6PC2 coding variants influencing glycemic traits define an effector transcript at the G6PC2-ABCB11 locus.

    Directory of Open Access Journals (Sweden)

    Anubha Mahajan

    2015-01-01

    Full Text Available Genome wide association studies (GWAS for fasting glucose (FG and insulin (FI have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P<5×10-7 evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF=1.5% influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1% influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p.Tyr207Ser influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D, the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights.

  6. Identification and Functional Characterization of G6PC2 Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the G6PC2-ABCB11 Locus

    Science.gov (United States)

    Mahajan, Anubha; Sim, Xueling; Ng, Hui Jin; Manning, Alisa; Rivas, Manuel A.; Highland, Heather M.; Locke, Adam E.; Grarup, Niels; Im, Hae Kyung; Cingolani, Pablo; Flannick, Jason; Fontanillas, Pierre; Fuchsberger, Christian; Gaulton, Kyle J.; Teslovich, Tanya M.; Rayner, N. William; Robertson, Neil R.; Beer, Nicola L.; Rundle, Jana K.; Bork-Jensen, Jette; Ladenvall, Claes; Blancher, Christine; Buck, David; Buck, Gemma; Burtt, Noël P.; Gabriel, Stacey; Gjesing, Anette P.; Groves, Christopher J.; Hollensted, Mette; Huyghe, Jeroen R.; Jackson, Anne U.; Jun, Goo; Justesen, Johanne Marie; Mangino, Massimo; Murphy, Jacquelyn; Neville, Matt; Onofrio, Robert; Small, Kerrin S.; Stringham, Heather M.; Syvänen, Ann-Christine; Trakalo, Joseph; Abecasis, Goncalo; Bell, Graeme I.; Blangero, John; Cox, Nancy J.; Duggirala, Ravindranath; Hanis, Craig L.; Seielstad, Mark; Wilson, James G.; Christensen, Cramer; Brandslund, Ivan; Rauramaa, Rainer; Surdulescu, Gabriela L.; Doney, Alex S. F.; Lannfelt, Lars; Linneberg, Allan; Isomaa, Bo; Tuomi, Tiinamaija; Jørgensen, Marit E.; Jørgensen, Torben; Kuusisto, Johanna; Uusitupa, Matti; Salomaa, Veikko; Spector, Timothy D.; Morris, Andrew D.; Palmer, Colin N. A.; Collins, Francis S.; Mohlke, Karen L.; Bergman, Richard N.; Ingelsson, Erik; Lind, Lars; Tuomilehto, Jaakko; Hansen, Torben; Watanabe, Richard M.; Prokopenko, Inga; Dupuis, Josee; Karpe, Fredrik; Groop, Leif; Laakso, Markku; Pedersen, Oluf; Florez, Jose C.; Morris, Andrew P.; Altshuler, David; Meigs, James B.; Boehnke, Michael; McCarthy, Mark I.; Lindgren, Cecilia M.; Gloyn, Anna L.

    2015-01-01

    Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P<5×10-7) evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF)=1.5%) influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1%) influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding) GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p.Tyr207Ser) influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights. PMID:25625282

  7. The analysis of a large Danish family supports the presence of a susceptibility locus for adenoma and colorectal cancer on chromosome 11q24

    DEFF Research Database (Denmark)

    Rudkjøbing, Laura Aviaja; Eiberg, Hans; Mikkelsen, Hanne Birte

    2015-01-01

    benefit from prophylactic screening. Consequently, all family members are asked to follow a screening program. The purpose of this study was to localize a new gene which causes colorectal cancer. We performed a linkage analysis using data from a SNP6.0 chip in one large family with 12 affected family....... Major rearrangements were excluded after karyotyping. The linkage analysis with SNP6 data revealed three candidate areas, on chromosome 2, 6 and 11 respectively, with a LOD score close to two and no negative LOD scores. After extended linkage analysis, the area on chromosome 6 was excluded, leaving...... areas on chromosome 2 and chromosome 11 with the highest possible LOD scores of 2.6. Two other studies have identified 11q24 as a candidate area for colorectal cancer susceptibility and this area is supported by our results....

  8. Genome-wide association study implicates testis-sperm specific FKBP6 as a susceptibility locus for impaired acrosome reaction in stallions.

    Directory of Open Access Journals (Sweden)

    Terje Raudsepp

    Full Text Available Impaired acrosomal reaction (IAR of sperm causes male subfertility in humans and animals. Despite compelling evidence about the genetic control over acrosome biogenesis and function, the genomics of IAR is as yet poorly understood, providing no molecular tools for diagnostics. Here we conducted Equine SNP50 Beadchip genotyping and GWAS using 7 IAR-affected and 37 control Thoroughbred stallions. A significant (PA and g.11040379C>A (p.166H>N in exon 4 that were significantly associated with the IAR phenotype both in the GWAS cohort (n = 44 and in a large multi-breed cohort of 265 horses. All IAR stallions were homozygous for the A-alleles, while this genotype was found only in 2% of controls. The equine FKBP6 was exclusively expressed in testis and sperm and had 5 different transcripts, of which 4 were novel. The expression of this gene in AC/AG heterozygous controls was monoallelic, and we observed a tendency for FKBP6 up-regulation in IAR stallions compared to controls. Because exon 4 SNPs had no effect on the protein structure, it is likely that FKBP6 relates to the IAR phenotype via regulatory or modifying functions. In conclusion, FKBP6 was considered a susceptibility gene of incomplete penetrance for IAR in stallions and a candidate gene for male subfertility in mammals. FKBP6 genotyping is recommended for the detection of IAR-susceptible individuals among potential breeding stallions. Successful use of sperm as a source of DNA and RNA propagates non-invasive sample procurement for fertility genomics in animals and humans.

  9. Genome-wide association study implicates testis-sperm specific FKBP6 as a susceptibility locus for impaired acrosome reaction in stallions.

    Science.gov (United States)

    Raudsepp, Terje; McCue, Molly E; Das, Pranab J; Dobson, Lauren; Vishnoi, Monika; Fritz, Krista L; Schaefer, Robert; Rendahl, Aaron K; Derr, James N; Love, Charles C; Varner, Dickson D; Chowdhary, Bhanu P

    2012-01-01

    Impaired acrosomal reaction (IAR) of sperm causes male subfertility in humans and animals. Despite compelling evidence about the genetic control over acrosome biogenesis and function, the genomics of IAR is as yet poorly understood, providing no molecular tools for diagnostics. Here we conducted Equine SNP50 Beadchip genotyping and GWAS using 7 IAR-affected and 37 control Thoroughbred stallions. A significant (Phorse chromosome 13 in FK506 binding protein 6 (FKBP6). The gene belongs to the immunophilins FKBP family known to be involved in meiosis, calcium homeostasis, clathrin-coated vesicles, and membrane fusions. Direct sequencing of FKBP6 exons in cases and controls identified SNPs g.11040315G>A and g.11040379C>A (p.166H>N) in exon 4 that were significantly associated with the IAR phenotype both in the GWAS cohort (n = 44) and in a large multi-breed cohort of 265 horses. All IAR stallions were homozygous for the A-alleles, while this genotype was found only in 2% of controls. The equine FKBP6 was exclusively expressed in testis and sperm and had 5 different transcripts, of which 4 were novel. The expression of this gene in AC/AG heterozygous controls was monoallelic, and we observed a tendency for FKBP6 up-regulation in IAR stallions compared to controls. Because exon 4 SNPs had no effect on the protein structure, it is likely that FKBP6 relates to the IAR phenotype via regulatory or modifying functions. In conclusion, FKBP6 was considered a susceptibility gene of incomplete penetrance for IAR in stallions and a candidate gene for male subfertility in mammals. FKBP6 genotyping is recommended for the detection of IAR-susceptible individuals among potential breeding stallions. Successful use of sperm as a source of DNA and RNA propagates non-invasive sample procurement for fertility genomics in animals and humans.

  10. Identification of shared genetic susceptibility locus for coronary artery disease, type 2 diabetes and obesity: a meta-analysis of genome-wide studies

    Directory of Open Access Journals (Sweden)

    Wu Chaoneng

    2012-06-01

    Full Text Available Abstract Type 2 diabetes (2DM, obesity, and coronary artery disease (CAD are frequently coexisted being as key components of metabolic syndrome. Whether there is shared genetic background underlying these diseases remained unclear. We performed a meta-analysis of 35 genome screens for 2DM, 36 for obesity or body mass index (BMI-defined obesity, and 21 for CAD using genome search meta-analysis (GSMA, which combines linkage results to identify regions with only weak evidence and provide genetic interactions among different diseases. For each study, 120 genomic bins of approximately 30 cM were defined and ranked according to the best linkage evidence within each bin. For each disease, bin 6.2 achieved genomic significanct evidence, and bin 9.3, 10.5, 16.3 reached suggestive level for 2DM. Bin 11.2 and 16.3, and bin 10.5 and 9.3, reached suggestive evidence for obesity and CAD respectively. In pooled all three diseases, bin 9.3 and 6.5 reached genomic significant and suggestive evidence respectively, being relatively much weaker for 2DM/CAD or 2DM/obesity or CAD/obesity. Further, genomewide significant evidence was observed of bin 16.3 and 4.5 for 2DM/obesity, which is decreased when CAD was added. These findings indicated that bin 9.3 and 6.5 are most likely to be shared by 2DM, obesity and CAD. And bin 16.3 and 4.5 are potentially common regions to 2DM and obesity only. The observed shared susceptibility regions imply a partly overlapping genetic aspects of disease development. Fine scanning of these regions will definitely identify more susceptibility genes and causal variants.

  11. An ectopic CTCF-dependent transcriptional insulator influences the choice of Vβ gene segments for VDJ recombination at TCRβ locus.

    Science.gov (United States)

    Shrimali, Sweety; Srivastava, Surabhi; Varma, Garima; Grinberg, Alex; Pfeifer, Karl; Srivastava, Madhulika

    2012-09-01

    Insulators regulate transcription as they modulate the interactions between enhancers and promoters by organizing the chromatin into distinct domains. To gain better understanding of the nature of chromatin domains defined by insulators, we analyzed the ability of an insulator to interfere in VDJ recombination, a process that is critically dependent on long-range interactions between diverse types of cis-acting DNA elements. A well-established CTCF-dependent transcriptional insulator, H19 imprint control region (H19-ICR), was inserted in the mouse TCRβ locus by genetic manipulation. Analysis of the mutant mice demonstrated that the insulator retains its CTCF and position-dependent enhancer-blocking potential in this heterologous context in vivo. Remarkably, the inserted H19-ICR appears to have the ability to modulate cis-DNA interactions between recombination signal sequence elements of the TCRβ locus leading to a dramatically altered usage of Vβ segments for Vβ-to-DβJβ recombination in the mutant mice. This reveals a novel ability of CTCF to govern long range cis-DNA interactions other than enhancer-promoter interactions and suggests that CTCF-dependent insulators may play a diverse and complex role in genome organization beyond transcriptional control. Our functional analysis of mutated TCRβ locus supports the emerging role of CTCF in governing VDJ recombination.

  12. An ectopic CTCF-dependent transcriptional insulator influences the choice of Vβ gene segments for VDJ recombination at TCRβ locus

    Science.gov (United States)

    Shrimali, Sweety; Srivastava, Surabhi; Varma, Garima; Grinberg, Alex; Pfeifer, Karl; Srivastava, Madhulika

    2012-01-01

    Insulators regulate transcription as they modulate the interactions between enhancers and promoters by organizing the chromatin into distinct domains. To gain better understanding of the nature of chromatin domains defined by insulators, we analyzed the ability of an insulator to interfere in VDJ recombination, a process that is critically dependent on long-range interactions between diverse types of cis-acting DNA elements. A well-established CTCF-dependent transcriptional insulator, H19 imprint control region (H19-ICR), was inserted in the mouse TCRβ locus by genetic manipulation. Analysis of the mutant mice demonstrated that the insulator retains its CTCF and position-dependent enhancer-blocking potential in this heterologous context in vivo. Remarkably, the inserted H19-ICR appears to have the ability to modulate cis-DNA interactions between recombination signal sequence elements of the TCRβ locus leading to a dramatically altered usage of Vβ segments for Vβ-to-DβJβ recombination in the mutant mice. This reveals a novel ability of CTCF to govern long range cis-DNA interactions other than enhancer–promoter interactions and suggests that CTCF-dependent insulators may play a diverse and complex role in genome organization beyond transcriptional control. Our functional analysis of mutated TCRβ locus supports the emerging role of CTCF in governing VDJ recombination. PMID:22718969

  13. Influence of delta ferrite on corrosion susceptibility of AISI 304 austenitic stainless steel

    Directory of Open Access Journals (Sweden)

    Lawrence O. Osoba

    2016-12-01

    Full Text Available In the current study, the influence of delta (δ ferrite on the corrosion susceptibility of AISI 304 austenitic stainless steel was evaluated in 1Molar concentration of sulphuric acid (H2SO4 and 1Molar concentration of sodium chloride (NaCl. The study was performed at ambient temperature using electrochemical technique—Tafel plots to evaluate the corrosive tendencies of the austenitic stainless steel sample. The as-received (stainless steel specimen and 60% cold-worked (stainless steel specimens were isothermally annealed at 1,100°C for 2 h and 1 h, respectively, and quenched in water. The results obtained show that the heat-treated specimen and the 60% cold-worked plus heat-treated specimen exhibited higher corrosion susceptibility than the as-received specimen, which invariably contained the highest fraction of δ ferrite particles. The finding shows that the presence of δ ferrite, in which chromium (Cr, the main corrosion inhibitor segregates, does not degrade and or reduces the resistance to aqueous corrosion of the austenitic stainless steel material.

  14. Selection of SNP subsets for association studies in candidate genes: comparison of the power of different strategies to detect single disease susceptibility locus effects

    Directory of Open Access Journals (Sweden)

    Deleuze Jean-Francois

    2006-04-01

    Full Text Available Abstract Background The recent advances in genotyping and molecular techniques have greatly increased the knowledge of the human genome structure. Millions of polymorphisms are reported and freely available in public databases. As a result, there is now a need to identify among all these data, the relevant markers for genetic association studies. Recently, several methods have been published to select subsets of markers, usually Single Nucleotide Polymorphisms (SNPs, that best represent genetic polymorphisms in the studied candidate gene or region. Results In this paper, we compared four of these selection methods, two based on haplotype information and two based on pairwise linkage disequilibrium (LD. The methods were applied to the genotype data on twenty genes with different patterns of LD and different numbers of SNPs. A measure of the efficiency of the different methods to select SNPs was obtained by comparing, for each gene and under several single disease susceptibility models, the power to detect an association that will be achieved with the selected SNP subsets. Conclusion None of the four selection methods stands out systematically from the others. Methods based on pairwise LD information turn out to be the most interesting methods in a context of association study in candidate gene. In a context where the number of SNPs to be tested in a given region needs to be more limited, as in large-scale studies or wide genome scans, one of the two methods based on haplotype information, would be more suitable.

  15. Motivated malleability: Frontal cortical asymmetry predicts the susceptibility to social influence.

    Science.gov (United States)

    Schnuerch, Robert; Pfattheicher, Stefan

    2017-07-16

    Humans, just as many other animals, regulate their behavior in terms of approaching stimuli associated with pleasure and avoiding stimuli linked to harm. A person's current and chronic motivational direction - that is, approach versus avoidance orientation - is reliably reflected in the asymmetry of frontal cortical low-frequency oscillations. Using resting electroencephalography (EEG), we show that frontal asymmetry is predictive of the tendency to yield to social influence: Stronger right- than left-side frontolateral activation during a resting-state session prior to the experiment was robustly associated with a stronger inclination to adopt a peer group's judgments during perceptual decision-making (Study 1). We posit that this reflects the role of a person's chronic avoidance orientation in socially adjusted behavior. This claim was strongly supported by additional survey investigations (Studies 2a, 2b, 2c), all of which consistently revealed that trait avoidance was positively linked to the susceptibility to social influence. The present contribution thus stresses the relevance of chronic avoidance orientation in social conformity, refining (yet not contradicting) the longstanding view that socially influenced behavior is motivated by approach-related goals. Moreover, our findings valuably underscore and extend our knowledge on the association between frontal cortical asymmetry and a variety of psychological variables.

  16. Retinoid levels influence enterohemorrhagic Escherichia coli infection and Shiga toxin 2 susceptibility in mice.

    Science.gov (United States)

    Cabrera, Gabriel; Fernández-Brando, Romina J; Abrey-Recalde, María Jimena; Baschkier, Ariela; Pinto, Alipio; Goldstein, Jorge; Zotta, Elsa; Meiss, Roberto; Rivas, Marta; Palermo, Marina S

    2014-09-01

    Enterohemorrhagic Escherichia coli (EHEC) is a food-borne pathogen that produces Shiga toxin (Stx) and causes hemorrhagic colitis. Under some circumstances, Stx produced within the intestinal tract enters the bloodstream, leading to systemic complications that may cause the potentially fatal hemolytic-uremic syndrome. Although retinoids like vitamin A (VA) and retinoic acid (RA) are beneficial to gut integrity and the immune system, the effect of VA supplementation on gastrointestinal infections of different etiologies has been controversial. Thus, the aim of this work was to study the influence of different VA status on the outcome of an EHEC intestinal infection in mice. We report that VA deficiency worsened the intestinal damage during EHEC infection but simultaneously improved survival. Since death is associated mainly with Stx toxicity, Stx was intravenously inoculated to analyze whether retinoid levels affect Stx susceptibility. Interestingly, while VA-deficient (VA-D) mice were resistant to a lethal dose of Stx2, RA-supplemented mice were more susceptible to it. Given that peripheral blood polymorphonuclear cells (PMNs) are known to potentiate Stx2 toxicity, we studied the influence of retinoid levels on the absolute number and function of PMNs. We found that VA-D mice had decreased PMN numbers and a diminished capacity to produce reactive oxygen species, while RA supplementation had the opposite effect. These results are in line with the well-known function of retinoids in maintaining the homeostasis of the gut but support the idea that they have a proinflammatory effect by acting, in part, on the PMN population. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  17. The methylenetetrahydrofolate reductase gene variant C677T influences susceptibility to migraine with aura

    Directory of Open Access Journals (Sweden)

    Sundholm James

    2004-02-01

    Full Text Available Abstract Background The C677T variant in the methylenetetrahydrofolate reductase (MTHFR gene is associated with increased levels of circulating homocysteine and is a mild risk factor for vascular disease. Migraine, with and without aura (MA and MO, is a prevalent and complex neurovascular disorder that may also be affected by genetically influenced hyperhomocysteinaemia. To determine whether the C677T variant in the MTHFR gene is associated with migraine susceptibility we utilised unrelated and family-based case-control study designs. Methods A total of 652 Caucasian migraine cases were investigated in this study. The MTHFR C677T variant was genotyped in 270 unrelated migraine cases and 270 controls as well as 382 affected subjects from 92 multiplex pedigrees. Results In the unrelated case-control sample we observed an over-representation of the 677T allele in migraine patients compared to controls, specifically for the MA subtype (40% vs. 33% (χ2 = 5.70, P = 0.017. The Armitage test for trend indicated a significant dosage effect of the risk allele (T for MA (χ2 = 5.72, P = 0.017. This linear trend was also present in the independent family-based sample (χ2 = 4.25, Padjusted = 0.039. Overall, our results indicate that the T/T genotype confers a modest, yet significant, increase in risk for the MA subtype (odds ratio: 2.0 – 2.5. No increased risk for the MO subtype was observed (P > 0.05. Conclusions In Caucasians, the C677T variant in the MTHFR gene influences susceptibility to MA, but not MO. Investigation into the enzyme activity of MTHFR and the role of homocysteine in the pathophysiology of migraine is warranted.

  18. Influence of the factor V Leiden mutation on infectious disease susceptibility and outcome

    DEFF Research Database (Denmark)

    Benfield, Thomas L; Dahl, Mortens; Nordestgaard, Borge G

    2005-01-01

    The effect of the coagulation factor V Leiden mutation on infectious disease susceptibility and outcome is controversial.......The effect of the coagulation factor V Leiden mutation on infectious disease susceptibility and outcome is controversial....

  19. Genome-wide association studies in women of African ancestry identified 3q26.21 as a novel susceptibility locus for oestrogen receptor negative breast cancer.

    Science.gov (United States)

    Huo, Dezheng; Feng, Ye; Haddad, Stephen; Zheng, Yonglan; Yao, Song; Han, Yoo-Jeong; Ogundiran, Temidayo O; Adebamowo, Clement; Ojengbede, Oladosu; Falusi, Adeyinka G; Zheng, Wei; Blot, William; Cai, Qiuyin; Signorello, Lisa; John, Esther M; Bernstein, Leslie; Hu, Jennifer J; Ziegler, Regina G; Nyante, Sarah; Bandera, Elisa V; Ingles, Sue A; Press, Michael F; Deming, Sandra L; Rodriguez-Gil, Jorge L; Nathanson, Katherine L; Domchek, Susan M; Rebbeck, Timothy R; Ruiz-Narváez, Edward A; Sucheston-Campbell, Lara E; Bensen, Jeannette T; Simon, Michael S; Hennis, Anselm; Nemesure, Barbara; Leske, M Cristina; Ambs, Stefan; Chen, Lin S; Qian, Frank; Gamazon, Eric R; Lunetta, Kathryn L; Cox, Nancy J; Chanock, Stephen J; Kolonel, Laurence N; Olshan, Andrew F; Ambrosone, Christine B; Olopade, Olufunmilayo I; Palmer, Julie R; Haiman, Christopher A

    2016-11-01

    Multiple breast cancer loci have been identified in previous genome-wide association studies, but they were mainly conducted in populations of European ancestry. Women of African ancestry are more likely to have young-onset and oestrogen receptor (ER) negative breast cancer for reasons that are unknown and understudied. To identify genetic risk factors for breast cancer in women of African descent, we conducted a meta-analysis of two genome-wide association studies of breast cancer; one study consists of 1,657 cases and 2,029 controls genotyped with Illumina’s HumanOmni2.5 BeadChip and the other study included 3,016 cases and 2,745 controls genotyped using Illumina Human1M-Duo BeadChip. The top 18,376 single nucleotide polymorphisms (SNP) from the meta-analysis were replicated in the third study that consists of 1,984 African Americans cases and 2,939 controls. We found that SNP rs13074711, 26.5 Kb upstream of TNFSF10 at 3q26.21, was significantly associated with risk of oestrogen receptor (ER)-negative breast cancer (odds ratio [OR]=1.29, 95% CI: 1.18-1.40; P = 1.8 × 10 − 8). Functional annotations suggest that the TNFSF10 gene may be involved in breast cancer aetiology, but further functional experiments are needed. In addition, we confirmed SNP rs10069690 was the best indicator for ER-negative breast cancer at 5p15.33 (OR = 1.30; P = 2.4 × 10 − 10) and identified rs12998806 as the best indicator for ER-positive breast cancer at 2q35 (OR = 1.34; P = 2.2 × 10 − 8) for women of African ancestry. These findings demonstrated additional susceptibility alleles for breast cancer can be revealed in diverse populations and have important public health implications in building race/ethnicity-specific risk prediction model for breast cancer.

  20. Friends' drinking norms and male adolescents' alcohol consumption: The moderating role of performance-based peer influence susceptibility.

    Science.gov (United States)

    Teunissen, Hanneke A; Kuntsche, Emmanuel; Scholte, Ron H J; Spijkerman, Renske; Prinstein, Mitchell J; Engels, Rutger C M E

    2016-12-01

    This study examined whether the relationship between friends' drinking norms and male adolescents' alcohol use is moderated by performance-based peer influence susceptibility. Seventy-three male adolescents (M = 17 years) from three schools in the Netherlands were exposed to the drinking norms of "peers" (electronic confederates) in a chat room experiment. These peers were either popular or unpopular, and conveyed pro- or anti-alcohol norms. Peer influence susceptibility was defined as the change in adolescents' answers before and after exposure to the peer norms. Multilevel regression analyses indicated that the relationship between friends' drinking norms and adolescents' alcohol use (assessed during eight weekends) was moderated by susceptibility to the pro-alcohol norms of popular peers. This relationship was stronger for adolescents who were highly susceptible. These findings suggest that a behavioral measure of peer influence susceptibility could be useful in alcohol prevention programs to select adolescents at risk for negative peer socialization. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. All rights reserved.

  1. OAS1: a multiple sclerosis susceptibility gene that influences disease severity.

    LENUS (Irish Health Repository)

    O'Brien, M

    2012-02-01

    BACKGROUND: Type 1 interferons upregulate oligoadenylate synthetase 1 (OAS1). A single nucleotide polymorphism (SNP) in exon 7 of OAS1 results in differential RNAseL enzyme activity, the A allele coding for a truncated form with low activity and the G conferring high activity. We hypothesized that OAS1 genotypes would influence both susceptibility to multiple sclerosis (MS) and disease activity with the AA genotype being overrepresented and the GG genotype underrepresented in relapsing-remitting MS (RRMS) with increased disease activity. METHODS: We examined OAS1 genotype distribution in 401 patients with MS, 394 healthy controls, and 178 patients with RRMS receiving interferon-beta (IFNbeta) assessed as 1) having no or minimal disease activity on IFNbeta, 2) having disease activity despite IFNbeta, and 3) 65 patients with RRMS with highly active disease. RESULTS: The OAS1 genotype distribution differed between patients with MS and controls (p = 0.000003), with lower frequency of GG homozygotes in patients with MS (6%) compared with controls (17%). In relation to disease severity, 34 (32%) patients with no or minimal disease activity on IFNbeta had the AA and 8 (8%) the GG genotype; of patients with disease activity despite IFNbeta, 27 (51%) were AA, while only 1 (2%) was GG (p = 0.03). Median time to first relapse on IFNbeta was 24 months in patients with RRMS with AA genotype and 33 months with AG or GG genotype (p = 0.04). The GG genotype was absent in 65 patients with highly active RRMS (p = 0.03). CONCLUSIONS: A functional OAS1 SNP, AA genotype, confers susceptibility to MS and the GG genotype may protect against increased disease activity.

  2. Chitinase-3-like 1 protein (CHI3L1) locus influences cerebrospinal fluid levels of YKL-40.

    Science.gov (United States)

    Deming, Yuetiva; Black, Kathleen; Carrell, David; Cai, Yefei; Del-Aguila, Jorge L; Fernandez, Maria Victoria; Budde, John; Ma, ShengMei; Saef, Benjamin; Howells, Bill; Bertelsen, Sarah; Huang, Kuan-Lin; Sutphen, Courtney L; Tarawneh, Rawan; Fagan, Anne M; Holtzman, David M; Morris, John C; Goate, Alison M; Dougherty, Joseph D; Cruchaga, Carlos

    2016-11-10

    Alzheimer's disease (AD) pathology appears several years before clinical symptoms, so identifying ways to detect individuals in the preclinical stage is imperative. The cerebrospinal fluid (CSF) Tau/Aβ42 ratio is currently the best known predictor of AD status and cognitive decline, and the ratio of CSF levels of chitinase-3-like 1 protein (CHI3L1, YKL-40) and amyloid beta (Aβ42) were reported as predictive, but individual variability and group overlap inhibits their utility for individual diagnosis making it necessary to find ways to improve sensitivity of these biomarkers. We used linear regression to identify genetic loci associated with CSF YKL-40 levels in 379 individuals (80 cognitively impaired and 299 cognitively normal) from the Charles F and Joanne Knight Alzheimer's Disease Research Center. We tested correlations between YKL-40 and CSF Tau/Aβ42 ratio, Aβ42, tau, and phosphorylated tau (ptau181). We used studentized residuals from a linear regression model of the log-transformed, standardized protein levels and the additive reference allele counts from the most significant locus to adjust YKL-40 values and tested the differences in correlations with CSF Tau/Aβ42 ratio, Aβ42, tau, and ptau181. We found that genetic variants on the CH13L1 locus were significantly associated with CSF YKL-40 levels, but not AD risk, age at onset, or disease progression. The most significant variant is a reported expression quantitative trait locus for CHI3L1, the gene which encodes YKL-40, and explained 12.74 % of the variance in CSF YKL-40 in our study. YKL-40 was positively correlated with ptau181 (r = 0.521) and the strength of the correlation significantly increased with the addition of genetic information (r = 0.573, p = 0.006). CSF YKL-40 levels are likely a biomarker for AD, but we found no evidence that they are an AD endophenotype. YKL-40 levels are highly regulated by genetic variation, and by including genetic information the strength of the

  3. Identification of subpopulations of prairie voles differentially susceptible to peer influence to decrease high alcohol intake.

    Science.gov (United States)

    Anacker, Allison M J; Ryabinin, Andrey E

    2013-01-01

    Peer influences are critical in the decrease of alcohol (ethanol) abuse and maintenance of abstinence. We previously developed an animal model of inhibitory peer influences on ethanol drinking using prairie voles and here sought to understand whether this influential behavior was due to specific changes in drinking patterns and to variation in a microsatellite sequence in the regulatory region of the vasopressin receptor 1a gene (avpr1a). Adult prairie voles' drinking patterns were monitored in a lickometer apparatus that recorded each lick a subject exhibited during continuous access to water and 10% ethanol during periods of isolation, pair housing of high and low drinkers, and subsequent isolation. Analysis of fluid consumption confirmed previous results that high drinkers typically decrease ethanol intake when paired with low drinkers, but that a subset of voles do not decrease. Analysis of bout structure revealed differences in the number of ethanol drinking bouts in the subpopulations of high drinkers when paired with low drinkers. Lickometer drinking patterns analyzed by visual and by cross-correlation analyses demonstrated that pair housing did not increase the rate of subjects drinking in bouts occurring at the same time. The length of the avpr1a microsatellite did not predict susceptibility to peer influence or any other drinking behaviors. In summary, subpopulations of high drinkers were identified, by fluid intake and number of drinking bouts, which did or did not lower their ethanol intake when paired with a low drinking peer, and these subpopulations should be explored for testing the efficacy of treatments to decrease ethanol use in groups that are likely to be responsive to different types of therapy.

  4. Identification of subpopulations of prairie voles differentially susceptible to peer influence to decrease high alcohol intake

    Directory of Open Access Journals (Sweden)

    Allison M.J. Anacker

    2013-07-01

    Full Text Available Peer influences are critical in the decrease of alcohol (ethanol abuse and maintenance of abstinence. We previously developed an animal model of inhibitory peer influences on ethanol drinking using prairie voles and here sought to understand whether this influential behavior was due to specific changes in drinking patterns and to variation in a microsatellite sequence in the regulatory region of the vasopressin receptor 1a gene (avpr1a. Adult prairie voles’ drinking patterns were monitored in a lickometer apparatus that recorded each lick a subject exhibited during continuous access to water and 10% ethanol during periods of isolation, pair housing of high and low drinkers, and subsequent isolation. Analysis of fluid consumption confirmed previous results that high drinkers typically decrease ethanol intake when paired with low drinkers, but that a subset of voles do not decrease. Analysis of bout structure revealed differences in the number of ethanol drinking bouts in the subpopulations of high drinkers when paired with low drinkers. Lickometer drinking patterns analyzed by visual and by cross-correlation analyses demonstrated that pair housing did not increase the rate of subjects drinking in bouts occurring at the same time. The length of the avpr1a microsatellite did not predict susceptibility to peer influence or any other drinking behaviors. In summary, subpopulations of high drinkers were identified by fluid intake and number of drinking bouts, which did or did not lower their ethanol intake when paired with a low drinking peer, and these subpopulations should be explored for testing the efficacy of treatments to decrease ethanol use in groups that are likely to be responsive to different types of therapy.

  5. A locus closely linked to Mtv7 on mouse chromosome 1 influences development of acute versus chronic graft-versus-host disease in a murine model.

    Science.gov (United States)

    Allen, R D; Slayback, D L; Harper, J M; Aguirre, T L; Dobkins, J A

    2000-04-01

    The relationship between acute and chronic graft-versus-host disease (GVHD) is not well understood. A murine model of acute and chronic GVHD is the B6D2F1 parent-->F1 model in which transfer of C57BL/6 parental strain lymphoid cells to B6D2F1 recipients results in development of Th1-mediated acute GVHD, whereas transfer of DBA/2 parental strain lymphoid cells to B6D2F1 recipients results in development of Th2-mediated chronic GVHD. Numerous studies have investigated the reason for the differential development of acute versus chronic GVHD in this model but have as yet failed to identify the factor that determines which type of T helper cell will predominate and thereby which type of GVHD will develop. In this report, we demonstrate, using congenic strains of mice, that a locus in the vicinity of the Mtv7 locus on Chromosome 1 of the mouse significantly influences development of acute versus chronic GVHD in the B6D2F1 model.

  6. Friends' drinking norms and male adolescents' alcohol consumption: The moderating role of performance-based peer influence susceptibility

    NARCIS (Netherlands)

    Teunissen, H.A.; Kuntsche, E.N.; Scholte, R.H.J.; Spijkerman, R.; Prinstein, M.J.; Engels, R.C.M.E.

    2016-01-01

    This study examined whether the relationship between friends' drinking norms and male adolescents' alcohol use is moderated by performance-based peer influence susceptibility. Seventy-three male adolescents (M = 17 years) from three schools in the Netherlands were exposed to the drinking norms of

  7. ESR1 is co-expressed with closely adjacent uncharacterised genes spanning a breast cancer susceptibility locus at 6q25.1.

    Directory of Open Access Journals (Sweden)

    Anita K Dunbier

    2011-04-01

    important influences on the recently identified relationship between SNPs in this region and breast cancer risk.

  8. TMEM187-IRAK1 Polymorphisms Associated with Rheumatoid Arthritis Susceptibility in Tunisian and French Female Populations: Influence of Geographic Origin

    Directory of Open Access Journals (Sweden)

    Olfa Khalifa

    2017-01-01

    Full Text Available Polymorphisms have been identified in the Xq28 locus as risk loci for rheumatoid arthritis (RA. Here, we investigated the association between three polymorphisms in the Xq28 region containing TMEM187 and IRAK1 (rs13397, rs1059703, and rs1059702 in two unstudied populations: Tunisian and French. The rs13397 G and rs1059703 T major alleles were significantly increased in RA patients (n=408 compared with age-matched controls (n=471 in both Tunisian and French women. These results were confirmed by a meta-analysis replication study including two independent Greek and Korean cohorts. The rs1059702 C major allele was significantly associated with RA, only with French women. In the French population, the GTC haplotype displayed a protective effect against RA, while the ATC, GCC, and GTT haplotypes conferred significant risk for RA. No association for these haplotypes was found in the Tunisian population. Our results replicated for the first time the association of the three Xq28 polymorphisms with RA risk in Tunisian and French populations and suggested that RA susceptibility is associated with TMEM187-IRAK1 polymorphisms in women. Our data further support the involvement of X chromosome in RA susceptibility and evidence ethnicities differences that might be explained by differences in the frequencies of SE HLA-DRB1 alleles between both populations.

  9. Speaking rate effects on locus equation slope

    Science.gov (United States)

    Berry, Jeff; Weismer, Gary

    2013-01-01

    A locus equation describes a 1st order regression fit to a scatter of vowel steady-state frequency values predicting vowel onset frequency values. Locus equation coefficients are often interpreted as indices of coarticulation. Speaking rate variations with a constant consonant–vowel form are thought to induce changes in the degree of coarticulation. In the current work, the hypothesis that locus slope is a transparent index of coarticulation is examined through the analysis of acoustic samples of large-scale, nearly continuous variations in speaking rate. Following the methodological conventions for locus equation derivation, data pooled across ten vowels yield locus equation slopes that are mostly consistent with the hypothesis that locus equations vary systematically with coarticulation. Comparable analyses between different four-vowel pools reveal variations in the locus slope range and changes in locus slope sensitivity to rate change. Analyses across rate but within vowels are substantially less consistent with the locus hypothesis. Taken together, these findings suggest that the practice of vowel pooling exerts a non-negligible influence on locus outcomes. Results are discussed within the context of articulatory accounts of locus equations and the effects of speaking rate change. PMID:24535890

  10. The diabetes type 1 locus Idd6 modulates activity of CD4+CD25+ regulatory T-cells.

    Science.gov (United States)

    Rogner, Ute Christine; Lepault, Françoise; Gagnerault, Marie-Claude; Vallois, David; Morin, Joëlle; Avner, Philip; Boitard, Christian

    2006-01-01

    The genetic locus Idd6 confers susceptibility to the spontaneous development of type 1 diabetes in the NOD mouse. Our studies on disease resistance of the congenic mouse strain NOD.C3H 6.VIII showed that Idd6 influences T-cell activities in the peripheral immune system and suggest that a major mechanism by which the Idd6 locus modifies diabetes development is via modulation of regulatory T-cell activities. Our transfer experiments using total splenocytes and purified T-cells demonstrated that the locus specifically controls the efficiency of disease protection mediated by the regulatory CD4(+)CD25(+) T-cell subset. Our data also implicate the Idd6 locus in controlling the balance between infiltrating lymphocytes and antigen-presenting cells within the pancreatic islet.

  11. Genome-Wide Linkage Scan for Prostate Cancer Susceptibility in Finland: Evidence for a Novel Locus on 2q37.3 and confirmation of signal on 17q21-q22

    Science.gov (United States)

    Cropp, Cheryl D.; Simpson, Claire L; Wahlfors, Tiina; Ha, Nati; George, Asha; Jones, MaryPat S.; Harper, Ursula; Ponciano-Jackson, Damaris; Green, Tiffany A.; Tammela, Teuvo L. J.; Bailey-Wilson, Joan; Schleutker, Johanna

    2011-01-01

    Genome-wide linkage studies have been used to localize rare and highly penetrant prostate cancer (PRCA) susceptibility genes. Linkage studies performed in different ethnic backgrounds and populations have been somewhat disparate, resulting in multiple, often irreproducible signals because of genetic heterogeneity and high sporadic background of the disease. Our first genome-wide linkage study and subsequent fine-mapping study of Finnish hereditary prostate cancer (HPC) families gave evidence of linkage to one region. Here, we conducted subsequent scans with microsatellites and SNPs in a total of 69 Finnish HPC families. GENEHUNTER-PLUS was used for parametric and non-parametric analyses. Our microsatellite genome-wide linkage study provided evidence of linkage to 17q12-q23, with a heterogeneity LOD (HLOD) score of 3.14 in a total of 54 of the 69 families. Genome-wide SNP analysis of 59 of the 69 families gave a highest HLOD score of 3.40 at 2q37.3 under a dominant high penetrance model. Analyzing all 69 families by combining microsatellite and SNP maps also yielded HLOD scores of > 3.3 in two regions (2q37.3 and 17q12-q21.3). These significant linkage peaks on chromosome 2 and 17 confirm previous linkage evidence of a locus on 17q from other populations and provide a basis for continued research into genetic factors involved in PRCA. Fine-mapping analysis of these regions is ongoing and candidate genes at linked loci are currently under analysis. PMID:21207418

  12. Genome-wide linkage scan for prostate cancer susceptibility in Finland: evidence for a novel locus on 2q37.3 and confirmation of signal on 17q21-q22.

    Science.gov (United States)

    Cropp, Cheryl D; Simpson, Claire L; Wahlfors, Tiina; Ha, Nati; George, Asha; Jones, MaryPat S; Harper, Ursula; Ponciano-Jackson, Damaris; Green, Tiffany A; Tammela, Teuvo L J; Bailey-Wilson, Joan; Schleutker, Johanna

    2011-11-15

    Genome-wide linkage studies have been used to localize rare and highly penetrant prostate cancer (PRCA) susceptibility genes. Linkage studies performed in different ethnic backgrounds and populations have been somewhat disparate, resulting in multiple, often irreproducible signals because of genetic heterogeneity and high sporadic background of the disease. Our first genome-wide linkage study and subsequent fine-mapping study of Finnish hereditary prostate cancer (HPC) families gave evidence of linkage to one region. Here, we conducted subsequent scans with microsatellites and SNPs in a total of 69 Finnish HPC families. GENEHUNTER-PLUS was used for parametric and nonparametric analyses. Our microsatellite genome-wide linkage study provided evidence of linkage to 17q12-q23, with a heterogeneity LOD (HLOD) score of 3.14 in a total of 54 of the 69 families. Genome-wide SNP analysis of 59 of the 69 families gave a highest HLOD score of 3.40 at 2q37.3 under a dominant high penetrance model. Analyzing all 69 families by combining microsatellite and SNP maps also yielded HLOD scores of > 3.3 in two regions (2q37.3 and 17q12-q21.3). These significant linkage peaks on chromosome 2 and 17 confirm previous linkage evidence of a locus on 17q from other populations and provide a basis for continued research into genetic factors involved in PRCA. Fine-mapping analysis of these regions is ongoing and candidate genes at linked loci are currently under analysis. Copyright © 2011 UICC.

  13. Application of multiple locus variable number of tandem repeat analysis (MLVA), phage typing and antimicrobial susceptibility testing to subtype Salmonella enterica serovar Typhimurium isolated from pig farms, pork slaughterhouses and meat producing plants in Ireland.

    Science.gov (United States)

    Prendergast, D M; O'Grady, D; Fanning, S; Cormican, M; Delappe, N; Egan, J; Mannion, C; Fanning, J; Gutierrez, M

    2011-08-01

    Salmonella enterica subsp. enterica serovar Typhimurium is a common zoonotic pathogen encountered in Irish pigs and the pork industry and its characterisation using highly discriminatory typing methods is necessary for epidemiological studies, outbreak investigation and control. Multiple locus variable number of tandem repeat analysis (MLVA), phage typing and antimicrobial susceptibility testing were applied to characterise 301 S. typhimurium isolates of porcine origin isolated from farms, slaughterhouses and pork meat producing plants in Ireland over a four-year period. 154 MLVA patterns were obtained compared to 19 phage types and 38 AMR patterns, and MLVA was particularly useful for discriminating isolates of the same phage type, e.g. DT104 and DT104b, or isolates that were Untypable or in the category of "react with phage but does not conform to a recognised phage type" (RDNC) by the phage typing method. Cluster analysis of MLVA profiles using a minimum spanning tree (MST) demonstrated two major clusters (I and II), which showed to have a clear association with phage types, cluster I associated to phage types DT104, U302 and DT120 and cluster II associated to DT193 and U288. The results of this present study showed that MLVA is highly discriminatory and permitted the identification of identical profiles among isolates obtained at different points of the pork food chain. The same MLVA profile was observed in some cases among isolates with different phage types. While this can be explained by the fact that some phage types are closely related, it also indicates that combining phage typing and MLVA enhances strain typing of S. typhimurium. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Influence of sound-conditioning on noise-induced susceptibility of distortion-product otoacoustic emissions.

    Science.gov (United States)

    Luebke, Anne E; Stagner, Barden B; Martin, Glen K; Lonsbury-Martin, Brenda L

    2015-07-01

    Cochlear damage caused by loud sounds can be attenuated by "sound-conditioning" methods. The amount of adaptation for distortion product otoacoustic emissions (DPOAEs) measured in alert rabbits previously predicted an ear's susceptibility to a subsequent noise exposure. The present study investigated if sound-conditioning influenced the robustness of such DPOAE adaptation, and if such conditioning elicited more protection by increasing the amount of DPOAE adaptation. Toward this end, rabbits were divided into two study groups: (1) experimental animals exposed to a sound-conditioning protocol, and (2) unconditioned control animals. After base-line measures, all rabbits were exposed to an overstimulation paradigm consisting of an octave band noise, and then re-assessed 3 weeks post-exposure to determine permanent changes in DPOAEs. A major result was that prior sound-conditioning protected reductions in DPOAE levels by an average of 10-15 dB. However, DPOAE adaptation decreased with sound-conditioning, so that such conditioning was no longer related to noise-induced reductions in DPOAEs. Together, these findings suggest that sound-conditioning affected neural pathways other than those that likely mediate DPOAE adaptation (e.g., medial olivocochlear efferent and/or middle-ear muscle reflexes).

  15. The relationship between secondhand smoke exposure, pro-tobacco social influences, and smoking susceptibility among nonsmoking Zambian adolescents.

    Science.gov (United States)

    Agaku, Israel Terungwa; Maliselo, Tino; Ayo-Yusuf, Olalekan A

    2015-02-01

    We tested the hypothesis that the extent of secondhand smoke (SHS) exposure among nonsmoking adolescents would be associated with their overall exposure to pro-tobacco social influences. Data were analyzed using descriptive and multivariate methods from the 2011 Zambia Global Youth Tobacco Survey. The odds of SHS exposure increased with increasing exposure to pro-tobacco advertisements. About 39.5% of the gap in SHS exposure between nonsmokers with low versus high smoking susceptibility was attributable to differences in parental or peer smoking. Sustained efforts are needed to denormalize tobacco use in order to reduce youth susceptibility to tobacco use.

  16. The influence of a single nucleotide polymorphism within CNDP1 on susceptibility to diabetic nephropathy in Japanese women with type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Mahiro Kurashige

    Full Text Available BACKGROUND: Several linkage analyses have mapped a susceptibility locus for diabetic nephropathy to chromosome 18q22-23, and polymorphisms within the carnosine dipeptidase 1 gene (CNDP1, located on 18q22.3, have been shown to be associated with diabetic nephropathy in European subjects with type 2 diabetes. However, the association of this locus with diabetic nephropathy has not been evaluated in the Japanese population. In this study, we examined the association of polymorphisms within the CNDP1/CNDP 2 locus with diabetic nephropathy in Japanese subjects with type 2 diabetes. METHODOLOGY/PRINCIPAL FINDINGS: We genotyped a leucine repeat polymorphism (D18S880 that is within CNDP1 along with 29 single nucleotide polymorphisms (SNPs in the CNDP1/CNDP2 locus for 2,740 Japanese subjects with type 2 diabetes (1,205 nephropathy cases with overt nephropathy or with end-stage renal disease [ESRD], and 1,535 controls with normoalbuminuria. The association of each polymorphism with diabetic nephropathy was analysed by performing logistic regression analysis. We did not observe any association between D18S880 and diabetic nephropathy in Japanese subjects with type 2 diabetes. None of the 29 SNPs within the CNDP1/CNDP2 locus were associated with diabetic nephropathy, but a subsequent sex-stratified analysis revealed that 1 SNP in CNDP1 was nominally associated with diabetic nephropathy in women (rs12604675-A; p = 0.005, odds ratio [OR] = 1.76, 95% confidence interval [CI], 1.19-2.61. Rs12604675 was associated with overt proteinuria (p = 0.002, OR = 2.18, 95% CI, 1.32-3.60, but not with ESRD in Japanese women with type 2 diabetes. CONCLUSIONS/SIGNIFICANCE: Rs12604675-A in CNDP1 may confer susceptibility to overt proteinuria in Japanese women with type 2 diabetes.

  17. Influence of tectonic folding on rockfall susceptibility, American Fork Canyon, Utah, USA

    Directory of Open Access Journals (Sweden)

    J. A. Coe

    2007-01-01

    Full Text Available We examine rockfall susceptibility of folded strata in the Sevier fold-thrust belt exposed in American Fork Canyon in north-central Utah. Large-scale geologic mapping, talus production data, rock-mass-quality measurements, and historical rockfall data indicate that rockfall susceptibility is correlated with limb dip and curvature of the folded, cliff-forming Mississippian limestones. On fold limbs, rockfall susceptibility increases as dip increases. This relation is controlled by several factors, including an increase in adverse dip conditions and apertures of discontinuities, and shearing by flexural slip during folding that has reduced the friction angles of discontinuities by smoothing surface asperities. Susceptibility is greater in fold hinge zones than on adjacent limbs primarily because there are greater numbers of discontinuities in hinge zones. We speculate that susceptibility increases in hinge zones as fold curvature becomes tighter.

  18. Downregulation of FoxC2 Increased Susceptibility to Experimental Colitis: Influence of Lymphatic Drainage Function?

    Science.gov (United States)

    Becker, Felix; Potepalov, Sergey; Shehzahdi, Romana; Bernas, Michael; Witte, Marlys; Abreo, Fleurette; Traylor, James; Orr, Wayne A.; Tsunoda, Ikuo

    2015-01-01

    Background: Although inflammation-induced expansion of the intestinal lymphatic vasculature (lymphangiogenesis) is known to be a crucial event in limiting inflammatory processes, through clearance of interstitial fluid and immune cells, considerably less is known about the impact of an impaired lymphatic clearance function (as seen in inflammatory bowel diseases) on this cascade. We aimed to investigate whether the impaired intestinal lymphatic drainage function observed in FoxC2(+/−) mice would influence the course of disease in a model of experimental colitis. Methods: Acute dextran sodium sulfate colitis was induced in wild-type and haploinsufficient FoxC2(+/−) mice, and survival, disease activity, colonic histopathological injury, neutrophil, T-cell, and macrophage infiltration were evaluated. Functional and structural changes in the intestinal lymphatic vessel network were analyzed, including submucosal edema, vessel morphology, and lymphatic vessel density. Results: We found that FoxC2 downregulation in FoxC2(+/−) mice significantly increased the severity and susceptibility to experimental colitis, as displayed by lower survival rates, increased disease activity, greater histopathological injury, and elevated colonic neutrophil, T-cell, and macrophage infiltration. These findings were accompanied by structural (dilated torturous lymphatic vessels) and functional (greater submucosal edema, higher immune cell burden) changes in the intestinal lymphatic vasculature. Conclusions: These results indicate that sufficient lymphatic clearance plays a crucial role in limiting the initiation and perpetuation of experimental colitis and those disturbances in the integrity of the intestinal lymphatic vessel network could intensify intestinal inflammation. Future therapies might be able to exploit these processes to restore and maintain adequate lymphatic clearance function in inflammatory bowel disease. PMID:25822012

  19. Downregulation of FoxC2 Increased Susceptibility to Experimental Colitis: Influence of Lymphatic Drainage Function?

    Science.gov (United States)

    Becker, Felix; Potepalov, Sergey; Shehzahdi, Romana; Bernas, Michael; Witte, Marlys; Abreo, Fleurette; Traylor, James; Orr, Wayne A; Tsunoda, Ikuo; Alexander, Jonathan Steven

    2015-06-01

    Although inflammation-induced expansion of the intestinal lymphatic vasculature (lymphangiogenesis) is known to be a crucial event in limiting inflammatory processes, through clearance of interstitial fluid and immune cells, considerably less is known about the impact of an impaired lymphatic clearance function (as seen in inflammatory bowel diseases) on this cascade. We aimed to investigate whether the impaired intestinal lymphatic drainage function observed in FoxC2 mice would influence the course of disease in a model of experimental colitis. Acute dextran sodium sulfate colitis was induced in wild-type and haploinsufficient FoxC2 mice, and survival, disease activity, colonic histopathological injury, neutrophil, T-cell, and macrophage infiltration were evaluated. Functional and structural changes in the intestinal lymphatic vessel network were analyzed, including submucosal edema, vessel morphology, and lymphatic vessel density. We found that FoxC2 downregulation in FoxC2 mice significantly increased the severity and susceptibility to experimental colitis, as displayed by lower survival rates, increased disease activity, greater histopathological injury, and elevated colonic neutrophil, T-cell, and macrophage infiltration. These findings were accompanied by structural (dilated torturous lymphatic vessels) and functional (greater submucosal edema, higher immune cell burden) changes in the intestinal lymphatic vasculature. These results indicate that sufficient lymphatic clearance plays a crucial role in limiting the initiation and perpetuation of experimental colitis and those disturbances in the integrity of the intestinal lymphatic vessel network could intensify intestinal inflammation. Future therapies might be able to exploit these processes to restore and maintain adequate lymphatic clearance function in inflammatory bowel disease.

  20. The influence of land use change on landslide susceptibility zonation: the Briga catchment test site (Messina, Italy).

    Science.gov (United States)

    Reichenbach, P; Busca, C; Mondini, A C; Rossi, M

    2014-12-01

    The spatial distribution of landslides is influenced by different climatic conditions and environmental settings including topography, morphology, hydrology, lithology, and land use. In this work, we have attempted to evaluate the influence of land use change on landslide susceptibility (LS) for a small study area located in the southern part of the Briga catchment, along the Ionian coast of Sicily (Italy). On October 1, 2009, the area was hit by an intense rainfall event that triggered abundant slope failures and resulted in widespread erosion. After the storm, an inventory map showing the distribution of pre-event and event landslides was prepared for the area. Moreover, two different land use maps were developed: the first was obtained through a semi-automatic classification of digitized aerial photographs acquired in 1954, the second through the combination of supervised classifications of two recent QuickBird images. Exploiting the two land use maps and different land use scenarios, LS zonations were prepared through multivariate statistical analyses. Differences in the susceptibility models were analyzed and quantified to evaluate the effects of land use change on the susceptibility zonation. Susceptibility maps show an increase in the areal percentage and number of slope units classified as unstable related to the increase in bare soils to the detriment of forested areas.

  1. HIV-1 subtype influences susceptibility and response to monotherapy with the protease inhibitor lopinavir/ritonavir.

    Science.gov (United States)

    Sutherland, K A; Ghosn, J; Gregson, J; Mbisa, J L; Chaix, M L; Cohen Codar, I; Delfraissy, J F; Delaugerre, C; Gupta, R K

    2015-01-01

    PI susceptibility results from a complex interplay between protease and Gag proteins, with Gag showing wide variation across HIV-1 subtypes. We explored the impact of pre-treatment susceptibility on the outcome of lopinavir/ritonavir monotherapy. Treatment-naive individuals who experienced lopinavir/ritonavir monotherapy failure from the MONARK study were matched (by subtype, viral load and baseline CD4 count) with those who achieved virological response ('successes'). Successes were defined by viral load protease was amplified from patient samples for in vitro phenotypic susceptibility testing, with susceptibility expressed as fold change (FC) relative to a subtype B reference strain. Baseline lopinavir susceptibility was lower in viral failures compared with viral successes, but the differences were not statistically significant (median lopinavir susceptibility: 4.4 versus 8.5, respectively, P = 0.17). Among CRF02_AG/G patients, there was a significant difference in lopinavir susceptibility between the two groups (7.1 versus 10.4, P = 0.047), while in subtype B the difference was not significant (2.7 versus 3.4, P = 0.13). Subtype CRF02_AG/G viruses had a median lopinavir FC of 8.7 compared with 3.1 for subtype B (P = 0.001). We report an association between reduced PI susceptibility (using full-length Gag-protease sequences) at baseline and subsequent virological failure on lopinavir/ritonavir monotherapy in antiretroviral-naive patients harbouring subtype CRF02_AG/G viruses. We speculate that this may be important in the context of suboptimal adherence in determining viral failure. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

  2. HLA class II alleles influence rheumatoid arthritis susceptibility and autoantibody status in South Indian Tamil population.

    Science.gov (United States)

    Mariaselvam, C M; Fortier, C; Charron, D; Krishnamoorthy, R; Tamouza, R; Negi, V S

    2016-11-01

    Rheumatoid arthritis (RA) is a complex multifactorial autoimmune disease characterized by inflammatory arthritis. The precise etiology and pathogenesis of RA remains elusive but evidence points towards stochastic interactions between genetic and environmental factors. This study investigated the distribution of human leucocyte antigen (HLA)-DRB1/DQB1 alleles in South Indian patients with rheumatoid arthritis (RA) and their influence on RA susceptibility and clinical phenotype. Low resolution HLA-DRB1 and -DQB1 typing was performed in 271 RA patients and 233 healthy controls by polymerase chain reaction (PCR) using sequence-specific primers (SSP). HLA-DRB1*10 was found to be more frequent in patients (Pc = 0.004, OR = 2.23, 95% CI = 1.5-3.34) than controls. This difference persisted in RF positive (Pc = 9 × 10(-6) , OR = 2.45, 95% CI = 1.62-3.74), ACPA positive (Pc = 0.007, OR = 2.10, 95% CI = 1.35-3.29), ACPA negative (Pc = 0.001, OR = 2.45, 95% CI = 1.50-3.97) and both RF and ACPA positive subgroup of patients (Pc = 0.003, OR = 2.22, 95% CI = 1.41-3.51). On the contrary, the HLA-DRB1*13 (Pc = 0.01, OR = 0.43, 95% CI = 0.25-0.73) and HLA-DRB1*14 (Pc = 0.003, OR = 0.43, 95% CI = 0.26-0.69) alleles were over-represented in controls than patients. Further, distribution of the prominent Caucasian RA risk allele DRB1*04 did not differ between patients and controls in our study population. We did not find any association between DQB1 alleles and RA susceptibility or autoantibody status. The haplotypes DQB1*05-DRB1*10 (P = 6.8 × 10(-6) , OR = 2.46, 95% CI = 1.63-3.79) and DQB1*06-DRB1*15 (P = 0.03, OR = 1.41, 95% CI = 1.02-1.96) were more frequent in patients while DQB1*05-DRB1*14 (P = 8.4 × 10(-4) , OR = 0.44, 95% CI = 0.26-0.74) and DQB1*06-DRB1*13 (P = 9.5 × 10(-4) , OR = 0.40, 95% CI = 0.21-0.72) were higher in controls. To conclude, HLA-DRB1*10 is associated with RA while HLA-DRB1*13 and HLA-DRB1*14 alleles confer protection in south Indian Tamils. © 2016 John

  3. Revisiting the health effects of psychological stress-its influence on susceptibility to ionizing radiation: a mini-review.

    Science.gov (United States)

    Wang, Bing; Katsube, Takanori; Begum, Nasrin; Nenoi, Mitsuru

    2016-07-01

    Both psychological stress (PS) and ionizing radiation (IR) cause varied detrimental effects on humans. There has been no direct evidence so far showing PS alone could cause cancer; however, long-lasting PS may affect our overall health and ability to cope with cancer. Due to their living conditions and occupations, some people may encounter concurrent exposure to both PS and IR to a high extent. In addition to possible health effects resulting directly from exposure to IR on these people, fear of IR exposure is also a cause of PS. The question of whether PS would influence susceptibility to IR, radiocarcinogenesis in particular, is of great concern by both the academic world and the public. Recently, investigations using animal PS models demonstrated that PS could modulate susceptibility to IR, causing increased susceptibility to radiocarcinogenesis in Trp53-heterozygous mice, hematological toxicity in peripheral blood and elevated chromosome aberration (dicentrics) frequency in splenocytes of Trp53-wild-type mice. To actively reduce health risk from exposure to IR, further studies are needed to cumulate more evidence and provide insights into the mechanisms underlying the alterations in susceptibility due to PS modulation. This mini-review gives a general overview of the significance of PS effects on humans and experimental animals, with a special focus on summarizing the latest weight-of-evidence approaches to radiobiological studies on PS-induced alterations in susceptibility in experimental animal models. The susceptibility being investigated is mainly in the context of the impact of the modulatory effect of PS on radiocarcinogenesis; we seek to improve understanding of the combined effects of exposure to both PS and IR in order to facilitate, via active intervention, strategies for radiation risk reduction. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  4. Low-temperature magnetic susceptibility of concentrated ferrofluids: The influence of polydispersity

    Energy Technology Data Exchange (ETDEWEB)

    Ivanov, Alexey O., E-mail: Alexey.Ivanov@usu.ru; Elfimova, Ekaterina A.

    2015-01-15

    In this paper we address the question of theoretical explanation of extremely high low-temperature initial magnetic susceptibility of concentrated ferrofluids. These laboratory synthesized samples [A.F. Pshenichnikov, A.V. Lebedev, J. Chem. Phys. 121(11) (2004) 5455; Colloid J. 67(2) (2005) 189] demonstrated the record-breaking values χ∼120–150 at temperatures ∼ 230–240 K. The existing models predict such high susceptibility only under the assumption of unreasonably large dipolar coupling constant, which is out of the range of applicability. Here we calculate the second virial contribution to susceptibility for polydisperse ferrofluid, modeled by the dipolar hard sphere fluid. In the resulting expression there exists the parameter, which plays a part of dipolar coupling constant and which is defined in a form of double averaging of high powers of particle sizes over the granulometric distribution. For real particle size distribution this effective parameter at least twice exceeds the commonly defined polydisperse dipolar coupling constant. We show that the low-temperature magnetic susceptibility of the record-breaking ferrofluids could be explained theoretically on the basis of the first terms of the polydisperse second virial contribution in combination with the second-order modified mean field model. - Highlights: • Record-breaking magnetic susceptibility of ferrofluids at low temperatures. • Second virial contribution to magnetic susceptibility of polydisperse ferrofluids. • Interparticle dipole correlations are more pronounced in dense ferrofluids. • Presented model describes the ferrofluid susceptibility χ∼120 at temperature 240 K.

  5. Landslide Susceptibility Across the Pacific Northwest: The Heavy Influence of Transportation Inventories

    Science.gov (United States)

    Stanley, Thomas; Kirschbaum, Dalia

    2017-04-01

    Some of the largest and best landslide databases in the United States of America describe the Pacific Northwest region. Nevertheless, these inventories are not a comprehensive listing of historic landslides. In particular, landslide dates tend to be recorded by state transportation agencies, which imposes a spatial bias upon any subsequent analysis. This reporting bias complicates not only the identification of landslide triggering conditions, but also hinders empirical calculations of landslide susceptibility. Although many strategies for bias mitigation could be employed, the simplest approach delivers generally plausible results that are most reliable in the most critical locations: along major highways and rail lines. This work tests logistic regression models that were fitted in zones with landslide reports, then applied regionally. Due to the destabilizing effects of excavation and other anthropogenic disturbances, the models may overestimate susceptibility in undeveloped areas. However, the susceptibility of developed sites should be as accurate as the modeling technique and input data allow.

  6. Influence of doxorubicin on fluconazole susceptibility and efflux pump gene expression of Candida dubliniensis.

    LENUS (Irish Health Repository)

    Schulz, Bettina

    2012-05-01

    The effect of doxorubicin (DOX) on the fluconazole (FLU) susceptibility of C. dubliniensis was investigated. Isolates were exposed to DOX and FLU in a chequerboard assay and resistance gene expressions were analysed after DOX exposure. The susceptibility of the yeast to FLU was decreased in the presence of DOX in the chequerboard assay with FIC indices suggesting an antagonistic effect. Gene expression analyses showed an overexpression of CdCDR2. Hence, DOX was found to have an impact on resistance mechanisms in C. dubliniensis isolates.

  7. Identification of three QTLs with influence on susceptibility to helminth infections in pigs

    DEFF Research Database (Denmark)

    Nejsum, Peter; Thamsborg, Stig Milan; Göring, H. H.

      Intestinal helminth infections are causing health and welfare problems in both human and animal populations. A family, in which susceptibility towards Ascaris (large round worm) and Trichuris (whipworm) infections are segregating, was constructed. Our data demonstrate that genetic components ar...

  8. A Multi-locus Approach to Characterization of Major Quantitative Trait Loci Influencing Hb F Regulation in Chinese β-thalassemia Carriers.

    Science.gov (United States)

    Chan, Nelson C N; Lau, Kin-Mang; Cheng, Kelvin C K; Chan, Natalie P H; Ng, Margaret H L

    2016-11-01

    Genetic association studies showed that Hb F is under the influence of major quantitative trait loci (QTL) in β-thalassemia (β-thal) carriers. Single nucleotide polymorphisms (SNPs) at three major QTLs, BCL11A, HBS1L-MYB intergenic region and XmnI-HBG2 were individually validated in univariate models. However, their relative effect sizes on Hb F regulation are unknown. We genotyped 99 Chinese β-thal carriers for the three major QTLs and performed genetic association studies using three different statistical models, including mass univariate analysis, multivariate linear regression and partial least square regression structural equation modeling (PLS-SEM). Performances of the three models were compared and effect sizes of the three QTLs in a multivariate model were assessed. Traditional mass univariate analysis and multivariate linear regression showed limited statistical power in our small cohort and the latter was constrained by multicollinearity. Partial least structural equation modeling showed significant positive associations of each QTL (p Hb F regulation, together explained 34.4% of variance. The HBS1L-MYB intergenic region polymorphism (HMIP) demonstrated the highest effect on Hb F prediction with effect size f(2) 0.294. PLS-SEM offered a statistically powerful multivariate model for multi-locus genetic association studies. We reproduced findings of previous studies with a much smaller cohort and demonstrated HMIP as the strongest regulator of Hb F in Chinese β-thal carriers.

  9. A novel long non-coding RNA in the rheumatoid arthritis risk locus TRAF1-C5 influences C5 mRNA levels.

    Science.gov (United States)

    Messemaker, T C; Frank-Bertoncelj, M; Marques, R B; Adriaans, A; Bakker, A M; Daha, N; Gay, S; Huizinga, T W; Toes, R E M; Mikkers, H M M; Kurreeman, F

    2016-03-01

    Long non-coding RNAs (lncRNAs) can regulate the transcript levels of genes in the same genomic region. These locally acting lncRNAs have been found deregulated in human disease and some have been shown to harbour quantitative trait loci (eQTLs) in autoimmune diseases. However, lncRNAs linked to the transcription of candidate risk genes in loci associated to rheumatoid arthritis (RA) have not yet been identified. The TRAF1 and C5 risk locus shows evidence of multiple eQTLs and transcription of intergenic non-coding sequences. Here, we identified a non-coding transcript (C5T1lncRNA) starting in the 3' untranslated region (UTR) of C5. RA-relevant cell types express C5T1lncRNA and RNA levels are further enhanced by specific immune stimuli. C5T1lncRNA is expressed predominantly in the nucleus and its expression correlates positively with C5 mRNA in various tissues (P=0.001) and in peripheral blood mononuclear cells (P=0.02) indicating transcriptional co-regulation. Knockdown results in a concurrent decrease in C5 mRNA levels but not of other neighbouring genes. Overall, our data show the identification of a novel lncRNA C5T1lncRNA that is fully located in the associated region and influences transcript levels of C5, a gene previously linked to RA pathogenesis.

  10. Susceptibility to Peer Influence: Using a Performance-Based Measure to Identify Adolescent Males at Heightened Risk for Deviant Peer Socialization

    OpenAIRE

    Prinstein, Mitchell J.; Brechwald, Whitney A.; Cohen, Geoffrey L

    2011-01-01

    A substantial amount of research has suggested that adolescents’ attitudes and behaviors are influenced by peers; however, little is known regarding adolescents’ individual variability, or susceptibility, to peer influence. In this study, a performance-based index from an experimental paradigm was used to directly measure adolescents’ susceptibility to peers. A total of 36 adolescent boys participated in a “chat room” experiment in which they ostensibly were exposed to deviant or risky social...

  11. Susceptibility to bystander DNA damage is influenced by replication and transcriptional activity

    OpenAIRE

    Dickey, Jennifer S.; Baird, Brandon J.; Redon, Christophe E.; Avdoshina, Valeriya; Palchik, Guillermo; Wu, Junfang; Kondratyev, Alexei; Bonner, William M.; Martin, Olga A.

    2012-01-01

    Direct cellular DNA damage may lead to genome destabilization in unexposed, bystander, cells sharing the same milieu with directly damaged cells by means of the bystander effect. One proposed mechanism involves double strand break (DSB) formation in S phase cells at sites of single strand lesions in the DNA of replication complexes, which has a more open structure compared with neighboring DNA. The DNA in transcription complexes also has a more open structure, and hence may be susceptible to ...

  12. Influence of iron valency on the magnetic susceptibility of a microbially produced iron sulphide

    Energy Technology Data Exchange (ETDEWEB)

    Marius, M S; James, P A B; Bahaj, A S; Smallman, D J [University of Southampton, School of Civil Engineering and the Environment, Southampton, SO17 1BJ (United Kingdom)

    2005-01-01

    Microbial iron sulphide is well known as an adsorbent for the treatment of metallic ion polluted wastewater. Under certain culture conditions a highly magnetic iron sulphide can be produced which would enable a low cost biomagnetic separation process to be developed. This paper illustrates that by raising the ferrous content of a ferrous - ferric sulphate rich medium the magnetic susceptibility of the iron sulphide produced is increased.

  13. Influence of iron valency on the magnetic susceptibility of a microbially produced iron sulphide.

    Science.gov (United States)

    Marius, M. S.; James, P. A. B.; Bahaj, A. S.; Smallman, D. J.

    2005-01-01

    Microbial iron sulphide is well known as an adsorbent for the treatment of metallic ion polluted wastewater. Under certain culture conditions a highly magnetic iron sulphide can be produced which would enable a low cost biomagnetic separation process to be developed. This paper illustrates that by raising the ferrous content of a ferrous - ferric sulphate rich medium the magnetic susceptibility of the iron sulphide produced is increased.

  14. Environmental Discontinuity, Stress, and Sex Effects Upon Susceptibility to Social Influence

    Science.gov (United States)

    Zohner, Dorin

    1970-01-01

    Social influence was influenced most by prestige suggestion, conformity, and baseline suggestion, in that order. Differential effects of suggestion depended on the effects of type of discontinuity and sex. (MH)

  15. Influence of orthodontic adhesives and clean-up procedures on the stain susceptibility of enamel after debonding.

    Science.gov (United States)

    Joo, Hyun-Jin; Lee, Yong-Keun; Lee, Dong-Yul; Kim, Yae-Jin; Lim, Yong-Kyu

    2011-03-01

    To determine the influence of the type of orthodontic adhesive system, such as conventional acid-etching (CE) and self-etching primers (SEPs), on the stain susceptibility of enamel surface after debonding. Effects of clean-up procedures on the enamel surface were also determined. Two types and four brands of adhesive systems were investigated using 135 human premolars. Unbonded teeth were used as controls. Three-dimensional scanning of the enamel surface was performed before bracket bonding, after debonding, and after clean-up procedures. The color of each tooth was measured before bracket bonding and again after debonding and clean-up procedures. This was followed by methylene blue staining. The stain susceptibility of the enamel surface was measured after finishing only (F-condition) and after finishing/polishing (FP-condition). After debonding, the amount of residual adhesive resins in CE materials was greater than that in SEP materials. For the F-condition, staining color change in SEP materials was significantly higher than that in CE materials. For the FP-condition, staining color change in both CE and SEP materials was not different from those of the control. The SEP system would show less stain susceptibility if the thin residual adhesive resin layer after debonding is removed by polishing.

  16. An integrated transcriptomic and meta-analysis of hepatoma cells reveals factors that influence susceptibility to HCV infection.

    Directory of Open Access Journals (Sweden)

    Jamie I MacPherson

    Full Text Available Hepatitis C virus (HCV is a global problem. To better understand HCV infection researchers employ in vitro HCV cell-culture (HCVcc systems that use Huh-7 derived hepatoma cells that are particularly permissive to HCV infection. A variety of hyper-permissive cells have been subcloned for this purpose. In addition, subclones of Huh-7 which have evolved resistance to HCV are available. However, the mechanisms of susceptibility or resistance to infection among these cells have not been fully determined. In order to elucidate mechanisms by which hepatoma cells are susceptible or resistant to HCV infection we performed genome-wide expression analyses of six Huh-7 derived cell cultures that have different levels of permissiveness to infection. A great number of genes, representing a wide spectrum of functions are differentially expressed between cells. To focus our investigation, we identify host proteins from HCV replicase complexes, perform gene expression analysis of three HCV infected cells and conduct a detailed analysis of differentially expressed host factors by integrating a variety of data sources. Our results demonstrate that changes relating to susceptibility to HCV infection in hepatoma cells are linked to the innate immune response, secreted signal peptides and host factors that have a role in virus entry and replication. This work identifies both known and novel host factors that may influence HCV infection. Our findings build upon current knowledge of the complex interplay between HCV and the host cell, which could aid development of new antiviral strategies.

  17. Mediation of the link between Popularity and Peer Influence Susceptibility (SRA)

    NARCIS (Netherlands)

    Gommans, Rob; Cillessen, Antonius H. N.; Stevens, Gonneke W. J. M.; ter Bogt, Tom F. M.

    Peer influence processes shape adolescents’ attitudes and behaviors (Sandstrom, 2011). Peer status plays an important role in this process. On one hand, adolescents are more influenced by high-status than low-status peers (Cohen & Prinstein, 2006). On the other hand, adolescents’ own status plays a

  18. Enhanced susceptibility to a chemical carcinogen in rats carrying MHC-linked genes influencing development (GRC).

    Science.gov (United States)

    Rao, K N; Shinozuka, H; Kunz, H W; Gill, T J

    1984-07-15

    In an approach to testing the possible relationship between embryogenesis and carcinogenesis, we examined the susceptibility of rats carrying the grc, which is an MHC-linked gene complex affecting growth and development, to the development of the cellular and biochemical changes known to be associated with the induction of cancer. Genetically related strains which differed mainly by the presence or absence of the grc were fed a diet containing 0.02% N-2-acetylaminofluorene (AAF), and the induction of gamma-glutamyltranspeptidase (GGT)-positive foci, bile-duct proliferation and oval-cell proliferation in the livers of the two groups of animals were scored. All of the rats homozygous for the grc displayed GGT-positive foci (from three to six per section) and extensive bile-duct and oval-cell proliferation. By contrast, only 27% of the animals which did not carry the grc had GGT-positive foci in the liver, and these were present in smaller numbers (from one to three per section); there was no bile-duct or oval-cell proliferation. Biochemical studies of the liver and testes showed that the grc homozygotes had the metabolic abnormalities associated with the development of cancer: increased cholesterol biosynthesis; increased DNA synthesis, as indicated by an enhanced incorporation of 3H-thymidine into DNA; stimulation of the hexose monophosphate (HMP) pathway, as indicated by increased levels of glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD); and decreased levels of circulating lipoproteins. Both the morphological response of the rats carrying the grc to feeding AAF and the biochemical abnormalities that exist in these animal are consistent with the changes which eventually lead to cancer. Thus, there appears to be a relationship in rats between aberrations in the control of growth and development, susceptibility to the chemical induction of cancer and the control of cholesterol biosynthesis.

  19. IFNγ influences type I interferon response and susceptibility to Theiler's virus-induced demyelinating disease.

    Science.gov (United States)

    Bowen, Jenna L; Olson, Julie K

    2013-08-01

    Theiler's murine encephalomyelitis virus (TMEV) induces a demyelinating disease in susceptible SJL mice that has similarities to multiple sclerosis in humans. TMEV infection of susceptible mice leads to a persistent virus infection of the central nervous system (CNS), which promotes the development of demyelinating disease associated with an inflammatory immune response in the CNS. TMEV infection of resistant C57BL6 mice results in viral clearance without development of demyelinating disease. Interestingly, TMEV infection of resistant mice deficient in IFNγ leads to a persistent virus infection in the CNS and development of demyelinating disease. We have previously shown that the innate immune response affects development of TMEV- induced demyelinating disease, thus we wanted to determine the role of IFNγ during the innate immune response. TMEV-infected IFNγ-deficient mice had an altered innate immune response, including reduced expression of innate immune cytokines, especially type I interferons. Administration of type I interferons, IFNα and IFNß, to TMEV-infected IFNγ-deficient mice during the innate immune response restored the expression of innate immune cytokines. Most importantly, administration of type I interferons to IFNγ-deficient mice during the innate immune response decreased the virus load in the CNS and decreased development of demyelinating disease. Microglia are the CNS resident immune cells that express innate immune receptors. In TMEV-infected IFNγ-deficient mice, microglia had reduced expression of innate immune cytokines, and administration of type I interferons to these mice restored the innate immune response by microglia. In the absence of IFNγ, microglia from TMEV-infected mice had reduced expression of some innate immune receptors and signaling molecules, especially IRF1. These results suggest that IFNγ plays an important role in the innate immune response to TMEV by enhancing the expression of innate immune cytokines

  20. Susceptibility to Peer Influence: Using a Performance-Based Measure to Identify Adolescent Males at Heightened Risk for Deviant Peer Socialization

    Science.gov (United States)

    Prinstein, Mitchell J.; Brechwald, Whitney A.; Cohen, Geoffrey L.

    2011-01-01

    A substantial amount of research has suggested that adolescents' attitudes and behaviors are influenced by peers; however, little is known regarding adolescents' individual variability, or susceptibility, to peer influence. In this study, a performance-based index from an experimental paradigm was used to directly measure adolescents'…

  1. Influence of fruit maturity in the susceptibility of Navelina oranges to develop postharvest non-chilling peel pitting.

    Science.gov (United States)

    Alferez, Fernando; Zacarías, Lorenzo

    2014-04-01

    Peel pitting is a disorder occurring mostly during postharvest storage at non-chilling temperatures in different varieties of citrus fruit and consists in collapse of flavedo and albedo tissues that may affect oil glands. It has been demonstrated that during postharvest, sharp variations in water potential of cells from flavedo and albedo are sufficient to provoke fractures in cell walls from external albedo resulting in tissue collapse. However, morphology and composition of cells and cell walls in flavedo and albedo varies during fruit maturation and this may affect water flow through the different fruit peel layers and susceptibility of fruit to develop peel pitting. In this paper, we have studied the influence of the stage of maturation in the susceptibility of Navelina orange to develop peel pitting. Except in mature-green fruit, peel pitting increased with maturation after transferring fruit from 45% to 95% relative humidity and was also more severe as more dehydrated was the tissue before transference. Also, differences in water potential of fruit maintained at 45 or 95% relative humidity increased as fruit matured, suggesting that tissue reduces the ability of water adjustment during maturation. In this sense, only mature-green fruit flavedo was able to recover water potential when transferred from 45 to 95% relative humidity. Ethylene production upon transfer from low to high relative humidity increased only in mature tissue and was rapid and transient, and before initial symptoms of peel pitting. Flavedo and albedo water potential (ψw) was substantially reduced during fruit maturation. As lower was the ψw of freshly harvested fruit, minor variations were observed by changes in the storage relative humidity and higher the induced damage. Therefore, the increasing susceptibility of Navelina fruits to develop peel pitting with fruit maturation may be related to a reduced ability to regulate peel evapotranspiration and osmotic adjustment during postharvest

  2. Immune Modulation by Group B Streptococcus Influences Host Susceptibility to Urinary Tract Infection by Uropathogenic Escherichia coli

    Science.gov (United States)

    Kline, Kimberly A.; Schwartz, Drew J.; Gilbert, Nicole M.

    2012-01-01

    Urinary tract infection (UTI) is most often caused by uropathogenic Escherichia coli (UPEC). UPEC inoculation into the female urinary tract (UT) can occur through physical activities that expose the UT to an inherently polymicrobial periurethral, vaginal, or gastrointestinal flora. We report that a common urogenital inhabitant and opportunistic pathogen, group B Streptococcus (GBS), when present at the time of UPEC exposure, undergoes rapid UPEC-dependent exclusion from the murine urinary tract, yet it influences acute UPEC-host interactions and alters host susceptibility to persistent outcomes of bladder and kidney infection. GBS presence results in increased UPEC titers in the bladder lumen during acute infection and reduced inflammatory responses of murine macrophages to live UPEC or purified lipopolysaccharide (LPS), phenotypes that require GBS mimicry of host sialic acid residues. Taken together, these studies suggest that despite low titers, the presence of GBS at the time of polymicrobial UT exposure may be an overlooked risk factor for chronic pyelonephritis and recurrent UTI in susceptible groups, even if it is outcompeted and thus absent by the time of diagnosis. PMID:22988014

  3. Multiple sclerosis susceptibility-associated SNPs do not influence disease severity measures in a cohort of Australian MS patients.

    Directory of Open Access Journals (Sweden)

    Cathy J Jensen

    Full Text Available Recent association studies in multiple sclerosis (MS have identified and replicated several single nucleotide polymorphism (SNP susceptibility loci including CLEC16A, IL2RA, IL7R, RPL5, CD58, CD40 and chromosome 12q13-14 in addition to the well established allele HLA-DR15. There is potential that these genetic susceptibility factors could also modulate MS disease severity, as demonstrated previously for the MS risk allele HLA-DR15. We investigated this hypothesis in a cohort of 1006 well characterised MS patients from South-Eastern Australia. We tested the MS-associated SNPs for association with five measures of disease severity incorporating disability, age of onset, cognition and brain atrophy. We observed trends towards association between the RPL5 risk SNP and time between first demyelinating event and relapse, and between the CD40 risk SNP and symbol digit test score. No associations were significant after correction for multiple testing. We found no evidence for the hypothesis that these new MS disease risk-associated SNPs influence disease severity.

  4. Personality differences in the susceptibility to stress-eating: The influence of emotional control and impulsivity.

    Science.gov (United States)

    Van Blyderveen, Sherry; Lafrance, Adele; Emond, Michael; Kosmerly, Stacey; O'Connor, Megan; Chang, Felicia

    2016-12-01

    Stress has been associated with deviations from typical eating patterns, with respect to both food choice and overall caloric intake. Both increases and decreases in dietary intake have been previously noted in response to stress. The purpose of the present study was to determine whether the affect regulation strategies of emotional control and impulsivity predict susceptibility to eating in response to stress. Specifically, it was anticipated that emotional suppression would predict decreases in caloric intake, whereas impulsivity would predict increases in caloric intake, in response to a stressor. Participants were randomly assigned to view either a video designed to elicit stress or a control video. Food was provided during the video and the amount and type of food consumed was measured. Participants' nutritional intake was greater in the stress condition than in the control condition. One aspect of affect regulation, impulsivity, moderated this relationship, with a tendency for greater impulsivity to be associated with greater caloric intake in the stress condition. The degree of negative affect that participants experienced in the stress condition predicted food choice and overall caloric intake. Both emotional control and impulsivity moderated the relationship between negative affect and both food choice and caloric intake in the stress condition. The present study highlights the importance of considering the personality attributes of both impulsivity and emotional suppression in understanding stress eating. Copyright © 2016. Published by Elsevier Ltd.

  5. Candida vaginitis during contraceptive use: the influence of methods, antifungal susceptibility and virulence patterns.

    Science.gov (United States)

    Güzel, A B; Küçükgöz-Güleç, U; Aydin, M; Gümral, R; Kalkanci, A; Ilkit, M

    2013-11-01

    No consensus exists about whether contraceptives cause an increased risk of vaginitis, including vulvovaginal candidosis (VVC). We investigated 495 women (252 who used contraceptives; 243 who did not) for the presence of VVC. Antifungal susceptibility testing was performed for five antifungal agents and for boric acid, and three virulence factors were also examined. We recovered 129 (26.1%) monofungal populations from vaginal samples of women with acute VVC (AVVC, n = 18), symptomatic recurrent VVC (RVVC, n = 22) and asymptomatic RVVC (n = 28), as well as of other contraceptive users who carried Candida in their vaginas (n = 61). It is important to note that the women who had VVC used the same contraceptive methods (p > 0.05). Candida albicans was the most common species isolated (45%), followed by C. glabrata (40.3%). Most of the vaginal yeast isolates exhibited low minimum inhibitory concentration levels for the five antifungals tested. However, this was not the case for boric acid. In addition, the yeast fungi that was derived from the AVVC and RVVC patients showed higher amounts of haemolytic activity than the yeast fungi found among the controls (p contraception does not predispose women to VVC (p > 0.05). Also, both host- and organism-related factors were required to achieve optimal clinical treatment for VVC.

  6. Susceptibility to bystander DNA damage is influenced by replication and transcriptional activity

    Science.gov (United States)

    Dickey, Jennifer S.; Baird, Brandon J.; Redon, Christophe E.; Avdoshina, Valeriya; Palchik, Guillermo; Wu, Junfang; Kondratyev, Alexei; Bonner, William M.; Martin, Olga A.

    2012-01-01

    Direct cellular DNA damage may lead to genome destabilization in unexposed, bystander, cells sharing the same milieu with directly damaged cells by means of the bystander effect. One proposed mechanism involves double strand break (DSB) formation in S phase cells at sites of single strand lesions in the DNA of replication complexes, which has a more open structure compared with neighboring DNA. The DNA in transcription complexes also has a more open structure, and hence may be susceptible to bystander DSB formation from single strand lesions. To examine whether transcription predisposes non-replicating cells to bystander effect-induced DNA DSBs, we examined two types of primary cells that exhibit high levels of transcription in the absence of replication, rat neurons and human lymphocytes. We found that non-replicating bystander cells with high transcription rates exhibited substantial levels of DNA DSBs, as monitored by γ-H2AX foci formation. Additionally, as reported in proliferating cells, TGF-β and NO were found to mimic bystander effects in cell populations lacking DNA synthesis. These results indicate that cell vulnerability to bystander DSB damage may result from transcription as well as replication. The findings offer insights into which tissues may be vulnerable to bystander genomic destabilization in vivo. PMID:22941641

  7. Innate Susceptibility to Norovirus Infections Influenced by FUT2 Genotype in a United States Pediatric Population

    Science.gov (United States)

    Currier, Rebecca L.; Payne, Daniel C.; Staat, Mary A.; Selvarangan, Rangaraj; Shirley, S. Hannah; Halasa, Natasha; Boom, Julie A.; Englund, Janet A.; Szilagyi, Peter G.; Harrison, Christopher J.; Klein, Eileen J.; Weinberg, Geoffrey A.; Wikswo, Mary E.; Parashar, Umesh; Vinjé, Jan; Morrow, Ardythe L.

    2015-01-01

    Background. Norovirus is a leading cause of acute gastroenteritis (AGE). Noroviruses bind to gut histo-blood group antigens (HBGAs), but only 70%–80% of individuals have a functional copy of the FUT2 (“secretor”) gene required for gut HBGA expression; these individuals are known as “secretors.” Susceptibility to some noroviruses depends on FUT2 secretor status, but the population impact of this association is not established. Methods. From December 2011 to November 2012, active AGE surveillance was performed at 6 geographically diverse pediatric sites in the United States. Case patients aged norovirus by real-time reverse transcription polymerase chain reaction. Norovirus genotype was then determined by sequencing. Results. Norovirus was detected in 302 of 1465 (21%) AGE cases and 52 of 826 (6%) healthy controls. Norovirus AGE cases were 2.8-fold more likely than norovirus-negative controls to be secretors (P norovirus, GII.4. Control children of Meso-American ancestry were more likely than children of European or African ancestry to be secretors (96% vs 74%; P norovirus infection and varies by ancestry. GII.4 norovirus exclusively infected secretors. These findings are important to norovirus vaccine trials and design of agents that may block norovirus-HBGA binding. PMID:25744498

  8. Predictors of Susceptibility to Peer Influence regarding Substance Use in Adolescence

    Science.gov (United States)

    Allen, Joseph P.; Chango, Joanna; Szwedo, David; Schad, Megan; Marston, Emily

    2012-01-01

    The extent to which peer influences on substance use in adolescence systematically vary in strength based on qualities of the adolescent and his or her close friend was assessed in a study of 157 adolescents (age: M = 13.35, SD = 0.64), their close friends, and their parents assessed longitudinally with a combination of observational, analogue,…

  9. The influence of amylose-LPC complex formation on the susceptibility of wheat starch to amylase

    NARCIS (Netherlands)

    Ahmadi-Abhari, S.; Woortman, A.J.J.; Oudhuis, A.A.C.M.; Hamer, R.J.; Loos, K.

    2013-01-01

    This study was aimed to assess the role of lysophosphatidylcholine (LPC) in the development of slowly digestible starch (SDS). The influence of LPC, on the enzymatic degradation of diluted 9% wheat starch suspensions (w/w) was investigated, using an in vitro digestion method. Wheat starch

  10. The influence of amylose-LPC complex formation on the susceptibility of wheat starch to amylase

    NARCIS (Netherlands)

    Ahmadiabhari, Salomeh; Woortman, A. J. J.; Oudhuis, A. A. C. M.; Hamer, R. J.; Loos, K.

    2013-01-01

    This study was aimed to assess the role of lysophosphatidylcholine (LPC) in the development of slowly digestible starch (SOS). The influence of LPC, on the enzymatic degradation of diluted 9% wheat starch suspensions (w/w) was investigated, using an in vitro digestion method. Wheat starch

  11. Geologic and edaphic factors influencing susceptibility of forest soils to environmental change

    Science.gov (United States)

    Scott W. Bailey

    2000-01-01

    There is great diversity in the structure and function of the northern forest across the 20-state portion of the United States considered in this book. The interplay of many factors accounts for the mosaic of ecological regimes across the region. In particular, climate, physiography, geology, and soils influence dominance and distribution of vegetation communities...

  12. An Examination of the Influence of Self Efficacy, Locus of Control, and Perceptions of Parent Involvement on Academic Achievement of Urban High School Students

    Science.gov (United States)

    Myree, Claudia

    2011-01-01

    Current research indicates that there is an on-going concern for the graduation rate of African American students in urban settings. This particular study sought to investigate the impact of students' self-efficacy, locus of control, and parental involvement on academic achievement via a targeted sample of urban African American high school…

  13. Influence of low-molecular-weight glutenin subunit genes at Glu-A3 locus on wheat sodium dodecyl sulfate sedimentation volume and solvent retention capacity value.

    Science.gov (United States)

    Li, Zhixia; Si, Hongqi; Xia, Yunxiang; Ma, Chuanxi

    2015-08-15

    To understand the effect of low-molecular-weight (LMW) glutenin alleles at the Glu-A3 locus on sodium dodecyl sulfate (SDS) sedimentation volume and solvent retention capacity (SRC) values, 244 accessions of Chinese wheat (Triticum aestivum L.) mini core collections were investigated. In this study the significant differences in wholemeal flour SDS sedimentation volume and SRC values associated with specific glutenin alleles at the Glu-A3 locus were explained. Seven glutenin alleles at the Glu-A3 locus were confirmed by locus-specific polymerase chain reaction (PCR). SDS sedimentation volume and lactic acid SRC value were significantly affected by alleles Glu-A3b and Glu-A3g. Based on total average values, 28 varieties carrying Glu-A3b had significantly higher means of SDS sedimentation volume and lactic acid SRC value, whereas 19 varieties carrying Glu-A3g had significantly lower means. Alleles Glu-A3d and Glu-A3f significantly increased only SDS sedimentation volume and sucrose SRC value respectively. Correlation analysis showed that SDS sedimentation volume was uncorrelated with lactic acid SRC and sucrose SRC values. The Glu-A3 LMW glutenin subunit could predict 12.8% of the variance in SDS sedimentation volume, 4.7% in lactic acid SRC and 6.4% in sucrose SRC. © 2014 Society of Chemical Industry.

  14. Depression from childhood into late adolescence: Influence of gender, development, genetic susceptibility, and peer stress.

    Science.gov (United States)

    Hankin, Benjamin L; Young, Jami F; Abela, John R Z; Smolen, Andrew; Jenness, Jessica L; Gulley, Lauren D; Technow, Jessica R; Gottlieb, Andrea Barrocas; Cohen, Joseph R; Oppenheimer, Caroline W

    2015-11-01

    Depression is a debilitating mental illness with clear developmental patterns from childhood through late adolescence. Here, we present data from the Gene Environment Mood (GEM) study, which used an accelerated longitudinal cohort design with youth (N = 665) starting in 3rd, 6th, and 9th grades, and a caretaker, who were recruited from the general community, and were then assessed repeatedly through semistructured diagnostic interviews every 6 months over 3 years (7 waves of data) to establish and then predict trajectories of depression from age 8 to 18. First, we demonstrated that overall prevalence rates of depression over time, by age, gender, and pubertal status, in the GEM study closely match those trajectories previously obtained in past developmental epidemiological research. Second, we tested whether a genetic vulnerability-stress model involving 5-HTTLPR and chronic peer stress was moderated by developmental factors. Results showed that older aged adolescents with SS/SL genotype, who experienced higher peer chronic stress over 3 years, were the most likely to be diagnosed with a depressive episode over time. Girls experiencing greater peer chronic stress were the most likely to develop depression. This study used repeated assessments of diagnostic interviewing in a moderately large sample of youth over 3 years to show that depression rates increase in middle to late adolescence, or postpubertally, and that the gender difference in depression emerges earlier in adolescence (age 12.5), or postpubertally. Additionally, genetically susceptible older adolescents who experience chronic peer stress were the most likely to become depressed over time. (c) 2015 APA, all rights reserved).

  15. Health Psychological Constructs as Predictors of Doping Susceptibility in Adolescent Athletes

    Science.gov (United States)

    Blank, Cornelia; Schobersberger, Wolfgang; Leichtfried, Veronika; Duschek, Stefan

    2016-01-01

    Background Doping is a highly relevant problem in sport, even in adolescent athletes. Knowledge of the psychological factors that influence doping susceptibility in young elite athletes remains sparse. Objectives This study investigated the predictive potential of different health-psychological constructs and well-being on doping susceptibility. The main hypotheses to be tested were positive associations of fear of failure, external locus of control, and ego-oriented goal orientation as well as negative associations of confidence of success, task orientation, internal locus of control, and performance motivation with doping susceptibility. Low levels of well-being are furthermore expected to be associated with doping susceptibility. Methods Within this cross-sectional study, 1,265 Austrian junior athletes aged between 14 and 19 years responded to a paper-pencil questionnaire. Results Performance motivation was a negative, while depressive mood, self-esteem, fear of failure and ego-oriented goal orientation were positive predictors of doping susceptibility. In addition, participants who were offered performance enhancing substances in the past were particularly susceptible to doping. Conclusions The study corroborates the predictive value of classical psychological constructs in doping research, initially analyzed in view of adult athletes, also for adolescents’ doping susceptibility. PMID:28144408

  16. Health Psychological Constructs as Predictors of Doping Susceptibility in Adolescent Athletes.

    Science.gov (United States)

    Blank, Cornelia; Schobersberger, Wolfgang; Leichtfried, Veronika; Duschek, Stefan

    2016-12-01

    Doping is a highly relevant problem in sport, even in adolescent athletes. Knowledge of the psychological factors that influence doping susceptibility in young elite athletes remains sparse. This study investigated the predictive potential of different health-psychological constructs and well-being on doping susceptibility. The main hypotheses to be tested were positive associations of fear of failure, external locus of control, and ego-oriented goal orientation as well as negative associations of confidence of success, task orientation, internal locus of control, and performance motivation with doping susceptibility. Low levels of well-being are furthermore expected to be associated with doping susceptibility. Within this cross-sectional study, 1,265 Austrian junior athletes aged between 14 and 19 years responded to a paper-pencil questionnaire. Performance motivation was a negative, while depressive mood, self-esteem, fear of failure and ego-oriented goal orientation were positive predictors of doping susceptibility. In addition, participants who were offered performance enhancing substances in the past were particularly susceptible to doping. The study corroborates the predictive value of classical psychological constructs in doping research, initially analyzed in view of adult athletes, also for adolescents' doping susceptibility.

  17. Predictors of Susceptibility to Peer Influence Regarding Substance Use in Adolescence

    Science.gov (United States)

    Allen, Joseph P.; Chango, Joanna; Szwedo, David; Schad, Megan; Marston, Emily

    2012-01-01

    The extent to which peer influences on substance use in adolescence systematically vary in strength based on qualities of the adolescent and his or her close friend was assessed in a study of 157 adolescents (Age: M = 13.35, SD = 0.64), their close friends and their parents assessed longitudinally with a combination of observational, analogue, sociometric, and self-report measures from early to mid-adolescence. The degree to which adolescents changed their levels of substance use in accord with their peers' baseline levels of use was predicted by a range of theoretically-salient factors including: observed teen lack of autonomy and social support in prior interactions with mothers, low teen refusal skills, and the level of social acceptance of their close friend. Findings suggest the importance of both internal factors (e.g., autonomy and relatedness struggles) and external factors (e.g., social status of friends) in explaining why vulnerability to peer influence processes may be much greater for some adolescents than others. PMID:22188526

  18. Twins as a tool for evaluating the influence of genetic susceptibility in thyroid autoimmunity

    DEFF Research Database (Denmark)

    Brix, T H; Hegedüs, L

    2011-01-01

    the well known gender difference in the prevalence of autoimmune thyroid disease, the analyzes suggest that it is the same set of genes that operate in males and females. The lack of complete phenotypic concordance in monozygotic twin pairs indicates that also environmental and/or epigenetic factors...... are of importance. The impact of specific environmental and epigenetic exposures can be evaluated by investigating disease discordant twin pairs. Our studies show that skewed X chromosome inactivation is associated with clinically overt AITD but not with the presence of TPOAb in euthyroid individuals. It is now......By means of large twin cohorts, it has been possible to provide relatively valid and unbiased data regarding the influence of genetic and to some extent epigenetic factors in the aetiology of thyroid autoimmunity. The comparison of concordance rates between monozygotic and dizygotic twins provides...

  19. Genome-wide linkage scan in Dutch hereditary non-BRCA1/2 breast cancer families identifies 9q21-22 as a putative breast cancer susceptibility locus

    NARCIS (Netherlands)

    Oldenburg, Rogier A.; Kroeze-Jansema, Karin H. G.; Houwing-Duistermaat, Jeanine J.; Bayley, Jean-Pierre; Dambrot, Cheryl; van Asperen, Christi J.; van den Ouweland, Ans M. W.; Bakker, Bert; van Beers, Erik H.; Nederlof, Petra M.; Vasen, Hans; Hoogerbrugge, Nicoline; Cornelisse, Cees J.; Meijers-Heijboer, Hanne; Devilee, Peter

    2008-01-01

    Breast cancer accounts for over 20% of all female cancers. A positive family history remains one of the most important risk factors for the disease, with first-degree relatives of patients having a twofold elevated risk. Known breast cancer susceptibility genes such as BRCA1 and BRCA2 explain only

  20. Interaction between family history of alcoholism and Locus of Control in the opioid regulation of impulsive responding under the influence of alcohol.

    Science.gov (United States)

    Altamirano, Lee J; Fields, Howard L; D'Esposito, Mark; Boettiger, Charlotte A

    2011-11-01

    Naltrexone (NTX) is an opioid antagonist indicated for the treatment of alcoholism, which is not universally effective. Thus, identifying individual predictors of NTX's behavioral effects is critical to optimizing its therapeutic use. Moreover, given the high rate of relapse during treatment for alcoholism, understanding NTX's behavioral effects when combined with moderate ethanol intake is important. Our previous study of abstinent alcoholics and control subjects showed that a more internal Locus of Control score predicted increased impulsive choice on NTX (Mitchell et al., 2007, Neuropsychopharmacology 32:439-449). Here, we tested whether this predictive relationship remains in the context of moderate alcohol intake. In this study, we tested the effect of acute NTX (50 mg) on impulsive choice, motor inhibition, and attentional bias after ingestion of moderate ethanol (∼0.3 g/kg, n = 30 subjects). Subjects included those recruited from a pool of ∼1,200 UC Berkeley undergraduates on the basis of scores on the Barratt Impulsiveness Scale (BIS). Impulsive choice was positively correlated with breath alcohol concentration in placebo sessions. Locus of Control was again the sole predictor of NTX's effect on decision making among subjects with a family history of alcoholism. We also found a weak interaction between BIS scores and NTX's effect on impulsive choice. Our results reinforce the predictive relationship between Locus of Control and NTX's effect on decision making in those with a family history of alcoholism, suggesting a possible biological basis to this relationship. Copyright © 2011 by the Research Society on Alcoholism.

  1. Genetics of graft-versus-host disease, I. A locus on chromosome 1 influences development of acute graft-versus-host disease in a major histocompatibility complex mismatched murine model.

    Science.gov (United States)

    Allen, R D; Dobkins, J A; Harper, J M; Slayback, D L

    1999-02-01

    Graft-versus-host disease (GVHD) is the major complication occurring after bone marrow transplantation. The severity of GVHD varies widely, with this variation generally being attributed to variation in the degree of disparity between host and donor for minor histocompatibility antigens. However, it is also possible that other forms of polymorphism, such as polymorphisms in immune effector molecules, might play a significant role in determining GVHD severity. In order to investigate this hypothesis, we are studying the genetic factors that influence GVHD development in a murine model. We here report the first results of this analysis, which demonstrate that a locus on Chromosome 1 of the mouse, and possibly also a locus on Chromosome 4, exert considerable influence over the development of one aspect of acute GVHD - splenomegaly - in a parent-->F1 murine model. These results demonstrate that non-MHC genes can exert quite significant effects on the development of GVHD-associated pathology and that gene mapping can be used as a tool to identify these loci. Further analysis of such loci will allow identification of the mechanism whereby they influence GVHD and may lead in the future to improved selection of donors for human bone marrow transplantation.

  2. Influence of infection with Renibacterium salmoninarum on susceptibility of juvenile spring chinook salmon to gas bubble trauma

    Science.gov (United States)

    Weiland, L.K.; Mesa, M.G.; Maule, A.G.

    1999-01-01

    During experiments in our laboratory to assess the progression and severity of gas bubble trauma (GBT) in juvenile spring chinook salmon Oncorhynchus tshawytscha, we had the opportunity to assess the influence of Renibacterium salmoninarum (Rs), the causative agent of bacterial kidney disease, on the susceptibility of salmon to GBT. We exposed fish with an established infection of Rs to 120% total dissolved gas (TDG) for 96 h and monitored severity of GBT signs in the fins and gills, Rs infection level in kidneys by using an enzyme-linked immunosorbent assay (ELISA), and mortality. Mortality occurred rapidly after exposure to 120% TDG, with a LT20 (time necessary to kill 20% of the population) of about 37 h, which is at a minimum about 16% earlier than other bioassays we have conducted using fish that had no apparent signs of disease. Fish that died early (from 31 to 36 h and from 49 to 52 h) had significantly higher infection levels (mean ?? SE ELISA absorbance = 1.532 ?? 0.108) than fish that survived for 96h (mean ?? SE ELISA absorbance = 0.828 ?? 0.137). Fish that died early also had a significantly greater number of gill filaments occluded with bubbles than those that survived 96 h. Conversely, fish that survived for 96 h had a significantly higher median fin severity ranking than those that died early. Our results indicate that fish with moderate to high levels of Rs infection are more vulnerable to the effects of dissolved gas supersaturation (DGS) and die sooner than fish with lower levels of Rs infection. However, there is a substantial amount of individual variation in susceptibility to the apparent cumulative effects of DGS and Rs infection. Collectively, our findings have important implications to programs designed to monitor the prevalence and severity of GBT in juvenile salmonids in areas like the Columbia River basin and perhaps elsewhere.

  3. Commensal and probiotic bacteria influence intestinal barrier function and susceptibility to colitis in Nod1-/-; Nod2-/- mice.

    Science.gov (United States)

    Natividad, Jane M M; Petit, Valerie; Huang, Xianxi; de Palma, Giada; Jury, Jennifer; Sanz, Yolanda; Philpott, Dana; Garcia Rodenas, Clara L; McCoy, Kathy D; Verdu, Elena F

    2012-08-01

    The intestinal microbiota regulates key host functions. It is unknown whether modulation of the microbiota can affect a genetically determined host phenotype. Polymorphisms in the Nucleotide oligomerization domain (Nod)-like receptor family confer genetic risk for inflammatory bowel disease (IBD). We investigated whether the intestinal microbiota and the probiotic strain Bifidobacterium breve NCC2950 affect intestinal barrier function and responses to intestinal injury in Nod1(-/-); Nod2(-/-) mice. Specific pathogen-free (SPF) Nod1(-/-); Nod2(-/-) mice and mice gnotobiotically derived with altered Schaedler flora (ASF) biota were used. SPF Nod1(+/-); Nod2(+/-) littermates (generated by crossing SPF Nod1(-/-); Nod2(-/-) and germ-free C57BL/6 mice) and ASF Nod1(+/-); Nod2(+/-) mice were used as controls. SPF mice were gavaged daily with 10(9) -CFU B. breve for 14 days before colitis induction. Denaturing gradient gel electrophoresis (DGGE) and real-time polymerase chain reaction (PCR) were used to assess microbiota composition. Intestinal permeability was assessed by in vitro and in vivo techniques. Expressions of epithelial apical junction proteins, mucin, and antimicrobial proteins were assessed by quantitative reverse-transcription PCR (qRT-PCR) and immunofluorescence. Responses to intestinal injury were investigated using an acute experimental model of colitis. Under SPF conditions, Nod1(-/-); Nod2(-/-) mice had increased paracellular permeability, decreased E-cadherin, and lower colonic antimicrobial RegIII-γ expression compared to Nod1(+/-); Nod2(+/-) littermate controls. These changes were associated with increased susceptibility to colitis. ASF colonization or B. breve supplementation normalized RegIII-γ expression and decreased susceptibility to dextran sodium sulfate (DSS) colitis in Nod1(-/-); Nod2(-/-) mice. The intestinal microbiota influences colitis severity in Nod1(-/-); Nod2(-/-) mice. The results suggest that colonization strategies with defined

  4. Locus control regions

    National Research Council Canada - National Science Library

    Li, Qiliang; Peterson, Kenneth R; Fang, Xiangdong; Stamatoyannopoulos, George

    2002-01-01

    Locus control regions (LCRs) are operationally defined by their ability to enhance the expression of linked genes to physiological levels in a tissue-specific and copy number-dependent manner at ectopic chromatin sites...

  5. Duffy-Null–Associated Low Neutrophil Counts Influence HIV-1 Susceptibility in High-Risk South African Black Women

    Science.gov (United States)

    Ramsuran, Veron; Kulkarni, Hemant; He, Weijing; Mlisana, Koleka; Wright, Edwina J.; Werner, Lise; Castiblanco, John; Dhanda, Rahul; Le, Tuan; Dolan, Matthew J.; Guan, Weihua; Weiss, Robin A.; Clark, Robert A.; Abdool Karim, Salim S.; Ndung'u, Thumbi

    2011-01-01

    Background. The Duffy-null trait and ethnic netropenia are both highly prevalent in Africa. The influence of pre-seroconversion levels of peripheral blood cell counts (PBCs) on the risk of acquiring human immunodeficiency virus (HIV)–1 infection among Africans is unknown. Methods. The triangular relationship among pre-seroconversion PBC counts, host genotypes, and risk of HIV acquisition was determined in a prospective cohort of black South African high-risk female sex workers. Twenty-seven women had seroconversion during follow-up, and 115 remained HIV negative for 2 years, despite engaging in high-risk activity. Results. Pre-seroconversion neutrophil counts in women who subsequently had seroconversion were significantly lower, whereas platelet counts were higher, compared with those who remained HIV negative. Comprising 27% of the cohort, subjects with pre-seroconversion neutrophil counts of C) was significantly associated with neutrophil counts (P = 7.9 × 10−11). DARC −46C/C results in loss of DARC expression on erthyrocytes (Duffy-null) and resistance to Plasmodium vivax malaria, and in our cohort, only subjects with this genotype had pre-seroconversion neutrophil counts of <2500 cells/mm3. The risk of acquiring HIV infection was ∼3-fold greater in those with the trait of Duffy-null–associated low neutrophil counts, compared with all other study participants. Conclusions. Pre-seroconversion neutrophil and platelet counts influence risk of HIV infection. The trait of Duffy-null–associated low neutrophil counts influences HIV susceptibility. Because of the high prevalence of this trait among persons of African ancestry, it may contribute to the dynamics of the HIV epidemic in Africa. PMID:21507922

  6. Susceptibility of freshwater snails to the amphistome Calicophoron microbothrium and the influence of the species on susceptibility of Bulinus tropicus to Schistosoma haematobium and Schistosoma mattheei infections.

    Science.gov (United States)

    Chingwena, Givemore; Mukaratirwa, Samson; Kristensen, Thomas K; Chimberi, Moses

    2002-10-01

    The susceptibility of Bulinus tropicus, B. globosus, Biomphalana pfeifferi, Lymnaea natalensis, and Melanoides tuberculata to Calicophoron microbothrium was examined. Bulinus tropicus had the highest prevalence (65.0%), followed by B. pfeifferi (37.5%), B. globosus (6.8%), and M. tuberculata (5.9%). Lymnaea natalensis was refractory to infection. Bulinus tropicus snails infected with C. microbothrium alone or coinfected with either Schistosoma haematobium or S. mattheei 0, 7, 14, and 21 days after exposure to C. microbothrium produced C. microbothrium cercariae only.

  7. Influence of the beta-lactam resistance phenotype on the cefuroxime versus cefditoren susceptibility of Streptococcus pneumoniae and Haemophilus influenzae recovered from children with acute otitis media.

    Science.gov (United States)

    Fenoll, Asunción; Aguilar, Lorenzo; Robledo, Olga; Giménez, María-José; Tarragó, David; Granizo, Juan-José; Gimeno, Mercedes; Coronel, Pilar

    2007-08-01

    To study the influence of resistance phenotypes (based on sentinel antibiotics: penicillin and amoxicillin with/without clavulanate) on the cefuroxime versus cefditoren susceptibility of Streptococcus pneumoniae and Haemophilus influenzae recovered from children with acute otitis media. Middle ear isolates (193 S. pneumoniae and 114 H. influenzae) received in the Spanish Reference Laboratory (Instituto de Salud Carlos III) were tested. Antimicrobial susceptibility to penicillin, amoxicillin with/without clavulanate, cefuroxime and cefditoren was determined by agar dilution using Mueller-Hinton agar supplemented with 5% sheep blood for S. pneumoniae and Haemophilus Test Medium for H. influenzae. Strains were classified according to penicillin susceptibility (S. pneumoniae) or beta-lactamase production (H. influenzae). The decrease in penicillin susceptibility of S. pneumoniae (from the susceptible to the resistant category) decreased amoxicillin and cefuroxime susceptibility rates from 100% to 34% and 0%, respectively. All pneumococcal strains were inhibited by 0.5 mg/L cefditoren, including those from penicillin-resistant serotypes 14, 23F, 6B and 9V with higher amoxicillin versus penicillin MICs. Susceptibility rates of beta-lactamase-positive H. influenzae strains were 93.8% and 85.4% to amoxicillin/clavulanate and cefuroxime, respectively. Resistance to amoxicillin/clavulanate (MIC>or=8/4 mg/L) was 12.1% (8 out of 66) and 6.3% (3 out of 48) in beta-lactamase-negative and -positive strains, respectively. All H. influenzae strains were inhibited by Susceptibility to sentinel beta-lactams cannot predict activity of other members of the group. The addition of clavulanic acid to amoxicillin does not guarantee 100% coverage of H. influenzae, regardless of beta-lactamase production.

  8. Genetic variants near TIMP3 and high-density lipoprotein–associated loci influence susceptibility to age-related macular degeneration

    Science.gov (United States)

    Chen, Wei; Stambolian, Dwight; Edwards, Albert O.; Branham, Kari E.; Othman, Mohammad; Jakobsdottir, Johanna; Tosakulwong, Nirubol; Pericak-Vance, Margaret A.; Campochiaro, Peter A.; Klein, Michael L.; Tan, Perciliz L.; Conley, Yvette P.; Kanda, Atsuhiro; Kopplin, Laura; Li, Yanming; Augustaitis, Katherine J.; Karoukis, Athanasios J.; Scott, William K.; Agarwal, Anita; Kovach, Jaclyn L.; Schwartz, Stephen G.; Postel, Eric A.; Brooks, Matthew; Baratz, Keith H.; Brown, William L.; Brucker, Alexander J.; Orlin, Anton; Brown, Gary; Ho, Allen; Regillo, Carl; Donoso, Larry; Tian, Lifeng; Kaderli, Brian; Hadley, Dexter; Hagstrom, Stephanie A.; Peachey, Neal S.; Klein, Ronald; Klein, Barbara E. K.; Gotoh, Norimoto; Yamashiro, Kenji; Ferris, Frederick; Fagerness, Jesen A.; Reynolds, Robyn; Farrer, Lindsay A.; Kim, Ivana K.; Miller, Joan W.; Cortón, Marta; Carracedo, Angel; Sanchez-Salorio, Manuel; Pugh, Elizabeth W.; Doheny, Kimberly F.; Brion, Maria; DeAngelis, Margaret M.; Weeks, Daniel E.; Zack, Donald J.; Chew, Emily Y.; Heckenlively, John R.; Yoshimura, Nagahisa; Iyengar, Sudha K.; Francis, Peter J.; Katsanis, Nicholas; Seddon, Johanna M.; Haines, Jonathan L.; Gorin, Michael B.; Abecasis, Gonçalo R.; Swaroop, Anand; Johnson, Robert N.; Ai, Everett; McDonald, H. Richard; Stolarczuk, Margaret; Pavan, Peter Reed; Billiris, Karina K.; Iyer, Mohan; Menosky, Matthew M.; Pautler, Scott E.; Millard, Sharon M.; Hubbard, Baker; Aaberg, Thomas; DuBois, Lindy; Lyon, Alice; Anderson-Nelson, Susan; Jampol, Lee M.; Weinberg, David V.; Muñana, Annie; Rozenbajgier, Zuzanna; Orth, David; Cohen, Jack; MacCumber, Matthew; MacCumber, Matthew; Figliulo, Celeste; Porcz, Liz; Folk, James; Boldt, H. Culver; Russell, Stephen R.; Ivins, Rachel; Hinz, Connie J.; Barr, Charles C.; Bloom, Steve; Jaegers, Ken; Kritchman, Brian; Whittington, Greg; Heier, Jeffrey; Frederick, Albert R.; Morley, Michael G.; Topping, Trexler; Davis, Heather L.; Bressler, Susan B.; Bressler, Neil M.; Doll, Warren; Trese, Michael; Capone, Antonio; Garretson, Bruce R.; Hassan, Tarek S.; Ruby, Alan J.; Osentoski, Tammy; McCannel, Colin A.; Ruszczyk, Margaret J.; Grand, Gilbert; Blinder, Kevin; Holekamp, Nancy M.; Joseph, Daniel P.; Shah, Gaurav; Nobel, Ginny S.; Antoszyk, Andrew N.; Browning, David J.; Stallings, Alison H; Singerman, Lawrence J.; Miller, David; Novak, Michael; Pendergast, Scott; Zegarra, Hernando; Schura, Stephanie A.; Smith-Brewer, Sheila; Davidorf, Frederick H.; Chambers, Robert; Chorich, Louis; Salerno, Jill; Dreyer, Richard F.; Ma, Colin; Kopfer, Marcia R.; Klein, Michael L.; Wilson, David J.; Nolte, Susan K.; Grunwald, Juan E.; Brucker, Alexander J.; Dunaief, Josh; Fine, Stuart L.; Maguire, Albert M.; Stoltz, Robert A.; McRay, Monique N.; Fish, Gary Edd; Anand, Rajiv; Spencer, Rand; Arnwine, Jean; Chandra, Suresh R.; Altaweel, Michael; Blodi, Barbara; Gottlieb, Justin; Ip, Michael; Nork, T. Michael; Perry-Raymond, Jennie; Fine, Stuart L.; Maguire, Maureen G.; Brightwell-Arnold, Mary; Harkins, Sandra; Peskin, Ellen; Ying, Gui-Shuang; Kurinij, Natalie

    2010-01-01

    We executed a genome-wide association scan for age-related macular degeneration (AMD) in 2,157 cases and 1,150 controls. Our results validate AMD susceptibility loci near CFH (P < 10−75), ARMS2 (P < 10−59), C2/CFB (P < 10−20), C3 (P < 10−9), and CFI (P < 10−6). We compared our top findings with the Tufts/Massachusetts General Hospital genome-wide association study of advanced AMD (821 cases, 1,709 controls) and genotyped 30 promising markers in additional individuals (up to 7,749 cases and 4,625 controls). With these data, we identified a susceptibility locus near TIMP3 (overall P = 1.1 × 10−11), a metalloproteinase involved in degradation of the extracellular matrix and previously implicated in early-onset maculopathy. In addition, our data revealed strong association signals with alleles at two loci (LIPC, P = 1.3 × 10−7; CETP, P = 7.4 × 10−7) that were previously associated with high-density lipoprotein cholesterol (HDL-c) levels in blood. Consistent with the hypothesis that HDL metabolism is associated with AMD pathogenesis, we also observed association with AMD of HDL-c—associated alleles near LPL (P = 3.0 × 10−3) and ABCA1 (P = 5.6 × 10−4). Multilocus analysis including all susceptibility loci showed that 329 of 331 individuals (99%) with the highest-risk genotypes were cases, and 85% of these had advanced AMD. Our studies extend the catalog of AMD associated loci, help identify individuals at high risk of disease, and provide clues about underlying cellular pathways that should eventually lead to new therapies. PMID:20385819

  9. Obesity-susceptibility loci and their influence on adiposity-related traits in transition from adolescence to adulthood--the HUNT study.

    Science.gov (United States)

    Cuypers, Koenraad Frans; Loos, Ruth J F; Kvaløy, Kirsti; Kulle, Bettina; Romundstad, Pål; Holmen, Turid Lingaas

    2012-01-01

    Obesity-susceptibility loci have been related to adiposity traits in adults and may affect body fat estimates in adolescence. There are indications that different sets of obesity-susceptibility loci influence level of and change in obesity-related traits from adolescence to adulthood. To investigate whether previously reported obesity-susceptible loci in adults influence adiposity traits in adolescence and change in BMI and waist circumference (WC) from adolescence into young adulthood. We also examined whether physical activity modifies the effects of these genetic loci on adiposity-related traits. Nine obesity-susceptibility variants were genotyped in 1 643 adolescents (13-19 years old) from the HUNT study, Norway, who were followed-up into young adulthood. Lifestyle was assessed using questionnaires and anthropometric measurements were taken. The effects of genetic variants individually and combined in a genetic predisposition score (GPS) on obesity-related traits were studied cross-sectionally and longitudinally. A modifying effect of physical activity was tested. The GPS was significantly associated to BMI (B: 0.046 SD/allele [0.020, 0.073], p = 0.001) in adolescence and in young adulthood (B: 0.041 SD/allele [0.015, 0.067], p = 0.002) as it was to waist circumference (WC). The GPS was not associated to change in BMI (p = 0.762) or WC (p = 0.726). We found no significant interaction effect between the GPS and physical activity. Our observations suggest that obesity-susceptibility loci established in adults affect BMI and WC already in adolescence. However, an association with change in adiposity-related traits from adolescence to adulthood could not be verified for these loci. Neither could an attenuating effect of physical activity on the association between the obesity-susceptibility genes and body fat estimates be revealed.

  10. Obesity-Susceptibility Loci and Their Influence on Adiposity-Related Traits in Transition from Adolescence to Adulthood - The HUNT Study

    Science.gov (United States)

    Cuypers, Koenraad Frans; Loos, Ruth J. F.; Kvaløy, Kirsti; Kulle, Bettina; Romundstad, Pål; Holmen, Turid Lingaas

    2012-01-01

    Introduction Obesity-susceptibility loci have been related to adiposity traits in adults and may affect body fat estimates in adolescence. There are indications that different sets of obesity-susceptibility loci influence level of and change in obesity-related traits from adolescence to adulthood. Objectives To investigate whether previously reported obesity-susceptible loci in adults influence adiposity traits in adolescence and change in BMI and waist circumference (WC) from adolescence into young adulthood. We also examined whether physical activity modifies the effects of these genetic loci on adiposity-related traits. Methods Nine obesity-susceptibility variants were genotyped in 1 643 adolescents (13–19 years old) from the HUNT study, Norway, who were followed-up into young adulthood. Lifestyle was assessed using questionnaires and anthropometric measurements were taken. The effects of genetic variants individually and combined in a genetic predisposition score (GPS) on obesity-related traits were studied cross-sectionally and longitudinally. A modifying effect of physical activity was tested. Results The GPS was significantly associated to BMI (B: 0.046 SD/allele [0.020, 0.073], p = 0.001) in adolescence and in young adulthood (B: 0.041 SD/allele [0.015, 0.067], p = 0.002) as it was to waist circumference (WC). The GPS was not associated to change in BMI (p = 0.762) or WC (p = 0.726). We found no significant interaction effect between the GPS and physical activity. Conclusions Our observations suggest that obesity-susceptibility loci established in adults affect BMI and WC already in adolescence. However, an association with change in adiposity-related traits from adolescence to adulthood could not be verified for these loci. Neither could an attenuating effect of physical activity on the association between the obesity-susceptibility genes and body fat estimates be revealed. PMID:23094032

  11. Locus of control in children of divorce.

    Science.gov (United States)

    Kalter, N; Alpern, D; Spence, R; Plunkett, J W

    1984-08-01

    Scores on the Nowicki-Strickland Locus of Control Scale for Children (N-SLOCSC) were compared for third and fifth grade boys and girls from intact versus maritally disrupted family backgrounds. Significant main effects for each independent variable revealed that fifth graders more than third, boys more than girls, and the marital disruption more than the intact group, exhibited higher internality in their locus of control scores. These findings strongly suggest that experiencing a parental divorce in childhood has a significant influence on generalized perceptions of personal control and effectance, perceptions which may ultimately mediate both short- and long-term outcomes in children's post-divorce adjustment.

  12. Association between the European GWAS-identified susceptibility locus at chromosome 4p16 and the risk of atrial septal defect: a case-control study in Southwest China and a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Li Zhao

    Full Text Available Atrial septal defect (ASD is the third most frequent type of congenital heart anomaly, featuring shunting of blood between the two atria. Gene-environment interaction remains to be an acknowledged cause for ASD occurrence. A recent European genome-wide association study (GWAS of congenital heart disease (CHD identified 3 susceptibility SNPs at chromosome 4p16 associated with ASD: rs870142, rs16835979 and rs6824295. A Chinese-GWAS of CHD conducted in the corresponding period did not reveal the 3 susceptibility SNPs, but reported 2 different risk SNPs: rs2474937 and rs1531070. Therefore, we aimed to investigate the associations between the 3 European GWAS-identified susceptibility SNPs and ASD risk in the Han population in southwest China. Additionally, to increase the robustness of our current analysis, we conducted a meta-analysis combining published studies and our current case-control study. We performed association, linkage disequilibrium, and haplotype analysis among the 3 SNPs in 190 ASD cases and 225 age-, sex-, and ethnicity-matched healthy controls. Genotype and allele frequencies among the 3 SNPs showed statistically significant differences between the cases and controls. Our study found that individuals carrying the allele T of rs870142, the allele A of rs16835979, and the allele T of rs6824295 had a respective 50.1% (odds ratio (OR = 1.501, 95% confidence interval (CI = 1.122-2.009, PFDR-BH = 0.018, 48.5% (OR = 1.485, 95%CI = 1.109-1.987, PFDR-BH = 0.012, and 38.6% (OR = 1.386, 95%CI = 1.042-1.844, PFDR-BH = 0.025 increased risk to develop ASD than wild-type allele carriers in our study cohort. In the haplotype analysis, we identified a disease-risk haplotype (TAT (OR = 1.540, 95%CI = 1.030-2.380, PFDR-BH = 0.016. Our meta-analysis also showed that the investigated SNP was associated with ASD risk (combined OR (95%CI = 1.35 (1.24-1.46, P < 0.00001. Our study provides compelling evidence to motivate better understanding of the etiology

  13. Human genetic susceptibility and infection with Leishmania peruviana

    Energy Technology Data Exchange (ETDEWEB)

    Shaw, M.A.; Davis, C.R.; Collins, A. [and others

    1995-11-01

    Racial differences, familial clustering, and murine studies are suggestive of host genetic control of Leishmania infections. Complex segregation analysis has been carried out by use of the programs POINTER and COMDS and data from a total population survey, comprising 636 nuclear families, from an L. perurviana endemic area. The data support genetic components controlling susceptibility to clinical leishmaniasis, influencing severity of disease and resistance to disease among healthy individuals. A multifactorial model is favored over a sporadic model. Two-locus models provided the best fit to the data, the optimal model being a recessive gene (frequency .57) plus a modifier locus. Individuals infected at an early age and with recurrent lesions are genetically more susceptible than those infected with a single episode of disease at a later age. Among people with no lesions, those with a positive skin-test response are genetically less susceptible than those with a negative response. The possibility of the involvement of more than one gene together with environmental effects has implications for the design of future linkage studies. 31 refs., 7 tabs.

  14. How do species, population and active ingredient influence insecticide susceptibility in Culicoides biting midges (Diptera: Ceratopogonidae) of veterinary importance?

    National Research Council Canada - National Science Library

    Venail, Roger; Lhoir, Jonathan; Fall, Moussa; del Río, Ricardo; Talavera, Sandra; Labuschagne, Karien; Miranda, Miguel; Pagès, Nonito; Venter, Gert; Rakotoarivony, Ignace; Allène, Xavier; Scheid, Bethsabée; Gardès, Laëtitia; Gimonneau, Geoffrey; Lancelot, Renaud; Garros, Claire; Cêtre-Sossah, Catherine; Balenghien, Thomas; Carpenter, Simon; Baldet, Thierry

    2015-01-01

    .... The objective of the present study is to determine baseline susceptibility of multiple Culicoides vector species and populations in Europe and Africa to the most commonly used insecticide active ingredients...

  15. The CCL3L1-CCR5 genotype influences the development of AIDS, but not HIV susceptibility or the response to HAART

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharya, Tanmoy [Los Alamos National Laboratory; Stanton, Jennifer [NORTHWESTERN UNIV; Kim, Eun - Young [NORTHWESTERN UNIV; Kunstman, Kevin [NORTHWESTERN UNIV; Phair, John [NORTHWESTERN UNIV; Jacobson, Lisa P [JOHNS HOPKINS UNIV; Wolinsky, Steven M [NORTHWESTERN UNIV

    2008-01-01

    A selective advantage against infectious diseases such as HIV/AIDS is associated with differences in the genes relevant to immunity and virus replication. The CC chemokine receptor 5 (CCR5), the principal coreceptor for HIV, and its chemokine ligands, including CCL3L1, influences the CD4+ target cells susceptibility to infection. The CCL3L1 gene is in a region of segmental duplication on the q-arm of human chromosome 17. Increased numbers of CCL3L1 gene copies that affect the gene expression phenotype might have substantial protective effects. Here we show that the population-specific CCL3L1 gene copy number and the CCR5 {Delta}32 protein-inactivating deletion that categorizes the CCL3L1-CCR5 genotype do not influence HIV/AIDS susceptibility or the robustness of immune recovery after the initiation of highly active antiretroviral therapy (HAART).

  16. Antigen-specific influence of GM/KM allotypes on IgG isotypes and association of GM allotypes with susceptibility to Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Giha, Hayder A; Nasr, Amre; Iriemenam, Nnaemeka C

    2009-01-01

    malaria-free period. The GM/KM allotypes of the donors were determined. RESULTS: The GM 1,17 5,13,14,6 phenotype was associated with a higher incidence of malaria compared with the non-1,17 5,13,14,6 phenotypes (P = 0.037). Paradoxically, the carriers of the GM 1,17 5,13,14,6 phenotype had significantly......-dependent. DISCUSSION: The results show that GM but not KM allotypes appeared to influence host susceptibility to uncomplicated malaria as well as the antibody profile of the donors, and the carriers of the GM 1,17 5,13,14,6 phenotype were the most susceptible CONCLUSIONS: The GM allotypes have significant influence......BACKGROUND: Plasmodium falciparum malaria is a complex disease in which genetic and environmental factors influence susceptibility. IgG isotypes are in part genetically controlled, and GM/KM allotypes are believed to be involved in this control. METHODS: In this study, 216 individuals from...

  17. Pro-Tobacco Influences and Susceptibility to Smoking Cigarettes Among Middle and High School Students—United States, 2011

    Science.gov (United States)

    Dube, Shanta R.; Arrazola, René A.; Lee, Joann; Engstrom, Martha; Malarcher, Ann

    2015-01-01

    Purpose Smoking is a leading cause of cancer, and most smokers begin during adolescence. We examined the proportion of adolescents exposed to pro-tobacco advertising and assessed the association between this exposure and susceptibility to smoking. Methods Data from the 2011 National Youth Tobacco Survey were used to calculate the proportion of susceptible middle school (MS) and high school (HS) students exposed to pro-tobacco advertisements through stores, magazines, and the Internet. Following previous work, susceptibility to smoking cigarettes was defined as “never smoked but open to trying cigarettes.” Results In 2011, 81.5% of MS students and 86.9% of HS students were exposed to tobacco advertisements in stores; 48.2% of MS students and 54.0% of HS students were exposed to such advertising in magazines. Exposure to tobacco advertisements on the Internet was similar for MS (40.8%) and HS students (40.2%). Of those surveyed, 22.5% of MS students and 24.2% of HS students were susceptible to trying cigarettes. Exposure to magazine advertising declined from 71.8% in 2000 to 46.1% in 2009 among susceptible MS students; however, exposure increased to 55.4% in 2011. Tobacco advertising seen through the Internet among susceptible HS students increased from 25.9% in 2000 to 44.7% in 2011. Conclusions Adolescents continue to be exposed to pro-tobacco advertisements. Adolescents susceptible to smoking are more likely to report exposure to pro-tobacco advertisements. In addition to continued monitoring, more effective interventions to eliminate youth exposure to pro-tobacco marketing are needed. PMID:23601611

  18. Influence of antioxidant compounds, total sugars and genetic background on the chilling injury susceptibility of a non-melting peach (Prunus persica (L.) Batsch) progeny.

    Science.gov (United States)

    Abidi, Walid; Cantín, Celia M; Jiménez, Sergio; Giménez, Rosa; Moreno, María Ángeles; Gogorcena, Yolanda

    2015-01-01

    To identify genotypes with good organoleptic properties, antioxidant-rich content and low susceptibility to chilling injury (CI), fruits from 130 peach cultivars were studied over three consecutive years. Pomological traits, l-ascorbic acid, flavonoids, total phenolics, relative antioxidant capacity (RAC) and sugars were determined. Major symptoms of CI developed at 5 °C, such as leatheriness, flesh browning, bleeding and loss of flavor, were evaluated. The population exhibited wide phenotypic variation in agronomic and biochemical traits. Six genotypes with high total phenolics, RAC, flavonoids and total sugars were selected. The progeny also showed variability for all evaluated CI symptoms, and 16 genotypes showed considerably lower susceptibility to CI. After 2 weeks of cold storage, leatheriness and bleeding were the main CI symptoms observed, whereas flesh browning was predominant after 4 weeks. It was possible to find varieties with high phenolic concentration and relatively low or intermediate CI susceptibility (22, 33, 68, 80, 81, 96 and 120). However, the correlations observed between CI and phenolic contents highlight their potential influence on susceptibility to internal browning. This relationship should be considered in the current breeding programs to select cultivars with high bioactive compound contents, health-enhancing properties and good postharvest performance. © 2014 Society of Chemical Industry.

  19. Susceptibility of Snails to Infection with Schistosomes is influenced by Temperature and Expression of Heat Shock Proteins

    Science.gov (United States)

    Knight, Matty; Elhelu, O; Smith, M; Haugen, B; Miller, A; Raghavan, N; Wellman, C; Cousin, C; Dixon, F; Mann, V; Rinaldi, G; Ittiprasert, W; Brindley, PJ

    2015-01-01

    The freshwater snail, Biomphalaria glabrata is the obligate intermediate host for the transmission of the parasitic trematode, Schistosoma mansoni the causative agent of the chronic debilitating neglected tropical disease, schistosomiasis. We showed previously that in juvenile snails, early and significant induction of stress manifested by the expression of stress proteins, Hsp 70, Hsp 90 and reverse transcriptase (RT) of the non- LTR retrotransposon, nimbus, is a characteristic feature of juvenile susceptible NMRI but not resistant BS-90 snails. These latter, however, could be rendered susceptible after mild heat shock at 32°C, revealing that resistance in the BS-90 resistant snail to schistosomes is a temperature dependent trait. Here we tested the hypothesis that maintenance of BS-90 resistant snails at the permissive temperature for several generations affects the resistance phenotype displayed at the non-permissive temperature of 25°C. The progeny of BS-90 snails bred and maintained through several generations (F1 to F4) at 32°C were susceptible to the schistosome infection when returned to room temperature, shedding cercariae at four weeks post-infection. Moreover, the study of expression levels of the heat shock protein (Hsp) 70 protein by ELISA and western blot analysis, showed that this protein is also differentially expressed between susceptible and resistant snails, with susceptible snails expressing more protein than their resistant counterparts after early exposure to wild-type but not to radiation-attenuated miracidia. These data suggested that in the face of global warming, the ability to sustain a reduction in schistosomiasis by using refractory snails as a strategy to block transmission of the disease might prove challenging since non-lethal elevation in temperature, affects snail susceptibility to S. mansoni. PMID:26504668

  20. Influence of electron beam welding parameters and metallurgical factors on intergranular liquation cracking susceptibility of cast alloy 718

    Science.gov (United States)

    Woo, Insu; Kang, Chungyun; Nishimoto, Kazutoshi

    2001-07-01

    The factors affecting intergranular liquation cracking susceptibility in electron beam welds were investigated for cast alloy 718. The materials used were as-received plates and heat-treated plates with three different levels of grain size. Liquation cracking susceptibility in HAZ was evaluated by a bead-on-plate test and a restraint/relaxation U-type hot cracking test. The penetrated shapes in the welds were classified into wine cup-like Type W and nail head-like Type N. For a given beam current, Type w and Type N were observed at the lower and higher welding speeds, respectively. Welding defects, i.e., underfills and microcracks were seen in the electron beam welds. Compared with Type W, the liquation cracking was more sensitive for the Type N bead cross sectional shape. Furthermore, it easily occurred at grain boundaries in Region II, i.e., very near the nail head necked part. According to the restraint/relaxation U-type hot cracking test, the liquation cracking susceptibility decreased with decreasing grain size or with homogenization heat treatment. These results suggested that the liquation cracking susceptibility in cast alloy 718 electron beam welds could be improved by using the Type W bead cross sectional shape, a decreasing the grain size and using appropriate heat treatment before welding.

  1. Genetic polymorphism of interleukin-6 influences susceptibility to HBV-related hepatocellular carcinoma in a male Chinese Han population.

    Science.gov (United States)

    Tang, Shengli; Yuan, Yufeng; He, Yueming; Pan, Dingyu; Zhang, Yongxi; Liu, Yuanyuan; Liu, Quanyan; Zhang, Zhonglin; Liu, Zhisu

    2014-04-01

    As a multifunctional cytokine, interleukin-6 (IL-6) plays a key role in chronic inflammation as well as tumor growth and progression of hepatitis B virus (HBV) infection. Recent studies have implicated that single nucleotide polymorphism (SNP) -572C>G (rs1800796) located within the promoter region of IL-6 gene was associated with susceptibility to several diseases. Here, a case-control study was undertaken to investigate the association between this polymorphism and HBV-related hepatocellular carcinoma (HCC) susceptibility in a Chinese Han population. A total of 900 patients with chronic HBV infection, including 505 HBV-related HCC patients and 395 HBV infected patients without HCC were enrolled, and rs1800796 polymorphism was genotyped by the TaqMan method and DNA sequencing technology. The results indicated no significant association between rs1800796 polymorphism and the risk of HBV-related HCC in all subjects; however, a significant difference was identified in male subjects. Under the dominant model, male subjects with the G allele (CG/GG) have higher susceptibility to HBV-related HCC than those with CC genotype after adjusting confounding factors (P=0.012, odds ratio [OR] 1.68, 95% confidence interval [95% CI] 1.15-2.42). Our results suggested that rs1800796 polymorphism of IL-6 gene was associated with susceptibility to HBV-related HCC in a male Chinese Han population. Copyright © 2014 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  2. Expression analyses of the genes harbored by the type 2 diabetes and pediatric BMI associated locus on 10q23

    Directory of Open Access Journals (Sweden)

    Zhao Jianhua

    2012-09-01

    Full Text Available Abstract Background There is evidence that one of the key type 2 diabetes (T2D loci identified by GWAS exerts its influence early on in life through its impact on pediatric BMI. This locus on 10q23 harbors three genes, encoding hematopoietically expressed homeobox (HHEX, insulin-degrading enzyme (IDE and kinesin family member 11 (KIF11, respectively. Methods We analyzed the impact of adipogeneis on the mRNA and protein expression levels of these genes in the human adipocyte Simpson-Golabi-Behmel syndrome (SGBS cell line in order to investigate which could be the culprit gene(s in this region of linkage disequilibrium. Results Following activation of differentiation with a PPARγ ligand, we observed ~20% decrease in IDE, ~40% decrease in HHEX and in excess of 80% decrease in KIF11 mRNA levels when comparing the adipocyte and pre-adipocyte states. We also observed decreases in KIF11 and IDE protein levels, but conversely we observed a dramatic increase in HHEX protein levels. Subsequent time course experiments revealed some marked changes in expression as early as three hours after activation of differentiation. Conclusion Our data suggest that the expression of all three genes at this locus are impacted during SGBS adipogenesis and provides insights in to the possible mechanisms of how the genes at this 10q23 locus could influence both adipocyte differentiation and susceptibility to T2D through insulin resistance.

  3. Identification of 19 new risk loci and potential regulatory mechanisms influencing susceptibility to testicular germ cell tumor.

    Science.gov (United States)

    Litchfield, Kevin; Levy, Max; Orlando, Giulia; Loveday, Chey; Law, Philip J; Migliorini, Gabriele; Holroyd, Amy; Broderick, Peter; Karlsson, Robert; Haugen, Trine B; Kristiansen, Wenche; Nsengimana, Jérémie; Fenwick, Kerry; Assiotis, Ioannis; Kote-Jarai, ZSofia; Dunning, Alison M; Muir, Kenneth; Peto, Julian; Eeles, Rosalind; Easton, Douglas F; Dudakia, Darshna; Orr, Nick; Pashayan, Nora; Bishop, D Timothy; Reid, Alison; Huddart, Robert A; Shipley, Janet; Grotmol, Tom; Wiklund, Fredrik; Houlston, Richard S; Turnbull, Clare

    2017-07-01

    Genome-wide association studies (GWAS) have transformed understanding of susceptibility to testicular germ cell tumors (TGCTs), but much of the heritability remains unexplained. Here we report a new GWAS, a meta-analysis with previous GWAS and a replication series, totaling 7,319 TGCT cases and 23,082 controls. We identify 19 new TGCT risk loci, roughly doubling the number of known TGCT risk loci to 44. By performing in situ Hi-C in TGCT cells, we provide evidence for a network of physical interactions among all 44 TGCT risk SNPs and candidate causal genes. Our findings implicate widespread disruption of developmental transcriptional regulators as a basis of TGCT susceptibility, consistent with failed primordial germ cell differentiation as an initiating step in oncogenesis. Defective microtubule assembly and dysregulation of KIT-MAPK signaling also feature as recurrently disrupted pathways. Our findings support a polygenic model of risk and provide insight into the biological basis of TGCT.

  4. The influence of interparticle correlations and self-assembly on the dynamic initial magnetic susceptibility spectra of ferrofluids

    Science.gov (United States)

    Ivanov, A. O.; Kantorovich, S. S.; Elfimova, E. A.; Zverev, V. S.; Sindt, J. O.; Camp, P. J.

    2017-06-01

    Using computer simulations and a mean-field theoretical approach, we study how the growth in dipolar interparticle correlations manifests itself in the frequency-dependent initial magnetic susceptibility of a ferrofluid. Our recently developed theory gives the correct single-particle Debye-theory results in the low-concentration, non-interacting regime; and it yields the exact leading-order contributions from interparticle correlations. The susceptibility spectra are analysed in terms of the low-frequency behaviours of the real and imaginary parts, and the position of the peak in the imaginary part. By comparing the theoretical predictions to the results from Brownian dynamics simulations, it is possible to identify the conditions where correlations are important, but where self-assembly has not developed. We also provide a qualitative explanation for the behaviour of spectra beyond the mean-field limit.

  5. Generators of synchronous activity of the locus coeruleus during development.

    Science.gov (United States)

    Christie, M J

    1997-02-01

    The locus coeruleus is thought to play an important role in the development of the central nervous system through a coordinated release of noradrenaline. The influence of the locus coeruleus on its diverse targets is strongly synchronized by the existence of electrical and chemical coupling between neurones, afferent supply of the nucleus from restricted sources and diffuse innervation of target areas. Extensive coupling between neonatal locus coeruleus neurones produces rhythmic synchronized electrical activity and distributes afferent synaptic activity throughout the entire nucleus. The strength of electrical coupling declines with age but appears to persist to a limited extent in the adult.

  6. Susceptibility to Amoxicillin-Clavulanate-Induced Liver Injury Is Influenced by Multiple HLA Class I and II Alleles

    OpenAIRE

    Lucena, M. Isabel; Molokhia, Mariam; Shen, Yufeng; Thomas J Urban; Aithad, Guruprasad P.; Raúl J Andrade; Day, Christopher P.; Ruiz-Cabello, Francisco; Donaldson, Peter T.; Stephens, Camilla; Pirmohamed, Munir; Romero-Gómez, Manuel; Navarro, José María; Fontana, Roberto J.; Miller, Michael

    2011-01-01

    Producción Científica Background & Aims Drug-induced liver injury (DILI), especially from antimicrobial agents, is an important cause of serious liver disease. Amoxicillin-clavulanate (AC) is a leading cause of idiosyncratic DILI, but little is understood about genetic susceptibility to this adverse reaction. Methods We performed a genome-wide association study using 822,927 single-nucleotide polymorphism (SNP) markers from 201 White European and US cases of AC-DILI and 532 popula...

  7. Review article "Remarks on factors influencing shear wave velocities and their role in evaluating susceptibilities to earthquake-triggered slope instability: case study for the Campania area (Italy"

    Directory of Open Access Journals (Sweden)

    V. Paoletti

    2012-07-01

    Full Text Available Shear wave velocities have a fundamental role in connection with the mitigation of seismic hazards, as their low values are the main causes of site amplification phenomena and can significantly influence the susceptibility of a territory to seismic-induced landslides. The shear wave velocity (Vs and modulus (G of each lithological unit are influenced by factors such as the degree of fracturing and faulting, the porosity, the clay amount and the precipitation, with the latter two influencing the unit water content. In this paper we discuss how these factors can affect the Vs values and report the results of different analyses that quantify the reduction in the rock Vs and shear modulus values connected to the presence of clay and water. We also show that significant results in assessing seismic-induced slope failure susceptibility for land planning targets could be achieved through a careful evaluation, based only on literature studies, of the geo-lithological and geo-seismic features of the study area.

  8. Locus of Control Orientation: Parents, Peers, and Place.

    Science.gov (United States)

    Ahlin, Eileen M; Lobo Antunes, Maria João

    2015-09-01

    An internal locus of control contributes to positive youth outcomes such as a general well-being and academic success, while also serving as a protective factor against exposure to community violence and reducing negative behaviors like violence. Despite these benefits, very little is known about antecedents of an internal locus of control orientation. Without an understanding of what factors contribute to the development of an internal locus of control, it is not clear how to best encourage its formation. This study uses data from the Project on Human Development in Chicago Neighborhoods to examine whether various mesosystem variables (family management strategies, peer interactions, neighborhood context, and individual-level characteristics) are associated with an internal locus of control orientation among 1,076 youth ages 9-19 living in 78 Chicago neighborhoods. Study participants were Hispanic (46 %), African American (34 %), and White (15 %), and 50 % were female. The findings suggest that, while most levels of the mesosystem influence locus of control orientation, family management strategies are more prominent determinants of an internal locus of control than peers, neighborhood context, or individual characteristics. Parental supervision over the time a youth spends at home and family socioeconomic status are consistent predictors of an internal locus of control, while harsh discipline is associated with an external locus of control. The discussion examines the import of various parenting techniques in shaping an internal locus of control and considers future avenues for research to further unpack how antecedents of locus of control can vary across youth.

  9. INFLUENCE OF SICKLE CELL GENE ON THE ALLELIC DIVERSITY AT THE MSP-1 LOCUS OF PLASMODIUM FALCIPARUM IN ADULT PATIENTS WITH SEVERE MALARIA

    OpenAIRE

    Dilip Kumar Patel; Ranjeet Singh Mashon; Prasanta Purohit; Siris Patel; Satyabrata Meher; Snehadhini Dehury; Chhatray Marndi; Kishalaya Das; Bipin Kishore Kullu; Padmalaya Das

    2015-01-01

    Although several studies have supported that sickle cell trait (HbAS) protects against falciparum malaria, the exact mechanism by which sickle gene confers protection is unclear. Further, there is no information on the influence of the sickle gene on the parasitic diversity of P. falciparum population in severe symptomatic malaria. This study was undertaken to assess the effect of the sickle gene on the parasite densities and diversities in hospitalized adult patients with severe falciparum m...

  10. HLA and celiac disease susceptibility: new genetic factors bring open questions about the HLA influence and gene-dosage effects.

    Directory of Open Access Journals (Sweden)

    Luz María Medrano

    Full Text Available Celiac disease (CD is a chronic inflammatory disorder triggered after gluten ingestion in genetically susceptible individuals. The major genetic determinants are HLA-DQA1*05 and HLA-DQB1*02, which encode the DQ2 heterodimer. These alleles are commonly inherited in cis with DRB1*03∶01, which is associated with numerous immune-related disorders, in some cases contributing with a different amount of risk depending on the haplotype context. We aimed at investigating those possible differences involving DRB1*03∶01-carrying haplotypes in CD susceptibility. A family (274 trios and a case-control sample (369 CD cases/461 controls were analyzed. DRB1*03∶01-carrying individuals were classified according to the haplotype present (ancestral haplotype (AH 8.1, AH 18.2 or non-conserved haplotype after genotyping of HLA-DRB1, -DQA1, -DQB1, -B8, TNF -308, TNF -376 and the TNFa and TNFb microsatellites. We observe that the AH 8.1 confers higher risk than the remaining DRB1*03∶01-carrying haplotypes, and this effect only involves individuals possessing a single copy of DQB1*02. CD risk for these individuals is similar to the one conferred by inherit DQA1*05 and DQB1*02 in trans. It seems that an additional CD susceptibility factor is present in the AH 8.1 but not in other DRB1*03∶01-carrying haplotypes. This factor could be shared with individuals possessing DQ2.5 trans, according to the similar risk observed in those two groups of individuals.

  11. Susceptibility to SLE in South Indian Tamils may be influenced by genetic selection pressure on TLR2 and TLR9 genes.

    Science.gov (United States)

    Devaraju, Panneer; Gulati, Reena; Antony, Paul T; Mithun, C B; Negi, Vir S

    2015-03-01

    Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder with complex etiology. Genetics plays an important role in lupus pathogenesis through its influence on clinical and autoantibody phenotype of the disease. Toll like receptors (TLR) recognize molecular patterns of pathogens and activate the innate immune system. Their ability to identify nucleic acids makes them suitable candidates for investigation of their role in lupus pathogenesis. Hence, this study was carried out to analyze the G to A and C to T transitions in TLR2 and TLR9 genes respectively and to test their association with lupus susceptibility, clinical and autoantibody phenotypes in South Indian Tamils. Three hundred SLE patients fulfilling ACR 2012 criteria for SLE and 460 age, sex similar, ethnicity matched controls were recruited as cases and controls. TLR2 (R753Q) and TLR9 (-1237C/T) polymorphisms were analyzed by real time PCR. The TLR2 gene remained monomorphic in patients and controls, the frequency of the homozygous wild type allele being 100% and 99.6% respectively. Hence, it did not confer susceptibility to SLE. The more frequent T allele of TLR9 gene conferred a significant risk to develop SLE (p=0.011, OR 1.69, 95% CI 1.1-2.6). Both the polymorphisms did not influence clinical or autoantibody phenotype of the disease. Prevailing endemic infections in the Indian subcontinent may have exerted a selection pressure resulting in TLR2 gene remaining monomorphic and the TLR9 adapting to a mutation for its increased expression. These may have an additive effect in the presence of other genetic and environmental risk factors to confer susceptibility to SLE in South Indian Tamils. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation

    DEFF Research Database (Denmark)

    Ghoussaini, Maya; Edwards, Stacey L; Michailidou, Kyriaki

    2014-01-01

    GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Proje...

  13. PENGARUH LOCUS OF CONTROL INTERNAL, LOCUS OF CONTROL EKSTERNAL, MANAJEMEN WAKTU, DAN KREATIVITAS MENGAJAR TERHADAP MOTIVASI BERPRESTASI

    Directory of Open Access Journals (Sweden)

    Dita Alfitami

    2017-10-01

    Full Text Available The aims of this research were to know the influence of the internal locus of control, external locus of control, time management, and teaching creativity to achievement motivation (case study in introduction to Office Administration subject in class XI AP SMK N 1 Kendal lesson school year 2016/2017.The population in this study were all the tenth graders of the Office Administration study program at SMK Negeri 1 Kendal with the total number of 71 students. While the sample taken used was saturated samples because the population were less than 100 respondents. Data collection method used in this research, which use questionnaire. The data analysis using multiple linear regression analysis method, classic assumption test analysis, percentage descriptive analysis, and hypothesis test analysis with the help of SPSS 21 programs. The finding shows the results of multiple linear regression analysis obtained equation Y = -20,466 + 0,431 X1 + 0,301 X2 + 0,357 X3 + 0,364 X4+ e. Test of significance of regression equation with F test, obtained count = 43,846 with significance0.000 and less than 0,05. The amount of influence simultaneously or together from locus of control, external locus of control, time management, and teaching creativity to achievement motivation was71%. While influence in partial or individually for internal locus of control was 23,52%, external locus of control 12,67%, time management 22,84%, and teaching creativity 22,46%.

  14. Genome-wide association study identifies new prostate cancer susceptibility loci

    DEFF Research Database (Denmark)

    Schumacher, Fredrick R.; Berndt, Sonja I.; Siddiq, Afshan

    2011-01-01

    published GWAS with 7358 PrCa cases and 6732 controls, we identified a new susceptibility locus associated with overall PrCa risk at 2q37.3 (rs2292884, P= 4.3 x 10–8). We also confirmed a locus suggested by an earlier GWAS at 12q13 (rs902774, P= 8.6 x 10–9). The estimated per-allele odds ratios......Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males in developed countries and the second leading cause of cancer mortality, yet little is known regarding its etiology and factors that influence clinical outcome. Genome-wide association studies (GWAS) of PrCa have...

  15. Genotyping in the MHC locus: potential for defining predictive markers in sarcoidosis

    Directory of Open Access Journals (Sweden)

    Seitzer Ulrike

    2001-10-01

    Full Text Available Abstract In sarcoidosis, host genetic factors are discussed as contributing to disease susceptibility and course. Since tumor necrosis factor (TNF-α is a central mediator of granuloma formation and since elevated TNF-α levels are found during active phases of sarcoidosis, genetic polymorphisms correlating with influences on TNF-α levels are of special interest. The complete sequencing of the MHC region and the increase in the number of identified gene polymorphisms in this locus associated with TNF-α production offer the opportunity of detecting new genes associated with sarcoidosis and perhaps of defining disease-associated haplotypes that bear the potential of serving as predictive markers for this disease.

  16. Influence of Factor V Leiden on susceptibility to and outcome from critical illness: a genetic association study

    DEFF Research Database (Denmark)

    Benfield, Thomas; Ejrnæs, Karen; Juul, Klaus

    2010-01-01

    not appear to increase the risk of admission due to severe invasive infections. Nevertheless, in the subgroup of patients admitted to intensive care an increased risk and a poorer long-term outcome for individuals with critical illness were observed for FVL mutation carriers.......ABSTRACT: INTRODUCTION: Disturbance of the pro-coagulatant and anti-coagulant balance is associated with a poor outcome from critical illness. The objective of this study is to determine whether the Factor V Leiden (FVL) mutation is associated with susceptibility to or death from critical illness....... METHODS: A genetic association study involving four case cohorts comprising two Gram negative sepsis, one invasive pneumococcal disease and one intensive care unit cohort with a total of 1,249 patients. Controls were derived from a population-based cohort study (N = 8,147). DNA from patients and controls...

  17. Influence of Sickle Cell Gene on the Allelic Diversity at the msp-1 locus of Plasmodium falciparum in Adult Patients with Severe Malaria.

    Science.gov (United States)

    Patel, Dilip Kumar; Mashon, Ranjeet Singh; Purohit, Prasanta; Meher, Satyabrata; Dehury, Snehadhini; Marndi, Chhatray; Das, Kishalaya; Kullu, Bipin Kishore; Patel, Siris; Das, Padmalaya

    2015-01-01

    Although several studies have supported that sickle cell trait (HbAS) protects against falciparum malaria, the exact mechanism by which sickle gene confers protection is unclear. Further, there is no information on the influence of the sickle gene on the parasitic diversity of P. falciparum population in severe symptomatic malaria. This study was undertaken to assess the effect of the sickle gene on the parasite densities and diversities in hospitalized adult patients with severe falciparum malaria. The study was carried out in 166 adults hospitalized subjects with severe falciparum malaria at Sickle Cell Clinic and Molecular Biology Laboratory, Veer Surendra Sai Institute of Medical Sciences and Research, Burla, Odisha, India. They were divided into three groups on the basis of hemoglobin variants HbAA (n=104), HbAS (n=30) and HbSS (n=32). The msp-1 loci were genotyped using a PCR-based methodology. The parasite densities were significantly high in HbAA compared to HbAS and HbSS. The multiplicity of infection (MOI) and multi-clonality for msp-1 were significantly low in HbSS and HbAS compared to HbAA. The prevalence of K1 (pSickle gene was found to reduce both the parasite densities and diversity of P. falciparum in adults with severe malaria.

  18. INFLUENCE OF SICKLE CELL GENE ON THE ALLELIC DIVERSITY AT THE MSP-1 LOCUS OF PLASMODIUM FALCIPARUM IN ADULT PATIENTS WITH SEVERE MALARIA

    Directory of Open Access Journals (Sweden)

    Dilip Kumar Patel

    2015-08-01

    Full Text Available Although several studies have supported that sickle cell trait (HbAS protects against falciparum malaria, the exact mechanism by which sickle gene confers protection is unclear. Further, there is no information on the influence of sickle gene on parasitic diversity of P. falciparum population in severe symptomatic malaria.  This study was undertaken to assess the effect of the sickle gene on the parasite densities and diversities in hospitalized adult patients with severe falciparum malaria. The study was carried out in 166 adult hospitalized subjects with severe falciparum malaria at Sickle Cell Clinic and Molecular Biology Laboratory, Veer Surendra Sai Institute of Medical Sciences and Research, Burla, Odisha, India . They were divided into three groups on the basis of hemoglobin variants HbAA (n=104, HbAS (n=30 and HbSS (n=32. The msp-1 loci was genotyped using a PCR based methodology. The parasite densities were significantly high in HbAA compared to HbAS and HbSS. The multiplicity of infection (MOI and multiclonicity for msp-1 were significantly low in HbSS and HbAS compared to HbAA. The prevalence of K1 (p<0 .0001 and MAD20 (p=0.0003 alleles were significantly high in HbAA. The RO33 allele was detected at a higher frequency in HbSS and HbAS, compared to K1 and MAD20. Sickle gene was found to reduce both the parasite densities and diversity of P. falciparum in adults with severe malaria.

  19. Locus of control and competence.

    Science.gov (United States)

    Naditch, M P; DeMaio, T

    1975-12-01

    The relation of locus of control and competence in school achievement, social interactions, sports, and home related activities was examined. The sample consisted of 346 ninth-grade students, and competence was measured using self-report, antional battery test scores, grades, and sociometric ratings. Among males, locus of control was significantly related to competent performance only among those subjects who placed a high value on outcomes in each area. Among females, the pattern was exactly reversed. Locus of control and various forms of competence were related only in areas of low interest value. The implications of these findings were discussed.

  20. Influence of the basal core promoter and precore mutation on replication of hepatitis B virus and antiviral susceptibility of different genotypes.

    Science.gov (United States)

    Cui, Xiu-Ji; Cho, Yoo-Kyung; Song, Byung-Cheol

    2015-04-01

    Mutations in the basal core promoter (BCP) and precore (PC) regions of the hepatitis B virus (HBV) are more common in genotypes B and C than in genotype A, suggesting that these mutations might affect replication competency depending on genotype. The purpose of the study was to investigate the influence of these mutations on the capacity of HBV for replication and antiviral drug susceptibility according to genotype. Genotypes A, B, and C of HBV strains with a BCP mutation, PC mutation, or BCP + PC mutation were made by site-directed mutagenesis. Replication competency of each construct and susceptibility to nucleos(t) ide analogues were tested in an Huh7 cell line. In genotype A, the BCP and BCP + PC mutations increased the viral replication around 6.5 times compared with the wild type, and the PC mutation alone similarly increased the viral replication around three times. In genotypes B and C, all three mutant types increased viral replication to a similar extent, regardless of mutation pattern. Interestingly, the BCP mutation appeared to have a greater effect on viral replication in genotype A than in genotypes B and C. This finding was unexpected because the BCP mutation is more common in HBV genotypes B and C. Moreover, the BCP, PC, and BCP + PC mutations decreased the sensitivity of HBV to antiviral agents to various degrees (2- to 10-fold) regardless of genotype. In conclusion, BCP and PC mutations increased viral replication regardless of HBV genotype and decreased in vitro antiviral susceptibility to the nucleos(t) ide analogues. © 2015 Wiley Periodicals, Inc.

  1. Susceptibility to amoxicillin-clavulanate-induced liver injury is influenced by multiple HLA class I and II alleles.

    Science.gov (United States)

    Lucena, M Isabel; Molokhia, Mariam; Shen, Yufeng; Urban, Thomas J; Aithal, Guruprasad P; Andrade, Raúl J; Day, Christopher P; Ruiz-Cabello, Francisco; Donaldson, Peter T; Stephens, Camilla; Pirmohamed, Munir; Romero-Gomez, Manuel; Navarro, Jose Maria; Fontana, Robert J; Miller, Michael; Groome, Max; Bondon-Guitton, Emmanuelle; Conforti, Anita; Stricker, Bruno H C; Carvajal, Alfonso; Ibanez, Luisa; Yue, Qun-Ying; Eichelbaum, Michel; Floratos, Aris; Pe'er, Itsik; Daly, Mark J; Goldstein, David B; Dillon, John F; Nelson, Matthew R; Watkins, Paul B; Daly, Ann K

    2011-07-01

    Drug-induced liver injury (DILI), especially from antimicrobial agents, is an important cause of serious liver disease. Amoxicillin-clavulanate (AC) is a leading cause of idiosyncratic DILI, but little is understood about genetic susceptibility to this adverse reaction. We performed a genome-wide association study using 822,927 single nucleotide polymorphism (SNP) markers from 201 White European and US cases of DILI following AC administration (AC-DILI) and 532 population controls, matched for genetic background. AC-DILI was associated with many loci in the major histocompatibility complex. The strongest effect was with an HLA class II SNP (rs9274407, P=4.8×10(-14)), which correlated with rs3135388, a tag SNP of HLA-DRB1*1501-DQB1*0602 that was previously associated with AC-DILI. Conditioned on rs3135388, rs9274407 is still significant (P=1.1×10(-4)). An independent association was observed in the class I region (rs2523822, P=1.8×10(-10)), related to HLA-A*0201. The most significant class I and II SNPs showed statistical interaction (P=.0015). High-resolution HLA genotyping (177 cases and 219 controls) confirmed associations of HLA-A*0201 (P=2×10(-6)) and HLA-DQB1*0602 (P=5×10(-10)) and their interaction (P=.005). Additional, population-dependent effects were observed in HLA alleles with nominal significance. In an analysis of autoimmune-related genes, rs2476601 in the gene PTPN22 was associated (P=1.3×10(-4)). Class I and II HLA genotypes affect susceptibility to AC-DILI, indicating the importance of the adaptive immune response in pathogenesis. The HLA genotypes identified will be useful in studies of the pathogenesis of AC-DILI but have limited utility as predictive or diagnostic biomarkers because of the low positive predictive values. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  2. The influence of chronic renal failure on the spectrum and antimicrobial susceptibility of uropathogens in community-acquired acute pyelonephritis presenting as a positive urine culture

    Directory of Open Access Journals (Sweden)

    Shin Ho

    2011-04-01

    Full Text Available Abstract Background The role of chronic renal failure (CRF in the antimicrobial resistance of uropathogens in patients with community-acquired acute pyelonephritis (APN remains poorly understood. Method We performed a retrospective analysis of 502 adults (54 men, 448 women; mean age 61.7 ± 16.0 years, range 18-98 years who were treated for community-acquired APN at Kosin University Gospel Hospital (Busan, Republic of Korea during a ten-year period (January 2000 to December 2009. We evaluated the spectra and antimicrobial susceptibility profiles of uropathogens in CRF and non-CRF patients with community-acquired APN that presented as a positive urine culture. Results The 502 adult subjects were classified as either non-CRF APN patients (336 patients, 66.9% or CRF APN patients (166 patients, 33.1% according to their estimated glomerular filtration rate. No significant differences in the sensitivity of E. coli to a third cephalosporin, aminoglycoside (except gentamycin, or ciprofloxacin were observed between non-CRF and CRF patients. Conclusions In our series of patients with community-acquired APN that initially presented as a positive urine culture, CRF did not influence the isolation rates of different uropathogens or their patterns of susceptibility to antimicrobials.

  3. Conidial germination in Scedosporium apiospermum, S. aurantiacum, S. minutisporum and Lomentospora prolificans: influence of growth conditions and antifungal susceptibility profiles

    Directory of Open Access Journals (Sweden)

    Thaís Pereira de Mello

    2016-01-01

    Full Text Available In the present study, we have investigated some growth conditions capable of inducing the conidial germination in Scedosporium apiospermum, S. aurantiacum, S. minutisporum and Lomentospora prolificans. Germination in Sabouraud medium (pH 7.0, 37ºC, 5% CO2 showed to be a typically time-dependent event, reaching ~75% in S. minutisporum and > 90% in S. apiospermum, S. aurantiacum and L. prolificans after 4 h. Similar germination rate was observed when conidia were incubated under different media and pHs. Contrarily, temperature and CO2 tension modulated the germination. The isotropic conidial growth (swelling and germ tube-like projection were evidenced by microscopy and cytometry. Morphometric parameters augmented in a time-dependent fashion, evidencing changes in size and granularity of fungal cells compared with dormant 0 h conidia. In parallel, a clear increase in the mitochondrial activity was measured during the transformation of conidia-into-germinated conidia. Susceptibility profiles to itraconazole, fluconazole, voriconazole, amphotericin B and caspofungin varied regarding each morphotype and each fungal species. Overall, the minimal inhibitory concentrations for hyphae were higher than conidia and germinated conidia, except for caspofungin. Collectively, our study add new data about the conidia-into-hyphae transformation in Scedosporium and Lomentospora species, which is a relevant biological process of these molds directly connected to their antifungal resistance and pathogenicity mechanisms.

  4. ABA Suppresses Botrytis cinerea Elicited NO Production in Tomato to Influence H2O2 Generation and Increase Host Susceptibility

    Science.gov (United States)

    Sivakumaran, Anushen; Akinyemi, Aderemi; Mandon, Julian; Cristescu, Simona M.; Hall, Michael A.; Harren, Frans J. M.; Mur, Luis A. J.

    2016-01-01

    Abscisic acid (ABA) production has emerged a susceptibility factor in plant-pathogen interactions. This work examined the interaction of ABA with nitric oxide (NO) in tomato following challenge with the ABA-synthesizing pathogen, Botrytis cinerea. Trace gas detection using a quantum cascade laser detected NO production within minutes of challenge with B. cinerea whilst photoacoustic laser detection detected ethylene production – an established mediator of defense against this pathogen – occurring after 6 h. Application of the NO generation inhibitor N-Nitro-L-arginine methyl ester (L-NAME) suppressed both NO and ethylene production and resistance against B. cinerea. The tomato mutant sitiens fails to accumulate ABA, shows increased resistance to B. cinerea and we noted exhibited elevated NO and ethylene production. Exogenous application of L-NAME or ABA reduced NO production in sitiens and reduced resistance to B. cinerea. Increased resistance to B. cinerea in sitiens have previously been linked to increased reactive oxygen species (ROS) generation but this was reduced in both L-NAME and ABA-treated sitiens. Taken together, our data suggests that ABA can decreases resistance to B. cinerea via reduction of NO production which also suppresses both ROS and ethylene production. PMID:27252724

  5. ABA suppresses Botrytis cinerea elicited NO production in tomato to influence H2O2 generation and increase host susceptibility

    Directory of Open Access Journals (Sweden)

    Anushen eSivakumaran

    2016-05-01

    Full Text Available Abscisic acid (ABA production has emerged a susceptibility factor in plant-pathogen interactions. This work examined the interaction of ABA with NO in tomato following challenge with the ABA-synthesising pathogen, Botrytis cinerea. Trace gas detection using a quantum cascade laser detected NO production within minutes of challenge with B. cinerea whilst photoacoustic laser detection detected ethylene production – an established mediator of defence against this pathogen - occurring after 6 h. Application of the NO generation inhibitor N-Nitro-L-arginine methyl ester (L-NAME suppressed both NO and ethylene production and resistance against B. cinerea. The tomato mutant sitiens fails to accumulate ABA (abscisic acid, shows increased resistance to B. cinerea and we noted exhibited elevated NO and ethylene production. Exogenous application of L-NAME or ABA reduced NO production in sitiens and reduced resistance to B. cinerea. Increased resistance to B. cinerea in sitiens have previously been linked to increased reactive oxygen species (ROS generation but this was reduced in both L-NAME and ABA treated sitiens. Taken together, our data suggests that ABA can decreases resistance to B. cinerea via reduction of NO production which also suppresses both ROS and ethylene production.

  6. Influence of exposure patterns of nitrogen dioxide and modifications by ozone on susceptibility to bacterial infectious disease in mice

    Energy Technology Data Exchange (ETDEWEB)

    Graham, J.A.; Gardner, D.E.; Blommer, E.J.; House, D.E.; Menache, M.G.

    1987-01-01

    The nitrogen dioxide (NO/sub 2/) diurnal cycle found in urban communities usually consists of a low basal concentration upon which are superimposed higher-concentration peaks or spikes of short duration. Various components of the environmental-exposure mode were examined to assess effects of urban exposure profiles on susceptibility to infectious pulmonary disease. Mice were exposed to NO/sub 2/ peaks of 4.5 ppm for 1, 3.5, or 7 h, challenged with Streptococcus sp. either immediately or 18 h postexposure, and then observed for mortality. When the streptococcal challenges were immediately after NO/sub 2/ exposure, the mortality rate was directly related to the length of peak exposure, whether or not a basal exposure was used, and all peak lengths significantly increased mortality. When the challenge was delayed for 18 h after the peak exposure, spiked exposure, of 3.5 and 7 h increased mortality to the same degree. If a 1-h peak exposure to 4.5 ppm was superimposed twice daily upon a continuous basal NO/sub 2/ concentration of 1.5 ppm, there was a suggestive trend toward increased mortality near the end of the second week of exposure when challenge occurred immediately after the morning spike.

  7. ABA Suppresses Botrytis cinerea Elicited NO Production in Tomato to Influence H2O2 Generation and Increase Host Susceptibility.

    Science.gov (United States)

    Sivakumaran, Anushen; Akinyemi, Aderemi; Mandon, Julian; Cristescu, Simona M; Hall, Michael A; Harren, Frans J M; Mur, Luis A J

    2016-01-01

    Abscisic acid (ABA) production has emerged a susceptibility factor in plant-pathogen interactions. This work examined the interaction of ABA with nitric oxide (NO) in tomato following challenge with the ABA-synthesizing pathogen, Botrytis cinerea. Trace gas detection using a quantum cascade laser detected NO production within minutes of challenge with B. cinerea whilst photoacoustic laser detection detected ethylene production - an established mediator of defense against this pathogen - occurring after 6 h. Application of the NO generation inhibitor N-Nitro-L-arginine methyl ester (L-NAME) suppressed both NO and ethylene production and resistance against B. cinerea. The tomato mutant sitiens fails to accumulate ABA, shows increased resistance to B. cinerea and we noted exhibited elevated NO and ethylene production. Exogenous application of L-NAME or ABA reduced NO production in sitiens and reduced resistance to B. cinerea. Increased resistance to B. cinerea in sitiens have previously been linked to increased reactive oxygen species (ROS) generation but this was reduced in both L-NAME and ABA-treated sitiens. Taken together, our data suggests that ABA can decreases resistance to B. cinerea via reduction of NO production which also suppresses both ROS and ethylene production.

  8. Interpersonal Goals and Susceptibility to Peer Influence: Risk Factors for Intentions to Initiate Substance Use during Early Adolescence

    Science.gov (United States)

    Trucco, Elisa M.; Colder, Craig R.; Bowker, Julie C.; Wieczorek, William F.

    2011-01-01

    Though peer socialization theories are prominent in the adolescent substance use literature, variability in the degree to which adolescents are vulnerable to peer influence is likely, and few studies have examined this issue. This study examines the association between perceived peer substance use/approval of substance use and adolescent…

  9. Beliefs about alcohol and the college experience, locus of self, and college undergraduates’ drinking patterns.

    Science.gov (United States)

    Crawford, Lizabeth A; Novak, Katherine B

    2011-01-01

    The purpose of this study is to assess the extent to which locus of self (institutional versus impulse), measured using the Twenty Statements Test (TST), moderates the relationship between beliefs about alcohol and the college experience (BACE) and alcohol use among college undergraduates. Although the majority of our respondents listed more idiosyncratic personal characteristics and preferences than consensual social roles in response to the TST, the number of students classified as institutionals was notably higher than what has been reported within the literature. In opposition to our hypothesis that BACE would affect levels of alcohol consumption primarily among these individuals, our results indicated that the perception that alcohol use is integral to the college experience had a relatively minimal effect on drinking among respondents who defined themselves in terms of institutional roles. Moreover, multiple social roles themselves appeared to reduce the effects of BACE on levels of alcohol consumption. More impulse-oriented personal characteristics and preferences did not exhibit this moderating influence. Thus, our findings suggest that role occupation may be more important than locus of self in shaping students’ susceptibility to beliefs about drinking and college life.

  10. Fine Structure and Instability of the Ml-a Locus in Barley

    OpenAIRE

    Wise, Roger P.; Ellingboe, Albert H.

    1985-01-01

    There are many naturally occurring variants at the Ml-a locus in barley that confer resistance to the powdery mildew fungus Erysiphe graminis f. sp. hordei. Since the Ml-a locus is bracketed by Hor-1 and Hor-2, genes that encode storage proteins in the endosperm, the Ml-a locus is amenable to fine structure analysis. Rare susceptible recombinants, as judged by exchange of flanking markers, were recovered in F3 families from the Ml-a10 x Ml-a1, Ml-a1 x Ml-a15 and Ml-a6 x Ml-a13 crosses. Some...

  11. Does Mental Health Status Influence Susceptibility to the Physiologic Effects of Air Pollution? A Population Based Study of Canadian Children.

    Science.gov (United States)

    Dales, Robert E; Cakmak, Sabit

    2016-01-01

    Both air pollution exposure and the presence of mental illness are associated with an increased risk of physical illness. To determine whether or not children with less favourable mental health are more susceptible to pulmonary and cardiovascular effects of ambient air pollution, compared to those who are mentally healthy. We carried out a cross-sectional study of 1,883 children between the ages of 6 and 17 years of age who participated in the Canadian Health Measures population survey between 2007 and 2009. Subjects were assigned the air pollution values obtained from the National Air Pollution monitor closest to their neighborhood. Lung function, heart rate and blood pressure were stratified by indicators of mental health. The latter were ascertained by questions about feelings of happiness, a diagnosed mood disorder, and the emotional symptom subscale of the Strengths and Difficulties Questionnaire. Among those who reported a mood disorder, an interquartile increase in ozone was associated with increases in systolic and diastolic pressures of 3.8 mmHg (95% CI 1.6, 5.9) and 3.0mmHg (95%CI 0.9, 5.2) respectively, and a decreases in FVC of 7.6% (95% CI 2.9, 12.3). No significant changes in these variables were observed in those who did not report a mood disorder. Among those with unfavourable emotional symptoms, ozone was associated with a 6.4% (95% CI 1.7, 11.3) increase in heart rate, a 4.1% (95%CI 1.2, 7.1) increase in systolic blood pressure, and a 6.0% (95% CI 1.4, 10.6) decrease in FEVl. No significant effect was seen in these variables among those with no emotional symptoms. In the Canadian population, children who report mood disorders or unfavourable emotional symptoms appear to be more vulnerable to the adverse physiologic effects of air pollution.

  12. Does Mental Health Status Influence Susceptibility to the Physiologic Effects of Air Pollution? A Population Based Study of Canadian Children.

    Directory of Open Access Journals (Sweden)

    Robert E Dales

    Full Text Available Both air pollution exposure and the presence of mental illness are associated with an increased risk of physical illness.To determine whether or not children with less favourable mental health are more susceptible to pulmonary and cardiovascular effects of ambient air pollution, compared to those who are mentally healthy.We carried out a cross-sectional study of 1,883 children between the ages of 6 and 17 years of age who participated in the Canadian Health Measures population survey between 2007 and 2009. Subjects were assigned the air pollution values obtained from the National Air Pollution monitor closest to their neighborhood. Lung function, heart rate and blood pressure were stratified by indicators of mental health. The latter were ascertained by questions about feelings of happiness, a diagnosed mood disorder, and the emotional symptom subscale of the Strengths and Difficulties Questionnaire.Among those who reported a mood disorder, an interquartile increase in ozone was associated with increases in systolic and diastolic pressures of 3.8 mmHg (95% CI 1.6, 5.9 and 3.0mmHg (95%CI 0.9, 5.2 respectively, and a decreases in FVC of 7.6% (95% CI 2.9, 12.3. No significant changes in these variables were observed in those who did not report a mood disorder. Among those with unfavourable emotional symptoms, ozone was associated with a 6.4% (95% CI 1.7, 11.3 increase in heart rate, a 4.1% (95%CI 1.2, 7.1 increase in systolic blood pressure, and a 6.0% (95% CI 1.4, 10.6 decrease in FEVl. No significant effect was seen in these variables among those with no emotional symptoms.In the Canadian population, children who report mood disorders or unfavourable emotional symptoms appear to be more vulnerable to the adverse physiologic effects of air pollution.

  13. Influence of exposure patterns of nitrogen dioxide and modifications by ozone on susceptibility to bacterial infectious disease in mice

    Energy Technology Data Exchange (ETDEWEB)

    Graham, J.A.; Gardner, D.E.; Blommer, E.J.; House, D.E.; Menache, M.G.; Miller, F.J.

    1987-01-01

    The nitrogen dioxide (NO/sub 2/) diurnal cycle found in urban communities usually consists of a low basal concentration upon which are superimposed higher concentration peaks or spikes of short duration. Various components of this environmental exposure mode were examined to assess effects of urban exposure profiles on susceptibility to infectious pulmonary disease. Mice were exposed to NO/sub 2/ peaks of 4.5 ppm for 1, 3.5, or 7 h, challenged with Streptococcus sp. either immediately or 18 h postexposure, and then observed for mortality. When the streptococcal challenges were immediately after NO/sub 2/ exposure, the mortality rate was directly related to the length of peak exposure, whether or not a basal exposure was used, and all peak lengths significantly increased mortality. When the challenge was delayed for 18 h after the peak exposure, spiked exposures of 3.5 and 7 h increased mortality to the same degree. If a 1-h peak exposure to 4.5 ppm was superimposed twice daily upon a continuous basal NO/sub 2/ concentration of 1.5 ppm, there was a suggestive trend toward increased mortality near the end of the second week of exposure when challenge occurred immediately after the morning spike. Studies were also conducted to examine interactions with ozone (O/sub 3/) and NO/sub 2/, since urban air typically contains both of these oxidants. Using various combinations of basal and spiked exposure levels of NO/sub 2/ and O/sub 3/, synergistic results were obtained for streptococcal-induced mortality.

  14. Influence of the angle between cleavage and bedding on the anisotropy of magnetic susceptibility and the degree of phyllosilicate preferred orientation

    Science.gov (United States)

    Debacker, T. N.; Sintubin, M.

    2003-04-01

    Due to the common scarcity of strain markers and the often fine-grained lithologies, performing strain analyses in slate belts may be difficult. As an alternative, one may use methods such as phyllosilicate preferred orientation (X-ray pole figure goniometry) and anisotropy of magnetic susceptibility (AMS). However, a large number of factors influence the results of these analytical methods. One of the factors is the angle between cleavage and bedding. The study area is the Brabant Massif, a single-phase deformed, low-grade slate belt in N-Belgium consisting of a steep Cambrian core surrounded by Ordovician-Silurian sequences. In the southern part of the Cambrian core, the transition between steeply plunging folds, considered typical for the steep core, and gently plunging folds, considered characteristic for the peripheral Ordovician-Silurian sequences, occurs in homogeneous mudstones of the Lower Cambrian Oisquercq Formation. In these deposits mica and chlorite show a similar degree of preferred orientation. Mica is always aligned along the cleavage, whereas chlorite is aligned along the bedding. Clear intersection pole figure patterns characterise samples with large cleavage/bedding angles, whereas flattening fabrics only become apparent for samples with small cleavage/bedding angles. For both mica and chlorite, the degree of preferred orientation is higher for samples with small cleavage/bedding angles. The magnetic fabric shows prolate susceptibility ellipsoids for samples with large cleavage/bedding angles and oblate susceptibility ellipsoids for samples with small cleavage/bedding angles (cf. Housen et al., 1993). The short axis of the susceptibility ellipsoid is generally oriented perpendicular to bedding, occasionally perpendicular to cleavage or with an intermediate orientation. The long axis of the susceptibility ellipsoid is always parallel to the cleavage/bedding intersection. The shape parameter T shows an almost linear relationship with respect to

  15. Studies on schistosomiasis. 8. The influence of age on the susceptibility of sheep to infestation with Schistosoma mattheei.

    Science.gov (United States)

    Van Wyk, J A; Van Rensburg, L J; Heitmann, L P

    1976-06-01

    Twenty-eight Dorper wethers, allocated according to age into 4 groups of 7 animals each, and 1 group of 7 Merino wethers, were compared for susceptibility to Schistosoma mattheei infestation. The group mean ages of the Dorper sheep varied from 5-61 months and their live mass from 25-66 kg, while the Merinos were 8 months old and had a mean mass of 19 kg. Despite the marked differences in the age and live mass of the Dorper sheep and the inclusion of 2 breeds in the experiment, no statistically significant differences were found in cercariae which failed to penetrate the sheep the mean percentage development of cercariae to adult worms, worm distribution in the mesenteric and gastric radicles of the portal vein and the pulmonary arterial system, and worms not removed by perfusion. Significant differences between groups (5% significance level) were found, however, in the number of worms recovered from the hepatic portal system, and in the worm sex ratio. On 3 occasions the total number of eggs excreted per female schistosome in the mesentery per 24 hours differed significantly between groups, but each time a different group or groups of sheep were responsible for the variation which was probably due, therefore, not to the age or breed of the sheep, but to daily variations in individuals. Highly significant differences occurred in the infectivity of the 6 cercarial pools used for infestation in spite of standardized collection and handling of the cercariae. Possible reasons for this are discussed and a solution suggested. Frequent egg counts (5 per sheep per week) were done during the first 25 days of patency, until the sheep were slaughtered. Schistosome ova were detected in the faeces of only 1/18 sheep examined on Day +43 after infestation, and 3/17 on Day +44, whereafter this increased rapidly to 15/34 on Day +45, 25/33 on Day +46, etc. A highly significant correlation was found between the total worm egg excretion in the faeces of the sheep per day and the

  16. IκBα polymorphism at promoter region (rs2233408 influences the susceptibility of gastric cancer in Chinese

    Directory of Open Access Journals (Sweden)

    Sung Joseph JY

    2010-02-01

    Full Text Available Abstract Background Nuclear factor of kappa B inhibitor alpha (IκBα protein is implicated in regulating a variety of cellular process from inflammation to tumorigenesis. The objective of this study was to investigate the susceptibility of rs2233408 T/C genotype in the promoter region of IκBα to gastric cancer and the association of this polymorphism with clinicopathologic variables in gastric cancer patients. Methods A population-based case-control study was conducted between 1999 and 2006 in Guangdong Province, China. A total of 564 gastric cancer patients and 566 healthy controls were enrolled in this study. rs2233408 genotypes in IκBα were analyzed by TaqMan SNP genotyping assay. Results Both rs2233408 T homozygote (TT and T heterozygotes (TC and TT had significantly reduced gastric cancer risk (TT: OR = 0.250, 95% CI = 0.069-0.909, P = 0.035; TC and TT: OR = 0.721, 95% CI = 0.530-0.981, P = 0.037, compared with rs2233408 C homozygote (CC. rs2233408 T heterozygotes were significantly associated with reduced risk of intestinal-type gastric cancer with ORs of 0.648 (95% CI = 0.459-0.916, P = 0.014, but not with the diffuse or mix type of gastric cancer. The association between rs2233408 T heterozygotes and gastric cancer appeared more apparent in the older patients (age>40 (OR = 0.674, 95% CI = 0.484-0.939, P = 0.02. rs2233408 T heterozygotes was associated with non-cardiac gastric cancer (OR = 0.594, 95% CI = 0.411-0.859, P = 0.006, but not with cardiac gastric cancer. However, rs2233408 polymorphism was not associated with the prognosis of gastric cancer patients. Conclusions IκBα rs2233408 T heterozygotes were associated with reduced risk of gastric cancer, especially for the development of certain subtypes of gastric cancer in Chinese population.

  17. Ectopic expression of URA3 can influence the virulence phenotypes and proteome of Candida albicans but can be overcome by targeted reintegration of URA3 at the RPS10 locus.

    Science.gov (United States)

    Brand, Alexandra; MacCallum, Donna M; Brown, Alistair J P; Gow, Neil A R; Odds, Frank C

    2004-08-01

    Uridine auxotrophy, based on disruption of both URA3 alleles in diploid Candida albicans strain SC5314, has been widely used to select gene deletion mutants created in this fungus by "Ura-blasting" and PCR-mediated disruption. We compared wild-type URA3 expression with levels in mutant strains where URA3 was positioned either within deleted genes or at the highly expressed RPS10 locus. URA3 expression levels differed significantly and correlated with the specific activity of Ura3p, orotidine 5'-monophosphate decarboxylase. Reduced URA3 expression following integration at the GCN4 locus was associated with an attenuation of virulence. Furthermore, a comparison of the SC5314 (URA3) and CAI-4 (ura3) proteomes revealed that inactivation of URA3 caused significant changes in the levels of 14 other proteins. The protein levels of all except one were partially or fully restored by the reintegration of a single copy of URA3 at the RPS10 locus. Transcript levels of genes expressed ectopically at this locus in reconstituted heterozygous mutants also matched the levels found when the genes were expressed at their native loci. Therefore, phenotypic changes in C. albicans can be associated with the selectable marker rather than the target gene. Reintegration of URA3 at an appropriate expression locus such as RPS10 can offset most problems related to the phenotypic changes associated with gene knockout methodologies.

  18. Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Phelan, Catherine M; Kuchenbaecker, Karoline B; Tyrer, Jonathan P

    2017-01-01

    , including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low...

  19. IL-10 gene polymorphism c.-592C>A increases HPV infection susceptibility and influences IL-10 levels in HPV infected women.

    Science.gov (United States)

    Berti, Fernanda Costa Brandão; Pereira, Ana Paula Lombardi; Trugilo, Kleber Paiva; Cebinelli, Guilherme Cesar Martelossi; Silva, Lorena Flor da Rosa Santos; Lozovoy, Marcell Alysson Batisti; Simão, Andréa Name Colado; Watanabe, Maria Angelica Ehara; de Oliveira, Karen Brajão

    2017-09-01

    Interleukin-10 (IL-10) influences HPV infection and viral persistence, favoring cervical immunosuppression and cervical carcinogenesis. IL-10 levels may be influenced by HPV itself and by IL-10 polymorphisms, including rs1800872 (c.-592C>A). Therefore, we evaluated the influence of IL-10 c.-592C>A polymorphism in HPV infection and in IL-10 plasmatic/cervical levels in HPV infected and non-infected women. The study included 174 infected and 186 non-infected patients. Cervical epithelial scrapings were obtained to determine HPV DNA presence PCR. Peripheral blood samples were obtained to determine IL-10 polymorphism by PCR-RFLP, while IL-10 levels were assessed by ELISA. HPV was more prevalent among allele A carriers (pA polymorphism being associated with HPV infection. As demonstrated by binary logistic regression analysis, heterozygotes [ORadj=2.081 95% CI (1.222-3.544), p=0.007] and homozygotes [ORadj=3.745 95% CI (1.695-8.271), p=0.001] showed approximately 2 and 4 time's greater odds, respectively, of presenting HPV when compared to CC patients. Moreover, HPV infected patients carrying polymorphic allele A showed higher IL-10 cervical levels (p=0.039). Binary logistic regression analysis demonstrated that IL-10 cervical levels were not independently associated to CA+AA genotypes (p=0.162), neither to HPV's presence (p=0.061), thus IL-10 cervical levels are possibly increased because of both HPV and allele A presence. Taken together, these findings suggest that IL-10 c.-592C>A polymorphism is independently associated with HPV infection susceptibility exerting influence on IL-10 cervical levels in HPV infected women, thus contributing to cervical carcinogenesis. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Pobreza y Locus de Control

    Directory of Open Access Journals (Sweden)

    Joaquina Palomar Lever

    2004-01-01

    Full Text Available En este trabajo se busco conocer si existen diferencias en el locus de control según el nivel de pobreza en una población de 900 personas clasificadas en tres grupos: pobres extremos, pobres moderados y no pobres. Los sujetos estudiados compartieron la característica de ser personas económicamente independientes. Para este estudio se utilizaron como instrumentos de medición, un cuestionario sociodemográfico y una escala de locus de control. Los resultados muestran que los grupos de mayor ingreso familiar así como el grupo de no pobres y el de pobres moderados presentan en mayor medida un locus de control interno, mientras que el grupo de pobres extremos un mayor locus de control externo; por otro lado se observó que las personas de sexo masculino así como los de más edad (36 a 72 años presentan un locus de control más interno que aquellas personas de sexo femenino y de menor edad (19 a 35 años. Además, las personas con mayor nivel educativo (licenciatura y postgrado presentan una mayor tendencia hacia la internalidad en comparación con las personas de menor nivel educativo (sin escolaridad, primaria, secundaria y preparatoria. A su vez, se observó que la escolaridad de los padres influye en el locus de control. En términos generales, las variables que mejor predicen el locus de control fueron el ingreso familiar y la escolaridad de los sujetos

  1. Investigation of the 5q33.3 longevity locus and age-related phenotypes

    OpenAIRE

    Nygaard, Marianne; Thinggaard, Mikael; Christensen, Kaare; Christiansen, Lene

    2017-01-01

    A large meta-analysis recently found the 5q33.3 locus to be associated with survival to ≥ 90 years and lower all-cause mortality, thus suggesting it as a third human longevity locus alongside APOE and FOXO3A. The 5q33.3 locus has previously been associated with blood pressure regulation and cardiovascular diseases in middle-aged individuals. However, part of the influence on mortality appears to be independent of cardiovascular phenotypes, and the role of the 5q33.3 locus in longevity and sur...

  2. Locus of control and its relationship with mental health and adjustment among adolescent females

    Directory of Open Access Journals (Sweden)

    Madhu Jain

    2015-01-01

    Full Text Available Objective: There exists a plethora of researches which have identified the role of Locus of Control in maintaining sound mental health and adjustment. The present study examined the relationship of Locus of Control with Mental Health & overall Adjustment among adolescent females. Method: The participants consisted of 50 adolescent females. Mental Health Battery designed by Singh, Gupta (2000, Rotter′s Locus of Control Scale (1966 & Adjustment Inventory for College Students by Sinha & Singh (1995 were administered. Findings: The findings of the study revealed that adolescent females who possess internal locus of control showed better mental health & overall adjustment pattern which includes home, social, emotional, educational domains and health adjustment domain than those who possess external locus of control. Conclusion: The study highlights the pervasive influence of internal & external locus of control on mental health & adjustment among adolescent females.

  3. Genetic Polymorphism of Epidermal Growth Factor rs4444903 Influences Susceptibility to HCV-Related Liver Cirrhosis and Hepatocellular Carcinoma in a Chinese Han Population.

    Science.gov (United States)

    Zhang, Shitian; Qiao, Kunyan; Trieu, Congdoanh; Huo, Zhixiao; Dai, Qinghai; Du, Yanan; Lu, Wei; Hou, Wei

    2017-04-01

    Genetic polymorphism in the epidermal growth factor (EGF, rs4444903) gene has been demonstrated to be associated with the clinical deterioration in hepatitis C virus (HCV)-related liver cirrhosis (LC) and the development of hepatocellular carcinoma (HCC). Whether this single nucleotide polymorphism (SNP) influences susceptibility to HCV-related LC and HCC in the Chinese Han population is largely unknown. In this case-control study, a total of 187 Chinese Han patients with chronic HCV infection were enrolled, including 62 HCV-related LC patients, 46 HCV-related HCC patients, and 79 chronic hepatitis C (CHC) patients without LC and HCC, and the genetic polymorphism was genotyped via a matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) assay. The logistical regression analysis was employed to determine the correlation between the genetic polymorphism and risk of HCV-related LC and HCC. The distribution of EGF rs4444903 genotypes and alleles significantly differed between LC patients and CHC subjects (p = 0.045, p = 0.043, respectively). Under the recessive model, the GG genotype was significantly associated with a two-fold risk of HCV-related LC compared to the AA+AG genotype after an adjustment for age, gender, body mass index (BMI), duration of HCV infection, and HCV RNA level (OR = 2.188; 95% CI = 1.072 - 4.465; p = 0.031). Significant association was observed as well between the GG genotype and increased HCV-related HCC risk (OR = 3.104; 95% CI = 1.319 - 7.307; p = 0.010). The EGF rs4444903 GG genotype is associated with higher susceptibility to HCV-related LC and HCC in the Chinese Han population. Screening of host genetic polymorphisms might be helpful in designing effective and efficient LC and HCC surveillance programs for chronic HCV-infected patients.

  4. IFNG +874T/A polymorphism is not associated with American tegumentary leishmaniasis susceptibility but can influence Leishmania induced IFN-γ production

    Directory of Open Access Journals (Sweden)

    Sampaio Elizabeth P

    2007-04-01

    Full Text Available Abstract Background Interferon-gamma is a key cytokine in the protective responses against intracellular pathogens. A single nucleotide polymorphism (SNP located in the first intron of the human IFN-γ gene can putatively influence the secretion of cytokine with an impact on infection outcome as demonstrated for tuberculosis and other complex diseases. Our aim was to investigate the putative association of IFNG+874T/A SNP with American tegumentary leishmaniasis (ATL and also the influence of this SNP in the secretion of IFN-γ in vitro. Methods Brazilian ATL patients (78 cutaneous, CL, and 58 mucosal leishmaniasis, ML and 609 healthy volunteers were evaluated. The genotype of +874 region in the IFN-γ gene was carried out by Amplification Refractory Mutational System (ARMS-PCR. Leishmania-induced IFN-γ production on peripheral blood mononuclear cell (PBMC culture supernatants was assessed by ELISA. Results There are no differences between +874T/A SNP frequency in cases and controls or in ML versus CL patients. Cutaneous leishmaniasis cases exhibiting AA genotype produced lower levels of IFN-γ than TA/TT genotypes. In mucosal cases, high and low IFN-γ producers were clearly demonstrated but no differences in the cytokine production was observed among the IFNG +874T or A carriers. Conclusion Our results suggest that +874T/A polymorphism was not associated with either susceptibility or severity to leishmaniasis. Despite this, IFNG +874T/A SNP could be involved in the pathogenesis of leishmaniasis by influencing the amount of cytokine released by CL patients, although it could not prevent disease development. On the other hand, it is possible that in ML cases, other potential polymorphic regulatory genes such as TNF-α and IL-10 are also involved thus interfering with IFN-γ secretion.

  5. Relationship Among Achievement Motivation, Self-Esteem, Locus of ...

    African Journals Online (AJOL)

    The thrust of the study was to examine the relationship among achievement motivation, self-esteem, locus of control and academic performance of university students in a Nigerian University. The purpose was to determine the extent university student\\'s academic performance was influenced by these criterion variables.

  6. The Influence of Science Process Skills, Logical Thinking Abilities, Attitudes towards Science, and Locus of Control on Science Achievement among Form 4 Students in the Interior Division of Sabah, Malaysia

    Science.gov (United States)

    Fah, Lay Yoon

    2008-01-01

    The purpose of this study was to examine the direct and indirect effects of science process skills, logical thinking abilities, attitudes towards science, and locus of control on science achievement among Form 4 students in the Interior Division of Sabah, Malaysia. Research findings showed that there were low to moderate, positive but significant…

  7. Pobreza y Locus de Control

    OpenAIRE

    Joaquina Palomar Lever; Laura M. Valdés Trejo

    2004-01-01

    En este trabajo se busco conocer si existen diferencias en el locus de control según el nivel de pobreza en una población de 900 personas clasificadas en tres grupos: pobres extremos, pobres moderados y no pobres. Los sujetos estudiados compartieron la característica de ser personas económicamente independientes. Para este estudio se utilizaron como instrumentos de medición, un cuestionario sociodemográfico y una escala de locus de control. Los resultados muestran que los grupos d...

  8. Examining the relationship between health locus of control and God Locus of Health Control: Is God an internal or external source?

    Science.gov (United States)

    Boyd, Joni M; Wilcox, Sara

    2017-11-01

    For many people, the influence of believing in a higher power can elicit powerful effects. This study examined the relationship between God control, health locus of control, and frequency of religious attendance within 838 college students through online surveys. Regression analysis showed that chance and external locus of control and frequency of religious attendance were significant and positive predictors of God Locus of Health Control. The association of powerful others external locus of control and God Locus of Health Control differed by race (stronger in non-Whites than Whites) and somewhat by gender (stronger in women than men). For some people, the role of a supreme being, or God, should be considered when designing programs for improving health behaviors.

  9. Hispanics' locus of control, acculturation, and wellness attitudes.

    Science.gov (United States)

    Valentine, Sean R; Godkin, Jennie; Doughty, Graeme P

    2008-01-01

    There is reason to believe that various cultural attitudes and beliefs influence certain health behaviors, and additional research should identify the causes of such behaviors. This study explored the relationships among cultural identity, acculturation, locus of control, and health beliefs using a sample of 110 Hispanic individuals taking college classes in the southern or southwestern United States. Path analysis indicated that an external locus of control was positively related to health barrier perceptions and that acculturation was negatively related to health barrier perceptions. The findings suggest that Hispanics' perceived control over health outcomes and positive health beliefs could be enhanced with culturally perceptive counseling.

  10. The PTPN22 locus and rheumatoid arthritis: no evidence for an effect on risk independent of Arg620Trp.

    Directory of Open Access Journals (Sweden)

    Wan R Wan Taib

    2010-10-01

    Full Text Available The Trp(620 allotype of PTPN22 confers susceptibility to rheumatoid arthritis (RA and certain other classical autoimmune diseases. There has been a report of other variants within the PTPN22 locus that alter risk of RA; protective haplotype '5', haplotype group '6-10' and susceptibility haplotype '4', suggesting the possibility of other PTPN22 variants involved in the pathogenesis of RA independent of R620W (rs2476601. Our aim was to further investigate this possibility.A total of 4,460 RA cases and 4,481 controls, all European, were analysed. Single nucleotide polymorphisms rs3789607, rs12144309, rs3811021 and rs12566340 were genotyped over New Zealand (NZ and UK samples. Publically-available Wellcome Trust Case Control Consortium (WTCCC genotype data were used.The protective effect of haplotype 5 was confirmed (rs3789607; (OR = 0.91, P = 0.016, and a second protective effect (possibly of haplotype 6 was observed (rs12144309; OR = 0.90, P = 0.021. The previously reported susceptibility effect of haplotype 4 was not replicated; instead a protective effect was observed (rs3811021; OR = 0.85, P = 1.4×10(-5. Haplotypes defined by rs3789607, rs12144309 and rs3811021 coalesced with the major allele of rs12566340 within the adjacent BFK (B-cell lymphoma 2 (BCL2 family kin gene. We, therefore, tested rs12566340 for association with RA conditional on rs2476601; there was no evidence for an independent effect at rs12566340 (P = 0.76. Similarly, there was no evidence for an independent effect at rs12566340 in type 1 diabetes (P = 0.85.We have no evidence for a common variant additional to rs2476601 within the PTPN22 locus that influences the risk of RA. Arg620Trp is almost certainly the single common causal variant.

  11. Analysis and Presentation of Cumulative Antimicrobial Susceptibility Test Data--The Influence of Different Parameters in a Routine Clinical Microbiology Laboratory.

    Science.gov (United States)

    Kohlmann, Rebekka; Gatermann, Sören G

    2016-01-01

    Many clinical microbiology laboratories report on cumulative antimicrobial susceptibility testing (cAST) data on a regular basis. Criteria for generation of cAST reports, however, are often obscure and inconsistent. Whereas the CLSI has published a guideline for analysis and presentation of cAST data, national guidelines directed at clinical microbiology laboratories are not available in Europe. Thus, we sought to describe the influence of different parameters in the process of cAST data analysis in the setting of a German routine clinical microbiology laboratory during 2 consecutive years. We developed various program scripts to assess the consequences ensuing from different algorithms for calculation of cumulative antibiograms from the data collected in our clinical microbiology laboratory in 2013 and 2014. One of the most pronounced effects was caused by exclusion of screening cultures for multi-drug resistant organisms which decreased the MRSA rate in some cases to one third. Dependent on the handling of duplicate isolates, i.e. isolates of the same species recovered from successive cultures on the same patient during the time period analyzed, we recorded differences in resistance rates of up to 5 percentage points for S. aureus, E. coli and K. pneumoniae and up to 10 percentage points for P. aeruginosa. Stratification by site of care and specimen type, testing of antimicrobials selectively on resistant isolates, change of interpretation rules and analysis at genus level instead of species level resulted in further changes of calculated antimicrobial resistance rates. The choice of parameters for cAST data analysis may have a substantial influence on calculated antimicrobial resistance rates. Consequently, comparability of cAST reports from different clinical microbiology laboratories may be limited. We suggest that laboratories communicate the strategy used for cAST data analysis as long as national guidelines for standardized cAST data analysis and reporting

  12. Multiple independent variants in 6q21-22 associated with susceptibility to celiac disease in the Dutch, Finnish and Hungarian populations

    NARCIS (Netherlands)

    Einarsdottir, Elisabet; Bevova, Marianna R.; Zhernakova, Alexandra; Monsuur, Alienke; Koskinen, Lotta L. E.; van't Slot, Ruben; Mulder, Chris; Mearin, M. Luisa; Korponay-Szabo, Ilma R.; Kaukinen, Katri; Kurppa, Kalle; Kere, Juha; Maki, Markku; Wijmenga, Cisca; Saavalainen, Paivi

    Celiac disease is an inflammatory enteropathy caused by intolerance to gluten. Previous linkage studies in the Dutch, Finnish and Hungarian populations have revealed a locus on chromosome 6q21-22 conferring susceptibility to celiac disease. This locus has previously been implicated in susceptibility

  13. Dissection of a locus on mouse chromosome 5 reveals arthritis promoting and inhibitory genes

    DEFF Research Database (Denmark)

    Lindvall, Therese; Karlsson, Jenny; Holmdahl, Rikard

    2009-01-01

    ABSTRACT: INTRODUCTION: In a cross between the susceptible B10.RIII (H-2r) and resistant RIIIS/J (H-2r) mouse strains, a locus on mouse chromosome 5 (Eae39) was previously shown to control experimental autoimmune encephalomyelitis (EAE). Recently, quantitative trait loci (QTL), linked to disease...... with Eae39 congenic- and sub-interval congenic mice, carrying RIIIS/J genes on the B10.RIII genetic background, revealed three loci within Eae39 that control disease and anti-collagen antibody titers. Two of the loci promoted disease and the third locus was protecting from collagen induced arthritis...... development. By further breeding of mice with small congenic fragments, we identified a 3.2 Megabasepair (Mbp) interval that regulates disease. CONCLUSIONS: Disease promoting- and protecting genes within the Eae39 locus on mouse chromosome 5, control susceptibility to collagen induced arthritis. A disease...

  14. Locus of control in graduation students

    OpenAIRE

    Haider Zaidi, Imran; MS (Clinical Psychology) Scholar G.C University, Faisalabad, Pakistan; Mohsin, M. Naeem; Director Distance Learning Education G.C University, Faisalabad, Pakistan

    2013-01-01

    The current research focused on exploring the direction of Locus of control as well as gender difference on locus of control among graduation students in Pakistan. A 29 item Locus of Control questionnaire (Rotter, 1966) was used to measure locus of control. Sample of (N=200) individuals (n=100) men and (n=100) women selected from different academic institutes of Faisalabad division Punjab Pakistan. Independent sample t-test was used for statistical analysis. This study has consistent results ...

  15. Influence of human urine to antimicrobial susceptibility of clinical isolates of Klebsiella pneumoniae and Escherichia coli producing β-lactamase of different types

    Directory of Open Access Journals (Sweden)

    Ž. Žagar

    2007-02-01

    Full Text Available The purpose of the study was to determine the influence of human urine on the antibiotic susceptibilities of Klebsiella pneumoniae and Escherichia coli strains producing different types of extended-spectrum β-lactamases (ESBL. The study was performed on 26 ESBL negative strains of K. pneumoniae, 80 K. pneumoniae strains producing SHV-ESBLs (52-SHV-5, 31- SHV-2 and 7- SHV-12, 94 E. coli strains harbouring TEM- ESBLs and 14 E. coli strains possessing CTX-M group 1 β-lactamases. The minimum inhibitory concentrations of amoxycillin alone and combined with clavulanate (co-amoxilcav, cephalexin, cefuroxime, ceftazidime, cefotaxime, ceftriaxone, cefepime, gentamicin and ciprofloxacin were performed in parallel in Mueller-Hinton broth and urine by broth microdilution method. With ESBL negative strains, urine increased MIC90 of amoxycillin alone and combined with clavulanate, cephalexin, cefuroxime, ceftazidime, cefotaxime, ceftriaxone, cefepime, gentamicin and ciprofloxacin. Against SHV-5 producers, an increase in MIC90 was observed with cefotaxime, cefepime and ciprofloxacin when the test was performed in urine. SHV-2 producers showed elevated MIC90 of ceftazidime, cefotaxime, ceftriaxone and cefepime in the presence of urine, in contrast to SHV-12 producers which displayed elevated MIC90 only for cefotaxime. Urine increased MIC90 of amoxycillin/clavulanate, ceftazidime and cefepime against CTX-M producers, and of amoxycillin/clavulanate, cefotaxime, ceftriaxone, cefepime and ciprofloxacin for TEM producers. According to our results the activity of antibiotics used for the treatment of urinary tract infection could be overestimated by a standard in vitro testing. However, most of antibiotics used for the treatment of urinary tract infection achieve very high concentration in urine and that could abrogate the reduction of antimicrobial activity by biological fluid.

  16. A two-locus model of speciation.

    Science.gov (United States)

    Gregorius, H R

    1992-02-07

    Speciation is considered as the evolution of partial or complete cross-incompatibility between the carriers of genes (at a locus called "object locus") that distinguish the prospective species populations. The mating relations at the object locus are modified by the alleles at a second mating modifier locus. Based on a widely applicable concept of fitness and mating preference, it is shown that heterozygote disadvantage in fitness at the object locus is necessary for speciation, which corroborates Wallace's hypothesis. It is pointed out that the difference between sympatric and parapatric speciation essentially lies in the mechanisms stabilizing the polymorphism required at the object locus as a prerequisite for speciation. In the presence of recombination between the object and mating modifier locus speciation may be prevented by forces maintaining gametic phase imbalance between these loci such as can result from unidirectional gene flow between parapatric populations.

  17. A meta-analysis identifies adolescent idiopathic scoliosis association with LBX1 locus in multiple ethnic groups

    DEFF Research Database (Denmark)

    Londono, Douglas; Kou, Ikuyo; Johnson, Todd A

    2014-01-01

    BACKGROUND: Adolescent idiopathic scoliosis (AIS) is a common rotational deformity of the spine that presents in children worldwide, yet its etiology is poorly understood. Recent genome-wide association studies (GWAS) have identified a few candidate risk loci. One locus near the chromosome 10q24...... the International Consortium for Scoliosis Genetics (ICSG). METHODS: Here, we report the first ICSG study, a meta-analysis of the LBX1 locus in six Asian and three non-Asian cohorts. RESULTS: We find significant evidence for association of this locus with AIS susceptibility in all nine cohorts. Results for seven...

  18. Evaluation of two putative susceptibility loci for oral clefts in the Danish population

    DEFF Research Database (Denmark)

    Mitchell, L E; Murray, J C; O'Brien, S

    2001-01-01

    Previous studies suggest that the risk of nonsyndromic cleft lip with or without cleft palate (CL+/-P) and isolated cleft palate (CP) is influenced by genetic variation at several loci and that the relation between specific genetic variants and disease risk may be modified by environmental factors....... The present study evaluated potential associations between CL+/-P and CP and two putative clefting susceptibility loci, MSX1 and TGFB3, using data from a nationwide case-control study conducted in Denmark from 1991 to 1994. The potential effects of interactions between these genes and two common environmental...... exposures, first trimester exposure to maternal cigarette smoke and alcohol intake, were also examined. Analyses of these data provide evidence of an association between the risk of CP and variation at the TGFB3 locus. However, there is no evidence that the risk of CL+/-P or CP is influenced by gene...

  19. Influence of Growth Mode and Sucrose on Susceptibility of Streptococcus sanguis to Amine Fluorides and Amine Fluoride-Inorganic Fluoride Combinations

    Science.gov (United States)

    Embleton, J. V.; Newman, H. N.; Wilson, M.

    1998-01-01

    This study evaluated the susceptibility to amine fluorides (AmFs) of planktonic and biofilm cultures of Streptococcus sanguis grown with and without sucrose. Cultures were incubated with AmFs (250 mg of fluoride liter−1) for 1 min. The susceptibility of biofilms was less than that of the planktonic form and was further decreased by growth in the presence of sucrose. PMID:9726905

  20. Genetic Susceptibility to Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Sanja Kovacic

    2012-01-01

    Full Text Available Atherosclerosis is a complex multifocal arterial disease involving interactions of multiple genetic and environmental factors. Advances in techniques of molecular genetics have revealed that genetic ground significantly influences susceptibility to atherosclerotic vascular diseases. Besides further investigations of monogenetic diseases, candidate genes, genetic polymorphisms, and susceptibility loci associated with atherosclerotic diseases have been identified in recent years, and their number is rapidly increasing. This paper discusses main genetic investigations fields associated with human atherosclerotic vascular diseases. The paper concludes with a discussion of the directions and implications of future genetic research in arteriosclerosis with an emphasis on prospective prediction from an early age of individuals who are predisposed to develop premature atherosclerosis as well as to facilitate the discovery of novel drug targets.

  1. Association of susceptible genetic markers and autoantibodies in ...

    Indian Academy of Sciences (India)

    Although, the pathogenesis of RA is incompletely understood, genetic factors play a vital role in susceptibility to RA as the heritability of RA is between 50 and 60%, with the human leukocyte antigen (HLA) locus accounting for at least 30% of overall genetic risk. Non-HLA genes, i.e. tumour necrosis factor- (TNF-) within ...

  2. Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2

    NARCIS (Netherlands)

    N. Orr (Nick); F. Dudbridge (Frank); N. Dryden (Nicola); S. Maguire (Sarah); D. Novo (Daniela); E. Perrakis (Eleni); N. Johnson (Nichola); M. Ghoussaini (Maya); J. Hopper (John); M.C. Southey (Melissa); C. Apicella (Carmel); J. Stone (Jennifer); M.K. Schmidt (Marjanka); A. Broeks (Annegien); L.J. van 't Veer (Laura); F.B.L. Hogervorst (Frans); P.A. Fasching (Peter); L. Haeberle (Lothar); A.B. Ekici (Arif); M.W. Beckmann (Matthias W.); L.J. Gibson (Lorna); A. Aitken; H. Warren (Helen); E.J. Sawyer (Elinor); I.P. Tomlinson (Ian); M. Kerin (Michael); N. Miller (Nicola); B. Burwinkel (Barbara); F. Marme (Federick); A. Schneeweiss (Andreas); C. Sohn (Chistof); P. Guénel (Pascal); T. Truong (Thérèse); E. Cordina-Duverger (Emilie); M. Sanchez (Marie); S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); S.F. Nielsen (Sune); H. Flyger (Henrik); J. Benítez (Javier); M.P. Zamora (Pilar); J.I.A. Perez (Jose Ignacio Arias); P. Menéndez (Primitiva); H. Anton-Culver (Hoda); S.L. Neuhausen (Susan); H. Brenner (Hermann); A.K. Dieffenbach (Aida Karina); V. Arndt (Volker); C. Stegmaier (Christa); U. Hamann (Ute); H. Brauch (Hiltrud); C. Justenhoven (Christina); T. Brüning (Thomas); Y.-D. Ko (Yon-Dschun); H. Nevanlinna (Heli); K. Aittomäki (Kristiina); C. Blomqvist (Carl); S. Khan (Sofia); N.V. Bogdanova (Natalia); T. Dörk (Thilo); A. Lindblom (Annika); S. Margolin (Sara); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J.M. Hartikainen (J.); G. Chenevix-Trench (Georgia); J. Beesley (Jonathan); D. Lambrechts (Diether); M. Moisse (Matthieu); O.A.M. Floris; B. Beuselinck (B.); J. Chang-Claude (Jenny); A. Rudolph (Anja); P. Seibold (Petra); D. Flesch-Janys (Dieter); P. Radice (Paolo); P. Peterlongo (Paolo); B. Peissel (Bernard); V. Pensotti (Valeria); F.J. Couch (Fergus); J.E. Olson (Janet); S. Slettedahl (Seth); C. Vachon (Celine); G.G. Giles (Graham G.); R.L. Milne (Roger L.); C.A. McLean (Catriona Ann); C.A. Haiman (Christopher); B.E. Henderson (Brian); F.R. Schumacher (Fredrick); L. Le Marchand (Loic); J. Simard (Jacques); M.S. Goldberg (Mark); F. Labrèche (France); M. Dumont (Martine); V. Kristensen (Vessela); G.G. Alnæs (Grethe); S. Nord (Silje); A.-L. Borresen-Dale (Anne-Lise); W. Zheng (Wei); S.L. Deming-Halverson (Sandra); M. Shrubsole (Martha); J. Long (Jirong); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); M. Grip (Mervi); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); S. Tchatchou (Sandrine); P. Devilee (Peter); R.A.E.M. Tollenaar (Robertus A. E. M.); C.M. Seynaeve (Caroline); C.J. van Asperen (Christi); M. García-Closas (Montserrat); J.D. Figueroa (Jonine); S.J. Chanock (Stephen); J. Lissowska (Jolanta); K. Czene (Kamila); H. Darabi (Hatef); M. Eriksson (Mikael); D. Klevebring (Daniel); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); C.H.M. van Deurzen (Carolien); M. Kriege (Mieke); P. Hall (Per); J. Li (Jingmei); J. Liu (Jianjun); M.K. Humphreys (Manjeet); A. Cox (Angela); S.S. Cross (Simon); M.W.R. Reed (Malcolm); P.D.P. Pharoah (Paul); A.M. Dunning (Alison); M. Shah (Mitul); B. Perkins (Barbara); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska-Bieniek (Katarzyna); K. Durda (Katarzyna); A. Ashworth (Alan); A.J. Swerdlow (Anthony ); M. Jones (Michael); M. Schoemaker (Minouk); A. Meindl (Alfons); R.K. Schmutzler (Rita); C. Olswold (Curtis); S. Slager (Susan); A.E. Toland (Amanda); D. Yannoukakos (Drakoulis); K.R. Muir (K.); A. Lophatananon (Artitaya); S. Stewart-Brown (Sarah); P. Siriwanarangsan (Pornthep); K. Matsuo (Keitaro); H. Ito (Hidema); H. Iwata (Hisato); J. Ishiguro (Junko); A.H. Wu (Anna H.); C.-C. Tseng (Chiu-chen); D. Van Den Berg (David); D.O. Stram (Daniel O.); S.-H. Teo; C.H. Yip (Cheng Har); P. Kang (Peter); M.K. Ikram (Kamran); X.-O. Shu (Xiao-Ou); W. Lu (Wei); Y. Gao; H. Cai (Hui); D. Kang (Daehee); J.-Y. Choi (J.); S.K. Park (Sue); D-Y. Noh (Dong-Young); J.M. Hartman (Joost); X. Miao; W.-Y. Lim (Wei-Yen); S.C. Lee (Soo Chin); S. Sangrajrang (Suleeporn); V. Gaborieau (Valerie); P. Brennan (Paul); J.D. McKay (James); P.-E. Wu (Pei-Ei); M.-F. Hou (Ming-Feng); J-C. Yu (Jyh-Cherng); C-Y. Shen (Chen-Yang); W.J. Blot (William); Q. Cai (Qiuyin); L.B. Signorello (Lisa B.); C. Luccarini (Craig); C. Bayes (Caroline); S. Ahmed (Shahana); M. Maranian (Melanie); S. Healey (Sue); A. González-Neira (Anna); G. Pita (G.); M. Rosario Alonso; N. Álvarez (Nuria); D. Herrero (Daniel); D.C. Tessier (Daniel C.); D. Vincent (Daniel); F. Bacot (Francois); D. Hunter (David); S. Lindstrom (Stephen); J. Dennis (Joe); K. Michailidou (Kyriaki); M.K. Bolla (Manjeet); D.F. Easton (Douglas); I. dos Santos Silva (Isabel); O. Fletcher (Olivia); J. Peto (Julian)

    2015-01-01

    textabstractWe recently identified a novel susceptibility variant, rs865686, for estrogen-receptor positive breast cancer at 9q31.2. Here, we report a fine-mapping analysis of the 9q31.2 susceptibility locus using 43 160 cases and 42 600 controls of European ancestry ascertained from 52 studies and

  3. Locus of Control, Interest in Schooling and Science Achievement of Some Deaf and Typical Secondary School Students in Nigeria

    Science.gov (United States)

    Olatoye, R. Ademola; Aanu, E. Mosunmola

    2010-01-01

    This study compared locus of control, interest in school and science achievement of typical and deaf secondary school students. The study also investigated influence of students' locus of control and interest in school on general science achievement. Seventy two (72) deaf and 235 typical children were purposively selected from eight secondary…

  4. Rapid identification of a new gene influencing low amylose content in rice landraces (Oryza sativa L.) using genome-wide association study with specific-locus amplified fragment sequencing.

    Science.gov (United States)

    Yang, Xinghai; Nong, Baoxuan; Xia, Xiuzhong; Zhang, Zongqiong; Zeng, Yu; Liu, Kaiqiang; Deng, Guofu; Li, Danting

    2017-06-01

    Starch is the major component of milled rice, and amylose content (AC) affects eating quality. In this study, a genome-wide association study (GWAS) with specific-locus amplified fragment sequencing (SLAF-seq) data was performed for AC on a core collection of 419 rice landraces. Using the compressed mixed linear method based on the Q+K model, we identified a new gene, LAC6 (Chr6: 5.65-6.04 Mb), associated with AC in the low amylose content panel. The LAC6 candidate gene was detected by qRT-PCR in rice panicles. Results indicate that LOC_Os06g11130 was up-regulated, and LOC_Os06g11340 was significantly down-regulated, making it most likely a key candidate gene of LAC6. In conclusion, the findings provide a certain theoretiacal basis of molecular biology for genetic improvement of AC in rice and rice quality variety breeding.

  5. Complex interactions between new loci, Sluc1, Sluc2, Sluc3 and Sluc4, that influence the susceptibility to lung cancer in the mouse

    NARCIS (Netherlands)

    Fijneman, R.J.A.; Vries, de S.S.; Jansen, R.C.; Demant, P.

    1996-01-01

    Many complex traits, including susceptibility to lung cancer, are controlled by multiple genes - quantitative trait loci (QTLs). We facilitated the mapping of QTLs by making use of recombinant congenic strains (RCS), a system of mouse inbred strains in which the genetic complexity is reduced, and by

  6. Complex interactions of new quantitative trait loci, Sluc1, Sluc2, Sluc3, and Sluc4, that influence the susceptibility to lung cancer in the mouse

    NARCIS (Netherlands)

    Fijneman, Remond J.A.; Vries, Sandra S. de; Jansen, Ritsert C.; Demant, Peter

    1996-01-01

    Many complex traits, including susceptibility to lung cancer, are controlled by multiple genes - quantitative trait loci (QTLs). We facilitated the mapping of QTLs by making use of recombinant congenic strains (RCS), a system of mouse inbred strains in which the genetic complexity is reduced, and by

  7. Chemokine MCP1/CCL2 and RANTES/CCL5 gene polymorphisms influence Henoch–Schönlein purpura susceptibility and severity

    Directory of Open Access Journals (Sweden)

    Hsin-Hui Yu

    2015-04-01

    Conclusion: Our results support the fact that chemokines play important roles in the pathogenesis of HSP. MCP1/CCL2 gene polymorphisms were associated with susceptibility for HSP. RANTES/CCL5 gene polymorphisms may be related to disease severity and HSP nephritis.

  8. Locus of Control and Religious Orientation.

    Science.gov (United States)

    Talbott, Anne Marie; Heritage, Jeannette

    Rotter's Internal-External Locus of Control Scale has been the focus of much research since its introduction in 1966. To further that research, the relationships among locus of control, level of religious belief, attitudes toward women, attitudes toward feminism, attitudes toward homosexuality, gender, and traditional versus nontraditional…

  9. Impact of divorce on locus of control orientation in adult women: a longitudinal study.

    Science.gov (United States)

    Doherty, W J

    1983-04-01

    Using longitudinal data for adult women from the National Longitudinal Surveys of Labor Market Experience, this study examined the relation between getting divorced and changes in the individual's locus of control orientation. The sample contained 1,814 white women ages 32-46 years who were in their first marriage in 1969. Marital status and locus of control (an 11-item abbreviated version of Rotter's Internal-External Locus of Control Scale) were measured in 1969, 1972, and 1977. Based on previous literature on locus of control and life events and on divorce, stress, and mental health, the author hypothesized that divorced people, in comparison with those who remained married, would show a short-term increase in externality from 1969-1972, followed by a return over the next 5 years to levels of locus of control comparable to that of the group who remained married. It was also hypothesized that locus of control scores would not predict the likelihood of becoming divorced over the 8-year period. All three hypotheses were confirmed. The findings were discussed in the context of two larger theoretical issues: the influence of important life events on locus of control and the causal direction in the well-documented association between divorce and mental health.

  10. Changes in susceptibility of beech (Fagus sylvatica) seedlings towards Phytophthora citricola under the influence of elevated atmospheric CO2 and nitrogen fertilization.

    Science.gov (United States)

    Fleischmann, F; Raidl, S; Osswald, W F

    2010-04-01

    The growth-differentiation balance hypothesis (GDBH) predicts changes in susceptibility of plants against herbivores with changing resource availability. In the presented study we tested the validity of the GDBH for trees infected with a root pathogen. For this purpose Fagus sylvatica seedlings grown under different atmospheric CO(2)- and soil nitrogen regimes were infected with the root pathogen Phytophthora citricola. High nitrogen supply increased total biomass of beech regardless of the CO(2)-treatment, whereas elevated CO(2) enhanced biomass only in the high nitrogen treatment. The responses of beech under the different growing regimes to the Phytophthora root infection were not in line with the predictions of the GDBH. Enhanced susceptibility of beech against P. citricola was found in seedlings grown under elevated CO(2) and low nitrogen supply. Fifteen months after inoculation these plants were characterized by enhanced water use efficiency, by altered root-shoot ratios, and by enhanced specific root tip densities. 2009 Elsevier Ltd. All rights reserved.

  11. Linkage disequilibrium at the APA insecticidal seed protein locus of common bean (Phaseolus vulgaris L.).

    Science.gov (United States)

    Blair, Matthew W; Prieto, Sergio; Díaz, Lucy M; Buendía, Héctor F; Cardona, César

    2010-04-29

    An interesting seed protein family with a role in preventing insect herbivory is the multi-gene, APA family encoding the alpha-amylase inhibitor, phytohemagglutinin and arcelin proteins of common bean (Phaseolus vulgaris). Variability for this gene family exists and has been exploited to breed for insect resistance. For example, the arcelin locus has been successfully transferred from wild to cultivated common bean genotypes to provide resistance against the bruchid species Zabrotes subfasciatus although the process has been hampered by a lack of genetic tools for and understanding about the locus. In this study, we analyzed linkage disequilibrium (LD) between microsatellite markers at the APA locus and bruchid resistance in a germplasm survey of 105 resistant and susceptible genotypes and compared this with LD in other parts of the genome. Microsatellite allele diversity was found to vary with each of the eight APA-linked markers analyzed, and two markers within the APA locus were found to be diagnostic for bruchid resistance or susceptibility and for the different arcelin alleles inherited from the wild accessions. Arc1 was found to provide higher levels of resistance than Arc5 and the markers in the APA locus were highly associated with resistance showing that introgression of this gene-family from wild beans provides resistance in cultivated beans. LD around the APA locus was found to be intermediate compared to other regions of the genome and the highest LD was found within the APA locus itself for example between the markers PV-atct001 and PV-ag004. We found the APA locus to be an important genetic determinant of bruchid resistance and also found that LD existed mostly within the APA locus but not beyond it. Moderate LD was also found for some other regions of the genome perhaps related to domestication genes. The LD pattern may reflect the introgression of arcelin from the wild into the cultivated background through breeding. LD and association studies for

  12. Linkage disequilibrium at the APA insecticidal seed protein locus of common bean (Phaseolus vulgaris L.

    Directory of Open Access Journals (Sweden)

    Buendía Héctor F

    2010-04-01

    Full Text Available Abstract Background An interesting seed protein family with a role in preventing insect herbivory is the multi-gene, APA family encoding the α-amylase inhibitor, phytohemagglutinin and arcelin proteins of common bean (Phaseolus vulgaris. Variability for this gene family exists and has been exploited to breed for insect resistance. For example, the arcelin locus has been successfully transferred from wild to cultivated common bean genotypes to provide resistance against the bruchid species Zabrotes subfasciatus although the process has been hampered by a lack of genetic tools for and understanding about the locus. In this study, we analyzed linkage disequilibrium (LD between microsatellite markers at the APA locus and bruchid resistance in a germplasm survey of 105 resistant and susceptible genotypes and compared this with LD in other parts of the genome. Results Microsatellite allele diversity was found to vary with each of the eight APA-linked markers analyzed, and two markers within the APA locus were found to be diagnostic for bruchid resistance or susceptibility and for the different arcelin alleles inherited from the wild accessions. Arc1 was found to provide higher levels of resistance than Arc5 and the markers in the APA locus were highly associated with resistance showing that introgression of this gene-family from wild beans provides resistance in cultivated beans. LD around the APA locus was found to be intermediate compared to other regions of the genome and the highest LD was found within the APA locus itself for example between the markers PV-atct001 and PV-ag004. Conclusions We found the APA locus to be an important genetic determinant of bruchid resistance and also found that LD existed mostly within the APA locus but not beyond it. Moderate LD was also found for some other regions of the genome perhaps related to domestication genes. The LD pattern may reflect the introgression of arcelin from the wild into the cultivated

  13. Gene susceptibility identification in a longitudinal study confirms new loci in the development of chronic obstructive pulmonary disease and influences lung function decline.

    Science.gov (United States)

    Xie, Jungang; Wu, Hongxu; Xu, Yuzhu; Wu, Xiaojie; Liu, Xue; Shang, Jin; Zhao, Jianping; Zhao, Junling; Wang, Jianmiao; Dela Cruz, Charles S; Xiong, Weining; Xu, Yongjian

    2015-04-18

    To identify COPD associated gene susceptibility and lung function in a longitudinal cohort including COPD and subjects who were at risk for developing COPD, and to replicate this in two cross-sectional and longitudinal populations in Chinese Han population. Three cohorts were recruited in this study, including an 18-year follow-up population (306 COPD and 743 control subjects) in one village in 1992 and it changed to 409 COPD and 611 controls in 2010, a 2 year follow-up study in another village (374 COPD and 377 controls) and another 2 year follow-up one in a city (541 COPD and 560 controls) in 2010. Sixteen candidate single nucleotide polymorphisms (SNPs) were selected for genotyping. Among them, 5SNPs in or near HHIP, 1SNP in IREB2 and 1SNP in FAM13A were previously reported to be associated with COPD susceptibility or lung function decline. And another 9SNPs were selected from HapMap website as HHIP tags. In 2010, totaling 1,324 COPD patients and 1,548 healthy controls were finally included in our genetic susceptibility analyses. We identified two new regions showing an association with COPD susceptibility in the Human Hedgehog interacting protein (HHIP) rs11100865 and rs7654947, and we confirmed that the family with sequence similarity 13 member A gene (FAM13A) rs7671167 was associated with the development of COPD in Chinese Han population. And the HHIP rs7654947 and FAM13A rs7671167 were associated with lung function decline, and this result was replicated in other two populations. These results suggest an important role of the HHIP and FAM13A regions as genetic risk factors for COPD development and lung function decline in Chinese Han population. Future research on these genes should focus on the molecular mechanisms of these genes on developing COPD and creating therapies to alleviate reduced lung function.

  14. Genetic background (DDD/Sgn versus C57BL/6J) strongly influences postnatal growth of male mice carrying the A(y) allele at the agouti locus: identification of quantitative trait loci associated with diabetes and body weight loss.

    Science.gov (United States)

    Suto, Jun-ichi; Satou, Kunio

    2013-05-04

    Mice carrying the A(y) allele at the agouti locus become obese and are heavier than their non-A(y) littermates. However, this does not hold true for the genetic background of the DDD mouse strain. At 22 weeks of age, DDD.Cg-A(y) females are heavier than DDD females, whereas DDD.Cg-A(y) males are lighter than DDD males. This study aimed to determine the possible cause and identify the genes responsible for the lower body weight of DDD.Cg-A(y) males. Growth curves of DDD.Cg-A(y) mice were analyzed and compared with those of B6.Cg-A(y) mice from 5 to 25 weeks. In DDD.Cg-A(y) males, body weight gain stopped between 16 and 17 weeks and the body weight gradually decreased; thus, the lower body weight was a consequence of body weight loss. Quantitative trait locus (QTL) mapping was performed in backcrossed (BC) males of DDD × (B6 × DDD.Cg-A(y)) F(1)-A(y) mice. For the body weight at 25 weeks, significant QTLs were identified on chromosomes 1 and 4. The DDD allele was associated with a lower body weight at both loci. In particular, the QTL on chromosome 4 interacted with the A(y) allele. Furthermore, suggestive QTLs for plasma glucose and high molecular weight adiponectin levels were coincidentally mapped to chromosome 4. The DDD allele was associated with increased glucose and decreased adiponectin levels. When the body weight at 25 weeks and plasma glucose levels were considered as dependent and independent variables, respectively, BC A(y) males were classified into two groups according to statistical analysis using the partition method. Mice of one group had significantly higher glucose and lower adiponectin levels than those of the other group and exhibited body weight loss as observed with DDD-A(y) males. The lower body weight of DDD.Cg-A(y) male mice was a consequence of body weight loss. Diabetes mellitus has been suggested to be a possible contributory factor causing body weight loss. The QTL on distal chromosome 4 contained the major responsible genes. This QTL

  15. Genetic background (DDD/Sgn versus C57BL/6J) strongly influences postnatal growth of male mice carrying the Ay allele at the agouti locus: identification of quantitative trait loci associated with diabetes and body weight loss

    Science.gov (United States)

    2013-01-01

    Background Mice carrying the Ay allele at the agouti locus become obese and are heavier than their non-Ay littermates. However, this does not hold true for the genetic background of the DDD mouse strain. At 22 weeks of age, DDD.Cg-Ay females are heavier than DDD females, whereas DDD.Cg-Ay males are lighter than DDD males. This study aimed to determine the possible cause and identify the genes responsible for the lower body weight of DDD.Cg-Ay males. Results Growth curves of DDD.Cg-Ay mice were analyzed and compared with those of B6.Cg-Ay mice from 5 to 25 weeks. In DDD.Cg-Ay males, body weight gain stopped between 16 and 17 weeks and the body weight gradually decreased; thus, the lower body weight was a consequence of body weight loss. Quantitative trait locus (QTL) mapping was performed in backcrossed (BC) males of DDD × (B6 × DDD.Cg-Ay) F1-Ay mice. For the body weight at 25 weeks, significant QTLs were identified on chromosomes 1 and 4. The DDD allele was associated with a lower body weight at both loci. In particular, the QTL on chromosome 4 interacted with the Ay allele. Furthermore, suggestive QTLs for plasma glucose and high molecular weight adiponectin levels were coincidentally mapped to chromosome 4. The DDD allele was associated with increased glucose and decreased adiponectin levels. When the body weight at 25 weeks and plasma glucose levels were considered as dependent and independent variables, respectively, BC Ay males were classified into two groups according to statistical analysis using the partition method. Mice of one group had significantly higher glucose and lower adiponectin levels than those of the other group and exhibited body weight loss as observed with DDD-Ay males. Conclusions The lower body weight of DDD.Cg-Ay male mice was a consequence of body weight loss. Diabetes mellitus has been suggested to be a possible contributory factor causing body weight loss. The QTL on distal chromosome 4 contained the major responsible genes

  16. Changes in susceptibility of beech (Fagus sylvatica) seedlings towards Phytophthora citricola under the influence of elevated atmospheric CO{sub 2} and nitrogen fertilization

    Energy Technology Data Exchange (ETDEWEB)

    Fleischmann, F., E-mail: fleischmann@wzw.tum.d [Phytopathology of Woody Plants, Technische Universitaet Muenchen, Am Hochanger 13, 85354 Freising (Germany); Raidl, S. [Department Biology I and GeoBioCenterLMU, Systematic Mycology, Ludwig Maximilians Universitaet Muenchen, Menzinger Strasse 67, 80638 Muenchen (Germany); Osswald, W.F. [Phytopathology of Woody Plants, Technische Universitaet Muenchen, Am Hochanger 13, 85354 Freising (Germany)

    2010-04-15

    The growth-differentiation balance hypothesis (GDBH) predicts changes in susceptibility of plants against herbivores with changing resource availability. In the presented study we tested the validity of the GDBH for trees infected with a root pathogen. For this purpose Fagus sylvatica seedlings grown under different atmospheric CO{sub 2}- and soil nitrogen regimes were infected with the root pathogen Phytophthora citricola. High nitrogen supply increased total biomass of beech regardless of the CO{sub 2}-treatment, whereas elevated CO{sub 2} enhanced biomass only in the high nitrogen treatment. The responses of beech under the different growing regimes to the Phytophthora root infection were not in line with the predictions of the GDBH. Enhanced susceptibility of beech against P. citricola was found in seedlings grown under elevated CO{sub 2} and low nitrogen supply. Fifteen months after inoculation these plants were characterized by enhanced water use efficiency, by altered root-shoot ratios, and by enhanced specific root tip densities. - Susceptibility of Fagus sylvatica to the root pathogen Phytophthora citricola increased under elevated CO{sub 2}

  17. Detecting marker-disease association by testing for Hardy-Weinberg disequilibrium at a marker locus.

    Science.gov (United States)

    Nielsen, D M; Ehm, M G; Weir, B S

    1998-01-01

    We review and extend a recent suggestion that fine-scale localization of a disease-susceptibility locus for a complex disease be done on the basis of deviations from Hardy-Weinberg equilibrium among affected individuals. This deviation is driven by linkage disequilibrium between disease and marker loci in the whole population and requires a heterogeneous genetic basis for the disease. A finding of marker-locus Hardy-Weinberg disequilibrium therefore implies disease heterogeneity and marker-disease linkage disequilibrium. Although a lack of departure of Hardy-Weinberg disequilibrium at marker loci implies that disease susceptibilityweighted linkage disequilibria are zero, given disease heterogeneity, it does not follow that the usual measures of linkage disequilibrium are zero. For disease-susceptibility loci with more than two alleles, therefore, care is needed in the drawing of inferences from marker Hardy-Weinberg disequilibria. PMID:9867708

  18. Susceptibility Genes in Thyroid Autoimmunity

    Directory of Open Access Journals (Sweden)

    Yoshiyuki Ban

    2005-01-01

    Full Text Available The autoimmune thyroid diseases (AITD are complex diseases which are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility in combination with external factors (e.g. dietary iodine is believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been employed to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions that are linked with AITD, and in some of these loci, putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves' disease (GD and Hashimoto's thyroiditis (HT and some are common to both the diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g. HLA, CTLA-4 and thyroid specific genes (e.g. TSHR, Tg. Most likely, these loci interact and their interactions may influence disease phenotype and severity.

  19. A dominant chromatin opening activity in 5' hypersensitive site 3 of the human β-globin locus control region.

    NARCIS (Netherlands)

    J. Ellis (James); K.C. Tan-Un; A. Harper; D. Michalovich (David); P.J. Fraser (Peter); N. Yannoutsos (Nikos); F.G. Grosveld (Frank)

    1996-01-01

    textabstractSingle-copy human beta-globin transgenes are very susceptible to suppression by position effects of surrounding closed chromatin. However, these position effects are overcome by a 20 kbp DNA fragment containing the locus control region (LCR). Here we show that the 6.5 kbp microlocus LCR

  20. Role of the locus coeruleus in enhanced orexin A-induced spontaneous physical activity in obesity-resistant rats

    National Research Council Canada - National Science Library

    Teske, Jennifer A; Perez-Leighton, Claudio E; Billington, Charles J; Kotz, Catherine M

    2013-01-01

    Orexin/hypocretin terminals innervate noradrenergic locus coeruleus (LC) neurons that project to the prefrontral cortex, which may influence spontaneous physical activity (SPA) and energy balance. Obesity-resistant...

  1. Raising Issues of Student Locus of Control: Beginning a Longitudinal Study

    Science.gov (United States)

    Smith, Carol A.; Mihans, Richard J., II

    2009-01-01

    Locus of control is considered the belief in one's ability to influence life events. Someone who accepts both positive and negative outcomes and consequences as the result of their own behaviour is considered "internal" whereas someone who considers others to have influence over both positive (luck) and negative (others' fault) results…

  2. Assessing God Locus of Control as a Factor in College Students' Alcohol Use and Sexual Behavior

    Science.gov (United States)

    Moore, Erin W.

    2014-01-01

    Objectives: This study explored God locus of control beliefs (ie, God's control over behavior) regarding their influence on alcohol use and sexual behavior as an alternative religiosity measure to religious behaviors, which does not capture perceived influence of religiosity. Additionally, demographic differences in religious beliefs were…

  3. Social capital, political trust, and health locus of control: a population-based study.

    Science.gov (United States)

    Lindström, Martin

    2011-02-01

    To investigate the association between political trust in the Riksdag and lack of belief in the possibility to influence one's own health (external locus of control), taking horizontal trust into account. The 2008 public health survey in Skåne is a cross-sectional postal questionnaire study with a 55% participation rate. A random sample of 28,198 persons aged 18-80 years participated. Logistic regression models were used to investigate the associations between political trust in the Riksdag (an aspect of vertical trust) and lack of belief in the possibility to influence one's own health (external locus of control). The multiple regression analyses included age, country of birth, education, and horizontal trust in other people. A 33.7% of all men and 31.8% of all women lack internal locus of control. Low (external) health locus of control is more common in higher age groups, among people born outside Sweden, with lower education, low horizontal trust, low political trust, and no opinion concerning political trust. Respondents with not particularly strong political trust, no political trust at all and no opinion have significantly higher odds ratios of external locus of control throughout the multiple regression analyses. Low political trust in the Riksdag seems to be independently associated with external health locus of control.

  4. EL LOCUS DE DISTRIBUCION COMO COROLARIO DEL LOCUS DE CONTROL

    Directory of Open Access Journals (Sweden)

    Luisa Mayoral

    2009-01-01

    Full Text Available Este es un artículo científico acerca del Locus de Distribución, surgido de un estudio realizado con una población de docentes y alumnos universitarios. Respecto de los primeros, se ha indagado acerca de las atribuciones que se realizaban en torno a las recompensas y sanciones, que ellos distribuían a sus alumnos. Respecto de los segundos, se ha buscado determinar la valoración que estos realizaban de sus profesores, en términos de aquellas atribuciones. Para ello, se utilizaron dos paradigmas clásicamente empleados para verificar la existencia de una norma: el paradigma de la autopresentación (docentes, y el paradigma de los juicios (alumnos. La cuestión planteada fue determinar si en el caso de los comportamientos distributivos de refuerzos, las causas se atribuían a variables externas -en particular a los receptores de esos refuerzos- y si esas formas de atribución eran conocidas y valoradas o no, por los alumnos. De los resultados, surgió la confirmación de nuestra hipótesis de explicaciones externas en materia de comportamientos distributivos de sanciones en el ámbito de la docencia y la valoración positiva de estas atribuciones por los alumnos.

  5. RHD maternal-fetal genotype incompatibility increases schizophrenia susceptibility.

    Science.gov (United States)

    Palmer, Christina G S; Turunen, Joni A; Sinsheimer, Janet S; Minassian, Sonia; Paunio, Tiina; Lönnqvist, Jouko; Peltonen, Leena; Woodward, J Arthur

    2002-12-01

    Fetal events and obstetric complications are associated with schizophrenia. Here we report the results of a family-based candidate-gene study that assesses the role of maternal-fetal genotype incompatibility at the RHD locus in schizophrenia. We adapted the case-parent-trio log-linear modeling approach to test for RHD maternal-fetal genotype incompatibility and to distinguish this effect from a high-risk allele at or near the RHD locus and from a direct maternal effect alone. Eighty-eight patient-parent trios, 72 patient-mother pairs, and 21 patient-father pairs were genotyped at the RHD locus. Of the 181 patients, 62% were male and 81% were second born or later. Only three patients were born after prophylaxis against maternal isoimmunization had become common practice. There was significant evidence for an RHD maternal-fetal genotype incompatibility, and the incompatibility parameter was estimated at 2.6. There was no evidence to support linkage/association with schizophrenia at or near the RHD locus nor any evidence to support the role of maternal genotype effect alone. Our results replicate previous findings that implicate the RHD locus in schizophrenia, and the candidate-gene design of this study allows the elimination of alternative explanations for the role of this locus in disease. Thus, the present study provides increasing evidence that the RHD locus increases schizophrenia risk through a maternal-fetal genotype incompatibility mechanism that increases risk of an adverse prenatal environment (e.g., Rh incompatibility) rather than through linkage/association with the disorder, linkage disequilibrium with an unknown nearby susceptibility locus, or a direct maternal effect alone. This is the first candidate-gene study to explicitly test for and provide evidence of a maternal-fetal genotype incompatibility mechanism in schizophrenia.

  6. Susceptibility to HIV-1 infection is influenced by toll like receptor-2 (-196 to -174) polymorphism in a north Indian population.

    Science.gov (United States)

    Vidyant, Sanjukta; Chatterjee, Animesh; Agarwal, Vikas; Dhole, Tapan N

    2017-08-01

    Toll like receptors (TLRs) are pattern recognition receptors that recognize molecular patterns of pathogens and play an important role in innate immunity. Recent studies have identified that a single nucleotide polymorphism (SNP) in the TLR gene impairs the response to TLR ligands in some individuals and is associated with susceptibility to various infectious diseases. The present study aimed to investigate the role of four SNPs in the TLR2 gene [-196 to -174 Ins/Del, 2258 G/A (Arg753Gln), 2029 C/T (Arg677Trp) and 1892 C/A (Pro631His)] with respect to susceptibility and progression to HIV-1 in North Indian individuals. The study population consisted of 160 HIV-1 seropositive patients stratified on the basis of disease severity (stages I, II and III) and 270 HIV-1 seronegative individuals. The subjects were genotyped for TLR2 gene polymorphism by polymerase chain reaction restriction fragment length polymorphism. In the present study, we found that the TLR2 Del mutant genotype [odds ratio (OR) = 2.138; p = 0.001] and allele (OR = 1.562; p = 0.002) was at a higher frequency in patients with HIV-1 infection compared to healthy controls and was significantly associated with the risk of HIV-1 infection and disease susceptibility. Furthermore, we also found that TLR2 Del homozygous genotype was at a lower frequency in stage III (19.35%) compared to stage I (50.87%; OR = 1.901) and stage II (43.05%; OR = 1.514) and was associated with a reduced risk of HIV-1 disease progression. The present study reports for the first time that the TLR2-196 to -174 Ins/Del polymorphism is a risk factor for HIV-1 transmission in HIV-1 infected North Indian individuals. Copyright © 2017 John Wiley & Sons, Ltd.

  7. Translocations affecting human immunoglobulin heavy chain locus

    Directory of Open Access Journals (Sweden)

    Sklyar I. V.

    2014-03-01

    Full Text Available Translocations involving human immunoglobulin heavy chain (IGH locus are implicated in different leukaemias and lymphomas, including multiple myeloma, mantle cell lymphoma, Burkitt’s lymphoma and diffuse large B cell lymphoma. We have analysed published data and identified eleven breakpoint cluster regions (bcr related to these cancers within the IgH locus. These ~1 kbp bcrs are specific for one or several types of blood cancer. Our findings could help devise PCR-based assays to detect cancer-related translocations, to identify the mechanisms of translocations and to help in the research of potential translocation partners of the immunoglobulin locus at different stages of B-cell differentiation.

  8. Age and prior blood feeding of Anopheles gambiae influences their susceptibility and gene expression patterns to ivermectin-containing blood meals.

    Science.gov (United States)

    Seaman, Jonathan A; Alout, Haoues; Meyers, Jacob I; Stenglein, Mark D; Dabiré, Roch K; Lozano-Fuentes, Saul; Burton, Timothy A; Kuklinski, Wojtek S; Black, William C; Foy, Brian D

    2015-10-15

    Ivermectin has been proposed as a novel malaria transmission control tool based on its insecticidal properties and unique route of acquisition through human blood. To maximize ivermectin's effect and identify potential resistance/tolerance mechanisms, it is important to understand its effect on mosquito physiology and potential to shift mosquito population age-structure. We therefore investigated ivermectin susceptibility and gene expression changes in several age groups of female Anopheles gambiae mosquitoes. The effect of aging on ivermectin susceptibility was analyzed in three age groups (2, 6, and 14-days) of colonized female Anopheles gambiaemosquitoes using standard survivorship assays. Gene expression patterns were then analyzed by transcriptome sequencing on an Illumina HiSeq 2500 platform. RT-qPCR was used to validate transcriptional changes and also to examine expression in a different, colonized strain and in wild mosquitoes, both of which blood fed naturally on an ivermectin-treated person. Mosquitoes of different ages and blood meal history died at different frequencies after ingesting ivermectin. Mortality was lowest in 2-day old mosquitoes exposed on their first blood meal and highest in 6-day old mosquitoes exposed on their second blood meal. Twenty-four hours following ivermectin ingestion, 101 and 187 genes were differentially-expressed relative to control blood-fed, in 2 and 6-day groups, respectively. Transcription patterns of select genes were similar in membrane-fed, colonized, and naturally-fed wild vectors. Transcripts from several unexpected functional classes were highly up-regulated, including Niemann-Pick Type C (NPC) genes, peritrophic matrix-associated genes, and immune-response genes, and these exhibited different transcription patterns between age groups, which may explain the observed susceptibility differences. Niemann-Pick Type 2 genes were the most highly up-regulated transcripts after ivermectin ingestion (up to 160 fold) and

  9. Genetic polymorphism at the CLOCK gene locus and major depression.

    Science.gov (United States)

    Desan, P H; Oren, D A; Malison, R; Price, L H; Rosenbaum, J; Smoller, J; Charney, D S; Gelernter, J

    2000-06-12

    Genetic analysis in both mouse and Drosophila has indicated that the product of the CLOCK gene is an essential component of a circadian rhythm timing system. A single nucleotide polymorphism (SNP), T3111C, in the 3' flanking region of the human CLOCK gene has been identified. Homozygotes or heterozygotes for the 3111C allele have been reported to have higher mean scores on a measure of evening preference for activity (vs. morning preference) than subjects homozygous for the 3111T allele. Since major depression is hypothesized to be closely linked to circadian rhythms, we explored whether this polymorphism might be related to susceptibility to major depression. We also ascertained allele frequency in an African-American control population, to begin to evaluate population variation at this locus. CLOCK T3111C allele frequencies were determined in 280 European American (EA) subjects, 143 with a history of major depression and 137 screened controls, and in 58 African American (AA) screened control subjects, using a polymerase chain reaction (PCR) - restriction fragment length polymorphism (RFLP) method. There was no significant difference between EA depressed and control subjects in allele frequency. There was a significant difference in allele frequency between EA and AA subjects, demonstrating a potential for population stratification. In none of these groups were significant deviations from Hardy-Weinberg equilibrium found. The present data do not support an association between CLOCK gene alleles at the T3111C locus and major depression.

  10. Magnetic susceptibilities of minerals

    Science.gov (United States)

    Rosenblum, Sam; Brownfield, I.K.

    2000-01-01

    Magnetic separation of minerals is a topic that is seldom reported in the literature for two reasons. First, separation data generally are byproducts of other projects; and second, this study requires a large amount of patience and is unusually tedious. Indeed, we suspect that most minerals probably are never investigated for this property. These data are timesaving for mineralogists who concentrate mono-mineralic fractions for chemical analysis, age dating, and for other purposes. The data can certainly be used in the ore-beneficiation industries. In some instances, magnetic-susceptibility data may help in mineral identification, where other information is insufficient. In past studies of magnetic separation of minerals, (Gaudin and Spedden, 1943; Tille and Kirkpatrick, 1956; Rosenblum, 1958; Rubinstein and others, 1958; Flinter, 1959; Hess, 1959; Baker, 1962; Meric and Peyre, 1963; Rojas and others, 1965; and Duchesne, 1966), the emphasis has been on the ferromagnetic and paramagnetic ranges of extraction. For readers interested in the history of magnetic separation of minerals, Krumbein and Pettijohn (1938, p. 344-346) indicated nine references back to 1848. The primary purpose of this paper is to report the magnetic-susceptibility data on as many minerals as possible, similar to tables of hardness, specific gravity, refractive indices, and other basic physical properties of minerals. A secondary purpose is to demonstrate that the total and best extraction ranges are influenced by the chemistry of the minerals. The following notes are offered to help avoid problems in separating a desired mineral concentrate from mixtures of mineral grains.

  11. Relationship between nursing students' epistemological beliefs and locus of control.

    Science.gov (United States)

    Yilmaz, Aylin; Kaya, Hülya

    2010-10-01

    The aim of this study was to determine the relationship between nursing students' epistemologic beliefs and locus of control, and the research was conducted at Istanbul University Florence Nightingale School of Nursing with 350 nursing students. Data were collected using the Turkish version of the Epistemological beliefs questionnaire and Rotter's Internal-External Locus of Control Scale. In the data analysis number, percentage, mean, correlation analysis, one-way analysis of variance and Tukey HSD test were used. The findings as whole indicated that nursing students' epistemological beliefs that "The Belief of Learning Depends on Effort (Effort)" showed a greater degree of development than their beliefs about the two other dimensions as named "The Belief of Learning Depends on Ability (Ability)" and "The Belief That There is Only One Unchanging Truth (Unchanging Truth)" in this study, while their belief that there is Unchanging Truth was not developed when compared to the other two. There was a positive correlation between nursing students locus of control and Effort and Ability dimensions, but a significant correlation was not found with Unchanging Truth dimension. This researcher suggests that research should be carried out to determine nursing students' epistemological beliefs and the factors influencing them in an environment to promote the development of these beliefs, and thus the research can be used to learn about the development of the epistemological beliefs. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. Locus of control and decision to abort.

    Science.gov (United States)

    Dixon, P N; Strano, D A; Willingham, W

    1984-04-01

    The relationship of locus of control to deciding on an abortion was investigated by administering Rotter's Locus of Control Scale to 118 women immediately prior to abortion and 2 weeks and 3 months following abortion. Subjects' scores were compared across the 3 time periods, and the abortion group's pretest scores were compared with those of a nonpregnant control, group. As hypothesized, the aborting group scored significantly more internal than the general population but no differences in locus of control were found across the 3 time period. The length of delay in deciding to abort an unwanted pregnancy following confirmation was also assessed. Women seeking 1st trimester abortions were divided into internal and external groups on the Rotter Scale and the lengths of delay were compared. The hypothesis that external scores would delay the decision longer than internal ones was confirmed. The results confirm characteristics of the locus of control construct and add information about personality characteristics of women undergoing abortion.

  13. A Revised Measure of Locus of Control

    Science.gov (United States)

    Clifford, Margaret M.

    1976-01-01

    A revised measure of locus of control for children and a summary of its descriptive statistics is presented. The nature of the instrument is discussed in light of Weiner's two-dimensional attribution table. (Author/MS)

  14. Maintaining (Locus of) Control? Assessing the Impact of Locus of Control on Education Decisions and Wages

    OpenAIRE

    Piatek, Rémi; Pinger, Pia

    2010-01-01

    This paper demonstrates that locus of control, i.e. whether individuals believe that reinforcement in life comes from their own actions instead of being determined by luck or destiny, is an important predictor of the decision to obtain higher education. Furthermore, the authors find that premarket locus of control, defined as locus of control measured at the time of schooling - before the individual enters the labor market - does not significantly affect later wages after controlling for educ...

  15. Culture, gender and locus of control

    DEFF Research Database (Denmark)

    Ottsen, Christina Lundsgaard; Johannessen, Kim Berg; Berntsen, Dorthe

    The current study is a cross-cultural comparison between the Middle East and Scandinavia. Two societies that offer a unique opportunity to examine gender differences in personal goals and how goals are affected by locus of control.......The current study is a cross-cultural comparison between the Middle East and Scandinavia. Two societies that offer a unique opportunity to examine gender differences in personal goals and how goals are affected by locus of control....

  16. The relationship between locus of control and ethical behaviour among employees in the financial sector

    Directory of Open Access Journals (Sweden)

    E. Boshoff

    2011-06-01

    Full Text Available Unethical behaviour is a rapidly escalating trend in the current work situation, where – within organisations – there appears to be a decrease in ethical behaviour at a national as well as international level. Employees within the financial sector form a specific area of interest concerning ethical behaviour in South Africa. Various incidents of unethical conduct are reported within the financial sector, necessitating a specific focus on factors which may influence ethical behaviour. Current research supports a person-situation-interaction approach to ethical decision-making, where both individual and situational factors influence the decisions of individuals. Research indicate that individual factors such as locus of control may influence ethical behaviour. The way these variables are related among employees in the financial sector in South Africa, however, has not as yet been demonstrated. In order to determine the relationship between locus of control and ethical behaviour, Schepers’Locus of Control Questionnaire and the Work Beliefs Questionnaire were administered to 100 employees in the financial sector in Bloemfontein. Statistically significant relationships(p≤0,05 were found between internal locus of control and ethical behaviour, external locus of control and ethical behaviour, as well as autonomy and ethical behaviour. Recommendations were made in the light of the results regarding the development of strategies and interventions to minimise unethical behaviour within organisations.

  17. Lactotransferrin gene functional polymorphisms do not influence susceptibility to human immunodeficiency virus-1 mother-to-child transmission in different ethnic groups

    Directory of Open Access Journals (Sweden)

    Luisa Zupin

    2015-04-01

    Full Text Available Lactotransferrin, also known as lactoferrin, is an iron binding glycoprotein that displays antiviral activity against many different infectious agents, including human immunodeficiency virus (HIV-1. Lactotransferrin is present in the breast milk and in the female genitourinary mucosa and it has been hypothesised as a possible candidate to prevent mother-to-child HIV-1 transmission. To verify if two functional polymorphisms, Thr29Ala and Arg47Lys, in the lactotransferrin encoding gene (LTF could affect HIV-1 infection and vertical transmission, a preliminary association study was performed in 238 HIV-1 positive and 99 HIV-1 negative children from Brazil, Italy, Africa and India. No statistically significant association for the Thr29Ala and Arg47Lys LTF polymorphisms and HIV-1 susceptibility in the studied populations was found. Additionally LTF polymorphisms frequencies were compared between the four different ethnic groups.

  18. Young women's condom use: the influence of acceptance of sexuality, control over the sexual encounter, and perceived susceptibility to common STDs.

    Science.gov (United States)

    Bryan, A D; Aiken, L S; West, S G

    1997-09-01

    A comprehensive model of the determinants of condom use among young women was developed, tested, and replicated, with longitudinal follow-up to assess predictive utility of the model for condom use over time. Participants in Study 1 and Study 2 were 198 female undergraduates (mean age, 18.6 years) and 238 female undergraduates (mean age, 19.1 years), respectively. Acceptance of sexuality and control over the sexual encounter were related to a multidimensional measure of condom use self-efficacy, which predicted condom use intentions. Perceived susceptibility to STDs was both directly related to intentions and indirectly related through perceived benefits and attitudes about condom use. Intentions predicted subsequent reports of condom use. The model suggests foci for condom use interventions for young women.

  19. Influence of the amino acid residues at 70 in M protein of porcine reproductive and respiratory syndrome virus on viral neutralization susceptibility to the serum antibody.

    Science.gov (United States)

    Fan, Baochao; Liu, Xing; Bai, Juan; Zhang, Tingjie; Zhang, Qiaoya; Jiang, Ping

    2016-03-22

    Porcine reproductive and respiratory syndrome virus (PRRSV) is mainly responsible for the significant economic losses in pig industry in the world. The adaptive immune responses of the host act as an important source of selective pressure in the evolutionary process of the virus. In the previous study, we confirmed that the amino acid (aa) residues at 102 and 104 sites in GP5 played an important role in escaping from the neutralizing antibodies (NAbs) against highly pathogenic PRRSV (HP-PRRSV). In this study, we further analyzed the aa mutants affecting neutralization susceptibility of NAbs in other structure proteins in NAbs resistant variants. Based on the different aa residues of the structural proteins between the resistant virus BB20s and the parent virus BB, 12 recombinant PRRSV strains containing these aa residue substitutions were constructed using reverse genetic techniques. The neutralizing antibody (NA) titers of the recombinant strains were tested on MARC-145 and porcine alveolar macrophages (PAMs). And the NAbs binding abilities of parent and rescued viruses were tested by using ELISA method. By using the neutralization assay, it was revealed that the NA titer of N4 serum with rBB/Ms was significantly lower than that with rBB. Meanwhile, NA titer of the serum with rBB20s/M was significantly higher than that with rBB20s. The ELISA binding results showed that rBB/Ms had higher binding inability to N4 than did rBB. And alignment of M protein revealed that the variant aa residue lysine (K) at 70 was also existed in field type 2 and vaccine PRRSV strains. The aa residue at 70 in M protein of PRRSV played an important role in regulating neutralization susceptibility to the porcine serum NAbs. It may be helpful for monitoring the antigen variant strains in the field and developing new vaccine against PRRSV in the future.

  20. Comparing health locus of control in patients with Spasmodic Dysphonia, Functional Dysphonia and Nonlaryngeal Dystonia.

    Science.gov (United States)

    Haselden, Karen; Powell, Theresa; Drinnan, Mike; Carding, Paul

    2009-11-01

    Locus of Control (LoC) refers to an individuals' perception of whether they are in control of life events. Health Locus of Control refers to whether someone feels they have influence over their health. Health Locus of Control has not been studied in any depth in voice-disordered patients. The objective of this study was to examine Health Locus of Control in three patient groups: (1) Spasmodic Dysphonia, (2) Functional Dysphonia and (3) a nondysphonic group with Nonlaryngeal Dystonia. LoC was measured and compared in a total of 57 patients using the Multidimensional Health Locus of Control Scales (diagnostic specific) Form C. Internal, Chance, and Powerful others LoC were measured and comparisons were made using one-way analysis of variance. Contrary to expectations Internal LoC was found to be significantly higher in the Functional Dysphonia group when compared to the other two groups. There was no significant difference between the groups in Chance or Powerful others LoC. The two organic groups, Spasmodic Dysphonia and Nonlaryngeal Dystonia, were more alike in Internal Health Locus of Control than the Functional Dysphonia group. The diagnostic nature of the groups was reflected in their LoC scores rather than their voice loss. These results contribute to the debate about the etiology of Spasmodic Dysphonia and will be of interest to those involved in the psychology of voice and those managing voice-disordered patients.

  1. The relationship between the perception of own locus of control and aggression of adolescent boys

    Directory of Open Access Journals (Sweden)

    Lettie Breet

    2010-01-01

    Full Text Available Aggression is increasingly seen in most parts of South African society. Aggressive behaviour of boys in secondary school often results from frustrations caused by perceived high expectations of others regarding the role, locus of control, and personality of boys. Locus of control plays an important role in a person's perception concerning a situation and possible reactions to what is happening, or should be happening. A 56-item questionnaire, based on Rotter's "Locus of control" questionnaire, and the DIAS Scale were used. The questionnaire was completed by 440 boys in Grades 9, 10, and 11. Various factor, item and differential statistical analyses were conducted. Three constructs were identified, i.e. physical, verbal, and indirect aggression. Results indicated that locus of control has a significant influence on verbal and indirect aggression. The differential analysis indicated that contextual variables (language of tuition, age, and grade play a significant, but not substantial, role in aggression. Furthermore, boys with an internal locus of control are significantly and substantially less aggressive than boys with an external locus of control, with respect to physical, verbal and indirect aggression.

  2. Health locus of control: Its relationship with medication adherence and medication wastage.

    Science.gov (United States)

    West, Lorna Marie; Borg Theuma, Ruth; Cordina, Maria

    2017-12-09

    Non-adherence is a significant factor contributing to medication wastage. Whilst there is some evidence on the influence of patients' health locus of control in relation to adherence, there has been little inquiry into its relationship with mediation wastage. To determine the relationship between medication adherence and health locus of control as well as medication wastage and health locus of control in patients with chronic conditions. Outpatients having a diagnosis of asthma, cardiovascular conditions, or diabetes participated in a cross-sectional study employing a self-administered questionnaire. The questionnaire determined presence of unused medication (wastage), adherence using 'Tool for Adherence Behaviour Screening' (TABS), and health locus of control using 'Multidimensional Health Locus of Control' (MHLC) scale Form C. Logistic regression was performed to ascertain the effects of MHLC and demographics in relation to adherence and wastage. MHLC beliefs were divided into 8 types of health locus of control. One-Way ANOVA was used to assess differences between conditions and belief types. P-values ≤ .05 were considered significant. There were 330 patients recruited (58% male; age, mean±(SD): 61 ± 15 years; 110 asthma, 110 cardiovascular, 110 diabetes). In terms of health locus of control, females had higher 'doctors' beliefs (p = .054) and significantly lower 'other people' beliefs (p = adherence. Lower 'doctors' beliefs and higher 'other people' beliefs were significantly associated with wastage (p = adherence (p = medication, followed by 'pure internal' believers. 'Pure powerful others external' had the highest presence of unused medication. Healthcare professionals should take into account patients' health locus of control beliefs whilst conducting an intervention with patients; this can impact positively medication adherence and minimisation of medication wastage. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Jurors' locus of control and defendants' attractiveness in death penalty sentencing.

    Science.gov (United States)

    Beckham, Crystal M; Spray, Beverly J; Pietz, Christina A

    2007-06-01

    The authors examined the relationship between jurors' locus of control and defendants' attractiveness in death penalty sentencing. Ninety-eight participants voluntarily served as mock jurors. The authors administered J. B. Rotter's (1966) Internal-External Locus of Control Scale to participants and then randomly assigned them to a group with either an attractive or an unattractive defendant (represented by photographs). Participants read a murder vignette and selected a punishment--either a lifetime jail sentence or the death penalty-for the defendant. Results indicated that neither jurors' locus of control nor defendants' attractiveness influenced sentencing. However, jurors' age and gender significantly influenced sentencing. Men, with the exception of the youngest men, were more likely than women to choose the death penalty. Additionally, young women were more likely than older women to select the death penalty. The authors discuss the implications of these results for the study of jury behavior and bias.

  4. Susceptibility to lethal cerebral malaria is regulated by epistatic interaction between chromosome 4 (Berr6) and chromosome 1 (Berr7) loci in mice.

    Science.gov (United States)

    Torre, S; van Bruggen, R; Kennedy, J M; Berghout, J; Bongfen, S E; Langat, P; Lathrop, M; Vidal, S M; Gros, P

    2013-06-01

    In humans, cerebral malaria is a rare but often lethal complication of infection with Plasmodium parasites, the occurrence of which is influenced by complex genetic factors of the host. We used a mouse model of experimental cerebral malaria (ECM) with Plasmodium berghei ANKA to study genetic factors regulating appearance of neurological symptoms and associated lethality. In a genome-wide screen of N-ethyl-N-nitrosourea-mutagenized mice derived from C57BL/6J (B6) and 129S1/SvImJ (129) mouse strains, we detected a strong interaction between the genetic backgrounds of these strains, which modulates ECM resistance. We have mapped a major gene locus to central chromosome 4 (log of the odds (LOD) 6.7; 79.6-97.3 Mb), which we designate Berr8. [corrected]. B6 alleles at Berr6 are associated with resistance, and are inherited in a co-dominant fashion. In mice heterozygous for Berr6 B6/129 alleles, resistance to ECM is strongly modulated by a second locus, Berr7, that maps to the proximal portion of chromosome 1 (LOD 4.03; 41.4 Mb). 129 alleles at Berr7 are associated with ECM resistance in a dosage-dependent fashion. Results are discussed in view of the possible role of this two-locus system in susceptibility to unrelated inflammatory conditions in mice and humans.

  5. Influence of oviposition preference in reduced susceptibility of Ottawa Valley white spruce (picea glauce) to spruce budmoth (zeiraphera canadensis) in New Brunswick: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Quiring, D.T.; Butterworth, E.W.

    1995-12-31

    In New Brunswick, efforts to control populations of spruce budmoth by spraying adults with insecticides or pheromones have produced encouraging results. An alternative technique, the selection of less-susceptible spruce, would aid in the development of an integrated management program for this insect pest. Differences in spruce damage as revealed in previous studies could be due to oviposition choice and/or to host suitability. However, researchers must determine the distribution of eggs laid by the spruce budmoth before they can determine whether some families of spruce have low levels of damage because they are avoided by ovipositing females and/or because they are less suitable for egg and larval development. This report presents results from studies carried out to quantify the number of eggs laid on trees from different families. Investigators collected tree branch samples from plantations and a seed orchard in May, before bud burst or egg hatching commenced. They analysed variations in oviposition parameters (such as number of eggs and egg masses, number of eggs parasitized by Trichogramma minutum, and number of viable eggs) using analysis of variance. To determine whether differences in egg density were related to plant morphology, they also measured such parameters as shoot length and diameter, needle length, shot type, and needle density.

  6. The Influence of Pregnancy, Sexually Transmitted Diseases, and Human Immunodeficiency Virus Perceived Susceptibility Patterns on Sexual Risk Reduction for Adolescent Females

    Science.gov (United States)

    Kershaw, Trace S.; Ethier, Kathleen A.; Milan, Stephanie; Lewis, Jessica B.; Niccolai, Linda M.; Meade, Christina; Ickovics, Jeannette R.

    2005-01-01

    Risky sexual behavior can lead to pregnancy, sexually transmitted diseases (STDs), and human immunodeficiency virus (HIV). Our study of 300 adolescent females takes an integrative approach by incorporating these multiple outcomes to assess the influence of risk perceptions on sexual behavior by (1) identifying subgroups of perceived susceptibility…

  7. Genetic susceptibility to pancreatic cancer.

    Science.gov (United States)

    Klein, Alison P

    2012-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in both men and women in the United States. However, it has the poorest prognosis of any major tumor type, with a 5-yr survival rate of approximately 5%. Cigarette smoking, increased body mass index, heavy alcohol consumption, and a diagnosis of diabetes mellitus have all been demonstrated to increase risk of pancreatic cancer. A family history of pancreatic cancer has also been associated with increased risk suggesting inherited genetic factors also play an important role, with approximately 5-10% of pancreatic cancer patients reporting family history of pancreatic cancer. While the genetic basis for the majority of the familial clustering of pancreatic cancer remains unclear, several important pancreatic cancer genes have been identified. These consist of high penetrance genes including BRCA2 or PALB2, to more common genetic variation associated with a modest increase risk of pancreatic cancer such as genetic variation at the ABO blood group locus. Recent advances in genotyping and genetic sequencing have accelerated the rate at which novel pancreatic cancer susceptibility genes have been identified with several genes identified within the past few years. This review addresses our current understanding of the familial aggregation of pancreatic cancer, established pancreatic cancer susceptablity genes and how this knowledge informs risk assessment and screening for high-risk families. Copyright © 2011 Wiley Periodicals, Inc.

  8. Genetic Susceptibility to Pancreatic Cancer

    Science.gov (United States)

    Klein, Alison P.

    2013-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in both men and women in the United States. However, it has the poorest prognosis of any major tumor type, with a 5-yr survival rate of approximately 5%. Cigarette smoking, increased body mass index, heavy alcohol consumption, and a diagnosis of diabetes mellitus have all been demonstrated to increase risk of pancreatic cancer. A family history of pancreatic cancer has also been associated with increased risk suggesting inherited genetic factors also play an important role, with approximately 5–10% of pancreatic cancer patients reporting family history of pancreatic cancer. While the genetic basis for the majority of the familial clustering of pancreatic cancer remains unclear, several important pancreatic cancer genes have been identified. These consist of high penetrance genes including BRCA2 or PALB2, to more common genetic variation associated with a modest increase risk of pancreatic cancer such as genetic variation at the ABO blood group locus. Recent advances in genotyping and genetic sequencing have accelerated the rate at which novel pancreatic cancer susceptibility genes have been identified with several genes identified within the past few years. This review addresses our current understanding of the familial aggregation of pancreatic cancer, established pancreatic cancer susceptablity genes and how this knowledge informs risk assessment and screening for high-risk families. PMID:22162228

  9. The Effect of Compensation Studies on Disadvantaged Children's Self Concept Levels and Locus of Control

    Science.gov (United States)

    Sadioglu, Ömür

    2017-01-01

    The aim of this study is to determine the effect of "Bir Umut Ol Benim Için" (Be My Hope) project which was prepared for the children who were disadvantaged by being influenced from several risk factors as compared to their peers on the self-concepts and locus of controls of the children. The study group consisted of 33 children who were…

  10. Impact of Computer Expertise, Locus of Control and Self-Esteem on ...

    African Journals Online (AJOL)

    The present study considered the influence of self-esteem, locus of control and computer expertise on computer-induced stress in a cross sectional survey. One hundred and fifty cyber café users drawn from 10 cyber cafes randomly chosen from University of Ibadan and its environs participated in the study. Of the 150 ...

  11. Locus of Control and Self-Esteem as Predictors of Teacher ...

    African Journals Online (AJOL)

    Individual's perception of self has potential to enhance or impede his or her success at work. In view of this, there is a need to examine the relationship between locus of control and self-esteem as they jointly influence teachers' frustration in Lagos state, Nigeria. The participants were two hundred (200) teachers (100 males ...

  12. Kartenorientierte Isolierung des Rar1 Locus

    OpenAIRE

    Lahaye, Thomas

    1999-01-01

    The Mla12 allele of the barley-Mla locus confers resistance to powdery mildew isolates expressing the matching avirulence gene avrMla12. The Rar1 (Required for Mla12-specified resistance) locus has been found to be part of the Mla12-governed signal transduction pathway. Previous analysis has demonstrated that rar1-mutant alleles abolish not only Mla12 but also other R gene specificities. To elucidate the molecular mechanisms of R-gene mediated plant defence Rar1 was isolated by map-based clon...

  13. Locus of control in relation to flow

    Directory of Open Access Journals (Sweden)

    Celeste M Taylor

    2006-03-01

    Full Text Available The principal objective of the study was to examine the relationship between locus of control and optimal experience (flow in carrying out work and/or study activities. Two questionnaires measuring the aforementioned constructs were administered to a group of first and second-year Human Resource Management students (n=168 between the ages of 16 and 30. The results suggest that more frequent experience of flow is positively correlated with Autonomy and Internal Locus of Control. Limitations, lines of future research, implications and further contributions are discussed.

  14. Genetic Polymorphism of MTHFR C677T Influences Susceptibility to HBV-Related Hepatocellular Carcinoma in a Chinese Population: a Case-Control Study.

    Science.gov (United States)

    Qiao, Kunyan; Zhang, Shitian; Trieu, Congdoanh; Dai, Qinghai; Huo, Zhixiao; Du, Yanan; Lu, Wei; Hou, Wei

    2017-04-01

    Methylene tetrahydrofolate reductase (MTHFR) is the key enzyme of folic acid metabolism and the C677T mutation is associated with decreased enzyme activity. Several studies have shown its regulatory role in carcinogenesis and tumor growth. HBV (hepatitis B virus)-related HCC (hepatocellular carcinoma) is one of the most common liver cancers worldwide. Therefore, the present case-control study aimed to investigate the role of genetic polymorphism of MTHFR C677T in the development and progression of HBV-related HCC in a Chinese population. Subjects enrolled included 204 HBV-related HCC patients and 211 HBV infected patients without HCC. MTHFR C677T polymorphism was genotyped via a DNA microarray-based assay. The relationship between the MTHFR C677T polymorphism and HBV-related HCC was analyzed. The genotype frequencies of MTHFR C677T were statistically different between the HCC and control groups (p = 0.025). The TT genotype was associated with elevated risk of HBV-related HCC in a Chinese population under different genetic models after an adjustment for age, gender, HBV infection duration, and HCC family history (T vs. C, OR = 1.462, 95% CI: 1.090 - 1.962, p = 0.011; TT vs. CC, OR = 2.151, 95% CI: 1.143 - 4.049, p = 0.018; TT vs. CC+CT, OR = 1.918, 95% CI: 1.215 - 3.026, p = 0.005). When stratified with the known duration of HBV infection, subjects with HBV infection duration of more than 20 years and carrying the homozygous TT genotype had a higher susceptibility to HCC than those with the C allele (CC/CT) (OR = 2.568, 95% CI: 1.244 - 5.303; p = 0.011). There was no significant association between MTHFR C677T genotypes and HCC stages based on BCLC staging system. MTHFR C677T polymorphism with TT genotype could be a factor that increases the risk of HBVrelated HCC in a Chinese population, especially those with HBV infection duration of more than 20 years.

  15. The effects of risk perception and flight experience on airline pilots' locus of control with regard to safety operation behaviors.

    Science.gov (United States)

    You, Xuqun; Ji, Ming; Han, Haiyan

    2013-08-01

    The primary objective of this paper was to integrate two research traditions, social cognition approach and individual state approach, and to understand the relationships between locus of control (LOC), risk perception, flight time, and safety operation behavior (SOB) among Chinese airline pilots. The study sample consisted of 193 commercial airline pilots from China Southern Airlines Ltd. The results showed that internal locus of control directly affected pilot safety operation behavior. Risk perception seemed to mediate the relationship between locus of control and safety operation behaviors, and total flight time moderated internal locus of control. Thus, locus of control primarily influences safety operation behavior indirectly by affecting risk perception. The total effect of internal locus of control on safety behaviors is larger than that of external locus of control. Furthermore, the safety benefit of flight experience is more pronounced among pilots with high internal loci of control in the early and middle flight building stages. Practical implications for aviation safety and directions for future research are also discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Emotional intelligence and OCB: The moderating role of work locus of control.

    Science.gov (United States)

    Turnipseed, David L

    2017-07-10

    This study sought to identify linkages between Mayer, Salovey, and Caruso's (2008) four dimensions of emotional intelligence (EI) and organizational citizenship behavior, and the moderating influence of locus of control. Using a sample of 290 employed students, the present study examines the effects of the dimensions of EI on OCB directed at individuals (OCB-I) and OCB directed at the organization (OCB-O). Emotionally intelligent individuals were hypothesized to engage in more organizational citizenship behavior (OCB) than individuals with lower EI. Work locus of control was hypothesized to moderate the emotional intelligence-OCB linkage, with high internals having a stronger emotional intelligence to OCB linkage. Results indicate that the EI dimensions of perceiving, understanding, and managing emotions had positive effects on OCB-I and OCB-O. Using emotions was not linked to OCB. Locus of control strengthened the EI to OCB-I link, but had no effect on the OCB-O linkage.

  17. Generalizability of diagnostic-prescriptive teaching strategies across student locus of control and multiple instructional units

    Science.gov (United States)

    Benson, Jean S.; Yeany, Russell H.

    The influence of locus of control and diagnostic testing with prescribed remediation on immediate and retained science achievement was the focus of the study. To test the generalizability of the results across instructional units and to check on the existence of a treatment warm-up period, the experiment was conducted across three biology units. The results supported the existence of the warm-up period with no significant effects of diagnosis and remediation during the first unit. On later units and on the retention measure, the experimental subjects achieved significantly more than the control. No locus of control X treatment interactions were found; although, in one unit, the internal locus of control subjects achieved significantly higher than externals.

  18. Phylogenetic Analysis of the SNORD116 Locus

    Directory of Open Access Journals (Sweden)

    Matthew A. Kocher

    2017-11-01

    Full Text Available The SNORD116 small nucleolar RNA locus (SNORD116@ is contained within the long noncoding RNA host gene SNHG14 on human chromosome 15q11-q13. The SNORD116 locus is a cluster of 28 or more small nucleolar (sno RNAs; C/D box (SNORDs. Individual RNAs within the cluster are tandem, highly similar sequences, referred to as SNORD116-1, SNORD116-2, etc., with the entire set referred to as SNORD116@. There are also related SNORD116 loci on other chromosomes, and these additional loci are conserved among primates. Inherited chromosomal 15q11-q13 deletions, encompassing the SNORD116@ locus, are causative for the paternally-inherited/maternally-imprinted genetic condition, Prader–Willi syndrome (PWS. Using in silico tools, along with molecular-based and sequenced-based confirmation, phylogenetic analysis of the SNORD116@ locus was performed. The consensus sequence for the SNORD116@ snoRNAs from various species was determined both for all the SNORD116 snoRNAs, as well as those grouped using sequence and location according to a human grouping convention. The implications of these findings are put in perspective for studying SNORD116 in patients with inherited Prader–Willi syndrome, as well as model organisms.

  19. Aspirations, Attributions, and Locus of Control.

    Science.gov (United States)

    Samuel, William; McNall, Sidne J.

    Self-evaluation is thought to play a major role in personality and motivation. Preliminary experience with success or failure, levels of aspiration, attributions for performance, and locus of control may all be interrelated factors in human motivation. After receiving success, failure, or no feedback on a concept formation task, subjects (N=90)…

  20. Locus of Equity and Brand Extension

    NARCIS (Netherlands)

    S.M.J. van Osselaer (Stijn); J.W. Alba (Joseph)

    2003-01-01

    textabstractPrevailing wisdom assumes that brand equity increases when a brand touts its desirable attributes. We report conditions under which the use of attribute information to promote a product can shift the locus of equity from brand to attribute, thereby reducing the attractiveness of

  1. Genetic heterogeneity in breast cancer susceptibility.

    Science.gov (United States)

    Andersen, T I

    1996-01-01

    Approximately 20% of breast cancer patients have a family history of the disease, and in one-fourth of these cases breast cancer appears to be inherited as an autosomally dominant trait. Five genes and gene regions involved in breast cancer susceptibility have been uncovered. Germ-line mutations in the recently cloned BRCA1 gene at 17q21 is considered to be responsible for the disease in a majority of the breast-ovarian cancer families and in 40-45% of the site-specific breast cancer families, but appears not to be involved in families with both male and female breast cancer cases. The BRCA2 locus at 13q12-q13 appears to be involved in 40-45% of the site-specific breast cancer families, and in most of the families with affected males. The gene located in this region, however, does not seem to confer susceptibility to ovarian cancer. The TP53 gene is involved in breast cancer development in the Li-Fraumeni syndrome and Li-Fraumeni syndrom-like families, whereas germ-line mutations in the androgen receptor (AR) gene is present in a subset of male breast cancers. Furthermore, females who are obligate carriers of ataxia telangiectasia (AT) have a 4-12 times relative risk of developing breast cancer as compared with the general female population, indicating that germ-line mutations in AT also confer susceptibility to breast cancer.

  2. Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2

    National Research Council Canada - National Science Library

    ...; Orr, Nick; Dudbridge, Frank; den, Nicola; Maguire, Sarah; Novo, Daniela; Perrakis, Eleni; Johnson, Nichola; Ghoussaini, Maya; Hopper, John; Southey, Melissa; Apicella, Carmel; Stone, Jennifer; Schmidt, Marjanka; Broeks, Annegien; Veer, Laura; Hogervorst, Frans; Fasching, Peter; Haeberle, Lothar; Ekici, Arif; Beckmann, Matthias W; Gibson, Lorna; Aitken, A; Warren, Helen; Sawyer, Elinor; Tomlinson, Ian; Kerin, Michael; Miller, Nicola; Burwinkel, Barbara; Marme, Federick; Schneeweiss, Aneas; Sohn, Chistof; Guénel, Pascal; Truong, Thérèse; Cordina-Duverger, Emilie; Sanchez, Marie; Bojesen, Stig; Nordestgaard, Børge; Nielsen, Sune; Flyger, Henrik; Benítez, Javier; Zamora, Pilar; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Anton-Culver, Hoda; Neuhausen, Susan; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Hamann, Ute; Brauch, Hiltrud; Justenhoven, Christina; Brüning, Thomas; Ko, Yon-Dschun; Nevanlinna, Heli; Aittomäki, Kristiina; Blomqvist, Carl; Khan, Sofia; Bogdanova, Natalia; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, J; Chenevix-Trench, Georgia; Beesley, Jonathan; Lambrechts, Diether; Moisse, Matthieu; Floris, O.A.M; Beuselinck, B; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Peissel, Bernard; Pensotti, Valeria; Couch, Fergus; Olson, Janet; Slettedahl, Seth; Vachon, Celine; Giles, Graham G; Milne, Roger L; McLean, Catriona Ann; Haiman, Christopher; Henderson, Brian; Schumacher, Freick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark; Labrèche, France; Dumont, Martine; Kristensen, Vessela; Alnæs, Grethe Grenaker; Nord, Silje; Borresen-Dale, Anne-Lise; Zheng, Wei

    2015-01-01

    .... Here, we report a fine-mapping analysis of the 9q31.2 susceptibility locus using 43 160 cases and 42 600 controls of European ancestry ascertained from 52 studies and a further 5795 cases and 6624 controls of Asian ancestry from nine studies...

  3. Primary Infection by Erysiphe graminis f.sp. hordei of Barley Mutants with Resistance Genes in the ml-o Locus

    DEFF Research Database (Denmark)

    Jørgensen, Jørgen Helms; Mortensen, K.

    1977-01-01

    Ten barley mutants and one barley line, each with an independently arisen resistance gene in the ml-o locus, and some susceptible cultivars were inoculated with Erysiphe graminis f. sp. hordei conidia suspended in a fluorochemical liquid. The germination percentage of the conidia was not affected...

  4. Replication Study and Meta-Analysis in European Samples Supports Association of the 3p21.1 Locus with Bipolar Disorder

    DEFF Research Database (Denmark)

    Vassos, Evangelos; Steinberg, Stacy; Cichon, Sven

    2012-01-01

    Common genetic polymorphisms at chromosome 3p21.1, including rs2251219 in polybromo 1 (PBRM1), have been implicated in susceptibility to bipolar affective disorder (BP) through genome-wide association studies. Subsequent studies have suggested that this is also a risk locus for other psychiatric...

  5. Bulky carcinogen-DNA adducts and exposure to environmental and occupational sources of polycyclic aromatic hydrocarbons. Influence of susceptibility genotypes on adduct level

    Energy Technology Data Exchange (ETDEWEB)

    Sabro Nielsen, P.

    1996-12-31

    PAH exposure, whether it is of occupational or environmental origin, is thought to result in an elevated risk of cancer especially in the lungs. DNA damage is considered an important step in the carcinogenic effect of PAH. Hence, methods that elucidate the steps in the carcinogenic process are important to understand the action of PAH. It may prove useful in the exposure assessment and in combination with classical epidemiological methods give better basis for risk estimation. The objective in this thesis was to evaluate the feasibility of the {sup 32}P-postlabeling method to detect carcinogen-DNA adducts for assessing exposure to DNA damaging compounds in different occupationally and environmentally exposed groups. The studies included groups, that have an elevated cancer risk due to occupational exposure to PAH. Exposure levels were supposed to be relatively low according to reports on occupational and environmental air quality programs. Another aim was to evaluate the influence of polymorphisms in metabolizing enzyme genes on DNA adduct levels. A third objective was to establish some kind of baseline DNA adduct level for individuals with supposed low exposure, and compare it to the more exposed groups. A fourth aim in these studies was to examine if biomarkers of genotoxic exposure could be useful in epidemiological studies to identify groups at risk and thereby contribute with better exposure estimates in the study of PAH related cancer risk. (EG).

  6. Susceptibility to malignant hyperthermia

    NARCIS (Netherlands)

    Snoeck, Marcus Matheus Johannes

    2004-01-01

    In this thesis the author studied the diagnostic procedures for susceptibility to malignant hyperthermia (MH), with special emphasis upon refining the biological diagnostic test and improving protocols and guidelines for investigation of MH susceptibility. MH is a pharmacogenetic disease of skeletal

  7. The Impact of Locus of Control on Language Achievement

    Science.gov (United States)

    Nodoushan, Mohammad Ali Salmani

    2012-01-01

    This study hypothesized that students' loci of control affected their language achievement. 198 (N = 198) EFL students took the Rotter's (1966) locus of control test and were classified as locus-internal (ni = 78), and locus-external (ne = 120). They then took their ordinary courses and at the end of the semester, they were given their exams.…

  8. Monocot and dicot MLO powdery mildew susceptibility factors are functionally conserved in spite of the evolution of class-specific molecular features

    NARCIS (Netherlands)

    Appiano, M.; Catalano, D.; Santillan Martinez, M.I.; Lotti, C.; Zheng Zheng, Zheng; Visser, R.G.F.; Ricciardi, L.; Bai, Y.; Pavan, S.N.C.

    2015-01-01

    Background Specific members of the plant Mildew Locus O (MLO) protein family act as susceptibility factors towards powdery mildew (PM), a worldwide-spread fungal disease threatening many cultivated species. Previous studies indicated that monocot and dicot MLO susceptibility proteins are

  9. Selenoprotein S (SEPS1 gene -105G>A promoter polymorphism influences the susceptibility to gastric cancer in the Japanese population

    Directory of Open Access Journals (Sweden)

    Nagasaka Mitsuo

    2009-01-01

    Full Text Available Abstract Background Inflammation is a key factor in the process of carcinogenesis from chronic gastritis induced by Helicobacter pylori. Selenoprotein S (SEPS1 is involved in the control of the inflammatory response in the endoplasmic reticulum (ER. Recently the -105G>A polymorphism in the promoter of SEPS1 was shown to increase pro-inflammatory cytokine expression. We examined the association between this polymorphism and the risk of gastric cancer. Methods We took stomach biopsies during endoscopies of 268 Japanese gastric cancer patients (193 males and 75 females, average age 65.3, and 306 control patients (184 males and 122 females, average age 62.7 and extracted the DNA from the biopsy specimens. All subjects provided written informed consent. For the genotyping of the SEPS1 promoter polymorphism at position -105G>A, PCR-RFLP methods were used and the PCR products were digested with PspGI. Logistic-regression analysis was used to estimate odds ratios (OR and 95% confidence intervals (CI, adjusting for age, sex, and H. pylori infection status. Results Among cases, the distribution of genotypes was as follows: 88.4% were GG, 11.2% were GA, and 0.4% were AA. Among controls, the distribution was as follows: 92.5% were GG, 7.2% were GA, and 0.3% were AA. Among males, carrying the A allele was associated with an increased odds of gastric cancer, compared with the GG genotype (OR: 2.0, 95% CI 1.0–4.1, p = 0.07. Compared with the GG genotype, carrying the A allele was significantly associated with increased risks of intestinal type gastric cancer (OR: 2.0, 95%CI 1.0–3.9, p Conclusion The -105G>A promoter polymorphism of SEPS1 was associated with the intestinal type of gastric cancer. This polymorphism may influence the inflammatory conditions of gastric mucosa. Larger population-based studies are needed for clarifying the relation between inflammatory responses and SEPS1 polymorphism.

  10. Anisotropy of the magnetic susceptibility of gallium

    Science.gov (United States)

    Pankey, T.

    1960-01-01

    The bulk magnetic susceptibilities of single gallium crystals and polycrystalline gallium spheres were measured at 25??C. The following anisotropic diamagnetic susceptibilities were found: a axis (-0.119??0. 001)??10-6 emu/g, b axis (-0.416??0.002)??10 -6 emu/g, and c axis (-0.229??0.001) emu/g. The susceptibility of the polycrystalline spheres, assumed to be the average value for the bulk susceptibility of gallium, was (-0.257??0.003)??10-6 emu/g at 25??C, and (-0.299??0.003)??10-6 emu/g at -196??C. The susceptibility of liquid gallium was (0.0031??0.001) ??10-6 emu/g at 30??C and 100??C. Rotational diagrams of the susceptibilities in the three orthogonal planes of the unit cell were not sinusoidal. The anisotropy in the single crystals was presumably caused by the partial overlap of Brillouin zone boundaries by the Fermi-energy surface. The large change in susceptibility associated with the change in state was attributed to the absence of effective mass influence in the liquid state. ?? 1960 The American Institute of Physics.

  11. Posttraumatic Stress Disorder Following Stillbirth: Trauma Characteristics, Locus of Control, Posttraumatic Cognitions.

    Science.gov (United States)

    Chung, Man Cheung; Reed, Jacqueline

    2017-06-01

    This study examined the incidence of PTSD and psychiatric co-morbidity among women who experienced stillbirth and investigated the relationship between locus of control, trauma characteristics of stillbirth, posttraumatic cognitions, PTSD and co-morbid psychiatric symptoms following stillbirth. Fifty women recorded information on stillbirth experiences, and completed the Posttraumatic Stress Diagnostic Scale, General Health Questionnaire-28, Edinburgh Post-natal Depression Scale, Rotter's Locus of Control Scale and the Posttraumatic Cognitions Inventory. 60, 28 and 12 % met the diagnostic criteria for probable full-PTSD, partial and no-PTSD respectively. Sixty-two percent and 54 % scored at or above the cutoff of the General Health Questionnaire-28 and postnatal depression respectively. Women who experienced stillbirth reported significantly more psychiatric co-morbid and post-natal depressive symptoms than the comparison group. Both groups were similar in locus of control. Women who experienced stillbirth reported negative cognitions about the self the most. After adjusting for postnatal depression, trauma characteristics were significantly correlated with Posttraumatic cognitions which, in turn, were significantly correlated with PTSD and psychiatric co-morbidity. Locus of control was not significantly correlated with psychological outcomes. Mediational analyses showed that negative cognitions about self mediated the relationship between trauma characteristics and psychiatric co-morbidity only. Women reported a high incidence of probable PTSD and co-morbid psychiatric symptoms following stillbirth. Stillbirth trauma characteristics influenced how they negatively perceived themselves. This then specifically influenced general psychological problems rather than PTSD symptoms.

  12. The role of MHC haplotypes H2d/H2b in mouse resistance/susceptibility to cyst formation is influenced by the lineage of infective Toxoplasma gondii strain

    Directory of Open Access Journals (Sweden)

    Marianne G. Resende

    2008-03-01

    Full Text Available Toxoplasma gondii strains displaying the Type I/III genotype are associated with acquired ocular toxoplasmosis in humans. Here, we used a mice model to characterize some immunological mechanisms involved in host resistance to infection with such strains. We have chosen the Type I/III strains D8, G2 and P-Br, which cause a chronic infection in mice that resembles human toxoplamosis. Mice deficient of molecules MyD88, IFN-gamma, and IL-12 were susceptible to all three parasite strains. This finding indicates the importance of innate mechanisms in controlling infection. On the other hand, MHC haplotype did not influenced resistance/susceptibility; since mice lineages displaying a same genetic background but different MHC haplotypes (H2b or H2d developed similar mortality and cyst numbers after infection with those strains. In contrast, the C57BL/6 genetic background, and not MHC haplotype, was critical for development of intestinal inflammation caused by any of the studied strains. Finally, regarding effector mechanisms, weobserved that B and CD8+ T lymphocytes controlled survival,whereas the inducible nitric oxide synthase influenced cyst numbers in brains of mice infected with Type I/III strains. These findings are relevant to further understanding of the immunologic mechanisms involved in host protection and pathogenesis during infection with T. gondii.Cepas de Toxoplasma gondii que apresentam o genótipo I/III são associadas a toxoplasmose ocular adquirida em humanos. No presente trabalho, nós utilizamos um modelo da doença em camundongos para caracterizar mecanismos imunológicos envolvidos na resistência do hospedeiro à infecção por aquelas cepas. Escolhemos as cepas D8, G2 e P-Br, que causam infecção crônica em camundongos, semelhante à toxoplasmose humana. Camundongos deficientes em MyD88, IFN-G e IL-12 foram susceptíveis a infecções com todas as três linhagens do parasita. Esses dados indicam a importância de mecanismos

  13. The electricity sector susceptibility of European countries to climate change

    Science.gov (United States)

    Klein, Daniel R.; Olonscheck, Mady; Walther, Carsten; Kropp, Jürgen P.

    2014-05-01

    Due to the close relationship between electricity consumption, production and temperature, the electricity systems of countries are particularly susceptible to climate change. Based on a number of quantitative influencing factors, we provide a relative index for 21 European countries. This allows relevant stakeholders to identify the main influencing factors that determine the electricity system susceptibility of their country. The index was determined using 14 influencing factors that include those that increase or decrease susceptibility. This includes information on monthly mean temperature, electricity consumption, import, export and production by energy source for the period 2000-2011. Moreover, we consider the results of nine global climate models regarding future temperature changes as well as data on air conditioner prevalence by country. A quantitative relative ranked index describing the susceptibility of each country's electricity system is provided. In both Luxembourg and Greece, which top the list, the inability to meet electricity demand with inland production as well as a heavy reliance on combustible fuel electricity production explain part of the high relative susceptibility. Summer electricity consumption (another influencing factor) is expected to increase in Greece where current relatively warm temperatures, in the context of the countries included in this study, are expected to increase in the future. Comparatively, Norway was the least susceptible country based on our index. Norway is expected to benefit from rising projected temperatures, which will decrease winter electricity consumption and limit susceptibility. Furthermore, Norway's current electricity production exceeds consumption demand and is largely based on hydro, which also decreases susceptibility. The findings of this study enable policy makers, scientists and energy managers to examine the most important influencing factors that increase susceptibility and focus their adaptation

  14. Characterization of histone H3K27 modifications in the {beta}-globin locus

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yea Woon [Department of Molecular Biology, College of Natural Sciences, Pusan National University, Pusan 609-735 (Korea, Republic of); Kim, AeRi, E-mail: kimaeri@pusan.ac.kr [Department of Molecular Biology, College of Natural Sciences, Pusan National University, Pusan 609-735 (Korea, Republic of)

    2011-02-11

    Research highlights: {yields} The {beta}-globin locus control region is hyperacetylated and monomethylated at histone H3K27. {yields} Highly transcribed globin genes are marked by H3K27ac, but H3K27me2 is remarkable at silent globin genes in erythroid K562 cells. {yields} Association of PRC2 subunits is comparable with H3K27me3 pattern. {yields} Modifications of histone H3K27 are established in an enhancer-dependent manner. -- Abstract: Histone H3K27 is acetylated or methylated in the environment of nuclear chromatin. Here, to characterize the modification pattern of H3K27 in locus control region (LCR) and to understand the correlation of various H3K27 modifications with transcriptional activity of genes, we analyzed the human {beta}-globin locus using the ChIP assay. The LCR of the human {beta}-globin locus was enriched by H3K27ac and H3K27me1 in erythroid K562 cells. The highly transcribed globin genes were hyperacetylated at H3K27, but the repressed globin genes were highly dimethylated at this lysine in these cells. However, in non-erythroid 293FT cells, the {beta}-globin locus was marked by a high level of H3K27me3. EZH2 and SUZ12, subunits of polycomb repressive complex 2, were comparably detected with the H3K27me3 pattern in K562 and 293FT cells. In addition, H3K27ac, H3K27me1 and H3K27me3 were established in an enhancer-dependent manner in a model minichromosomal locus containing an enhancer and its target gene. Taken together, these results show that H3K27 modifications have distinctive correlations with the chromatin state or transcription level of genes and are influenced by an enhancer.

  15. 240 INFLUENCES OF PEER RELATIONS AND LOCUS OF ...

    African Journals Online (AJOL)

    scale of EPQ by Eysenck & Eysenck (1975) = .32. Procedure. The instruments were administered to the participants simultaneously by either of the researchers. They were given to the students who were allowed to either go home with them or to respond to them immediately. Incidental sampling method was used in ...

  16. Murine and human b locus pigmentation genes encode a glycoprotein (gp75) with catalase activity

    Energy Technology Data Exchange (ETDEWEB)

    Halaban, R.; Moellmann, G. (Yale Univ. School of Medicine, New Haven, CT (USA))

    1990-06-01

    Melanogenesis is regulated in large part by tyrosinase, and defective tyrosinase leads to albinism. The mechanisms for other pigmentation determinants (e.g., those operative in tyrosinase-positive albinism and in murine coat-color mutants) are not yet known. One murine pigmentation gene, the brown (b) locus, when mutated leads to a brown (b/b) or hypopigmentated (B{sup lt}/B{sup lt}) coat versus the wild-type black (B/B). The authors show that the b locus codes for a glycoprotein with the activity of a catalase (catalase B). Only the c locus protein is a tyrosinase. Because peroxides may be by-products of melanogenic activity and hydrogen peroxide in particular is known to destroy melanin precursors and melanin, they conclude that pigmentation is controlled not only by tyrosinase but also by a hydroperoxidase. The studies indicate that catalase B is identical with gp75, a known human melanosomal glycoprotein; that the b mutation is in a heme-associated domain; and that the B{sup lt} mutation renders the protein susceptible to rapid proteolytic degradation.

  17. Health locus of control as a psychological factor in improving treatment results in adolescents with primary hypertension and diabetes

    Directory of Open Access Journals (Sweden)

    Marta Anna Biernacka

    2016-10-01

    Full Text Available Background The belief that an individual can influence and control the course of events is a factor which enables a person to overcome difficulties. Some studies, however, have questioned the universality of this statement. This study aims to investigate and explore the relationship between the self-health locus of control and the effectiveness of cooperation in the treatment process in adolescents with chronic diseases. Participants and procedure One hundred and sixty-four adolescent patients suffering from chronic diseases (61 girls and 103 boys ranging from 11 to 17 years old participated in the study. Eighty-seven had primary hypertension and 77 had type 1 diabetes. To investigate their sense of health control we used the Health Locus of Control Scale (HLC. Cooperation in the treatment process was assessed using a 4-item scale completed by a doctor. Results Better results in the treatment were positively correlated with a better internal health locus of control. A negative correlation between the chance health locus of control and results in the treatment was found. Differences in the health locus of control proved to be dependent on gender, age and different clinical groups. Conclusions Health locus of control in patients with chronic diseases seems to be a crucial factor in determining the results of the treatment process in such patients.

  18. Relationship between healthy lifestyle behaviors and health locus of control and health-specific self-efficacy in university students.

    Science.gov (United States)

    Açıkgöz Çepni, Serap; Kitiş, Yeter

    2017-07-01

    To investigate the relationship between the healthy lifestyle behaviors and the health locus of control and health-specific self-efficacy in university students. The study included 572 undergraduate students of a university in the central Anatolia region of Turkey. The data were collected with the General Characteristics Form, the Health-Promoting Lifestyle Profile II, the Multidimensional Health Locus of Control Scale, and the Perceived Health Competence Scale and investigated with the structural equation model. Health-specific self-efficacy was an important predictor of healthy lifestyle behaviors. The Internal health locus of control influenced the healthy lifestyle behaviors through health-specific self-efficacy. The other dimension was the Powerful Others health locus of control that affected healthy lifestyle behaviors, both directly and indirectly, through health-specific self-efficacy. There was a chance that the health locus of control had a negative effect on healthy lifestyle behaviors through self-efficacy. Health-specific self-efficacy is an important prerequisite for changes in healthy lifestyle behaviors, which supports Pender's model. The subscales of the health locus of control vary in their effects on healthy lifestyle behaviors, which partly supports Pender's model. Nurses, by using this model, can examine ways of improving these cognitive-perceptual factors and implement health education programs that are directed towards improving them in young persons. © 2016 Japan Academy of Nursing Science.

  19. Pushing around the locus of selection: evidence for the flexible-selection hypothesis.

    Science.gov (United States)

    Vogel, Edward K; Woodman, Geoffrey F; Luck, Steven J

    2005-12-01

    Attention operates at an early stage in some experimental paradigms and at a late stage in others, which suggests that the locus of selection is flexible. The present study was designed to determine whether the locus of selection can vary flexibly within a single experimental paradigm as a function of relatively modest variations in stimulus and task parameters. In the first experiment, a new method for assessing the locus of selection was developed. Specifically, attention can influence perceptual encoding only if it is directed to the target before a perceptual representation of the target has been formed, whereas attention can influence postperceptual processes even if attention is cued after perception is complete. Event-related potentials were used to confirm the validity of this method. The subsequent experiments used cueing tasks in which subjects were required to perceive and remember a set of objects, and the difficulty of the perception and memory components of the task were varied. When the task overloaded perception but not working memory, attention influenced the formation of perceptual representations but not the storage of these representations in memory; when the task overloaded working memory but not perception, attention influenced the transfer of perceptual representations into memory but not the formation of the perceptual representations. Thus, attention operates to select relevant information at whatever stage or stages of processing are overloaded by a particular stimulus-task combination.

  20. Mutation at the Evi1 locus in Junbo mice causes susceptibility to otitis media.

    Directory of Open Access Journals (Sweden)

    Nicholas Parkinson

    2006-10-01

    Full Text Available Otitis media (OM, inflammation of the middle ear, remains the most common cause of hearing impairment in children. It is also the most common cause of surgery in children in the developed world. There is evidence from studies of the human population and mouse models that there is a significant genetic component predisposing to OM, yet nothing is known about the underlying genetic pathways involved in humans. We identified an N-ethyl-N-nitrosourea-induced dominant mouse mutant Junbo with hearing loss due to chronic suppurative OM and otorrhea. This develops from acute OM that arises spontaneously in the postnatal period, with the age of onset and early severity dependent on the microbiological status of the mice and their air quality. We have identified the causal mutation, a missense change in the C-terminal zinc finger region of the transcription factor Evi1. This protein is expressed in middle ear basal epithelial cells, fibroblasts, and neutrophil leukocytes at postnatal day 13 and 21 when inflammatory changes are underway. The identification and characterization of the Junbo mutant elaborates a novel role for Evi1 in mammalian disease and implicates a new pathway in genetic predisposition to OM.

  1. Genomewide scan identifies susceptibility locus for dyslexia on Xq27 in an extended Dutch family.

    NARCIS (Netherlands)

    Kovel, C.G.F. de; Hol, F.A.; Heister, J.G.A.M.; Willemen, J.J.H.T.; Sandkuijl, L.A.; Franke, B.; Padberg, G.W.A.M.

    2004-01-01

    CONTEXT: Dyslexia is a common disorder with a strong genetic component, but despite significant research effort, the aetiology is still largely unknown. OBJECTIVE: To identify loci contributing to dyslexia risk. METHODS: This was a genomewide linkage analysis in a single large family. Dutch families

  2. Three-locus identification, genotyping, and antifungal susceptibilities of medically important Trichosporon species from China.

    Science.gov (United States)

    Guo, Li-Na; Xiao, Meng; Kong, Fanrong; Chen, Sharon C-A; Wang, He; Sorrell, Tania C; Jiang, Wei; Dou, Hong-Tao; Li, Ruo-Yu; Xu, Ying-Chun

    2011-11-01

    Three reference and 45 clinical isolates of Trichosporon were analyzed by conventional phenotypic and molecular methods to determine the species and genotypes of Trichosporon isolates from China. Target loci for molecular methods included the internal transcribed spacer (ITS) region, the D1/D2 domain of the 26S rRNA gene, and the intergenic spacer 1 (IGS1) region. Identification of eight Trichosporon species was achieved, of which Trichosporon asahii was the most common. Of the sequence-based molecular methods, the one targeting the D1/D2 domain assigned 97.9% (47/48) of isolates (seven species) correctly, while tests targeting both the ITS and IGS1 regions correctly identified all 48 isolates. The commercial API 20C AUX and Vitek 2 Compact YST systems correctly identified 91.9% and 73% of isolates when their biochemical profiles were queried against those of species contained in the databases, respectively, and misidentified 63.6% and 36.4% of isolates of species that were unclaimed by the databases, respectively. The predominant genotype among T. asahii clinical isolates, genotype 4 (51.4%), is rarely found in other countries. Voriconazole and itraconazole were the most active drugs in vitro against all the Trichosporon species tested, while caspofungin and amphotericin B demonstrated poor activity.

  3. 19p13.1 is a triple-negative-specific breast cancer susceptibility locus

    DEFF Research Database (Denmark)

    Stevens, Kristen N; Fredericksen, Zachary; Vachon, Celine M

    2012-01-01

    -negative breast cancer risk when triple-negative cases were excluded (OR, 0.98; 95% CI, 0.89-1.07; P = 0.62). In addition, a combined analysis of triple-negative cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC; N = 3,566) identified a genome-wide significant association between rs8170...

  4. Identification of a shared genetic susceptibility locus for coronary heart disease and periodontitis

    NARCIS (Netherlands)

    Schaefer, A.S.; Richter, G.M.; Groessner-Schreiber, B.; Noack, D.; Nothnagel, M.; El Mokhtari, N.E.; Loos, B.G.; Jepsen, S.; Schreiber, S.

    2009-01-01

    Recent studies indicate a mutual epidemiological relationship between coronary heart disease (CHD) and periodontitis. Both diseases are associated with similar risk factors and are characterized by a chronic inflammatory process. In a candidate-gene association study, we identify an association of a

  5. Genome-wide pathway analysis identifies oxidative stress related gene MSRA as rheumatoid arthritis susceptibility locus

    NARCIS (Netherlands)

    Martin, Jose Ezequiel; Alizadeh, Behrooz Z.; Gonzalez-Gay, Miguel A.; Balsa, Alejandro; Pascual-Salcedo, Dora; Fernandez-Gutierrez, Benjamín; Raya, Enrique

    2010-01-01

    Objective: Genome-wide association studies (GWASs) carried out in rheumatoid arthritis (RA) have led to the discovery of several genetic associations with this disease. Still, the current associated genetic variations can explain only part of the genetic risk involved in RA, and it is well

  6. A Major Susceptibility Locus for Specific Language Impairment Is Located on 13q21

    OpenAIRE

    Bartlett, Christopher W.; Flax, Judy F.; Logue, Mark W.; Vieland, Veronica J.; Bassett, Anne S.; Tallal, Paula; Brzustowicz, Linda M.

    2002-01-01

    Children who fail to develop language normally—in the absence of explanatory factors such as neurological disorders, hearing impairment, or lack of adequate opportunity—are clinically described as having specific language impairment (SLI). SLI has a prevalence of ∼7% in children entering school and is associated with later difficulties in learning to read. Research indicates that genetic factors are important in the etiology of SLI. Studies have consistently demonstrated that SLI aggregates i...

  7. WNT2 Locus Is Involved in Genetic Susceptibility of Peyronie's Disease

    NARCIS (Netherlands)

    Dolmans, Guido H.; Werker, Paul M.; de Jong, Igle J.; Nijman, Rien J.; Wijmenga, Cisca; Ophoff, Roel A.

    Introduction. Peyronie's disease (PD) is a fibromatosis of the penis, with a pathology very similar to what is seen in the hand (palmar fascia) in Dupuytren's disease (DD). Recently, we performed a genome-wide association study and identified nine genetic loci containing common variants associated

  8. Multifactor dimensionality reduction reveals a three-locus epistatic interaction associated with susceptibility to pulmonary tuberculosis

    DEFF Research Database (Denmark)

    Collins, Ryan L; Hu, Ting; Wejse, Christian

    2013-01-01

    for this problem. The goal of the present study was to apply MDR to mining high-order epistatic interactions in a population-based genetic study of tuberculosis (TB). Results The study used a previously published data set consisting of 19 candidate single-nucleotide polymorphisms (SNPs) in 321 pulmonary TB cases...

  9. Support for a bipolar affective disorder susceptibility locus on chromosome 12q24.3

    DEFF Research Database (Denmark)

    Buttenschøn, Henriette Nørmølle; Foldager, Leslie; Zacharov, Tracey Flint

    2010-01-01

    Linkage and association studies of bipolar affective disorder (BAD) point out chromosome 12q24 as a region of interest.......Linkage and association studies of bipolar affective disorder (BAD) point out chromosome 12q24 as a region of interest....

  10. Dopamine D3 receptor gene locus: Association with schizophrenia, as well age of onset

    Energy Technology Data Exchange (ETDEWEB)

    Nimgsonkar, V.L.; Zhang, X.R.; Brar, J.S. [Univ. of Pittsburgh, PA (United States)] [and others

    1994-09-01

    Genetic factors are clearly involved in the etiology of schizophrenia, but their specific nature is unknown. If the genetic etiology is multifactorial or polygenic, the role of specific genes as susceptibility factors can be directly evaluated by examining allelic variation at these loci among cases in comparison with controls. Two studies have independently demonstrated an association of schizophrenia with homozygosity at the dopamine D3 receptor gene (D3RG) locus, using a biallelic polymorphism in the first exon of D3RG. These results are important because D3RG is a favored candidate gene. Three other studies have identified associations among sub-groups of patients, but the majority were negative. The present study involved patients with schizophrenia (DSM-III-R criteria) of Caucasian or African-American ethnicity (n=130). Two groups of controls, matched for ethnicity, were used: adults screened for schizophrenia (n=128) and unselected neonates (n=160). Multivariate analysis revealed an association between allele no. 1 homozygosity and schizophrenia in comparison with adult, but not neonatal controls. The association was most marked among Caucasian patients with a family history of schizophrenia (odds ratio 13.7, C.I. 1.8, 104.3). An association of the D3RG locus with age of onset (AOO) was also noted. The discrepancies in earlier studies may due to variations in control groups, differencies in mean AOO among different cohorts, or ethnic variations in susceptibility attributable to D3RG.

  11. Adolescent neurobiological susceptibility to social context

    Directory of Open Access Journals (Sweden)

    Roberta A. Schriber

    2016-06-01

    Full Text Available Adolescence has been characterized as a period of heightened sensitivity to social contexts. However, adolescents vary in how their social contexts affect them. According to neurobiological susceptibility models, endogenous, biological factors confer some individuals, relative to others, with greater susceptibility to environmental influences, whereby more susceptible individuals fare the best or worst of all individuals, depending on the environment encountered (e.g., high vs. low parental warmth. Until recently, research guided by these theoretical frameworks has not incorporated direct measures of brain structure or function to index this sensitivity. Drawing on prevailing models of adolescent neurodevelopment and a growing number of neuroimaging studies on the interrelations among social contexts, the brain, and developmental outcomes, we review research that supports the idea of adolescent neurobiological susceptibility to social context for understanding why and how adolescents differ in development and well-being. We propose that adolescent development is shaped by brain-based individual differences in sensitivity to social contexts – be they positive or negative – such as those created through relationships with parents/caregivers and peers. Ultimately, we recommend that future research measure brain function and structure to operationalize susceptibility factors that moderate the influence of social contexts on developmental outcomes.

  12. Adolescent Neurobiological Susceptibility to Social Context

    Science.gov (United States)

    Schriber, Roberta A.; Guyer, Amanda E.

    2016-01-01

    Adolescence has been characterized as a period of heightened sensitivity to social contexts. However, adolescents vary in how their social contexts affect them. According to neurobiological susceptibility models, endogenous, biological factors confer some individuals, relative to others, with greater susceptibility to environmental influences, whereby more susceptible individuals fare the best or worst of all individuals, depending on the environment they encounter (e.g., high vs. low parental warmth). Until recently, research guided by these theoretical frameworks has not incorporated direct measures of brain structure or function to index this sensitivity. Drawing on prevailing models of adolescent neurodevelopment and a growing number of neuroimaging studies on the interrelations among social contexts, the brain, and developmental outcomes, we review research that supports the idea of adolescent neurobiological susceptibility to social context for understanding why and how adolescents differ in development and well-being. We propose that adolescent development is shaped in part by brain-based individual differences in sensitivity to social contexts – be they positive or negative – such as those created through relationships with parents/caregivers and peers. As such, we recommend that future research measure brain function and structure to operationalize susceptibility factors that moderate the influence of social contexts on developmental outcomes. PMID:26773514

  13. Effect of locus of control on disordered eating in athletes: the mediational role of self-regulation of eating attitudes.

    Science.gov (United States)

    Scoffier, S; Paquet, Y; d'Arripe-Longueville, F

    2010-08-01

    This study examined the influence of locus of control on disordered eating as mediated by the self-regulation of eating attitudes. The assessment instruments were adapted for athletes as the entire sample of 179 volunteer University students (M(age)=21.12; SD=2.87) were all regularly involved in competition. The results showed that (a) an internal locus of control had a positive influence on the self-regulation of eating attitudes in social interaction contexts; (b) self-regulatory eating attitudes had a negative influence on disordered eating in contexts of negative affect, social interaction, and lack of anticipation of consequences on performance; and (c) an internal locus of control had an influence on disordered eating through the mediation of self-regulatory eating attitudes in social interaction contexts, and an external locus of control attributed to the coach and sports friends had an influence on disordered eating through the mediation of self-regulatory eating attitudes in contexts of negative affect, social interaction and lack of anticipation of consequences on performance. This study, combined with an earlier study from Scoffier, Maïano, and d'Arripe-Longueville (2009) on the antecedents of athletes' eating disorders, suggests the powerful impact of the social environment on the development of disordered eating in athletes. 2010 Elsevier Ltd. All rights reserved.

  14. Novel Crohn disease locus identified by genome-wide association maps to a gene desert on 5p13.1 and modulates expression of PTGER4.

    Directory of Open Access Journals (Sweden)

    Cécile Libioulle

    2007-04-01

    Full Text Available To identify novel susceptibility loci for Crohn disease (CD, we undertook a genome-wide association study with more than 300,000 SNPs characterized in 547 patients and 928 controls. We found three chromosome regions that provided evidence of disease association with p-values between 10(-6 and 10(-9. Two of these (IL23R on Chromosome 1 and CARD15 on Chromosome 16 correspond to genes previously reported to be associated with CD. In addition, a 250-kb region of Chromosome 5p13.1 was found to contain multiple markers with strongly suggestive evidence of disease association (including four markers with p < 10(-7. We replicated the results for 5p13.1 by studying 1,266 additional CD patients, 559 additional controls, and 428 trios. Significant evidence of association (p < 4 x 10(-4 was found in case/control comparisons with the replication data, while associated alleles were over-transmitted to affected offspring (p < 0.05, thus confirming that the 5p13.1 locus contributes to CD susceptibility. The CD-associated 250-kb region was saturated with 111 SNP markers. Haplotype analysis supports a complex locus architecture with multiple variants contributing to disease susceptibility. The novel 5p13.1 CD locus is contained within a 1.25-Mb gene desert. We present evidence that disease-associated alleles correlate with quantitative expression levels of the prostaglandin receptor EP4, PTGER4, the gene that resides closest to the associated region. Our results identify a major new susceptibility locus for CD, and suggest that genetic variants associated with disease risk at this locus could modulate cis-acting regulatory elements of PTGER4.

  15. Locus of control and online learning

    Directory of Open Access Journals (Sweden)

    Suretha Esterhuysen

    2004-10-01

    Full Text Available The integration of online learning in university courses is considered to be both inevitable and necessary. Thus there is an increasing need to raise awareness among educators and course designers about the critical issues impacting on online learning. The aim of this study, therefore, was to assess the differences between two groups of first-year Business Sciences learners (online and conventional learners in terms of biographic and demographic characteristics and locus of control. The study population consisted of 586 first-year learners of whom 185 completed the Locus of Control Inventory (LCI. The results show that the two groups of learners do not differ statistically significantly from each other with respect to locus of control. The findings and their implications are also discussed. Opsomming Die integrasie van aanlyn-leer in universiteitskursusse word beskou as sowel onafwendbaar as noodsaaklik. Daar is dus ’n toenemende behoefte om bewustheid onder opvoedkundiges en kursusontwerpers te kweek oor die kritiese aspekte wat ’n impak op aanlyn-leer het (Morgan, 1996. Daarom was die doel van hierdie ondersoek om die verskille tussen twee groepe eerstejaarleerders in Bestuurs- en Ekonomiese Wetenskap (aanlyn en konvensionele leerders te bepaal ten opsigte van biografiese en demografiese eienskappe en lokus van beheer. Die populasie het bestaan uit 586 eerstejaarleerders waarvan 185 die Lokus van Beheer Vraelys voltooi het. Die resultate toon dat die twee groepe leerders nie statisties beduidend van mekaar verskil het met betrekking tot lokus van beheer nie. Die bevindinge en implikasies word ook bespreek.

  16. General self-esteem and locus of control of young sportsmen

    Directory of Open Access Journals (Sweden)

    Gašić-Pavišić Slobodanka

    2006-01-01

    Full Text Available This paper deals with the relationship between some elements of self-concept (general self-esteem and locus of control and going in for sport in adolescence. The relationship between going in for sport and variables of self-concept (general self-esteem and external locus of control was investigated in a sample of 300 adolescent boys and girls (150 sportsmen and 150 non-sportsmen. Modification of the Rosenberg’s General self-esteem scale and Bezinović-Savčić’s Scale of externality were used to measure variables of self-concept. The significant positive correlation between variables of going in for sport and general selfesteem, as well as negative ones between variables of going in for sport and external locus of control were found in the whole sample of subjects and in the sample of boys, but not of girls. The sex role stereotypes and greater importance that the culture puts on success in sport for boys have contributed to such results. The sex differences in correlations between variables of self-concept and going in for sport suggest that going in for sport influences general self-esteem and locus of control in adolescents through social feedback and social evaluation of sport achievement and physical fitness. .

  17. Cut Locus Construction using Deformable Simplicial Complexes

    DEFF Research Database (Denmark)

    Misztal, Marek Krzysztof; Bærentzen, Jakob Andreas; Anton, François

    2011-01-01

    In this paper we present a method for appproximating cut loci for a given point p on Riemannian 2D manifolds, closely related to the notion of Voronoi diagrams. Our method finds the cut locus by advecting a front of points equally distant from p along the geodesics originating at p and finding th...... the domain to have disk topology. We test our method for tori of revolution and compare our results to the benchmark ones from [2]. The method, however, is generic and can be easily adapted to construct cut loci for other manifolds of genera other than 1....

  18. An empirical assessment of the construct "work locus of control"

    Directory of Open Access Journals (Sweden)

    Allan Maram

    1998-06-01

    Full Text Available This study is concerned with the domain specificity of the locus of control construct within the workplace. The research investigated whether Specter's (1988 work locus of control scale, a work centred conceptualisation of Rotter's (1966 locus of control measure/ demonstrated evidence of criterion - related validity. This was done by assessing its relationship to leader-member exchange and organisational commitment. The results indicated that work locus of control correlated with both leader-member exchange and organisational commitment and that leadermember exchange acted as a mediator of the relationship between work locus of control and organisational commitment. This is consistent with results from a similar study undertaken by Kinicki & Vecchio (1994 who employed Rotter's (1966 general locus of control measure. The current research demonstrated stronger relationship than Kinicki & Vecchio's (1994 study, which suggests that Specter's (1988 domain specific scale may predict work behaviour more precisely than Rotter's (1966 more general measure.

  19. The genetics of feto-placental development: A study of acid phosphatase locus 1 and adenosine deaminase polymorphisms in a consecutive series of newborn infants

    Directory of Open Access Journals (Sweden)

    Bergamaschi Antonio

    2008-09-01

    Full Text Available Abstract Background Acid phosphatase locus 1 and adenosine deaminase locus 1 polymorphisms show cooperative effects on glucose metabolism and immunological functions. The recent observation of cooperation between the two systems on susceptibility to repeated spontaneous miscarriage prompted us to search for possible interactional effects between these genes and the correlation between birth weight and placental weight. Deviation from a balanced development of the feto-placental unit has been found to be associated with perinatal morbidity and mortality and with cardiovascular diseases in adulthood. Methods We examined 400 consecutive newborns from the Caucasian population of Rome. Birth weight, placental weight, and gestational length were registered. Acid phosphatase locus 1 and adenosine deaminase locus 1 phenotypes were determined by starch gel electrophoresis and correlation analysis was performed by SPSS programs. Informed verbal consent to participate in the study was obtained from the mothers. Results Highly significant differences in birth weight-placental weight correlations were observed among acid phosphatase locus 1 phenotypes (p = 0.005. The correlation between birth weight and placental weight was markedly elevated in subjects carrying acid phosphatase locus 1 phenotypes with medium-low F isoform concentration (A, CA and CB phenotypes compared to those carrying acid phosphatase locus 1 phenotypes with medium-high F isoform concentration (BA and B phenotypes (p = 0.002. Environmental and developmental variables were found to exert a significant effect on birth weight-placental weight correlation in subjects with medium-high F isoform concentrations, but only a marginal effect was observed in those with medium-low F isoform concentrations. The correlation between birth weight and placental weight is higher among carriers of the adenosine deaminase locus 1 allele*2, which is associated with low activity, than in homozygous adenosine

  20. Response to Selection in Finite Locus Models with Nonadditive Effects.

    Science.gov (United States)

    Esfandyari, Hadi; Henryon, Mark; Berg, Peer; Thomasen, Jørn Rind; Bijma, Piter; Sørensen, Anders Christian

    2017-05-01

    Under the finite-locus model in the absence of mutation, the additive genetic variation is expected to decrease when directional selection is acting on a population, according to quantitative-genetic theory. However, some theoretical studies of selection suggest that the level of additive variance can be sustained or even increased when nonadditive genetic effects are present. We tested the hypothesis that finite-locus models with both additive and nonadditive genetic effects maintain more additive genetic variance (VA) and realize larger medium- to long-term genetic gains than models with only additive effects when the trait under selection is subject to truncation selection. Four genetic models that included additive, dominance, and additive-by-additive epistatic effects were simulated. The simulated genome for individuals consisted of 25 chromosomes, each with a length of 1 M. One hundred bi-allelic QTL, 4 on each chromosome, were considered. In each generation, 100 sires and 100 dams were mated, producing 5 progeny per mating. The population was selected for a single trait (h2 = 0.1) for 100 discrete generations with selection on phenotype or BLUP-EBV. VA decreased with directional truncation selection even in presence of nonadditive genetic effects. Nonadditive effects influenced long-term response to selection and among genetic models additive gene action had highest response to selection. In addition, in all genetic models, BLUP-EBV resulted in a greater fixation of favorable and unfavorable alleles and higher response than phenotypic selection. In conclusion, for the schemes we simulated, the presence of nonadditive genetic effects had little effect in changes of additive variance and VA decreased by directional selection. © The American Genetic Association 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Locus of boundary crisis: expect infinitely many gaps.

    Science.gov (United States)

    Osinga, Hinke M

    2006-09-01

    Boundary crisis is a mechanism for destroying a chaotic attractor when one parameter is varied. In a two-parameter setting the locus of the boundary crisis is associated with curves of homoclinic or heteroclinic bifurcations of periodic saddle points. It is known that this locus has nondifferentiable points. We show here that the locus of boundary crisis is far more complicated than previously reported. It actually contains infinitely many gaps, corresponding to regions (of positive measure) where attractors exist.

  2. Impact of locus of control on health message effectiveness.

    Science.gov (United States)

    Kong, Ying; Shen, Fuyuan

    2011-10-01

    This article examined how individuals' locus of control might moderate the effect of health message frames. An experiment was conducted whereby participants read either individual- or social-responsibility message frames after their locus of control was primed. Results indicated that messages presented in individual-responsibility frames were more persuasive when people were primed with internal locus of control, whereas social-responsibility framed appeals were more persuasive when people were primed with external locus of control. These results were found for individuals in both high and low cognitive load conditions. Theoretical and practical implications of the findings are discussed.

  3. The Influence of Attributional Style on Substance Abuse and Risky Sexual Behavior among College Students

    Science.gov (United States)

    Burnett, Audrey J.; Sabato, Todd M.; Walter, Katherine Ott; Kerr, Dianne L.; Wagner, Laurie; Smith, Amy

    2013-01-01

    HIV, AIDS, STIs, and unwanted pregnancy continue to impact young adults in the U.S. at a disproportionate rate, particularly during the college years. Attributional style (i.e., locus of control) influences one's HIV risk. Internal locus of control indicates a lower risk of HIV infection, whereas an external locus of control signals an increased…

  4. The Influence of Attributional Style on Substance Use and Risky Sexual Behavior among College Students

    Science.gov (United States)

    Burnett, Audrey J.; Sabato, Todd M.; Wagner, Laurie; Smith, Amy

    2014-01-01

    HIV, AIDS, STIs, and unwanted pregnancy continue to impact young adults in the U. S. at a disproportionate rate, particularly during the college years. Attributional style (i.e., locus of control) influences one's HIV risk. Internal locus of control indicates a lower risk of HIV infection, whereas external locus of control signals an…

  5. Beyond the locus of spectrally pure colors

    Science.gov (United States)

    Fairchild, Mark D.

    2008-01-01

    The spectrum locus of a CIE chromaticity diagram defines the boundary within which all physically realizable color stimuli must fall. While that is a physical and mathematical reality that cannot be violated, it is possible to create colors that appear as if they were produced by physically impossible stimuli. This can be accomplished through careful control of the viewing conditions and states of adaptation. This paper highlights the importance of considering color appearance issues in the design of displays and specification of color gamuts and illustrates how the perceived color gamut can be manipulated significantly through the relationship between white-point and primary luminance levels without changing the chromaticity gamut of a display system. Using a color appearance model, such as CIECAM02, display color gamuts can be specified in perceptual terms such as lightness, chroma, brightness, and colorfulness rather than in strictly physical terms of the stimuli that create these perceptions. Examination of these perceptual gamuts, and their relationships to the viewing conditions, allows demonstration of the possibility of producing display gamuts that appear to reach beyond the locus of pure spectral colors when compared with typical display setups.

  6. MHC class I Dk locus and Ly49G2+ NK cells confer H-2k resistance to murine cytomegalovirus.

    Science.gov (United States)

    Xie, Xuefang; Stadnisky, Michael D; Brown, Michael G

    2009-06-01

    Essential NK cell-mediated murine CMV (MCMV) resistance is under histocompatibility-2(k) (H-2(k)) control in MA/My mice. We generated a panel of intra-H2(k) recombinant strains from congenic C57L.M-H2(k/b) (MCMV resistant) mice for precise genetic mapping of the critical interval. Recombination breakpoint sites were precisely mapped and MCMV resistance/susceptibility traits were determined for each of the new lines to identify the MHC locus. Strains C57L.M-H2(k)(R7) (MCMV resistant) and C57L.M-H2(k)(R2) (MCMV susceptible) are especially informative; we found that allelic variation in a 0.3-megabase interval in the class I D locus confers substantial difference in MCMV control phenotypes. When NK cell subsets responding to MCMV were examined, we found that Ly49G2(+) NK cells rapidly expand and selectively acquire an enhanced capacity for cytolytic functions only in C57L.M-H2(k)(R7). We further show that depletion of Ly49G2(+) NK cells before infection abrogated MCMV resistance in C57L.M-H2(k)(R7). We conclude that the MHC class I D locus prompts expansion and activation of Ly49G2(+) NK cells that are needed in H-2(k) MCMV resistance.

  7. Tomato susceptibility to Alternaria stem canker : Parameters involved in host-specific toxin-induced leaf necrosis

    NARCIS (Netherlands)

    Witsenboer, Hanneke M.A.; Kloosterziel, Karen M.; Hateboer, Guus; Nijkamp, H. John J.; Hille, Jacques

    1992-01-01

    AAL-toxin causes severe necrosis in leaves of susceptible tomato cultivars at nanomolar concentrations. In resistant tomato cultivars harbouring the semi-dominant Alternaria stem canker resistance locus necrosis is also observed, however at much higher toxin concentrations, in both lines the

  8. Identification of candidate MLO powdery mildew susceptibility genes in cultivated Solanaceae and functional characterization of tobacco NtMLO1

    NARCIS (Netherlands)

    Appiano, M.; Pavan, S.N.C.; Catalano, D.; Zheng Zheng, Zheng; Bracuto, V.; Lotti, C.; Visser, R.G.F.; Ricciardi, L.; Bai, Y.

    2015-01-01

    Specific homologs of the plant Mildew Locus O (MLO) gene family act as susceptibility factors towards the powdery mildew (PM) fungal disease, causing significant economic losses in agricultural settings. Thus, in order to obtain PM resistant phenotypes, a general breeding strategy has been proposed,

  9. Functional characterization of the powdery mildew susceptibility gene SmMLO1 in eggplant (Solanum melongena L.)

    NARCIS (Netherlands)

    Bracuto, Valentina; Appiano, Michela; Ricciardi, Luigi; Göl, Deniz; Visser, Richard G.F.; Bai, Yuling; Pavan, Stefano

    2017-01-01

    Eggplant (Solanum melongena L.) is one of the most important vegetables among the Solanaceae and can be a host to fungal species causing powdery mildew (PM) disease. Specific homologs of the plant Mildew Locus O (MLO) gene family are PM susceptibility factors, as their loss of function results in a

  10. Genetic susceptibility of periodontitis

    NARCIS (Netherlands)

    Laine, M.L.; Crielaard, W.; Loos, B.G.

    2012-01-01

    In this systematic review, we explore and summarize the peer-reviewed literature on putative genetic risk factors for susceptibility to aggressive and chronic periodontitis. A comprehensive literature search on the PubMed database was performed using the keywords ‘periodontitis’ or ‘periodontal

  11. Fourie susceptible.pmd

    African Journals Online (AJOL)

    Prof. Adipala Ekwamu

    a number of cultivars exhibited field resistance to halo blight and bacterial brown spot, all cultivars were more or less susceptible to .... Cerillos. Alubia. I. 91. 57. Kranskop. Red speckled sugar. II. 97. 63. OPS-RS1. Red speckled sugar. II. 96. 63. OPS-RS2. Red speckled sugar. I. 100. 61. OPS-RS3. Red speckled sugar. II. 97.

  12. Measured Self-Esteem and Locus of Control of Students Related to Video Game, Home Computer, and Television Viewing Involvement.

    Science.gov (United States)

    Wiggins, James D.

    This study was designed to investigate the influence of television on the lives of young people and the correlation between home computer programming, the playing of video games at home, and the playing of arcade games out of the home related to self-esteem and locus of control. Subjects were 405 students in grades 4 through 12 from 21 classrooms…

  13. Prenatal stress alters Fos protein expression in hippocampus and locus coeruleus stress-related brain structures.

    Science.gov (United States)

    Viltart, Odile; Mairesse, Jérôme; Darnaudéry, Muriel; Louvart, Hélène; Vanbesien-Mailliot, Christel; Catalani, Assia; Maccari, Stefania

    2006-07-01

    Prenatal stress (PS) durably influences responses of rats from birth throughout life by inducing deficits of the hypothalamo-pituitary-adrenal (HPA) axis feedback. The neuronal mechanisms sustaining such alterations are still unknown. The purpose of the present study was to determine whether in PS and control rats, the exposure to a mild stressor differentially induces Fos protein in hippocampus and locus coeruleus, brain areas involved in the feedback control of the HPA axis. Moreover, Fos protein expression was also evaluated in the hypothalamic paraventricular nucleus (PVN) that reflect the magnitude of the hormonal response to stress. Basal plasma corticosterone levels were not different between the groups, while, PS rats exhibited higher number of Fos-immunoreactive neurons than controls, in the hippocampus and locus coeruleus in basal condition. A higher basal expression of a marker of GABAergic synapses, the vGAT, was also observed in the hypothalamus of PS rats. Fifteen minutes after the end of the exposure to the open arm of the elevated plus-maze (mild stress) a similar increased plasma corticosterone levels was observed in both groups in parallel with an increased number of Fos-immunoreactive neurons in the PVN. Return to basal plasma corticosterone values was delayed only in the PS rats. On the contrary, after stress, no changes in Fos-immunoreactivity were observed in the hippocampus and locus coeruleus of PS rats compared to basal condition. After stress, only PS rats presented an elevation of the number of activated catecholaminergic neurons in the locus coeruleus. In conclusion, these results suggest for the first time that PS alters the neuronal activation of hippocampus and locus coeruleus implicated in the feedback mechanism of the HPA axis. These data give anatomical substrates to sustain the HPA axis hyperactivity classically described in PS rats after stress exposure.

  14. The 4q27 locus and prostate cancer risk

    Directory of Open Access Journals (Sweden)

    Hopper John L

    2010-02-01

    Full Text Available Abstract Background Chronic inflammation is considered to be implicated in the development of prostate cancer. In this study we are the first to investigate a potential association between variants in an autoimmune related region on chromosome 4q27 and prostate cancer risk. This region harbors two cytokine genes IL-2 and the recently described IL-21. Methods We genotyped six variants previously associated with autoimmune disease (namely rs13151961, rs13119723, rs17388568, rs3136534, rs6822844 and rs6840978 and one functional IL-2 promoter variant (rs2069762 for possible association with prostate cancer risk using the Australian Risk Factors for Prostate Cancer case-control Study. Results Overall, our results do not support an association between the seven variants at position 4q27 and prostate cancer risk. Per allele odds ratios (ORs were not significantly different from 1 (all P-values = 0.06. However, we found suggestive evidence for a significant association between the presence of the rs13119723 variant (located in a protein of unknown function and men with a family history of prostate cancer in first-degree relatives (P-value for interaction 0.02. The per allele OR associated with this variant was significantly higher than 1 (2.37; 95% C.I. = 1.01-5.57. Conclusions We suggest that genetic variation within the chromosome 4q27 locus might be associated with prostate cancer susceptibility in men with a family history of the disease. Furthermore, our study alludes to a potential role of unknown protein KIAA1109 in conferring this risk.

  15. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

    Science.gov (United States)

    Voight, Benjamin F; Scott, Laura J; Steinthorsdottir, Valgerdur; Morris, Andrew P; Dina, Christian; Welch, Ryan P; Zeggini, Eleftheria; Huth, Cornelia; Aulchenko, Yurii S; Thorleifsson, Gudmar; McCulloch, Laura J; Ferreira, Teresa; Grallert, Harald; Amin, Najaf; Wu, Guanming; Willer, Cristen J; Raychaudhuri, Soumya; McCarroll, Steve A; Langenberg, Claudia; Hofmann, Oliver M; Dupuis, Josée; Qi, Lu; Segrè, Ayellet V; van Hoek, Mandy; Navarro, Pau; Ardlie, Kristin; Balkau, Beverley; Benediktsson, Rafn; Bennett, Amanda J; Blagieva, Roza; Boerwinkle, Eric; Bonnycastle, Lori L; Boström, Kristina Bengtsson; Bravenboer, Bert; Bumpstead, Suzannah; Burtt, Noisël P; Charpentier, Guillaume; Chines, Peter S; Cornelis, Marilyn; Couper, David J; Crawford, Gabe; Doney, Alex S F; Elliott, Katherine S; Elliott, Amanda L; Erdos, Michael R; Fox, Caroline S; Franklin, Christopher S; Ganser, Martha; Gieger, Christian; Grarup, Niels; Green, Todd; Griffin, Simon; Groves, Christopher J; Guiducci, Candace; Hadjadj, Samy; Hassanali, Neelam; Herder, Christian; Isomaa, Bo; Jackson, Anne U; Johnson, Paul R V; Jørgensen, Torben; Kao, Wen H L; Klopp, Norman; Kong, Augustine; Kraft, Peter; Kuusisto, Johanna; Lauritzen, Torsten; Li, Man; Lieverse, Aloysius; Lindgren, Cecilia M; Lyssenko, Valeriya; Marre, Michel; Meitinger, Thomas; Midthjell, Kristian; Morken, Mario A; Narisu, Narisu; Nilsson, Peter; Owen, Katharine R; Payne, Felicity; Perry, John R B; Petersen, Ann-Kristin; Platou, Carl; Proença, Christine; Prokopenko, Inga; Rathmann, Wolfgang; Rayner, N William; Robertson, Neil R; Rocheleau, Ghislain; Roden, Michael; Sampson, Michael J; Saxena, Richa; Shields, Beverley M; Shrader, Peter; Sigurdsson, Gunnar; Sparsø, Thomas; Strassburger, Klaus; Stringham, Heather M; Sun, Qi; Swift, Amy J; Thorand, Barbara; Tichet, Jean; Tuomi, Tiinamaija; van Dam, Rob M; van Haeften, Timon W; van Herpt, Thijs; van Vliet-Ostaptchouk, Jana V; Walters, G Bragi; Weedon, Michael N; Wijmenga, Cisca; Witteman, Jacqueline; Bergman, Richard N; Cauchi, Stephane; Collins, Francis S; Gloyn, Anna L; Gyllensten, Ulf; Hansen, Torben; Hide, Winston A; Hitman, Graham A; Hofman, Albert; Hunter, David J; Hveem, Kristian; Laakso, Markku; Mohlke, Karen L; Morris, Andrew D; Palmer, Colin N A; Pramstaller, Peter P; Rudan, Igor; Sijbrands, Eric; Stein, Lincoln D; Tuomilehto, Jaakko; Uitterlinden, Andre; Walker, Mark; Wareham, Nicholas J; Watanabe, Richard M; Abecasis, Gonçalo R; Boehm, Bernhard O; Campbell, Harry; Daly, Mark J; Hattersley, Andrew T; Hu, Frank B; Meigs, James B; Pankow, James S; Pedersen, Oluf; Wichmann, H-Erich; Barroso, Inês; Florez, Jose C; Frayling, Timothy M; Groop, Leif; Sladek, Rob; Thorsteinsdottir, Unnur; Wilson, James F; Illig, Thomas; Froguel, Philippe; van Duijn, Cornelia M; Stefansson, Kari; Altshuler, David; Boehnke, Michael; McCarthy, Mark I

    2011-01-01

    By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combinedP < 5 × 10−8. These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits. PMID:20581827

  16. Potential linkage disequilibrium between schizophrenia and locus D22S278 on the long arm of chromosome 22

    Energy Technology Data Exchange (ETDEWEB)

    Moises, H.W.; Yang, L.; Havsteen, B. [Kiel Univ. (Germany)] [and others

    1995-10-09

    Locus D22S278 at 22q12 has been implicated in schizophrenia by sib-pair analysis. In order to replicate these results, we performed the transmission test for linkage disequilibrium (TDT) in 113 unrelated schizophrenic patients and their 226 parents. Evidence for potential linkage disequilibrium was obtained between schizophrenia and allele 243 of the marker AFM 182xd12 at the locus D22S278 (P = 0.02). The results of our study suggest a detectable oligogenic gene in a multigene system for schizophrenia closely linked to D22S278 on the long arm of chromosome 22. If confirmed by others, this finding could lead to the identification of a schizophrenia susceptibility gene. 12 refs., 1 tab.

  17. Locus - ASTRA | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available switchLanguage; BLAST Search Image Search Home About Archive Update History Data ...URL: ftp://ftp.biosciencedbc.jp/archive/astra/LATEST/astra_locus.zip File size: 887 KB Simple search URL htt...icing type (ex. cassette) About This Database Database Description Download License Update History of This Database Site Policy | Contact Us Locus - ASTRA | LSDB Archive ...

  18. Locus of Control and Its Affect on Achievement.

    Science.gov (United States)

    Tomlinson, Louise M.

    Locus of control is considered a primary factor in the difference between students' high and low achievement. This phenomenon is defined as a polar construct which refers to the degree to which individuals view their successes and failures as either contingent upon their own behaviors (internal locus of control) or independent of them (external…

  19. Metacognition: As a Predictor of One's Academic Locus of Control

    Science.gov (United States)

    Arslan, Serhat; Akin, Ahmet

    2014-01-01

    The purpose of this study is to examine the effect of metacognition on one's academic locus of control. The study's sample group consists of 451 university students enrolled in various programs at Sakarya University, Turkey. In this study, the Metacognitive Awareness Inventory and the Academic Locus of Control Scale were used. The correlations and…

  20. Changing Locus of Control: Steelworkers Adjusting to Forced Unemployment

    Science.gov (United States)

    Legerski, Elizabeth Miklya; Cornwall, Marie; O'Neil, Brock

    2006-01-01

    Using an abbreviated version of Levenson's (1981) locus of control scale, we examine change over time in the locus of control of displaced steelworkers. The first data collection occurred approximately six months after plant shutdown, the second occurred a year later. Utilizing a multidimensional measurement model, we test the major assumption…

  1. Locus of control and investment in risky assets

    NARCIS (Netherlands)

    Salamanca, N.; de Grip, A.; Fouarge, D.; Montizaan, R.M.

    2013-01-01

    Using representative household panel data, we show that the investment behavior of households is related to the economic locus of control of household heads. A household's internal locus of control in economic issues is positively related to its decision to hold risky assets as well as its share of

  2. Pharmacists as Entrepreneurs or Employees: The Role of Locus of ...

    African Journals Online (AJOL)

    Purpose: To investigate whether locus of control distinguished between pharmacists who chose to become entrepreneurs and those who took up employee roles in pharmaceutical establishments. Methods: The enlarged version of Rotter's I-E scale designed to measure an individual's locus of control was used to survey a ...

  3. A new strategy for estimating two-locus recombination fractions ...

    Indian Academy of Sciences (India)

    Linkage analysis is now being widely used to map markers on each chromosome in the human genome, to map genetic diseases, and to identify genetic forms of common diseases. Two-locus linkage analysis and multi-locus analysis have been investigated comprehensively, and many computer programs have been ...

  4. Nucleotide variation at the methionine synthase locus in an ...

    African Journals Online (AJOL)

    Nucleotide variation at the methionine synthase (MetE) locus within and among populations of an endangered forest tree Fokienia hodginsii in Vietnam was investigated in the present study. A total of 12 populations were sampled across Vietnam. The length of the sequenced locus varied from 1567 to 1559 bp. A total of 42 ...

  5. Health Beliefs and Locus of Control as Predictors of Cancer ...

    African Journals Online (AJOL)

    OR= 0.35, p < 0.05), internal locus of control (OR = 1.43, p < 0.05) and health risks behaviour (OR= 0.42, p < 0.05) all significantly predicted cervical cancer screening behaviour of women. Keywords: Health beliefs, Health locus of control, cancer ...

  6. Pharmacists as Entrepreneurs or Employees: The Role of Locus of ...

    African Journals Online (AJOL)

    Patrick Erah

    Methods: The enlarged version of Rotter's I-E scale designed to measure an individual's locus of ..... Research Instrument: The instrument used to .... qualified pharmacists who chose to become entrepreneurs and those who chose employee status in organisations. Those who showed more locus of control internality are ...

  7. Is this Red Spot the Blue Spot (locus ceruleum)?

    Energy Technology Data Exchange (ETDEWEB)

    Choe, Won Sick; Lee, Yu Kyung; Lee, Min Kyung; Hwang, Kyung Hoon [Gachon University Gil Hospital, Incheon (Korea, Republic of)

    2010-06-15

    The authors report brain images of 18F-FDG-PET in a case of schizophrenia. The images showed strikingly increased bilateral uptake in the locus ceruleum. The locus ceruleum is called the blue spot and known to be a center of the norepinephrinergic system.

  8. The relationship between internal and external locus of control of ...

    African Journals Online (AJOL)

    The method of this study was descriptive and correlational type. The statistic population in this study included parents of children, male and ... Research samples were assessed by using questionnaires Rutter locus of control and aggression. The results of the analysis showed that there is relationship between internal locus ...

  9. Personality and Locus of Control among School Children

    Science.gov (United States)

    Pandya, Archana A.; Jogsan, Yogesh A.

    2013-01-01

    The main purpose of this investigation is to find out the sex differences in personality traits and locus of control among school children. A total 60 children (30 boys and 30 girls) were taken as a sample. The research tool for personality, children personality questionnaire was used, which was made by Cattell and Porter. Locus of control was…

  10. Turkish population data on the short tandem repeat locus TPOX

    DEFF Research Database (Denmark)

    Vural, B; Poda, M; Atlioglu, E

    1998-01-01

    Allele and genotype frequencies were determined for the STR (short tandem repeat) locus TPOX in a random Turkish population sample of 200 individuals.......Allele and genotype frequencies were determined for the STR (short tandem repeat) locus TPOX in a random Turkish population sample of 200 individuals....

  11. Meta-analysis of 8q24 for seven cancers reveals a locus between NOV and ENPP2 associated with cancer development

    Directory of Open Access Journals (Sweden)

    Brisbin Abra G

    2011-12-01

    Full Text Available Abstract Background Human chromosomal region 8q24 contains several genes which could be functionally related to cancer, including the proto-oncogene c-MYC. However, the abundance of associations around 128 Mb on chromosome 8 could mask the appearance of a weaker, but important, association elsewhere on 8q24. Methods In this study, we completed a meta-analysis of results from nine genome-wide association studies for seven types of solid-tumor cancers (breast, prostate, pancreatic, lung, ovarian, colon, and glioma to identify additional associations that were not apparent in any individual study. Results Fifteen SNPs in the 8q24 region had meta-analysis p-values NOV and ENPP2, which have been shown to play a role in tumor development and motility. An additional region consisting of 5 markers from 128,478,000 bp - 128,524,000 (around gene POU5F1B had p-values Conclusions Further research in this area is warranted as these results demonstrate that the chromosomal region 8q24 may contain a locus that influences general cancer susceptibility between 120,576 and 120,630 kb.

  12. Optoactivation of Locus Ceruleus Neurons Evokes Bidirectional Changes in Thermal Nociception in Rats

    Science.gov (United States)

    Hickey, Louise; Li, Yong; Fyson, Sarah J.; Watson, Thomas C.; Perrins, Ray; Hewinson, James; Teschemacher, Anja G.; Furue, Hidemasa; Lumb, Bridget M.

    2014-01-01

    Pontospinal noradrenergic neurons are thought to form part of a descending endogenous analgesic system that exerts inhibitory influences on spinal nociception. Using optogenetic targeting, we tested the hypothesis that excitation of the locus ceruleus (LC) is antinociceptive. We transduced rat LC neurons by direct injection of a lentiviral vector expressing channelrhodopsin2 under the control of the PRS promoter. Subsequent optoactivation of the LC evoked repeatable, robust, antinociceptive (+4.7°C ± 1.0, p nociception that are produced by specific subpopulations of noradrenergic neurons. This reflects an underlying functional heterogeneity of the influence of the LC on the processing of nociceptive information. PMID:24647936

  13. Escala de Locus de controle ELCO/TELEBRÁS Scale of Locus of control - ELCO

    Directory of Open Access Journals (Sweden)

    Luiz Pasquali

    1998-01-01

    Full Text Available Com base na teoria de Rotter e Escala de Levenson foi elaborada uma escala de Locus de Controle Organizacional (ELCO, composta por 28 itens. A escala foi validada com uma amostra de 350 empregados do Sistema Telebrás. Verificou-se a presença dos 2 fatores previstos na teoria, a saber: internalidade e externalidade, aparecendo a escala de externalidade, com 18 itens, bem estruturada (alfa = 0.81 e a de internalidade, com 10 itens, deixando a desejar no que se refere à consistência interna (alfa = 0.66. Com os dados desta pesquisa foi feita também análise do Locus de Controle desses mesmos empregados. A constatação mais saliente foi a de que o nível de internalidade caiu com o aumento do nível escolar e o aumento da experiência profissional desses mesmos empregados. Estes resultados surpreendentes foram interpretados em termos da situação típica da empresa, que está passando por um período de transição, a saber: a passagem da condição de empresa estatal para empresa privada, o que seria motivo da perda de confiança dos empregados na própria competência, particularmente por parte daqueles com maior competência intelectual e maior experiência profissional. Fez-se igualmente reparos na qualidade psicométrica da escala e da própria teoria do Locus de controle, no sentido de que esta precisa ser melhor axiomatizada para possibilitar a elaboração de escalas mais precisas para a medida dos construtos que propõe.A scale with 28 items, the Organizational Locus of Control (ELCO, was built based on Rotter’s theory and Levenson’s scale. ELCO was validated on a sample of 350 employees of Telebrás, a governmental firm in Brazil. As foreseen from the theory, a principal-axis factoring showed the presence of the expected two factors, namely internal and external locus of control. The external locus of control factor, composed of 18 items, showed good internal consistency (alpha =.81 whereas the internal factor, with 10 items

  14. Locus of control, optimism, and recollections of depression and self-reported cognitive functioning following treatment for colorectal cancer.

    Science.gov (United States)

    Wilson, Carlene; Giles, Kristy; Nettelbeck, Ted; Hutchinson, Amanda

    2017-10-18

    To investigate the effects of disposition (locus of control, optimism, depression) on recollections of cognitive functioning following cancer treatment. Participants were survivors of colorectal cancer (n = 88) and their spouses (n = 40). Survivors retrospectively rated their cognitive functioning and depression, as experienced following treatment; and currently rated their dispositions for optimism and locus of control. Survivors' spouses likewise provided their recollections of survivors' cognitive functioning and depression at time following treatment. Correlations between survivors' and spouses' ratings for cognitive functioning were statistically significant but not for depression. Results supported validity of survivors' longer-term retrospective reports. Although internal locus of control correlated positively with retrospectively self-reported cognitive functioning, and negatively with retrospectively self-reported depression, moderated hierarchical multiple regression found independent contribution of internal locus of control was limited to predicting quality of life; and that, among variables tested, depression correlated strongest with cognitive functioning. Neither internal locus of control nor optimism in colorectal cancer survivors influences correlation between cognition and depression. Health care providers should note individual differences in responses to treatment and be alert to the impact of depression on perceived everyday functioning. This article is protected by copyright. All rights reserved.

  15. Patients suffering from restless legs syndrome have low internal locus of control and poor psychological functioning compared to healthy controls.

    Science.gov (United States)

    Brand, Serge; Beck, Johannes; Hatzinger, Martin; Holsboer-Trachsler, Edith

    2013-01-01

    Restless legs syndrome (RLS) is a disturbing sensorimotor disorder negatively influencing both sleep and psychological functioning. The aim of the present study was to assess RLS patients with respect to locus of control, sleep-related personality traits, quality of life, and sleep as compared to healthy controls. Thirty-eight patients (18 females and 20 males; mean age: 56.06 years) diagnosed with RLS and an age- and gender-matched control group (n = 42) were recruited. Participants completed a series of questionnaires related to locus of control, personality traits, quality of life, and sleep. Compared to healthy controls, RLS patients had a lower internal locus of control, unfavourable sleep-related personality traits such as low self-confidence and higher mental arousal, poorer quality of life, and more depressive symptoms. Sleep was also affected. Multiple regression analyses showed that a low internal and a high external locus of control were predicted by RLS. The pattern of results suggests that RLS is associated with a low locus of control, negative personality traits, and poor quality of life as compared to healthy controls. Copyright © 2013 S. Karger AG, Basel.

  16. Marijuana Usage and Hypnotic Susceptibility

    Science.gov (United States)

    Franzini, Louis R.; McDonald, Roy D.

    1973-01-01

    Anonymous self-reported drug usage data and hypnotic susceptibility scores were obtained from 282 college students. Frequent marijuana users (more than 10 times) showed greater susceptibility to hypnosis than nonusers. (Author)

  17. Antibiotic susceptibility of ica-positive and ica-negative MRSA in different phases of biofilm growth.

    Science.gov (United States)

    Chopra, Shivani; Harjai, Kusum; Chhibber, Sanjay

    2015-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a clinically relevant pathogen because of its resistance to antibiotics and its ability to form potent biofilm. Both ica-negative as well as ica-positive MRSA strains are known to produce biofilm. In the present study, these strains were grown in biofilm mode and susceptibility of these to antibiotics was assessed. Our study suggests that antibiotic susceptibility of MRSA biofilm depends on the biochemical composition of its matrix. The biofilm matrix of ica-positive MRSA was mainly composed of poly-intercellular adhesion (PIA), whereas eDNA was a major constituent of ica-negative MRSA. The results showed that MRSA in planktonic growth was susceptible to clindamycin, vancomycin and minocycline. However, the MIC and MBC of vancomycin for the mature biofilm of ica-negative MRSA was 16 and 32 μg ml(-1), respectively. On the contrary, the MIC and MBC of vancomycin for ica-positive MRSA was >1024 μg ml(-1). The effect of vancomycin and minocycline on young and old biofilms was also determined. Vancomycin was quite effective in eradicating the young biofilm formed by ica-negative MRSA; however, it was completely ineffective on the biofilm of ica-positive MRSA. Minocycline at its highest clinical achievable concentration was found to be quite effective in eradicating the young biofilm formed by both the strains. The enzyme-linked immunosorbent assay (ELISA) results and dot blot assay suggest that the presence of ica locus influenced PIA production, which probably contributed towards the failure of vancomycin in eradicating the biofilm formed by ica-positive strain. However, none of the antibiotics used in this study was effective in eradicating the mature biofilms.

  18. A genome-wide association analysis identifies NMNAT2 and HCP5 as susceptibility loci for Kawasaki disease.

    Science.gov (United States)

    Kim, Jae-Jung; Yun, Sin Weon; Yu, Jeong Jin; Yoon, Kyung Lim; Lee, Kyung-Yil; Kil, Hong-Ryang; Kim, Gi Beom; Han, Myung-Ki; Song, Min Seob; Lee, Hyoung Doo; Ha, Kee Soo; Sohn, Sejung; Johnson, Todd A; Takahashi, Atsushi; Kubo, Michiaki; Tsunoda, Tatsuhiko; Ito, Kaoru; Onouchi, Yoshihiro; Hong, Young Mi; Jang, Gi Young; Lee, Jong-Keuk

    2017-08-31

    Kawasaki disease (KD), a systemic vasculitis of infants and children, manifests as fever and mucocutaneous inflammation. Although its etiology is largely unknown, the epidemiological data suggest that genetic factors are important in KD susceptibility. To identify genetic variants influencing KD susceptibility, we performed a genome-wide association study (GWAS) and replication study using a total of 915 children with KD and 4553 controls in the Korean population. Six single-nucleotide polymorphisms (SNPs) in three loci were associated significantly with KD susceptibility (P<1.0 × 10(-5)), including the previously reported BLK locus (rs6993775, odds ratio (OR)=1.52, P=2.52 × 10(-11)). The other two loci were newly identified: NMNAT2 on chromosome 1q25.3 (rs2078087, OR=1.33, P=1.15 × 10(-6)) and the human leukocyte antigen (HLA) region on chromosome 6p21.3 (HLA-C, HLA-B, MICA and HCP5) (rs9380242, rs9378199, rs9266669 and rs6938467; OR=1.33-1.51, P=8.93 × 10(-6) to 5.24 × 10(-8)). Additionally, SNP rs17280682 in NLRP14 was associated significantly with KD with a family history (18 cases vs 4553 controls, OR=6.76, P=5.46 × 10(-6)). These results provide new insights into the pathogenesis and pathophysiology of KD.Journal of Human Genetics advance online publication, 31 August 2017; doi:10.1038/jhg.2017.87.

  19. Individuality in vulnerability: influences on physical health.

    Science.gov (United States)

    Horner, K L

    1998-01-01

    The relation between personality traits, environmental stressors and their impact, coping behaviors, and health status was examined, as were pathways through which health is influenced by these individual difference variables. It was hypothesized that personality predicts susceptibility to stressors and coping mechanisms that modify the cognitive and affective reactions that influence health status. Two hundred and eighty- four university students completed self-report questionnaires. Ego resilience, low neuroticism, hardiness, internal locus of control, and extraversion loaded on a factor moderately related, indirectly, to health status. A path analysis testing sexes separately revealed that men with a vital personality (i.e. emotionally calm but flexible, self-reliant, and hardy) reported perceiving fewer environmental threats, using more efficacious coping behaviors, and experiencing lower levels of negative affect and better health status than did less self-possessed persons. Similar results emerged for women except that stressors predicted health status independently of personality influences. Moreover, the use of wishful thinking predicted health status directly for men but not for women. Personality appears to be related to poor health, through ineffective coping and consequent negative affect.