WorldWideScience

Sample records for surrounding specific loci

  1. Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes

    DEFF Research Database (Denmark)

    Broeks, Annegien; Schmidt, Marjanka K; Sherman, Mark E

    2011-01-01

    Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtype...

  2. Tissue-specific tagging of endogenous loci in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Kate Koles

    2016-01-01

    Full Text Available Fluorescent protein tags have revolutionized cell and developmental biology, and in combination with binary expression systems they enable diverse tissue-specific studies of protein function. However these binary expression systems often do not recapitulate endogenous protein expression levels, localization, binding partners and/or developmental windows of gene expression. To address these limitations, we have developed a method called T-STEP (tissue-specific tagging of endogenous proteins that allows endogenous loci to be tagged in a tissue specific manner. T-STEP uses a combination of efficient CRISPR/Cas9-enhanced gene targeting and tissue-specific recombinase-mediated tag swapping to temporally and spatially label endogenous proteins. We have employed this method to GFP tag OCRL (a phosphoinositide-5-phosphatase in the endocytic pathway and Vps35 (a Parkinson's disease-implicated component of the endosomal retromer complex in diverse Drosophila tissues including neurons, glia, muscles and hemocytes. Selective tagging of endogenous proteins allows, for the first time, cell type-specific live imaging and proteomics in complex tissues.

  3. Annotation of loci from genome-wide association studies using tissue-specific quantitative interaction proteomics

    NARCIS (Netherlands)

    Lundby, Alicia; Rossin, Elizabeth J.; Steffensen, Annette B.; Acha, Moshe Ray; Newton-Cheh, Christopher; Pfeufer, Arne; Lyneh, Stacey N.; Olesen, Soren-Peter; Brunak, Soren; Ellinor, Patrick T.; Jukema, J. Wouter; Trompet, Stella; Ford, Ian; Macfarlane, Peter W.; Krijthe, Bouwe P.; Hofman, Albert; Uitterlinden, Andre G.; Stricker, Bruno H.; Nathoe, Hendrik M.; Spiering, Wilko; Daly, Mark J.; Asselbergs, Ikea W.; van der Harst, Pim; Milan, David J.; de Bakker, Paul I. W.; Lage, Kasper; Olsen, Jesper V.

    2014-01-01

    Genome-wide association studies (GWAS) have identified thousands of loci associated with complex traits, but it is challenging to pinpoint causal genes in these loci and to exploit subtle association signals. We used tissue-specific quantitative interaction proteomics to map a network of five genes

  4. Annotation of loci from genome-wide association studies using tissue-specific quantitative interaction proteomics

    DEFF Research Database (Denmark)

    Lundby, Alicia; Rossin, Elizabeth J.; Steffensen, Annette B.;

    2014-01-01

    Genome-wide association studies (GWAS) have identified thousands of loci associated with complex traits, but it is challenging to pinpoint causal genes in these loci and to exploit subtle association signals. We used tissue-specific quantitative interaction proteomics to map a network of five genes...... involved in the Mendelian disorder long QT syndrome (LOTS). We integrated the LOTS network with GWAS loci from the corresponding common complex trait, QT-interval variation, to identify candidate genes that were subsequently confirmed in Xenopus laevis oocytes and zebrafish. We used the LOTS protein...... to propose candidates in GWAS loci for functional studies and to systematically filter subtle association signals using tissue-specific quantitative interaction proteomics....

  5. Camouflaging in a Complex Environment—Octopuses Use Specific Features of Their Surroundings for Background Matching

    OpenAIRE

    Noam Josef; Piero Amodio; Graziano Fiorito; Nadav Shashar

    2012-01-01

    Living under intense predation pressure, octopuses evolved an effective and impressive camouflaging ability that exploits features of their surroundings to enable them to "blend in." To achieve such background matching, an animal may use general resemblance and reproduce characteristics of its entire surroundings, or it may imitate a specific object in its immediate environment. Using image analysis algorithms, we examined correlations between octopuses and their backgrounds. Field experiment...

  6. Cholinergic enhancement reduces orientation-specific surround suppression but not visual crowding.

    Science.gov (United States)

    Kosovicheva, Anna A; Sheremata, Summer L; Rokem, Ariel; Landau, Ayelet N; Silver, Michael A

    2012-01-01

    Acetylcholine (ACh) reduces the spatial spread of excitatory fMRI responses in early visual cortex and receptive field size of V1 neurons. We investigated the perceptual consequences of these physiological effects of ACh with surround suppression and crowding, two phenomena that involve spatial interactions between visual field locations. Surround suppression refers to the reduction in perceived stimulus contrast by a high-contrast surround stimulus. For grating stimuli, surround suppression is selective for the relative orientations of the center and surround, suggesting that it results from inhibitory interactions in early visual cortex. Crowding refers to impaired identification of a peripheral stimulus in the presence of flankers and is thought to result from excessive integration of visual features. We increased synaptic ACh levels by administering the cholinesterase inhibitor donepezil to healthy human subjects in a placebo-controlled, double-blind design. In Experiment 1, we measured surround suppression of a central grating using a contrast discrimination task with three conditions: (1) surround grating with the same orientation as the center (parallel), (2) surround orthogonal to the center, or (3) no surround. Contrast discrimination thresholds were higher in the parallel than in the orthogonal condition, demonstrating orientation-specific surround suppression (OSSS). Cholinergic enhancement decreased thresholds only in the parallel condition, thereby reducing OSSS. In Experiment 2, subjects performed a crowding task in which they reported the identity of a peripheral letter flanked by letters on either side. We measured the critical spacing between the targets and flanking letters that allowed reliable identification. Cholinergic enhancement with donepezil had no effect on critical spacing. Our findings suggest that ACh reduces spatial interactions in tasks involving segmentation of visual field locations but that these effects may be limited to early

  7. Cholinergic enhancement reduces orientation-specific surround suppression but not visual crowding

    Directory of Open Access Journals (Sweden)

    Anna A. Kosovicheva

    2012-09-01

    Full Text Available Acetylcholine (ACh reduces the spatial spread of excitatory fMRI responses in early visual cortex and the receptive field sizes of V1 neurons. We investigated the perceptual consequences of these physiological effects of ACh with surround suppression and crowding, two tasks that involve spatial interactions between visual field locations. Surround suppression refers to the reduction in perceived stimulus contrast by a high-contrast surround stimulus. For grating stimuli, surround suppression is selective for the relative orientations of the center and surround, suggesting that it results from inhibitory interactions in early visual cortex. Crowding refers to impaired identification of a peripheral stimulus in the presence of flankers and is thought to result from excessive integration of visual features. We increased synaptic ACh levels by administering the cholinesterase inhibitor donepezil to healthy human subjects in a placebo-controlled, double-blind design. In Exp. 1, we measured surround suppression of a central grating using a contrast discrimination task with three conditions: 1 surround grating with the same orientation as the center (parallel, 2 surround orthogonal to the center, or 3 no surround. Contrast discrimination thresholds were higher in the parallel than in the orthogonal condition, demonstrating orientation-specific surround suppression (OSSS. Cholinergic enhancement reduced thresholds only in the parallel condition, thereby reducing OSSS. In Exp. 2, subjects performed a crowding task in which they reported the identity of a peripheral letter flanked by letters on either side. We measured the critical spacing between the target and flanking letters that allowed reliable identification. Cholinergic enhancement had no effect on critical spacing. Our findings suggest that ACh reduces spatial interactions in tasks involving segmentation of visual field locations but that these effects may be limited to early visual cortical

  8. A Geometric Comparison of the Transformation Loci with Specific and Mobile Capital

    Science.gov (United States)

    Colander, David; Gilbert, John; Oladi, Reza

    2008-01-01

    The authors show how the transformation loci in the specific factors model (capital specificity) and the Heckscher-Ohlin-Samuelson model (capital mobility) can be rigorously derived and easily compared by using geometric techniques on the basis of Savosnick geometry. The approach shows directly that the transformation locus with capital…

  9. Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche

    DEFF Research Database (Denmark)

    Perry, John R. B.; Day, Felix; Elks, Cathy E.

    2014-01-01

    . Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and gamma...

  10. Camouflaging in a complex environment--octopuses use specific features of their surroundings for background matching.

    Science.gov (United States)

    Josef, Noam; Amodio, Piero; Fiorito, Graziano; Shashar, Nadav

    2012-01-01

    Living under intense predation pressure, octopuses evolved an effective and impressive camouflaging ability that exploits features of their surroundings to enable them to "blend in." To achieve such background matching, an animal may use general resemblance and reproduce characteristics of its entire surroundings, or it may imitate a specific object in its immediate environment. Using image analysis algorithms, we examined correlations between octopuses and their backgrounds. Field experiments show that when camouflaging, Octopus cyanea and O. vulgaris base their body patterns on selected features of nearby objects rather than attempting to match a large field of view. Such an approach enables the octopus to camouflage in partly occluded environments and to solve the problem of differences in appearance as a function of the viewing inclination of the observer.

  11. Camouflaging in a Complex Environment—Octopuses Use Specific Features of Their Surroundings for Background Matching

    Science.gov (United States)

    Josef, Noam; Amodio, Piero; Fiorito, Graziano; Shashar, Nadav

    2012-01-01

    Living under intense predation pressure, octopuses evolved an effective and impressive camouflaging ability that exploits features of their surroundings to enable them to “blend in.” To achieve such background matching, an animal may use general resemblance and reproduce characteristics of its entire surroundings, or it may imitate a specific object in its immediate environment. Using image analysis algorithms, we examined correlations between octopuses and their backgrounds. Field experiments show that when camouflaging, Octopus cyanea and O. vulgaris base their body patterns on selected features of nearby objects rather than attempting to match a large field of view. Such an approach enables the octopus to camouflage in partly occluded environments and to solve the problem of differences in appearance as a function of the viewing inclination of the observer. PMID:22649542

  12. Camouflaging in a complex environment--octopuses use specific features of their surroundings for background matching.

    Directory of Open Access Journals (Sweden)

    Noam Josef

    Full Text Available Living under intense predation pressure, octopuses evolved an effective and impressive camouflaging ability that exploits features of their surroundings to enable them to "blend in." To achieve such background matching, an animal may use general resemblance and reproduce characteristics of its entire surroundings, or it may imitate a specific object in its immediate environment. Using image analysis algorithms, we examined correlations between octopuses and their backgrounds. Field experiments show that when camouflaging, Octopus cyanea and O. vulgaris base their body patterns on selected features of nearby objects rather than attempting to match a large field of view. Such an approach enables the octopus to camouflage in partly occluded environments and to solve the problem of differences in appearance as a function of the viewing inclination of the observer.

  13. Analysis of IMGSAC autism susceptibility loci: evidence for sex limited and parent of origin specific effects

    Science.gov (United States)

    Lamb, J; Barnby, G; Bonora, E; Sykes, N; Bacchelli, E; Blasi, F; Maestrini, E; Broxholme, J; Tzenova, J; Weeks, D; Bailey, A; Monaco, A; the, I

    2005-01-01

    Background and methods: Autism is a severe neurodevelopmental disorder, which has a complex genetic predisposition. The ratio of males to females affected by autism is approximately 4:1, suggesting that sex specific factors are involved in its development. We reported previously the results of a genomewide screen for autism susceptibility loci in 83 affected sibling pairs (ASP), and follow up analysis in 152 ASP. Here, we report analysis of an expanded sample of 219 ASP, using sex and parent of origin linkage modelling at loci on chromosomes 2, 7, 9, 15, and 16. Results: The results suggest that linkage to chromosomes 7q and 16p is contributed largely by the male–male ASP (MLS = 2.55 v 0.12, and MLS = 2.48 v 0.00, for the 145 male–male and 74 male–female/female–female ASP on chromosomes 7 and 16 respectively). Conversely linkage to chromosome 15q appears to be attributable to the male–female/female–female ASP (MLS = 2.62 v 0.00, for non-male and male–male ASP respectively). On chromosomes 2 and 9, all ASP contribute to linkage. These data, supported by permutation, suggest a possible sex limited effect of susceptibility loci on chromosomes 7, 15, and 16. Parent of origin linkage modelling indicates two distinct regions of paternal and maternal identity by descent sharing on chromosome 7 (paternal MLS = 1.46 at ∼112 cM, and maternal MLS = 1.83 at ∼135 cM; corresponding maternal and paternal MLS = 0.53 and 0.28 respectively), and maternal specific sharing on chromosome 9 (maternal MLS = 1.99 at ∼30 cM; paternal MLS = 0.02). Conclusion: These data support the possibility of two discrete loci underlying linkage of autism to chromosome 7, and implicate possible parent of origin specific effects in the aetiology of autism. PMID:15689451

  14. Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes

    DEFF Research Database (Denmark)

    Broeks, Annegien; Schmidt, Marjanka K; Sherman, Mark E

    2011-01-01

    3803662 (16q12), rs889312 (5q11), rs3817198 (11p15) and rs13387042 (2q35); however, only two of them (16q12 and 2q35) were associated with tumors with the core basal phenotype (P = 0.002). These analyses are consistent with different biological origins of breast cancers, and indicate that tumor......Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes...... were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations...

  15. Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

    Science.gov (United States)

    Perry, John R B; Day, Felix; Elks, Cathy E; Sulem, Patrick; Thompson, Deborah J; Ferreira, Teresa; He, Chunyan; Chasman, Daniel I; Esko, Tõnu; Thorleifsson, Gudmar; Albrecht, Eva; Ang, Wei Q; Corre, Tanguy; Cousminer, Diana L; Feenstra, Bjarke; Franceschini, Nora; Ganna, Andrea; Johnson, Andrew D; Kjellqvist, Sanela; Lunetta, Kathryn L; McMahon, George; Nolte, Ilja M; Paternoster, Lavinia; Porcu, Eleonora; Smith, Albert V; Stolk, Lisette; Teumer, Alexander; Tšernikova, Natalia; Tikkanen, Emmi; Ulivi, Sheila; Wagner, Erin K; Amin, Najaf; Bierut, Laura J; Byrne, Enda M; Hottenga, Jouke-Jan; Koller, Daniel L; Mangino, Massimo; Pers, Tune H; Yerges-Armstrong, Laura M; Hua Zhao, Jing; Andrulis, Irene L; Anton-Culver, Hoda; Atsma, Femke; Bandinelli, Stefania; Beckmann, Matthias W; Benitez, Javier; Blomqvist, Carl; Bojesen, Stig E; Bolla, Manjeet K; Bonanni, Bernardo; Brauch, Hiltrud; Brenner, Hermann; Buring, Julie E; Chang-Claude, Jenny; Chanock, Stephen; Chen, Jinhui; Chenevix-Trench, Georgia; Collée, J Margriet; Couch, Fergus J; Couper, David; Coviello, Andrea D; Cox, Angela; Czene, Kamila; D'adamo, Adamo Pio; Davey Smith, George; De Vivo, Immaculata; Demerath, Ellen W; Dennis, Joe; Devilee, Peter; Dieffenbach, Aida K; Dunning, Alison M; Eiriksdottir, Gudny; Eriksson, Johan G; Fasching, Peter A; Ferrucci, Luigi; Flesch-Janys, Dieter; Flyger, Henrik; Foroud, Tatiana; Franke, Lude; Garcia, Melissa E; García-Closas, Montserrat; Geller, Frank; de Geus, Eco E J; Giles, Graham G; Gudbjartsson, Daniel F; Gudnason, Vilmundur; Guénel, Pascal; Guo, Suiqun; Hall, Per; Hamann, Ute; Haring, Robin; Hartman, Catharina A; Heath, Andrew C; Hofman, Albert; Hooning, Maartje J; Hopper, John L; Hu, Frank B; Hunter, David J; Karasik, David; Kiel, Douglas P; Knight, Julia A; Kosma, Veli-Matti; Kutalik, Zoltan; Lai, Sandra; Lambrechts, Diether; Lindblom, Annika; Mägi, Reedik; Magnusson, Patrik K; Mannermaa, Arto; Martin, Nicholas G; Masson, Gisli; McArdle, Patrick F; McArdle, Wendy L; Melbye, Mads; Michailidou, Kyriaki; Mihailov, Evelin; Milani, Lili; Milne, Roger L; Nevanlinna, Heli; Neven, Patrick; Nohr, Ellen A; Oldehinkel, Albertine J; Oostra, Ben A; Palotie, Aarno; Peacock, Munro; Pedersen, Nancy L; Peterlongo, Paolo; Peto, Julian; Pharoah, Paul D P; Postma, Dirkje S; Pouta, Anneli; Pylkäs, Katri; Radice, Paolo; Ring, Susan; Rivadeneira, Fernando; Robino, Antonietta; Rose, Lynda M; Rudolph, Anja; Salomaa, Veikko; Sanna, Serena; Schlessinger, David; Schmidt, Marjanka K; Southey, Mellissa C; Sovio, Ulla; Stampfer, Meir J; Stöckl, Doris; Storniolo, Anna M; Timpson, Nicholas J; Tyrer, Jonathan; Visser, Jenny A; Vollenweider, Peter; Völzke, Henry; Waeber, Gerard; Waldenberger, Melanie; Wallaschofski, Henri; Wang, Qin; Willemsen, Gonneke; Winqvist, Robert; Wolffenbuttel, Bruce H R; Wright, Margaret J; Boomsma, Dorret I; Econs, Michael J; Khaw, Kay-Tee; Loos, Ruth J F; McCarthy, Mark I; Montgomery, Grant W; Rice, John P; Streeten, Elizabeth A; Thorsteinsdottir, Unnur; van Duijn, Cornelia M; Alizadeh, Behrooz Z; Bergmann, Sven; Boerwinkle, Eric; Boyd, Heather A; Crisponi, Laura; Gasparini, Paolo; Gieger, Christian; Harris, Tamara B; Ingelsson, Erik; Järvelin, Marjo-Riitta; Kraft, Peter; Lawlor, Debbie; Metspalu, Andres; Pennell, Craig E; Ridker, Paul M; Snieder, Harold; Sørensen, Thorkild I A; Spector, Tim D; Strachan, David P; Uitterlinden, André G; Wareham, Nicholas J; Widen, Elisabeth; Zygmunt, Marek; Murray, Anna; Easton, Douglas F; Stefansson, Kari; Murabito, Joanne M; Ong, Ken K

    2014-10-02

    Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.

  16. Parent-of-origin specific allelic associations among 106 genomic loci for age at menarche

    Science.gov (United States)

    Thompson, Deborah J; Ferreira, Teresa; He, Chunyan; Chasman, Daniel I; Esko, Tõnu; Thorleifsson, Gudmar; Albrecht, Eva; Ang, Wei Q; Corre, Tanguy; Cousminer, Diana L; Feenstra, Bjarke; Franceschini, Nora; Ganna, Andrea; Johnson, Andrew D; Kjellqvist, Sanela; Lunetta, Kathryn L; McMahon, George; Nolte, Ilja M; Paternoster, Lavinia; Porcu, Eleonora; Smith, Albert V; Stolk, Lisette; Teumer, Alexander; Tšernikova, Natalia; Tikkanen, Emmi; Ulivi, Sheila; Wagner, Erin K; Amin, Najaf; Bierut, Laura J; Byrne, Enda M; Hottenga, Jouke-Jan; Koller, Daniel L; Mangino, Massimo; Pers, Tune H; Yerges-Armstrong, Laura M; Zhao, Jing Hua; Andrulis, Irene L; Anton-Culver, Hoda; Atsma, Femke; Bandinelli, Stefania; Beckmann, Matthias W; Benitez, Javier; Blomqvist, Carl; Bojesen, Stig E; Bolla, Manjeet K; Bonanni, Bernardo; Brauch, Hiltrud; Brenner, Hermann; Buring, Julie E; Chang-Claude, Jenny; Chanock, Stephen; Chen, Jinhui; Chenevix-Trench, Georgia; Collée, J. Margriet; Couch, Fergus J; Couper, David; Coveillo, Andrea D; Cox, Angela; Czene, Kamila; D’adamo, Adamo Pio; Smith, George Davey; De Vivo, Immaculata; Demerath, Ellen W; Dennis, Joe; Devilee, Peter; Dieffenbach, Aida K; Dunning, Alison M; Eiriksdottir, Gudny; Eriksson, Johan G; Fasching, Peter A; Ferrucci, Luigi; Flesch-Janys, Dieter; Flyger, Henrik; Foroud, Tatiana; Franke, Lude; Garcia, Melissa E; García-Closas, Montserrat; Geller, Frank; de Geus, Eco EJ; Giles, Graham G; Gudbjartsson, Daniel F; Gudnason, Vilmundur; Guénel, Pascal; Guo, Suiqun; Hall, Per; Hamann, Ute; Haring, Robin; Hartman, Catharina A; Heath, Andrew C; Hofman, Albert; Hooning, Maartje J; Hopper, John L; Hu, Frank B; Hunter, David J; Karasik, David; Kiel, Douglas P; Knight, Julia A; Kosma, Veli-Matti; Kutalik, Zoltan; Lai, Sandra; Lambrechts, Diether; Lindblom, Annika; Mägi, Reedik; Magnusson, Patrik K; Mannermaa, Arto; Martin, Nicholas G; Masson, Gisli; McArdle, Patrick F; McArdle, Wendy L; Melbye, Mads; Michailidou, Kyriaki; Mihailov, Evelin; Milani, Lili; Milne, Roger L; Nevanlinna, Heli; Neven, Patrick; Nohr, Ellen A; Oldehinkel, Albertine J; Oostra, Ben A; Palotie, Aarno; Peacock, Munro; Pedersen, Nancy L; Peterlongo, Paolo; Peto, Julian; Pharoah, Paul DP; Postma, Dirkje S; Pouta, Anneli; Pylkäs, Katri; Radice, Paolo; Ring, Susan; Rivadeneira, Fernando; Robino, Antonietta; Rose, Lynda M; Rudolph, Anja; Salomaa, Veikko; Sanna, Serena; Schlessinger, David; Schmidt, Marjanka K; Southey, Mellissa C; Sovio, Ulla; Stampfer, Meir J; Stöckl, Doris; Storniolo, Anna M; Timpson, Nicholas J; Tyrer, Jonathan; Visser, Jenny A; Vollenweider, Peter; Völzke, Henry; Waeber, Gerard; Waldenberger, Melanie; Wallaschofski, Henri; Wang, Qin; Willemsen, Gonneke; Winqvist, Robert; Wolffenbuttel, Bruce HR; Wright, Margaret J; Boomsma, Dorret I; Econs, Michael J; Khaw, Kay-Tee; Loos, Ruth JF; McCarthy, Mark I; Montgomery, Grant W; Rice, John P; Streeten, Elizabeth A; Thorsteinsdottir, Unnur; van Duijn, Cornelia M; Alizadeh, Behrooz Z; Bergmann, Sven; Boerwinkle, Eric; Boyd, Heather A; Crisponi, Laura; Gasparini, Paolo; Gieger, Christian; Harris, Tamara B; Ingelsson, Erik; Järvelin, Marjo-Riitta; Kraft, Peter; Lawlor, Debbie; Metspalu, Andres; Pennell, Craig E; Ridker, Paul M; Snieder, Harold; Sørensen, Thorkild IA; Spector, Tim D; Strachan, David P; Uitterlinden, André G; Wareham, Nicholas J; Widen, Elisabeth; Zygmunt, Marek; Murray, Anna; Easton, Douglas F

    2014-01-01

    Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality1. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation2,3, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P<5×10−8) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1/WDR25, MKRN3/MAGEL2 and KCNK9) demonstrating parent-of-origin specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and gamma-aminobutyric acid-B2 receptor signaling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition. PMID:25231870

  17. Mating type loci of Sporisorium reilianum: novel pattern with three a and multiple b specificities.

    Science.gov (United States)

    Schirawski, Jan; Heinze, Bernadette; Wagenknecht, Martin; Kahmann, Regine

    2005-08-01

    Sporisorium reilianum and Ustilago maydis are two closely related smut fungi, which both infect maize but differ fundamentally in their mode of plant invasion and site of symptom development. As a prelude to studying the molecular basis of these differences, we have characterized the mating type loci of S. reilianum. S. reilianum has two unlinked mating type loci, a and b. Genes in both loci and adjacent regions show a high degree of synteny to the corresponding genes of U. maydis. The b locus occurs in at least five alleles and encodes two subunits of a heterodimeric homeodomain transcription factor, while the a locus encodes a pheromone/receptor system. However, in contrast to that of U. maydis, the a locus of S. reilianum exists in three alleles containing two active pheromone genes each. The alleles of the a locus appear to have arisen through recent recombination events within the locus itself. This has created a situation where each pheromone is specific for recognition by only one mating partner.

  18. Paralog-specific primers for the amplification of nuclear Loci in tetraploid barbels (barbus: cypriniformes).

    Science.gov (United States)

    Gante, Hugo F; Alves, Maria Judite; Dowling, Thomas E

    2011-01-01

    Thirty paralog-specific primers were developed, following an intron-primed exon-crossing strategy, for S7 and growth hormone genes in Barbus (subgenera Barbus and Luciobarbus). We found that paralog-specific amplification requires the use of only one paralog-specific primer, allowing their simultaneous use with universal exon-primed intron-crossing primers of broad taxonomic applicability. This hybrid annealing strategy guarantees both specificity and generality of amplification reactions and represents a step forward in the amplification of duplicated nuclear loci in polyploid organisms and members of multigene families. Assays of several representative taxa identified high levels of segregating single nucleotide polymorphisms (SNPs) and nucleotide diversity within each of these subgenera. Additionally, several insertions-deletions (indels) that are diagnostic across species are found in intronic regions. Therefore, these primers provide a reliable source of valuable nuclear SNP and indel data for population and species level studies of barbels, such as applied conservation and basic evolutionary studies.

  19. Age-specific survival of reintroduced swift fox in Badlands National Park and surrounding lands

    Science.gov (United States)

    Sasmal, Indrani; Klaver, Robert W.; Jenks, Jonathan A.; Schroeder, Greg M.

    2016-01-01

    In 2003, a reintroduction program was initiated at Badlands National Park (BNP), South Dakota, USA, with swift foxes (Vulpes velox) translocated from Colorado and Wyoming, USA, as part of a restoration effort to recover declining swift fox populations throughout its historical range. Estimates of age-specific survival are necessary to evaluate the potential for population growth of reintroduced populations. We used 7 years (2003–2009) of capture–recapture data of 243 pups, 29 yearlings, and 69 adult swift foxes at BNP and the surrounding area to construct Cormack–Jolly–Seber model estimates of apparent survival within a capture–mark–recapture framework using Program MARK. The best model for estimating recapture probabilities included no differences among age classes, greater recapture probabilities during early years of the monitoring effort than later years, and variation among spring, winter, and summer. Our top ranked survival model indicated pup survival differed from that of yearlings and adults and varied by month and year. The apparent annual survival probability of pups (0.47, SE = 0.10) in our study area was greater than the apparent annual survival probability of yearlings and adults (0.27, SE = 0.08). Our results indicate low survival probabilities for a reintroduced population of swift foxes in the BNP and surrounding areas. Management of reintroduced populations and future reintroductions of swift foxes should consider the effects of relative low annual survival on population demography.

  20. Estimation of Specific Effective Energy of Surrounding Organs with Prostate as the Source Organ

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jung Hoon; Lim, Chang Seon; Whang, Joo Ho [Kyunghee Univ., Konyang (Korea, Republic of)

    2008-10-15

    The incidence of prostate cancer has increased rapidly due to such as aging population and western dietary habits and it is the fifth most common cancer among male cancers and the most common cancer in urinary system. Prostate cancer is treated in various ways, but suitable treatments are selected case by case instead of particularly superior treatments chosen. One of them is cancer treatment via irradiation and it is widely available because of its simplicity and outstanding effectiveness; however compromised local selectivity inevitably results in side effects in surrounding tissues like bladder, urethra and rectum. These tough problems have been able to be solved since mid-1980s when radioisotope seeds such as {sup 1}'2{sup 5}I or {sup 103}Pd which could be implanted in the body were produced, and now much less invasive brachytherapy is widely used in the US and Europe. But there is a lack of investigations related to this therapy in Korea. In the present study, we intend to estimate specific effective energy of prostate and surrounding organs using {sup 125}I and {sup 103}Pd and thus provide basic data of radiation exposure assessments during prostate brachytherapy.

  1. Genome-wide association studies suggest sex-specific loci associated with abdominal and visceral fat

    Science.gov (United States)

    Sung, Yun Ju; Pérusse, Louis; Sarzynski, Mark A.; Fornage, Myriam; Sidney, Steve; Sternfeld, Barbara; Rice, Treva; Terry, Gregg; Jacobs, David R.; Katzmarzyk, Peter; Curran, Joanne E; Carr, John Jeffrey; Blangero, John; Ghosh, Sujoy; Després, Jean-Pierre; Rankinen, Tuomo; Rao, D.C.; Bouchard, Claude

    2015-01-01

    Background To identify loci associated with abdominal fat and replicate prior findings, we performed genome-wide association (GWA) studies of abdominal fat traits: subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), total adipose tissue (TAT) and visceral to subcutaneous adipose tissue ratio (VSR). Subjects and Methods Sex-combined and sex-stratified analyses were performed on each trait with (TRAIT-BMI) or without (TRAIT) adjustment for BMI, and cohort-specific results were combined via a fixed effects meta-analysis. A total of 2,513 subjects of European descent were available for the discovery phase. For replication, 2,171 European Americans and 772 African Americans were available. Results A total of 52 SNPs encompassing 7 loci showed suggestive evidence of association (p < 1.0 × 10−6) with abdominal fat in the sex-combined analyses. The strongest evidence was found on chromosome 7p14.3 between a SNP near BBS9 gene and VAT (rs12374818; p= 1.10 × 10−7), an association that was replicated (p = 0.02). For the BMI-adjusted trait, the strongest evidence of association was found between a SNP near CYCSP30 and VAT-BMI (rs10506943; p= 2.42 × 10−7). Our sex-specific analyses identified one genome-wide significant (p < 5.0 × 10−8) locus for SAT in women with 11 SNPs encompassing the MLLT10, DNAJC1 and EBLN1 genes on chromosome 10p12.31 (p = 3.97 × 10−8 to 1.13 × 10−8). The THNSL2 gene previously associated with VAT in women was also replicated (p= 0.006). The six gene/loci showing the strongest evidence of association with VAT or VAT-BMI were interrogated for their functional links with obesity and inflammation using the Biograph knowledge-mining software. Genes showing the closest functional links with obesity and inflammation were ADCY8 and KCNK9, respectively. Conclusions Our results provide evidence for new loci influencing abdominal visceral (BBS9, ADCY8, KCNK9) and subcutaneous (MLLT10/DNAJC1/EBLN1) fat, and confirmed a locus (THNSL2

  2. Dimension-specific signal modulation in visual search: evidence from inter-stimulus surround suppression.

    Science.gov (United States)

    Chan, Louis K H; Hayward, William G

    2012-04-18

    A fundamental task for the visual system is to determine where to attend next. In general, attention is guided by visual saliency. Computational models suggest that saliency values are estimated through an iterative process in which each visual item suppresses each other item's saliency, especially for those with close proximity. To investigate this proposal, we tested the effect of two salient distractors on visual search for a size target. While fixing the target-to-distractor distance, we manipulated the distance between two distractors. If two salient distractors suppressed each other when they were close together, they should interfere with search less; this was exactly what we found. However, we observed such a distance effect only for distractors of the same dimension (e.g., both defined in color) but not for those of different dimensions (e.g., one defined in color and the other in shape), displaying specificity to a perceptual dimension. Therefore, we conclude that saliency in visual search is calculated through a surround suppression process that occurs at a dimension-specific level.

  3. Efficient and allele-specific genome editing of disease loci in human iPSCs.

    Science.gov (United States)

    Smith, Cory; Abalde-Atristain, Leire; He, Chaoxia; Brodsky, Brett R; Braunstein, Evan M; Chaudhari, Pooja; Jang, Yoon-Young; Cheng, Linzhao; Ye, Zhaohui

    2015-03-01

    Efficient and precise genome editing is crucial for realizing the full research and therapeutic potential of human induced pluripotent stem cells (iPSCs). Engineered nucleases including CRISPR/Cas9 and transcription activator like effector nucleases (TALENs) provide powerful tools for enhancing gene-targeting efficiency. In this study, we investigated the relative efficiencies of CRISPR/Cas9 and TALENs in human iPSC lines for inducing both homologous donor-based precise genome editing and nonhomologous end joining (NHEJ)-mediated gene disruption. Significantly higher frequencies of NHEJ-mediated insertions/deletions were detected at several endogenous loci using CRISPR/Cas9 than using TALENs, especially at nonexpressed targets in iPSCs. In contrast, comparable efficiencies of inducing homologous donor-based genome editing were observed at disease-associated loci in iPSCs. In addition, we investigated the specificity of guide RNAs used in the CRISPR/Cas9 system in targeting disease-associated point mutations in patient-specific iPSCs. Using myeloproliferative neoplasm patient-derived iPSCs that carry an acquired JAK2-V617F point mutation and α1-antitrypsin (AAT) deficiency patient-derived iPSCs that carry an inherited Z-AAT point mutation, we demonstrate that Cas9 can specifically target either the mutant or the wild-type allele with little disruption at the other allele differing by a single nucleotide. Overall, our results demonstrate the advantages of the CRISPR/Cas9 system in allele-specific genome targeting and in NHEJ-mediated gene disruption.

  4. Genome-wide association studies identify four ER negative–specific breast cancer risk loci

    Science.gov (United States)

    Garcia-Closas, Montserrat; Couch, Fergus J; Lindstrom, Sara; Michailidou, Kyriaki; Schmidt, Marjanka K; Brook, Mark N; orr, Nick; Rhie, Suhn Kyong; Riboli, Elio; Feigelson, Heather s; Le Marchand, Loic; Buring, Julie E; Eccles, Diana; Miron, Penelope; Fasching, Peter A; Brauch, Hiltrud; Chang-Claude, Jenny; Carpenter, Jane; Godwin, Andrew K; Nevanlinna, Heli; Giles, Graham G; Cox, Angela; Hopper, John L; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dicks, Ed; Howat, Will J; Schoof, Nils; Bojesen, Stig E; Lambrechts, Diether; Broeks, Annegien; Andrulis, Irene L; Guénel, Pascal; Burwinkel, Barbara; Sawyer, Elinor J; Hollestelle, Antoinette; Fletcher, Olivia; Winqvist, Robert; Brenner, Hermann; Mannermaa, Arto; Hamann, Ute; Meindl, Alfons; Lindblom, Annika; Zheng, Wei; Devillee, Peter; Goldberg, Mark S; Lubinski, Jan; Kristensen, Vessela; Swerdlow, Anthony; Anton-Culver, Hoda; Dörk, Thilo; Muir, Kenneth; Matsuo, Keitaro; Wu, Anna H; Radice, Paolo; Teo, Soo Hwang; Shu, Xiao-Ou; Blot, William; Kang, Daehee; Hartman, Mikael; Sangrajrang, Suleeporn; Shen, Chen-Yang; Southey, Melissa C; Park, Daniel J; Hammet, Fleur; Stone, Jennifer; Veer, Laura J Van’t; Rutgers, Emiel J; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Peto, Julian; Schrauder, Michael G; Ekici, Arif B; Beckmann, Matthias W; Silva, Isabel dos Santos; Johnson, Nichola; Warren, Helen; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Lichtner, Peter; Lochmann, Magdalena; Justenhoven, Christina; Ko, Yon-Dschun; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Greco, Dario; Heikkinen, Tuomas; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Antonenkova, Natalia N; Margolin, Sara; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Balleine, Rosemary; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O; Neven, Patrick; Dieudonné, Anne-Sophie; Leunen, Karin; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Peterlongo, Paolo; Peissel, Bernard; Bernard, Loris; Olson, Janet E; Wang, Xianshu; Stevens, Kristen; Severi, Gianluca; Baglietto, Laura; Mclean, Catriona; Coetzee, Gerhard A; Feng, Ye; Henderson, Brian E; Schumacher, Fredrick; Bogdanova, Natalia V; Labrèche, France; Dumont, Martine; Yip, Cheng Har; Taib, Nur Aishah Mohd; Cheng, Ching-Yu; Shrubsole, Martha; Long, Jirong; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Tollenaar, Robertus A E M; Seynaeve, Caroline M; Kriege, Mieke; Hooning, Maartje J; Van den Ouweland, Ans M W; Van Deurzen, Carolien H M; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Balasubramanian, Sabapathy P; Cross, Simon S; Reed, Malcolm W R; Signorello, Lisa; Cai, Qiuyin; Shah, Mitul; Miao, Hui; Chan, Ching Wan; Chia, Kee Seng; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Ashworth, Alan; Jones, Michael; Tessier, Daniel C; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Vincent, Daniel; Bacot, Francois; Ambrosone, Christine B; Bandera, Elisa V; John, Esther M; Chen, Gary K; Hu, Jennifer J; Rodriguez-gil, Jorge L; Bernstein, Leslie; Press, Michael F; Ziegler, Regina G; Millikan, Robert M; Deming-Halverson, Sandra L; Nyante, Sarah; Ingles, Sue A; Waisfisz, Quinten; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel; Bui, Minh; Gibson, Lorna; Müller-Myhsok, Bertram; Schmutzler, Rita K; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Turnbull, Clare; Rahman, Nazneen; Meijers-Heijboer, Hanne; Uitterlinden, Andre G; Rivadeneira, Fernando; Olswold, Curtis; Slager, Susan; Pilarski, Robert; Ademuyiwa, Foluso; Konstantopoulou, Irene; Martin, Nicholas G; Montgomery, Grant W; Slamon, Dennis J; Rauh, Claudia; Lux, Michael P; Jud, Sebastian M; Bruning, Thomas; Weaver, Joellen; Sharma, Priyanka; Pathak, Harsh; Tapper, Will; Gerty, Sue; Durcan, Lorraine; Trichopoulos, Dimitrios; Tumino, Rosario; Peeters, Petra H; Kaaks, Rudolf; Campa, Daniele; Canzian, Federico; Weiderpass, Elisabete; Johansson, Mattias; Khaw, Kay-Tee; Travis, Ruth; Clavel-Chapelon, Françoise; Kolonel, Laurence N; Chen, Constance; Beck, Andy; Hankinson, Susan E; Berg, Christine D; Hoover, Robert N; Lissowska, Jolanta; Figueroa, Jonine D

    2013-01-01

    Estrogen receptor (ER)-negative tumors represent 20–30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry1. The etiology2 and clinical behavior3 of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition4. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10−12 and LGR6, P = 1.4 × 10−8), 2p24.1 (P = 4.6 × 10−8) and 16q12.2 (FTO, P = 4.0 × 10−8), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers. PMID:23535733

  5. Genome-wide association studies identify four ER negative-specific breast cancer risk loci.

    Science.gov (United States)

    Garcia-Closas, Montserrat; Couch, Fergus J; Lindstrom, Sara; Michailidou, Kyriaki; Schmidt, Marjanka K; Brook, Mark N; Orr, Nick; Rhie, Suhn Kyong; Riboli, Elio; Feigelson, Heather S; Le Marchand, Loic; Buring, Julie E; Eccles, Diana; Miron, Penelope; Fasching, Peter A; Brauch, Hiltrud; Chang-Claude, Jenny; Carpenter, Jane; Godwin, Andrew K; Nevanlinna, Heli; Giles, Graham G; Cox, Angela; Hopper, John L; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dicks, Ed; Howat, Will J; Schoof, Nils; Bojesen, Stig E; Lambrechts, Diether; Broeks, Annegien; Andrulis, Irene L; Guénel, Pascal; Burwinkel, Barbara; Sawyer, Elinor J; Hollestelle, Antoinette; Fletcher, Olivia; Winqvist, Robert; Brenner, Hermann; Mannermaa, Arto; Hamann, Ute; Meindl, Alfons; Lindblom, Annika; Zheng, Wei; Devillee, Peter; Goldberg, Mark S; Lubinski, Jan; Kristensen, Vessela; Swerdlow, Anthony; Anton-Culver, Hoda; Dörk, Thilo; Muir, Kenneth; Matsuo, Keitaro; Wu, Anna H; Radice, Paolo; Teo, Soo Hwang; Shu, Xiao-Ou; Blot, William; Kang, Daehee; Hartman, Mikael; Sangrajrang, Suleeporn; Shen, Chen-Yang; Southey, Melissa C; Park, Daniel J; Hammet, Fleur; Stone, Jennifer; Veer, Laura J Van't; Rutgers, Emiel J; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Peto, Julian; Schrauder, Michael G; Ekici, Arif B; Beckmann, Matthias W; Dos Santos Silva, Isabel; Johnson, Nichola; Warren, Helen; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Lichtner, Peter; Lochmann, Magdalena; Justenhoven, Christina; Ko, Yon-Dschun; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Greco, Dario; Heikkinen, Tuomas; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Antonenkova, Natalia N; Margolin, Sara; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Balleine, Rosemary; Tseng, Chiu-Chen; Berg, David Van Den; Stram, Daniel O; Neven, Patrick; Dieudonné, Anne-Sophie; Leunen, Karin; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Peterlongo, Paolo; Peissel, Bernard; Bernard, Loris; Olson, Janet E; Wang, Xianshu; Stevens, Kristen; Severi, Gianluca; Baglietto, Laura; McLean, Catriona; Coetzee, Gerhard A; Feng, Ye; Henderson, Brian E; Schumacher, Fredrick; Bogdanova, Natalia V; Labrèche, France; Dumont, Martine; Yip, Cheng Har; Taib, Nur Aishah Mohd; Cheng, Ching-Yu; Shrubsole, Martha; Long, Jirong; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Tollenaar, Robertus A E M; Seynaeve, Caroline M; Kriege, Mieke; Hooning, Maartje J; van den Ouweland, Ans M W; van Deurzen, Carolien H M; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Balasubramanian, Sabapathy P; Cross, Simon S; Reed, Malcolm W R; Signorello, Lisa; Cai, Qiuyin; Shah, Mitul; Miao, Hui; Chan, Ching Wan; Chia, Kee Seng; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Ashworth, Alan; Jones, Michael; Tessier, Daniel C; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Vincent, Daniel; Bacot, Francois; Ambrosone, Christine B; Bandera, Elisa V; John, Esther M; Chen, Gary K; Hu, Jennifer J; Rodriguez-Gil, Jorge L; Bernstein, Leslie; Press, Michael F; Ziegler, Regina G; Millikan, Robert M; Deming-Halverson, Sandra L; Nyante, Sarah; Ingles, Sue A; Waisfisz, Quinten; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel; Bui, Minh; Gibson, Lorna; Müller-Myhsok, Bertram; Schmutzler, Rita K; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Turnbull, Clare; Rahman, Nazneen; Meijers-Heijboer, Hanne; Uitterlinden, Andre G; Rivadeneira, Fernando; Olswold, Curtis; Slager, Susan; Pilarski, Robert; Ademuyiwa, Foluso; Konstantopoulou, Irene; Martin, Nicholas G; Montgomery, Grant W; Slamon, Dennis J; Rauh, Claudia; Lux, Michael P; Jud, Sebastian M; Bruning, Thomas; Weaver, Joellen; Sharma, Priyanka; Pathak, Harsh; Tapper, Will; Gerty, Sue; Durcan, Lorraine; Trichopoulos, Dimitrios; Tumino, Rosario; Peeters, Petra H; Kaaks, Rudolf; Campa, Daniele; Canzian, Federico; Weiderpass, Elisabete; Johansson, Mattias; Khaw, Kay-Tee; Travis, Ruth; Clavel-Chapelon, Françoise; Kolonel, Laurence N; Chen, Constance; Beck, Andy; Hankinson, Susan E; Berg, Christine D; Hoover, Robert N; Lissowska, Jolanta; Figueroa, Jonine D; Chasman, Daniel I; Gaudet, Mia M; Diver, W Ryan; Willett, Walter C; Hunter, David J; Simard, Jacques; Benitez, Javier; Dunning, Alison M; Sherman, Mark E; Chenevix-Trench, Georgia; Chanock, Stephen J; Hall, Per; Pharoah, Paul D P; Vachon, Celine; Easton, Douglas F; Haiman, Christopher A; Kraft, Peter

    2013-04-01

    Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10(-12) and LGR6, P = 1.4 × 10(-8)), 2p24.1 (P = 4.6 × 10(-8)) and 16q12.2 (FTO, P = 4.0 × 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.

  6. Identification and characterization of locus specific methylation patterns within novel loci undergoing hypermethylation during breast cancer pathogenesis

    DEFF Research Database (Denmark)

    Wojdacz, Tomasz K; Windeløv, Johanne Agerlin; Thestrup, Britta Boserup;

    2014-01-01

    biomarkers for early cancer detection and stratification of patients. METHODS: We used ultrahigh-resolution microarrays to compare genomewide methylation patterns of breast carcinomas (n = 20) and nonmalignant breast tissue (n = 5). Biomarker properties of a subset of discovered differentially methylated....... Analysis of the screening results showed that all DMRs tested displayed significant gains of methylation in the cancer tissue compared to the levels in control tissue. Interestingly, we observed two types of locus-specific methylation, with loci undergoing either predominantly full or heterogeneous...... methylation during carcinogenesis. Almost all tested DMRs (17 of 19) displayed low-level methylation in nonmalignant breast tissue, independently of locus-specific methylation patterns in cases. CONCLUSIONS: Specific loci can undergo either heterogeneous or full methylation during carcinogenesis, and loci...

  7. A probabilistic seismic hazard assessment for Greece and the surrounding region including site-specific considerations

    Directory of Open Access Journals (Sweden)

    P. Mäntyniemi

    2004-06-01

    Full Text Available A probabilistic approach was applied to map the seismic hazard in Greece and the surrounding region. The procedure does not require any specification of seismic sources or/and seismic zones and allows for the use of the whole seismological record, comprising both historical and instrumental data, available for the region of interest. The new seismic hazard map prepared for Greece and its vicinity specifies a 10% probability of exceedance of the given Peak Ground Acceleration (PGA values for shallow seismicity and intermediate soil conditions for an exposure time of 50 years. When preparing the map, the new PGA attenuation relation given by Margaris et al. (2001 was employed. The new map shows a spatial distribution of the seismic hazard that corresponds well with the features of shallow seismicity within the examined region. It depicts the level of seismic hazard in which the exceedance of the PGA value of 0.25 g may be expected to occur within limited areas. The highest estimated levels of seismic hazard inside the territory of Greece are found in the Northern Sporades Islands, where PGA values in excess of 0.50 g are reached at individual sites, and in the Zante Island in Western Greece, where PGA values in the range of 0.35 g to 0.40 g are obtained at more numerous localities. High values are also observed in the sea between the Karpathos and Rhodes islands, near the Island of Amorgos (Cyclades Archipelago and in the Southwestern Peloponnesus. The levels of seismic hazard at the sites of seven Greek cities (Athens, Jannena, Kalamata, Kozani, Larisa, Rhodes and Thessaloniki were also estimated in terms of probabilities that a given PGA value will be exceeded at least once during a time interval of 1, 50 and 100 years at those sites. These probabilities were based on the maximum horizontal PGA values obtained by applying the design earthquake procedure, and the respective median values obtained were 0.24 g for Athens, 0.28 g

  8. Mating Type Loci of Sporisorium reilianum: Novel Pattern with Three a and Multiple b Specificities

    OpenAIRE

    Schirawski, Jan; Heinze, Bernadette; Wagenknecht, Martin; Kahmann, Regine

    2005-01-01

    Sporisorium reilianum and Ustilago maydis are two closely related smut fungi, which both infect maize but differ fundamentally in their mode of plant invasion and site of symptom development. As a prelude to studying the molecular basis of these differences, we have characterized the mating type loci of S. reilianum. S. reilianum has two unlinked mating type loci, a and b. Genes in both loci and adjacent regions show a high degree of synteny to the corresponding genes of U. maydis. The b locu...

  9. A novel CpG island set identifies tissue-specific methylation at developmental gene loci.

    Directory of Open Access Journals (Sweden)

    Robert Illingworth

    2008-01-01

    Full Text Available CpG islands (CGIs are dense clusters of CpG sequences that punctuate the CpG-deficient human genome and associate with many gene promoters. As CGIs also differ from bulk chromosomal DNA by their frequent lack of cytosine methylation, we devised a CGI enrichment method based on nonmethylated CpG affinity chromatography. The resulting library was sequenced to define a novel human blood CGI set that includes many that are not detected by current algorithms. Approximately half of CGIs were associated with annotated gene transcription start sites, the remainder being intra- or intergenic. Using an array representing over 17,000 CGIs, we established that 6%-8% of CGIs are methylated in genomic DNA of human blood, brain, muscle, and spleen. Inter- and intragenic CGIs are preferentially susceptible to methylation. CGIs showing tissue-specific methylation were overrepresented at numerous genetic loci that are essential for development, including HOX and PAX family members. The findings enable a comprehensive analysis of the roles played by CGI methylation in normal and diseased human tissues.

  10. Cell-type-specific enrichment of risk-associated regulatory elements at ovarian cancer susceptibility loci.

    Science.gov (United States)

    Coetzee, Simon G; Shen, Howard C; Hazelett, Dennis J; Lawrenson, Kate; Kuchenbaecker, Karoline; Tyrer, Jonathan; Rhie, Suhn K; Levanon, Keren; Karst, Alison; Drapkin, Ronny; Ramus, Susan J; Couch, Fergus J; Offit, Kenneth; Chenevix-Trench, Georgia; Monteiro, Alvaro N A; Antoniou, Antonis; Freedman, Matthew; Coetzee, Gerhard A; Pharoah, Paul D P; Noushmehr, Houtan; Gayther, Simon A

    2015-07-01

    Understanding the regulatory landscape of the human genome is a central question in complex trait genetics. Most single-nucleotide polymorphisms (SNPs) associated with cancer risk lie in non-protein-coding regions, implicating regulatory DNA elements as functional targets of susceptibility variants. Here, we describe genome-wide annotation of regions of open chromatin and histone modification in fallopian tube and ovarian surface epithelial cells (FTSECs, OSECs), the debated cellular origins of high-grade serous ovarian cancers (HGSOCs) and in endometriosis epithelial cells (EECs), the likely precursor of clear cell ovarian carcinomas (CCOCs). The regulatory architecture of these cell types was compared with normal human mammary epithelial cells and LNCaP prostate cancer cells. We observed similar positional patterns of global enhancer signatures across the three different ovarian cancer precursor cell types, and evidence of tissue-specific regulatory signatures compared to non-gynecological cell types. We found significant enrichment for risk-associated SNPs intersecting regulatory biofeatures at 17 known HGSOC susceptibility loci in FTSECs (P = 3.8 × 10(-30)), OSECs (P = 2.4 × 10(-23)) and HMECs (P = 6.7 × 10(-15)) but not for EECs (P = 0.45) or LNCaP cells (P = 0.88). Hierarchical clustering of risk SNPs conditioned on the six different cell types indicates FTSECs and OSECs are highly related (96% of samples using multi-scale bootstrapping) suggesting both cell types may be precursors of HGSOC. These data represent the first description of regulatory catalogues of normal precursor cells for different ovarian cancer subtypes, and provide unique insights into the tissue specific regulatory variation with respect to the likely functional targets of germline genetic susceptibility variants for ovarian cancer.

  11. Measurement of spatial proximity and accessibility of chromosomal loci in yeast using Cre/loxP site-specific recombination

    OpenAIRE

    Lui, Doris; Burgess, Sean M.

    2009-01-01

    Several methods have been developed to measure interactions between homologous chromosomes during meiosis in budding yeast. These include cytological analysis of fixed, spread nuclei using fluorescence in situ Hybridization (FISH) (1, 2), visualization of GFP-labeled chromosomal loci in living cells (3), and Chromosome-Conformation Capture (3C) (4). Here we describe a quantitative genetic assay that uses exogenous site-specific recombination to monitor the level of homolog associations betwee...

  12. Sex-specific effects of NLRP6/AVR and ADM loci on susceptibility to essential hypertension in a Sardinian population.

    Directory of Open Access Journals (Sweden)

    Nicola Glorioso

    Full Text Available Coronary artery disease, heart failure, fatal arrhythmias, stroke, and renal disease are the most common causes of mortality for humans, and essential hypertension remains a major risk factor. Elucidation of susceptibility loci for essential hypertension has been difficult because of its complex, multifactorial nature involving genetic, environmental, and sex- and age-dependent nature. We investigated whether the 11p15.5 region syntenic to rat chromosome 1 region containing multiple blood pressure quantitative trait loci (QTL detected in Dahl rat intercrosses harbors polymorphisms that contribute to susceptibility/resistance to essential hypertension in a Sardinian population. Initial testing performed using microsatellite markers spanning 18 Mb of 11p15.5 detected a strong association between D11S1318 (at 2.1 Mb, P = 0.004 and D11S1346 (at 10.6 Mb, P = 0.00000004, suggesting that loci in close proximity to these markers may contribute to susceptibility in our Sardinian cohort. NLR family, pyrin domain containing 6/angiotensin-vasopressin receptor (NLRP6/AVR, and adrenomedullin (ADM are in close proximity to D11S1318 and D11S1346, respectively; thus we tested single nucleotide polymorphisms (SNPs within NLRP6/AVR and ADM for their association with hypertension in our Sardinian cohort. Upon sex stratification, we detected one NLRP6/AVR SNP associated with decreased susceptibility to hypertension in males (rs7948797G, P = 0.029; OR = 0.73 [0.57-0.94]. For ADM, sex-specific analysis showed a significant association between rs4444073C, with increased susceptibility to essential hypertension only in the male population (P = 0.006; OR = 1.44 [1.13-1.84]. Our results revealed an association between NLRP6/AVR and ADM loci with male essential hypertension, suggesting the existence of sex-specific NLRP6/AVR and ADM variants affecting male susceptibility to essential hypertension.

  13. Caucasian and Asian specific rheumatoid arthritis risk loci reveal limited replication and apparent allelic heterogeneity in north Indians.

    Directory of Open Access Journals (Sweden)

    Pushplata Prasad

    Full Text Available Genome-wide association studies and meta-analysis indicate that several genes/loci are consistently associated with rheumatoid arthritis (RA in European and Asian populations. To evaluate the transferability status of these findings to an ethnically diverse north Indian population, we performed a replication analysis. We investigated the association of 47 single-nucleotide polymorphisms (SNPs at 43 of these genes/loci with RA in a north Indian cohort comprising 983 RA cases and 1007 age and gender matched controls. Genotyping was done using Infinium human 660w-quad. Association analysis by chi-square test implemented in plink was carried out in two steps. Firstly, association of the index or surrogate SNP (r2>0.8, calculated from reference GIH Hap-Map population was tested. In the second step, evidence for allelic/locus heterogeneity at aforementioned genes/loci was assessed for by testing additional flanking SNPs in linkage equilibrium with index/surrogate marker.Of the 44 European specific index SNPs, neither index nor surrogate SNPs were present for nine SNPs in the genotyping array. Of the remaining 35, associations were replicated at seven genes namely PTPN22 (rs1217407, p = 3×10(-3; IL2-21 (rs13119723, p = 0.008; HLA-DRB1 (rs660895, p = 2.56×10(-5; rs6457617, p = 1.6×10(-09; rs13192471, p = 6.7×10(-16; TNFA1P3 (rs9321637, p = 0.03; CCL21 (rs13293020, p = 0.01; IL2RA (rs2104286, p = 1.9×10(-4 and ZEB1 (rs2793108, p = 0.006. Of the three Asian specific loci tested, rs2977227 in PADI4 showed modest association (p<0.02. Further, of the 140 SNPs (in LE with index/surrogate variant tested, association was observed at 11 additional genes: PTPRC, AFF3, CD28, CTLA4, PXK, ANKRD55, TAGAP, CCR6, BLK, CD40 and IL2RB. This study indicates limited replication of European and Asian index SNPs and apparent allelic heterogeneity in RA etiology among north Indians warranting independent GWAS in this population

  14. [Application of 17 Y-chromosome specific STR loci in paternity testing].

    Science.gov (United States)

    Deng, Zhi-Hui; Li, Qian; Wu, Shuang; Li, Da-Cheng; Yang, Bao-Cheng

    2008-06-01

    The purpose of this study was to explore the ability of discrimination of the AmpFlSTR Yfiler PCR amplification kit containing 17 Y-STR loci and the allelic mutation in the practice of paternity testing in Chinese population. 36 non-paternity father/son pairs and 84 confirmed father/son pairs, which had been previously genotyped by using Reliagene Y-PLEX 6 commercial kit and the "9 Y-STR multiplex with reduced-size amplicons" developed by our laboratory, were subjected to Y-STR genotyping at 17 loci using the AmpFlSTR Yfiler PCR amplification kit. 17 Y-STR loci were amplified in single multiplex and the PCR products were detected by using ABI Prism 3100 DNA Sequencer. The number of Y-STR exclusion for each non-paternity father/son pair and the mutation events for each confirmed father/son pair were calculated and the observed results were compared with our previous reported data determined by Reliagene Y-PLEX 6 kit and the "9 Y-STR multiplex with reduced-size amplicons". The results showed that out of 36 non-paternity father/son pairs subjected to Y-STR genotyping by using the AmpFlSTR Yfiler kit, one case with no Y-STR exclusion of paternity and 35 cases with more than 3 Y-STR exclusions for each father/son pair were observed. The percentage of cases with more than 3 Y-STR exclusions in all the tested non-paternity cases for Yfiler kit was 97.22% (35/36), which was more than that of Reliagene Y-PLEX 6 kit (92.11%, 35/38) and our "9 Y-STR multiplex with reduced-size amplicons" (91.67%, 33/36). Except for single father/son pair with no Y-STR exclusion, an average of 11.3 Y-STR exclusions was observed in other 35 non-paternity father/son pairs. In the 84 confirmed father/son pairs, 5 mutation events with a single unit repeat change at DYS437, DYS439, DYS635, DYS389II and DYS19, respectively, were identified using the Yfiler kit. The average mutation rate was estimated at 3.50 x 10(-3) per locus per generation. The cases with Y-STR mutation events in all tested

  15. Investigation of recurrent deletion loci specific to conventional renal cell carcinoma by comparative allelotyping in major epithelial carcinomas

    Directory of Open Access Journals (Sweden)

    Rashmi R Bhat (Singh

    2012-01-01

    Full Text Available Objective: Loss of heterozygosity (LOH studies were undertaken to investigate the consistently deleted loci/? tumor suppressor gene loci (TSG on 3p in conventional renal cell carcinoma (cRCC. Materials and Methods: LOH studies were performed by polymerase chain reaction (PCR using 15 micro satellite markers mapped in region 3p12-p26 on 40 paired cRCC tumors and normal kidney at Stages I-IV. Simultaneously, fluorescent in-situ hybridization (FISH studies were performed to investigate the allelic deletion of fragile histidine triad (FHIT. Results: Our studies revealed three affected regions; 3p12.2-p14.1, 3p14.2-p21.1, and 3p24.2-p26.1 with differential frequencies in Group I (Stage I and II and Group II (Stage III and IV. Incidence for D3S1234 (FHIT locus and D3S2454 (3p13 was 75% and 83% in Group I and II, respectively. Comparative allelotyping in epithelial malignancies like lung, bladder, and breast tumors revealed LOH (frequency 14−20% only in breast tumors for D3S2406, D3S1766 (distal to FHIT, and D3S1560 (distal to VHL, Von-Hippal Lindau. FISH using FHIT gene probe revealed deletions in cRCC (88%, breast (30%, and lung tumors (10% with no deletions in bladder tumors and leukemias, signifying the importance of FHIT in the pathogenesis of tumors of epithelial origin. Conclusion: Our findings suggested FHIT deletion as an early and VHL deletion as an early and/or late event in cRCC. Additionally, studies also disclosed the recurrent deletions of flanking loci to FHIT and VHL in cRCC. The dilemma of interstitial or continuous deletion on 3p needs to be resolved by implementation of latest sensitive molecular techniques that would further help to narrow down search for TSG loci specific to cRCC, other than VHL and FHIT.

  16. Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci

    DEFF Research Database (Denmark)

    Ellinghaus, David; Jostins, Luke; Spain, Sarah L

    2016-01-01

    86,000 individuals of European ancestry, we identified 244 independent multidisease signals, including 27 new genome-wide significant susceptibility loci and 3 unreported shared risk loci. Complex pleiotropy was supported when contrasting multidisease signals with expression data sets from human, rat...

  17. Tissue-Specific Enrichment of Lymphoma Risk Loci in Regulatory Elements.

    Science.gov (United States)

    Hayes, James E; Trynka, Gosia; Vijai, Joseph; Offit, Kenneth; Raychaudhuri, Soumya; Klein, Robert J

    2015-01-01

    Though numerous polymorphisms have been associated with risk of developing lymphoma, how these variants function to promote tumorigenesis is poorly understood. Here, we report that lymphoma risk SNPs, especially in the non-Hodgkin's lymphoma subtype chronic lymphocytic leukemia, are significantly enriched for co-localization with epigenetic marks of active gene regulation. These enrichments were seen in a lymphoid-specific manner for numerous ENCODE datasets, including DNase-hypersensitivity as well as multiple segmentation-defined enhancer regions. Furthermore, we identify putatively functional SNPs that are both in regulatory elements in lymphocytes and are associated with gene expression changes in blood. We developed an algorithm, UES, that uses a Monte Carlo simulation approach to calculate the enrichment of previously identified risk SNPs in various functional elements. This multiscale approach integrating multiple datasets helps disentangle the underlying biology of lymphoma, and more broadly, is generally applicable to GWAS results from other diseases as well.

  18. Susceptibility loci associated with specific and shared subtypes of lymphoid malignancies.

    Directory of Open Access Journals (Sweden)

    Joseph Vijai

    Full Text Available The genetics of lymphoma susceptibility reflect the marked heterogeneity of diseases that comprise this broad phenotype. However, multiple subtypes of lymphoma are observed in some families, suggesting shared pathways of genetic predisposition to these pathologically distinct entities. Using a two-stage GWAS, we tested 530,583 SNPs in 944 cases of lymphoma, including 282 familial cases, and 4,044 public shared controls, followed by genotyping of 50 SNPs in 1,245 cases and 2,596 controls. A novel region on 11q12.1 showed association with combined lymphoma (LYM subtypes. SNPs in this region included rs12289961 near LPXN, (P(LYM = 3.89×10(-8, OR = 1.29 and rs948562 (P(LYM = 5.85×10(-7, OR = 1.29. A SNP in a novel non-HLA region on 6p23 (rs707824, P(NHL = 5.72×10(-7 was suggestive of an association conferring susceptibility to lymphoma. Four SNPs, all in a previously reported HLA region, 6p21.32, showed genome-wide significant associations with follicular lymphoma. The most significant association with follicular lymphoma was for rs4530903 (P(FL = 2.69×10(-12, OR = 1.93. Three novel SNPs near the HLA locus, rs9268853, rs2647046, and rs2621416, demonstrated additional variation contributing toward genetic susceptibility to FL associated with this region. Genes implicated by GWAS were also found to be cis-eQTLs in lymphoblastoid cell lines; candidate genes in these regions have been implicated in hematopoiesis and immune function. These results, showing novel susceptibility regions and allelic heterogeneity, point to the existence of pathways of susceptibility to both shared as well as specific subtypes of lymphoid malignancy.

  19. Quantifying evidence for candidate gene polymorphisms: Bayesian analysis combining sequence-specific and quantitative trait loci colocation information.

    Science.gov (United States)

    Ball, Roderick D

    2007-12-01

    We calculate posterior probabilities for candidate genes as a function of genomic location. Posterior probabilities for quantitative trait loci (QTL) presence in a small interval are calculated using a Bayesian model-selection approach based on the Bayesian information criterion (BIC) and used to combine QTL colocation information with sequence-specific evidence, e.g., from differential expression and/or association studies. Our method takes into account uncertainty in estimation of number and locations of QTL and estimated map position. Posterior probabilities for QTL presence were calculated for simulated data with n = 100, 300, and 1200 QTL progeny and compared with interval mapping and composite-interval mapping. Candidate genes that mapped to QTL regions had substantially larger posterior probabilities. Among candidates with a given Bayes factor, those that map near a QTL are more promising for further investigation with association studies and functional testing or for use in marker-aided selection. The BIC is shown to correspond very closely to Bayes factors for linear models with a nearly noninformative Zellner prior for the simulated QTL data with n > or = 100. It is shown how to modify the BIC to use a subjective prior for the QTL effects.

  20. Identifying breast cancer risk loci by global differential allele-specific expression (DASE analysis in mammary epithelial transcriptome

    Directory of Open Access Journals (Sweden)

    Gao Chuan

    2012-10-01

    Full Text Available Abstract Background The significant mortality associated with breast cancer (BCa suggests a need to improve current research strategies to identify new genes that predispose women to breast cancer. Differential allele-specific expression (DASE has been shown to contribute to phenotypic variables in humans and recently to the pathogenesis of cancer. We previously reported that nonsense-mediated mRNA decay (NMD could lead to DASE of BRCA1/2, which is associated with elevated susceptibility to breast cancer. In addition to truncation mutations, multiple genetic and epigenetic factors can contribute to DASE, and we propose that DASE is a functional index for cis-acting regulatory variants and pathogenic mutations, and that global analysis of DASE in breast cancer precursor tissues can be used to identify novel causative alleles for breast cancer susceptibility. Results To test our hypothesis, we employed the Illumina® Omni1-Quad BeadChip in paired genomic DNA (gDNA and double-stranded cDNA (ds-cDNA samples prepared from eight BCa patient-derived normal mammary epithelial lines (HMEC. We filtered original array data according to heterozygous genotype calls and calculated DASE values using the Log ratio of cDNA allele intensity, which was normalized to the corresponding gDNA. We developed two statistical methods, SNP- and gene-based approaches, which allowed us to identify a list of 60 candidate DASE loci (DASE ≥ 2.00, P ≤ 0.01, FDR ≤ 0.05 by both methods. Ingenuity Pathway Analysis of DASE loci revealed one major breast cancer-relevant interaction network, which includes two known cancer causative genes, ZNF331 (DASE = 2.31, P = 0.0018, FDR = 0.040 and USP6 (DASE = 4.80, P = 0.0013, FDR = 0.013, and a breast cancer causative gene, DMBT1 (DASE=2.03, P = 0.0017, FDR = 0.014. Sequence analysis of a 5′ RACE product of DMBT1 demonstrated that rs2981745, a putative breast cancer risk locus, appears to be one of the causal variants leading to DASE

  1. A genome-wide screen in human embryonic stem cells reveals novel sites of allele-specific histone modification associated with known disease loci

    LENUS (Irish Health Repository)

    Prendergast, James G D

    2012-05-19

    AbstractBackgroundChromatin structure at a given site can differ between chromosome copies in a cell, and such imbalances in chromatin structure have been shown to be important in understanding the molecular mechanisms controlling several disease loci. Human genetic variation, DNA methylation, and disease have been intensely studied, uncovering many sites of allele-specific DNA methylation (ASM). However, little is known about the genome-wide occurrence of sites of allele-specific histone modification (ASHM) and their relationship to human disease. The aim of this study was to investigate the extent and characteristics of sites of ASHM in human embryonic stem cells (hESCs).ResultsUsing a statistically rigorous protocol, we investigated the genomic distribution of ASHM in hESCs, and their relationship to sites of allele-specific expression (ASE) and DNA methylation. We found that, although they were rare, sites of ASHM were substantially enriched at loci displaying ASE. Many were also found at known imprinted regions, hence sites of ASHM are likely to be better markers of imprinted regions than sites of ASM. We also found that sites of ASHM and ASE in hESCs colocalize at risk loci for developmental syndromes mediated by deletions, providing insights into the etiology of these disorders.ConclusionThese results demonstrate the potential importance of ASHM patterns in the interpretation of disease loci, and the protocol described provides a basis for similar studies of ASHM in other cell types to further our understanding of human disease susceptibility.

  2. Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci.

    Science.gov (United States)

    Jones, Gregory T; Tromp, Gerard; Kuivaniemi, Helena; Gretarsdottir, Solveig; Baas, Annette F; Giusti, Betti; Strauss, Ewa; Van't Hof, Femke N G; Webb, Thomas R; Erdman, Robert; Ritchie, Marylyn D; Elmore, James R; Verma, Anurag; Pendergrass, Sarah; Kullo, Iftikhar J; Ye, Zi; Peissig, Peggy L; Gottesman, Omri; Verma, Shefali S; Malinowski, Jennifer; Rasmussen-Torvik, Laura J; Borthwick, Kenneth M; Smelser, Diane T; Crosslin, David R; de Andrade, Mariza; Ryer, Evan J; McCarty, Catherine A; Böttinger, Erwin P; Pacheco, Jennifer A; Crawford, Dana C; Carrell, David S; Gerhard, Glenn S; Franklin, David P; Carey, David J; Phillips, Victoria L; Williams, Michael J A; Wei, Wenhua; Blair, Ross; Hill, Andrew A; Vasudevan, Thodor M; Lewis, David R; Thomson, Ian A; Krysa, Jo; Hill, Geraldine B; Roake, Justin; Merriman, Tony R; Oszkinis, Grzegorz; Galora, Silvia; Saracini, Claudia; Abbate, Rosanna; Pulli, Raffaele; Pratesi, Carlo; Saratzis, Athanasios; Verissimo, Ana R; Bumpstead, Suzannah; Badger, Stephen A; Clough, Rachel E; Cockerill, Gillian; Hafez, Hany; Scott, D Julian A; Futers, T Simon; Romaine, Simon P R; Bridge, Katherine; Griffin, Kathryn J; Bailey, Marc A; Smith, Alberto; Thompson, Matthew M; van Bockxmeer, Frank M; Matthiasson, Stefan E; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Blankensteijn, Jan D; Teijink, Joep A W; Wijmenga, Cisca; de Graaf, Jacqueline; Kiemeney, Lambertus A; Lindholt, Jes S; Hughes, Anne; Bradley, Declan T; Stirrups, Kathleen; Golledge, Jonathan; Norman, Paul E; Powell, Janet T; Humphries, Steve E; Hamby, Stephen E; Goodall, Alison H; Nelson, Christopher P; Sakalihasan, Natzi; Courtois, Audrey; Ferrell, Robert E; Eriksson, Per; Folkersen, Lasse; Franco-Cereceda, Anders; Eicher, John D; Johnson, Andrew D; Betsholtz, Christer; Ruusalepp, Arno; Franzén, Oscar; Schadt, Eric E; Björkegren, Johan L M; Lipovich, Leonard; Drolet, Anne M; Verhoeven, Eric L; Zeebregts, Clark J; Geelkerken, Robert H; van Sambeek, Marc R; van Sterkenburg, Steven M; de Vries, Jean-Paul; Stefansson, Kari; Thompson, John R; de Bakker, Paul I W; Deloukas, Panos; Sayers, Robert D; Harrison, Seamus C; van Rij, Andre M; Samani, Nilesh J; Bown, Matthew J

    2017-01-20

    Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. To identify additional AAA risk loci using data from all available genome-wide association studies. Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease. © 2016 The Authors.

  3. Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci

    Science.gov (United States)

    Tromp, Gerard; Kuivaniemi, Helena; Gretarsdottir, Solveig; Baas, Annette F.; Giusti, Betti; Strauss, Ewa; van‘t Hof, Femke N.G.; Webb, Thomas R.; Erdman, Robert; Ritchie, Marylyn D.; Elmore, James R.; Verma, Anurag; Pendergrass, Sarah; Kullo, Iftikhar J.; Ye, Zi; Peissig, Peggy L.; Gottesman, Omri; Verma, Shefali S.; Malinowski, Jennifer; Rasmussen-Torvik, Laura J.; Borthwick, Kenneth M.; Smelser, Diane T.; Crosslin, David R.; de Andrade, Mariza; Ryer, Evan J.; McCarty, Catherine A.; Böttinger, Erwin P.; Pacheco, Jennifer A.; Crawford, Dana C.; Carrell, David S.; Gerhard, Glenn S.; Franklin, David P.; Carey, David J.; Phillips, Victoria L.; Williams, Michael J.A.; Wei, Wenhua; Blair, Ross; Hill, Andrew A.; Vasudevan, Thodor M.; Lewis, David R.; Thomson, Ian A.; Krysa, Jo; Hill, Geraldine B.; Roake, Justin; Merriman, Tony R.; Oszkinis, Grzegorz; Galora, Silvia; Saracini, Claudia; Abbate, Rosanna; Pulli, Raffaele; Pratesi, Carlo; Saratzis, Athanasios; Verissimo, Ana R.; Bumpstead, Suzannah; Badger, Stephen A.; Clough, Rachel E.; Cockerill, Gillian; Hafez, Hany; Scott, D. Julian A.; Futers, T. Simon; Romaine, Simon P.R.; Bridge, Katherine; Griffin, Kathryn J.; Bailey, Marc A.; Smith, Alberto; Thompson, Matthew M.; van Bockxmeer, Frank M.; Matthiasson, Stefan E.; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Blankensteijn, Jan D.; Teijink, Joep A.W.; Wijmenga, Cisca; de Graaf, Jacqueline; Kiemeney, Lambertus A.; Lindholt, Jes S.; Hughes, Anne; Bradley, Declan T.; Stirrups, Kathleen; Golledge, Jonathan; Norman, Paul E.; Powell, Janet T.; Humphries, Steve E.; Hamby, Stephen E.; Goodall, Alison H.; Nelson, Christopher P.; Sakalihasan, Natzi; Courtois, Audrey; Ferrell, Robert E.; Eriksson, Per; Folkersen, Lasse; Franco-Cereceda, Anders; Eicher, John D.; Johnson, Andrew D.; Betsholtz, Christer; Ruusalepp, Arno; Franzén, Oscar; Schadt, Eric E.; Björkegren, Johan L.M.; Lipovich, Leonard; Drolet, Anne M.; Verhoeven, Eric L.; Zeebregts, Clark J.; Geelkerken, Robert H.; van Sambeek, Marc R.; van Sterkenburg, Steven M.; de Vries, Jean-Paul; Stefansson, Kari; Thompson, John R.; de Bakker, Paul I.W.; Deloukas, Panos; Sayers, Robert D.; Harrison, Seamus C.; van Rij, Andre M.; Samani, Nilesh J.

    2017-01-01

    Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies. Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease. PMID:27899403

  4. Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci

    DEFF Research Database (Denmark)

    Jones, Gregory T; Tromp, Gerard; Kuivaniemi, Helena

    2017-01-01

    Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. To identify additional AAA risk loci using data from all available genome-wide association...... studies (GWAS). Through a meta-analysis of 6 GWAS datasets and a validation study totalling 10,204 cases and 107,766 controls we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches we observed no new...... associations between the lead AAA SNPs and coronary artery disease, blood pressure, lipids or diabetes. Network analyses identified ERG, IL6R and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. The 4 new risk loci for AAA appear to be specific for AAA compared with other...

  5. Duplications of the Y-chromosome specific loci P25 and 92R7 and forensic implications

    DEFF Research Database (Denmark)

    Sanchez Sanchez, Juan Jose; Brión, Maria; Parson, Walther

    2004-01-01

    In the present study, we demonstrate that two commonly used Y-chromosome single nucleotide polymorphisms (SNPs), P25 and 92R7, are paralogous sequence variants (PSVs) originating from segmental duplications and that at least one of the sequence variants in each group of loci is polymorphic. Sever...

  6. Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci

    Science.gov (United States)

    Ellinghaus, David; Jostins, Luke; Spain, Sarah L; Cortes, Adrian; Bethune, Jörn; Han, Buhm; Park, Yu Rang; Raychaudhuri, Soumya; Pouget, Jennie G; Hübenthal, Matthias; Folseraas, Trine; Wang, Yunpeng; Esko, Tonu; Metspalu, Andres; Westra, Harm-Jan; Franke, Lude; Pers, Tune H; Weersma, Rinse K; Collij, Valerie; D'Amato, Mauro; Halfvarson, Jonas; Jensen, Anders Boeck; Lieb, Wolfgang; Degenhardt, Franziska; Forstner, Andreas J; Hofmann, Andrea; Schreiber, Stefan; Mrowietz, Ulrich; Juran, Brian D; Lazaridis, Konstantinos N; Brunak, Søren; Dale, Anders M; Trembath, Richard C; Weidinger, Stephan; Weichenthal, Michael; Ellinghaus, Eva; Elder, James T; Barker, Jonathan NWN; Andreassen, Ole A; McGovern, Dermot P; Karlsen, Tom H; Barrett, Jeffrey C; Parkes, Miles; Brown, Matthew A; Franke, Andre

    2016-01-01

    We simultaneously investigated the genetic landscape of ankylosing spondylitis, Crohn's disease, psoriasis, primary sclerosing cholangitis and ulcerative colitis to investigate pleiotropy and the relationship between these clinically related diseases. Using high-density genotype data from more than 86,000 individuals of European-ancestry we identified 244 independent multi-disease signals including 27 novel genome-wide significant susceptibility loci and 3 unreported shared risk loci. Complex pleiotropy was supported when contrasting multi-disease signals with expression data sets from human, rat and mouse, and epigenetic and expressed enhancer profiles. The comorbidities among the five immune diseases were best explained by biological pleiotropy rather than heterogeneity (a subgroup of cases that is genetically identical to another disease, possibly due to diagnostic misclassification, molecular subtypes, or excessive comorbidity). In particular, the strong comorbidity between primary sclerosing cholangitis and inflammatory bowel disease is likely the result of a unique disease, which is genetically distinct from classical inflammatory bowel disease phenotypes. PMID:26974007

  7. Quantitative founder-effect analysis of French Canadian families identifies specific loci contributing to metabolic phenotypes of hypertension.

    Science.gov (United States)

    Hamet, P; Merlo, E; Seda, O; Broeckel, U; Tremblay, J; Kaldunski, M; Gaudet, D; Bouchard, G; Deslauriers, B; Gagnon, F; Antoniol, G; Pausová, Z; Labuda, M; Jomphe, M; Gossard, F; Tremblay, G; Kirova, R; Tonellato, P; Orlov, S N; Pintos, J; Platko, J; Hudson, T J; Rioux, J D; Kotchen, T A; Cowley, A W

    2005-05-01

    The Saguenay-Lac St-Jean population of Quebec is relatively isolated and has genealogical records dating to the 17th-century French founders. In 120 extended families with at least one sib pair affected with early-onset hypertension and/or dyslipidemia, we analyzed the genetic determinants of hypertension and related cardiovascular and metabolic conditions. Variance-components linkage analysis revealed 46 loci after 100,000 permutations. The most prominent clusters of overlapping quantitative-trait loci were on chromosomes 1 and 3, a finding supported by principal-components and bivariate analyses. These genetic determinants were further tested by classifying families by use of LOD score density analysis for each measured phenotype at every 5 cM. Our study showed the founder effect over several generations and classes of living individuals. This quantitative genealogical approach supports the notion of the ancestral causality of traits uniquely present and inherited in distinct family classes. With the founder effect, traits determined within population subsets are measurably and quantitatively transmitted through generational lineage, with a precise component contributing to phenotypic variance. These methods should accelerate the uncovering of causal haplotypes in complex diseases such as hypertension and metabolic syndrome.

  8. A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci.

    Science.gov (United States)

    Hinds, David A; McMahon, George; Kiefer, Amy K; Do, Chuong B; Eriksson, Nicholas; Evans, David M; St Pourcain, Beate; Ring, Susan M; Mountain, Joanna L; Francke, Uta; Davey-Smith, George; Timpson, Nicholas J; Tung, Joyce Y

    2013-08-01

    Allergic disease is very common and carries substantial public-health burdens. We conducted a meta-analysis of genome-wide associations with self-reported cat, dust-mite and pollen allergies in 53,862 individuals. We used generalized estimating equations to model shared and allergy-specific genetic effects. We identified 16 shared susceptibility loci with association Pallergies at 6p21.32 in the class II human leukocyte antigen (HLA) region (rs17533090, P=1.7×10(-12)), which was strongly associated with cat allergy. Our study sheds new light on the shared etiology of immune and autoimmune disease.

  9. Examination of potential overlap in autism and language loci on chromosomes 2, 7, and 13 in two independent samples ascertained for specific language impairment.

    Science.gov (United States)

    Bartlett, Christopher W; Flax, Judy F; Logue, Mark W; Smith, Brett J; Vieland, Veronica J; Tallal, Paula; Brzustowicz, Linda M

    2004-01-01

    Specific language impairment is a neurodevelopmental disorder characterized by impairments essentially restricted to the domain of language and language learning skills. This contrasts with autism, which is a pervasive developmental disorder defined by multiple impairments in language, social reciprocity, narrow interests and/or repetitive behaviors. Genetic linkage studies and family data suggest that the two disorders may have genetic components in common. Two samples, from Canada and the US, selected for specific language impairment were genotyped at loci where such common genes are likely to reside. Significant evidence for linkage was previously observed at chromosome 13q21 in our Canadian sample (HLOD 3.56) and was confirmed in our US sample (HLOD 2.61). Using the posterior probability of linkage (PPL) to combine evidence for linkage across the two samples yielded a PPL over 92%. Two additional loci on chromosome 2 and 7 showed weak evidence for linkage. However, a marker in the cystic fibrosis transmembrane conductance regulator (7q31) showed evidence for association to SLI, confirming results from another group (O'Brien et al. 2003). Our results indicate that using samples selected for components of the autism phenotype may be a useful adjunct to autism genetics.

  10. A meta-analysis of thyroid-related traits reveals novel loci and gender-specific differences in the regulation of thyroid function.

    Directory of Open Access Journals (Sweden)

    Eleonora Porcu

    Full Text Available Thyroid hormone is essential for normal metabolism and development, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over their life span. In addition, even mild alterations in thyroid function are associated with weight changes, atrial fibrillation, osteoporosis, and psychiatric disorders. To identify novel variants underlying thyroid function, we performed a large meta-analysis of genome-wide association studies for serum levels of the highly heritable thyroid function markers TSH and FT4, in up to 26,420 and 17,520 euthyroid subjects, respectively. Here we report 26 independent associations, including several novel loci for TSH (PDE10A, VEGFA, IGFBP5, NFIA, SOX9, PRDM11, FGF7, INSR, ABO, MIR1179, NRG1, MBIP, ITPK1, SASH1, GLIS3 and FT4 (LHX3, FOXE1, AADAT, NETO1/FBXO15, LPCAT2/CAPNS2. Notably, only limited overlap was detected between TSH and FT4 associated signals, in spite of the feedback regulation of their circulating levels by the hypothalamic-pituitary-thyroid axis. Five of the reported loci (PDE8B, PDE10A, MAF/LOC440389, NETO1/FBXO15, and LPCAT2/CAPNS2 show strong gender-specific differences, which offer clues for the known sexual dimorphism in thyroid function and related pathologies. Importantly, the TSH-associated loci contribute not only to variation within the normal range, but also to TSH values outside the reference range, suggesting that they may be involved in thyroid dysfunction. Overall, our findings explain, respectively, 5.64% and 2.30% of total TSH and FT4 trait variance, and they improve the current knowledge of the regulation of hypothalamic-pituitary-thyroid axis function and the consequences of genetic variation for hypo- or hyperthyroidism.

  11. Analysis of specific absorption rate and internal electric field in human biological tissues surrounding an air-core coil-type transcutaneous energy transmission transformer.

    Science.gov (United States)

    Shiba, Kenji; Zulkifli, Nur Elina Binti; Ishioka, Yuji

    2017-06-01

    In this study, we analyzed the internal electric field E and specific absorption rate (SAR) of human biological tissues surrounding an air-core coil transcutaneous energy transmission transformer. Using an electromagnetic simulator, we created a model of human biological tissues consisting of a dry skin, wet skin, fat, muscle, and cortical bone. A primary coil was placed on the surface of the skin, and a secondary coil was located subcutaneously inside the body. The E and SAR values for the model representing a 34-year-old male subject were analyzed using electrical frequencies of 0.3-1.5 MHz. The transmitting power was 15 W, and the load resistance was 38.4 Ω. The results showed that the E values were below the International Commission on Non-ionizing Radiation Protection (ICNIRP) limit for the general public exposure between the frequencies of 0.9 and 1.5 MHz, and SAR values were well below the limit prescribed by the ICNIRP for the general public exposure between the frequencies of 0.3 and 1.2 MHz.

  12. Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci

    DEFF Research Database (Denmark)

    Jones, Gregory T; Tromp, Gerard; Kuivaniemi, Helena

    2017-01-01

    Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. To identify additional AAA risk loci using data from all available genome-wide association...

  13. Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci

    NARCIS (Netherlands)

    Jones, Gregory T.; Tromp, Gerard; Kuivaniemi, Helena; Gretarsdottir, Solveig; Baas, Annette F.; Giusti, Betti; Strauss, Ewa; van't Hof, Femke N. G.; Webb, Thomas R.; Erdman, Robert; Ritchie, Marylyn D.; Elmore, James R.; Verma, Anurag; Pendergrass, Sarah A; Kullo, Iftikhar J.; Zy, Zi Ye; Peissig, Peggy L.; Gottesman, Omri; Verma, Shefali S.; Malinowski, Jennifer; Rasmussen-Torvik, Laura J.; Borthwick, Kenneth M.; Smelser, Diane T.; Crosslin, David R; de Andrade, Mariza; Ryer, Evan J.; McCarty, Catherine A.; Bottinger, Erwin P.; Pacheco, Jennifer A.; Crawford, Dana C.; Carrell, David S; Gerhard, Glenn S.; Franklin, David P.; Carey, David J.; Phillips, Victoria L.; Williams, Michael J. A.; Wei, Wenhua; Blair, Ross; Hill, Andrew A.; Vasudevan, Thodor M.; Lewis, David R.; Thomson, Ian A.; Krysa, Jo; Hill, Geraldine B.; Roake, Justin; Merriman, Tony R.; Oszkinis, Grzegorz; Galora, Silvia; Saracini, Claudia; Abbate, Rosanna; Pulli, Raffaele; Pratesi, Carlo; Saratzis, Athanasios; Verissimo, Ana R.; Bumpstead, Suzannah; Badger, Stephen A.; Clough, Rachel E.; Cockerill, Gillian; Hafez, Hany; Scott, D. Julian A.; Futers, T. Simon; Romaine, Simon P. R.; Bridge, Katherine; Griffin, Kathryn J.; Bailey, Marc A.; Smith, Alberto; Thompson, Matthew; van Bockxmeer, Frank M.; Matthiasson, Stefan E.; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Blankensteijn, Jan D.; Teijink, Joep A. W.; Wijmenga, Cisca; de Graaf, Jacqueline; Kiemeney, Lambertus A.; Lindholt, Jes S.; Hughes, Anne E.; Bradley, Declan T.; Stirrups, Kathleen; Golledge, Jonathan; Norman, Paul E.; Powell, Janet T.; Humphries, Steve E.; Hamby, Stephen E.; Goodall, Alison H.; Nelson, Christopher P.; Sakalihasan, Natzi; Courtois, Audrey; Ferrell, Robert E.; Eriksson, Per; Folkersen, Lasse; Franco-Cereceda, Anders; Eicher, John D.; Johnson, Andrew D.; Betsholtz, Christer; Ruusalepp, Arno; Franzen, Oscar; Schadt, Eric; Bjorkegren, Johan L. M.; Lipovich, Leonard; Drolet, Anne M.; Verhoeven, Eric L.; Zeebregts, Clark J.; Geelkerken, Robert H.; Sambeek, Marc R.; van Sterkenburg, Steven M.; De Vries, Jean-Paul; Stefansson, Kari; Thompson, John R.; de Bakker, Paul I. W.; Deloukas, Panos; Sayers, Robert D.; Harrison, Seamus C.; van Rij, Andre M.; Samani, Nilesh J.; Bown, Matthew J.

    2017-01-01

    Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available geno

  14. Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci

    NARCIS (Netherlands)

    Jones, Gregory T; Tromp, Gerard; Kuivaniemi, Helena; Gretarsdottir, Solveig; Baas, Annette F; Giusti, Betti; Strauss, Ewa; Van't Hof, Femke N G; Webb, Thomas R; Erdman, Robert; Ritchie, Marylyn D; Elmore, James R; Verma, Anurag; Pendergrass, Sarah; Kullo, Iftikhar J; Ye, Zi; Peissig, Peggy L; Gottesman, Omri; Verma, Shefali S; Malinowski, Jennifer; Rasmussen-Torvik, Laura J; Borthwick, Kenneth M; Smelser, Diane T; Crosslin, David R; de Andrade, Mariza; Ryer, Evan J; McCarty, Catherine A; Böttinger, Erwin P; Pacheco, Jennifer A; Crawford, Dana C; Carrell, David S; Gerhard, Glenn S; Franklin, David P; Carey, David J; Phillips, Victoria L; Williams, Michael J A; Wei, Wenhua; Blair, Ross; Hill, Andrew A; Vasudevan, Thodor M; Lewis, David R; Thomson, Ian A; Krysa, Jo; Hill, Geraldine B; Roake, Justin; Merriman, Tony R; Oszkinis, Grzegorz; Galora, Silvia; Saracini, Claudia; Abbate, Rosanna; Pulli, Raffaele; Pratesi, Carlo; Saratzis, Athanasios; Verissimo, Ana R; Bumpstead, Suzannah; Badger, Stephen A; Clough, Rachel E; Cockerill, Gillian; Hafez, Hany; Scott, D Julian A; Futers, T Simon; Romaine, Simon P R; Bridge, Katherine; Griffin, Kathryn J; Bailey, Marc A; Smith, Alberto; Thompson, Matthew M; van Bockxmeer, Frank M; Matthiasson, Stefan E; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Blankensteijn, Jan D; Teijink, Joep A W; Wijmenga, Cisca; de Graaf, Jacqueline; Kiemeney, Lambertus A; Lindholt, Jes S; Hughes, Anne; Bradley, Declan T; Stirrups, Kathleen; Golledge, Jonathan; Norman, Paul E; Powell, Janet T; Humphries, Steve E; Hamby, Stephen E; Goodall, Alison H; Nelson, Christopher P; Sakalihasan, Natzi; Courtois, Audrey; Ferrell, Robert E; Eriksson, Per; Folkersen, Lasse; Franco-Cereceda, Anders; Eicher, John D; Johnson, Andrew D; Betsholtz, Christer; Ruusalepp, Arno; Franzén, Oscar; Schadt, Eric E; Björkegren, Johan L M; Lipovich, Leonard; Drolet, Anne M; Verhoeven, Eric L; Zeebregts, Clark J; Geelkerken, Robert H; van Sambeek, Marc R; van Sterkenburg, Steven M; de Vries, Jean-Paul; Stefansson, Kari; Thompson, John R; de Bakker, Paul I W|info:eu-repo/dai/nl/342957082; Deloukas, Panos; Sayers, Robert D; Harrison, Seamus C; van Rij, Andre M; Samani, Nilesh J; Bown, Matthew J

    2017-01-01

    RATIONALE: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. OBJECTIVE: To identify additional AAA risk loci using data from all available geno

  15. Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci

    NARCIS (Netherlands)

    Jones, Gregory T.; Tromp, Gerard; Kuivaniemi, Helena; Gretarsdottir, Solveig; Baas, Annette F.; Giusti, Betti; Strauss, Ewa; van't Hof, Femke N. G.; Webb, Thomas R.; Erdman, Robert; Ritchie, Marylyn D.; Elmore, James R.; Verma, Anurag; Pendergrass, Sarah A; Kullo, Iftikhar J.; Zy, Zi Ye; Peissig, Peggy L.; Gottesman, Omri; Verma, Shefali S.; Malinowski, Jennifer; Rasmussen-Torvik, Laura J.; Borthwick, Kenneth M.; Smelser, Diane T.; Crosslin, David R; de Andrade, Mariza; Ryer, Evan J.; McCarty, Catherine A.; Bottinger, Erwin P.; Pacheco, Jennifer A.; Crawford, Dana C.; Carrell, David S; Gerhard, Glenn S.; Franklin, David P.; Carey, David J.; Phillips, Victoria L.; Williams, Michael J. A.; Wei, Wenhua; Blair, Ross; Hill, Andrew A.; Vasudevan, Thodor M.; Lewis, David R.; Thomson, Ian A.; Krysa, Jo; Hill, Geraldine B.; Roake, Justin; Merriman, Tony R.; Oszkinis, Grzegorz; Galora, Silvia; Saracini, Claudia; Abbate, Rosanna; Pulli, Raffaele; Pratesi, Carlo; Saratzis, Athanasios; Verissimo, Ana R.; Bumpstead, Suzannah; Badger, Stephen A.; Clough, Rachel E.; Cockerill, Gillian; Hafez, Hany; Scott, D. Julian A.; Futers, T. Simon; Romaine, Simon P. R.; Bridge, Katherine; Griffin, Kathryn J.; Bailey, Marc A.; Smith, Alberto; Thompson, Matthew; van Bockxmeer, Frank M.; Matthiasson, Stefan E.; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Blankensteijn, Jan D.; Teijink, Joep A. W.; Wijmenga, Cisca; de Graaf, Jacqueline; Kiemeney, Lambertus A.; Lindholt, Jes S.; Hughes, Anne E.; Bradley, Declan T.; Stirrups, Kathleen; Golledge, Jonathan; Norman, Paul E.; Powell, Janet T.; Humphries, Steve E.; Hamby, Stephen E.; Goodall, Alison H.; Nelson, Christopher P.; Sakalihasan, Natzi; Courtois, Audrey; Ferrell, Robert E.; Eriksson, Per; Folkersen, Lasse; Franco-Cereceda, Anders; Eicher, John D.; Johnson, Andrew D.; Betsholtz, Christer; Ruusalepp, Arno; Franzen, Oscar; Schadt, Eric; Bjorkegren, Johan L. M.; Lipovich, Leonard; Drolet, Anne M.; Verhoeven, Eric L.; Zeebregts, Clark J.; Geelkerken, Robert H.; Sambeek, Marc R.; van Sterkenburg, Steven M.; De Vries, Jean-Paul; Stefansson, Kari; Thompson, John R.; de Bakker, Paul I. W.; Deloukas, Panos; Sayers, Robert D.; Harrison, Seamus C.; van Rij, Andre M.; Samani, Nilesh J.; Bown, Matthew J.

    2017-01-01

    Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available

  16. Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci

    NARCIS (Netherlands)

    Jones, Gregory T; Tromp, Gerard; Kuivaniemi, Helena; Gretarsdottir, Solveig; Baas, Annette F; Giusti, Betti; Strauss, Ewa; Van't Hof, Femke N G; Webb, Thomas R; Erdman, Robert; Ritchie, Marylyn D; Elmore, James R; Verma, Anurag; Pendergrass, Sarah; Kullo, Iftikhar J; Ye, Zi; Peissig, Peggy L; Gottesman, Omri; Verma, Shefali S; Malinowski, Jennifer; Rasmussen-Torvik, Laura J; Borthwick, Kenneth M; Smelser, Diane T; Crosslin, David R; de Andrade, Mariza; Ryer, Evan J; McCarty, Catherine A; Böttinger, Erwin P; Pacheco, Jennifer A; Crawford, Dana C; Carrell, David S; Gerhard, Glenn S; Franklin, David P; Carey, David J; Phillips, Victoria L; Williams, Michael J A; Wei, Wenhua; Blair, Ross; Hill, Andrew A; Vasudevan, Thodor M; Lewis, David R; Thomson, Ian A; Krysa, Jo; Hill, Geraldine B; Roake, Justin; Merriman, Tony R; Oszkinis, Grzegorz; Galora, Silvia; Saracini, Claudia; Abbate, Rosanna; Pulli, Raffaele; Pratesi, Carlo; Saratzis, Athanasios; Verissimo, Ana R; Bumpstead, Suzannah; Badger, Stephen A; Clough, Rachel E; Cockerill, Gillian; Hafez, Hany; Scott, D Julian A; Futers, T Simon; Romaine, Simon P R; Bridge, Katherine; Griffin, Kathryn J; Bailey, Marc A; Smith, Alberto; Thompson, Matthew M; van Bockxmeer, Frank M; Matthiasson, Stefan E; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Blankensteijn, Jan D; Teijink, Joep A W; Wijmenga, Cisca; de Graaf, Jacqueline; Kiemeney, Lambertus A; Lindholt, Jes S; Hughes, Anne; Bradley, Declan T; Stirrups, Kathleen; Golledge, Jonathan; Norman, Paul E; Powell, Janet T; Humphries, Steve E; Hamby, Stephen E; Goodall, Alison H; Nelson, Christopher P; Sakalihasan, Natzi; Courtois, Audrey; Ferrell, Robert E; Eriksson, Per; Folkersen, Lasse; Franco-Cereceda, Anders; Eicher, John D; Johnson, Andrew D; Betsholtz, Christer; Ruusalepp, Arno; Franzén, Oscar; Schadt, Eric E; Björkegren, Johan L M; Lipovich, Leonard; Drolet, Anne M; Verhoeven, Eric L; Zeebregts, Clark J; Geelkerken, Robert H; van Sambeek, Marc R; van Sterkenburg, Steven M; de Vries, Jean-Paul; Stefansson, Kari; Thompson, John R; de Bakker, Paul I W|info:eu-repo/dai/nl/342957082; Deloukas, Panos; Sayers, Robert D; Harrison, Seamus C; van Rij, Andre M; Samani, Nilesh J; Bown, Matthew J

    2017-01-01

    RATIONALE: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. OBJECTIVE: To identify additional AAA risk loci using data from all available

  17. Inheritance of partial resistance against Colletotrichum lindemuthianum in Phaseolus vulgaris and co-localization of quantitative trait loci with genes involved in specific resistance.

    Science.gov (United States)

    Geffroy, V; Sévignac, M; De Oliveira, J C; Fouilloux, G; Skroch, P; Thoquet, P; Gepts, P; Langin, T; Dron, M

    2000-03-01

    Anthracnose, one of the most important diseases of common bean (Phaseolus vulgaris), is caused by the fungus Colletotrichum lindemuthianum. A "candidate gene" approach was used to map anthracnose resistance quantitative trait loci (QTL). Candidate genes included genes for both pathogen recognition (resistance genes and resistance gene analogs [RGAs]) and general plant defense (defense response genes). Two strains of C. lindemuthianum, identified in a world collection of 177 strains, displayed a reproducible and differential aggressiveness toward BAT93 and JaloEEP558, two parental lines of P. vulgaris representing the two major gene pools of this crop. A reliable test was developed to score partial resistance in aerial organs of the plant (stem, leaf, petiole) under controlled growth chamber conditions. BAT93 was more resistant than JaloEEP558 regardless of the organ or strain tested. With a recombinant inbred line (RIL) population derived from a cross between these two parental lines, 10 QTL were located on a genetic map harboring 143 markers, including known defense response genes, anthracnose-specific resistance genes, and RGAs. Eight of the QTL displayed isolate specificity. Two were co-localized with known defense genes (phenylalanine ammonia-lyase and hydroxyproline-rich glycoprotein) and three with anthracnose-specific resistance genes and/or RGAs. Interestingly, two QTL, with different allelic contribution, mapped on linkage group B4 in a 5.0 cM interval containing Andean and Mesoamerican specific resistance genes against C. lindemuthianum and 11 polymorphic fragments revealed with a RGA probe. The possible relationship between genes underlying specific and partial resistance is discussed.

  18. Genome-wide association study of prostate-specific antigen levels identifies novel loci independent of prostate cancer

    Science.gov (United States)

    Hoffmann, Thomas J.; Passarelli, Michael N.; Graff, Rebecca E.; Emami, Nima C.; Sakoda, Lori C.; Jorgenson, Eric; Habel, Laurel A.; Shan, Jun; Ranatunga, Dilrini K.; Quesenberry, Charles P.; Chao, Chun R.; Ghai, Nirupa R.; Aaronson, David; Presti, Joseph; Nordström, Tobias; Wang, Zhaoming; Berndt, Sonja I.; Chanock, Stephen J.; Mosley, Jonathan D.; Klein, Robert J.; Middha, Mridu; Lilja, Hans; Melander, Olle; Kvale, Mark N.; Kwok, Pui-Yan; Schaefer, Catherine; Risch, Neil; Van Den Eeden, Stephen K.; Witte, John S.

    2017-01-01

    Prostate-specific antigen (PSA) levels have been used for detection and surveillance of prostate cancer (PCa). However, factors other than PCa—such as genetics—can impact PSA. Here we present findings from a genome-wide association study (GWAS) of PSA in 28,503 Kaiser Permanente whites and 17,428 men from replication cohorts. We detect 40 genome-wide significant (P<5 × 10−8) single-nucleotide polymorphisms (SNPs): 19 novel, 15 previously identified for PSA (14 of which were also PCa-associated), and 6 previously identified for PCa only. Further analysis incorporating PCa cases suggests that at least half of the 40 SNPs are PSA-associated independent of PCa. The 40 SNPs explain 9.5% of PSA variation in non-Hispanic whites, and the remaining GWAS SNPs explain an additional 31.7%; this percentage is higher in younger men, supporting the genetic basis of PSA levels. These findings provide important information about genetic markers for PSA that may improve PCa screening, thereby reducing over-diagnosis and over-treatment. PMID:28139693

  19. Genome-wide patterns of genetic distances reveal candidate Loci contributing to human population-specific traits.

    Science.gov (United States)

    de Magalhães, João Pedro; Matsuda, Alex

    2012-03-01

    Modern humans originated in Africa before migrating across the world with founder effects and adaptations to new environments contributing to their present phenotypic diversity. Determining the genetic basis of differences between populations may provide clues about our evolutionary history and may have clinical implications. Herein, we develop a method to detect genes and biological processes in which populations most differ by calculating the genetic distance between modern populations and a hypothetical ancestral population. We apply our method to large-scale single nucleotide polymorphism (SNP) data from human populations of African, European and Asian origin. As expected, ancestral alleles were more conserved in the African populations and we found evidence of high divergence in genes previously suggested as targets of selection related to skin pigmentation, immune response, senses and dietary adaptations. Our genome-wide scan also reveals novel candidates for contributing to population-specific traits. These include genes related to neuronal development and behavior that may have been influenced by cultural processes. Moreover, in the African populations, we found a high divergence in genes related to UV protection and to the male reproductive system. Taken together, these results confirm and expand previous findings, providing new clues about the evolution and genetics of human phenotypic diversity. © 2011 The Authors Annals of Human Genetics © 2011 Blackwell Publishing Ltd/University College London.

  20. Finer characterization of Mycobacterium tuberculosis using spoligotyping and 15-loci MIRU-VNTRs reveals phylogeographical specificities of isolates circulating in Guyana and Suriname.

    Science.gov (United States)

    Streit, Elisabeth; Baboolal, Shirematee; Akpaka, Patrick E; Millet, Julie; Rastogi, Nalin

    2015-03-01

    In this study we used spoligotyping and 15-loci MIRU-VNTRs for a finer characterization of Mycobacterium tuberculosis strains isolated from patients residing in Guyana (n=74) and Suriname (n=80). The mean age of the patients was 38.5years (36.5 and 40.2years for Guyana vs. Suriname), with a male-to-female sex-ratio of 2.25 for Guyana vs. 4.27 in Suriname. Spoligotyping and 15-loci MIRU-VNTRs led to a total of 41 and 65 different patterns respectively, with an overall clustering rate of 83.8% vs. 68.8%. Combined spoligotyping and VNTR analysis led to the detection of 18 clusters of 2-41 isolates, with an overall clustering of 67.5% and a recent "n-1" transmission rate of 55.8%. Importantly, Guyana was characterized by a significantly higher percentage of clustered isolates than Suriname (79.7% vs. 56.3%; p=0.0019). Three big spoligo/MIRU (SIT/MIT) clusters containing >10 isolates each were shared between the 2 countries, and concerned: T1 sublineage cluster 53/861 (n=41, 37 in Guyana vs. 4 in Suriname); EAI6-BGD1 sublineage cluster 1340/860 (n=16, 3 in Guyana vs. 13 in Suriname); and T1 sublineage cluster 131/146 (n=11, 6 in Guyana vs. 5 in Suriname); as well as 2 smaller clusters of 2 and 3 isolates respectively. However, the relative phylogeographical specificities of strains in circulation as well as a lack of drug-resistance observed among strains from Suriname suggested that trans-border transmission of drug-resistant isolates occurred less frequently than thought. Tracing and interrupting transmission channels of a specific clone (SIT53/15-MIT861) should become a priority in Guyana, not only because it is by far most abundant but also because it accounts for almost half of the drug resistant isolates (n=8/17, 47.1%) in our study, and clustered 5/12 (41.7%) MDR isolates.

  1. Genome-wide association study reveals constant and specific loci for hematological traits at three time stages in a White Duroc × Erhualian F2 resource population.

    Directory of Open Access Journals (Sweden)

    Zhiyan Zhang

    Full Text Available Hematological traits are important indicators of immune function and have been commonly examined as biomarkers of disease and disease severity in humans. Pig is an ideal biomedical model for human diseases due to its high degree of similarity with human physiological characteristics. Here, we conducted genome-wide association studies (GWAS for 18 hematological traits at three growth stages (days 18, 46 and 240 in a White Duroc × Erhualian F2 intercross. In total, we identified 38 genome-wide significant regions containing 185 genome-wide significant SNPs by single-marker GWAS or LONG-GWAS. The significant regions are distributed on pig chromosomes (SSC 1, 4, 5, 7, 8, 10, 11, 12, 13, 17 and 18, and most of significant SNPs reside on SSC7 and SSC8. Of the 38 significant regions, 7 show constant effects on hematological traits across the whole life stages, and 6 regions have time-specific effects on the measured traits at early or late stages. The most prominent locus is the genomic region between 32.36 and 84.49 Mb on SSC8 that is associated with multiple erythroid traits. The KIT gene in this region appears to be a promising candidate gene. The findings improve our understanding of the genetic architecture of hematological traits in pigs. Further investigations are warranted to characterize the responsible gene(s and causal variant(s especially for the major loci on SSC7 and SSC8.

  2. Conserved loci of leaf and stem rust fungi of wheat share synteny interrupted by lineage-specific influx of repeat elements

    Directory of Open Access Journals (Sweden)

    Fellers John P

    2013-01-01

    Full Text Available Abstract Background Wheat leaf rust (Puccinia triticina Eriks; Pt and stem rust fungi (P. graminis f.sp. tritici; Pgt are significant economic pathogens having similar host ranges and life cycles, but different alternate hosts. The Pt genome, currently estimated at 135 Mb, is significantly larger than Pgt, at 88 Mb, but the reason for the expansion is unknown. Three genomic loci of Pt conserved proteins were characterized to gain insight into gene content, genome complexity and expansion. Results A bacterial artificial chromosome (BAC library was made from P. triticina race 1, BBBD and probed with Pt homologs of genes encoding two predicted Pgt secreted effectors and a DNA marker mapping to a region of avirulence. Three BACs, 103 Kb, 112 Kb, and 166 Kb, were sequenced, assembled, and open reading frames were identified. Orthologous genes were identified in Pgt and local conservation of gene order (microsynteny was observed. Pairwise protein identities ranged from 26 to 99%. One Pt BAC, containing a RAD18 ortholog, shares syntenic regions with two Pgt scaffolds, which could represent both haplotypes of Pgt. Gene sequence is diverged between the species as well as within the two haplotypes. In all three BAC clones, gene order is locally conserved, however, gene shuffling has occurred relative to Pgt. These regions are further diverged by differing insertion loci of LTR-retrotransposon, Gypsy, Copia, Mutator, and Harbinger mobile elements. Uncharacterized Pt open reading frames were also found; these proteins are high in lysine and similar to multiple proteins in Pgt. Conclusions The three Pt loci are conserved in gene order, with a range of gene sequence divergence. Conservation of predicted haustoria expressed secreted protein genes between Pt and Pgt is extended to the more distant poplar rust, Melampsora larici-populina. The loci also reveal that genome expansion in Pt is in part due to higher occurrence of repeat-elements in this species.

  3. Impact of alleles at the Yellow Burley (Yb) loci and nitrogen fertilization rate on nitrogen utilization efficiency and tobacco-specific nitrosamine (TSNA) formation in air-cured tobacco.

    Science.gov (United States)

    Lewis, Ramsey S; Parker, Robert G; Danehower, David A; Andres, Karen; Jack, Anne M; Whitley, D Scott; Bush, Lowell P

    2012-06-27

    Tobacco-specific nitrosamine (TSNA) formation in tobacco is influenced by alkaloid levels and the availability of nitrosating agents. Tobacco types differ in their potential for TSNA accumulation due to genetic, agronomic, and curing factors. Highest TSNA concentrations are typically measured in burley tobaccos. One of the main genetic differences between burley and all other tobacco types is that this tobacco type is homozygous for recessive mutant alleles at the Yellow Burley 1 (Yb(1)) and Yellow Burley 2 (Yb(2)) loci. In addition, burley tobacco is typically fertilized at higher nitrogen (N) rates than most other tobacco types. This study utilized nearly isogenic lines (NILs) differing for the presence of dominant or recessive alleles at the Yb(1) and Yb(2) loci to investigate the potential influence of genes at these loci on TSNA accumulation. Three pairs of NILs were evaluated at three different nitrogen fertilization rates for alkaloid levels, nitrogen physiology measures, and TSNA accumulation after air-curing. As previously observed by others, positive correlations were observed between N application rates and TSNA accumulation. Recessive alleles at Yb(1) and Yb(2) were associated with increased alkaloid levels, reduced nitrogen use efficiency, reduced nitrogen utilization efficiency, and increased leaf nitrate nitrogen (NO(3)-N). Acting together, these factors contributed to significantly greater TSNA levels in genotypes possessing the recessive alleles at these two loci relative to those carrying the dominant alleles. The chlorophyll-deficient phenotype conferred by the recessive yb(1) and yb(2) alleles probably contributes in a substantial way to increase available NO(3)-N during curing and, consequently, increased potential for TSNA formation.

  4. Influenza H5N1 Virus of Birds Surrounding H5N1 Human Cases Have Specific Characteristics on the Matrix Protein

    Directory of Open Access Journals (Sweden)

    NI LUH PUTU INDI DHARMAYANTI

    2011-06-01

    Full Text Available The H5N1 influenza virus in Indonesia has caused more than 100 people died due to the virus infections. Cases in humans were mostly due to the virus spread from the infected birds. This study characterized molecularly the H5N1 virus from birds around the H5N1 infection cases in humans in Indonesia. Result from this study revealed that in several cases, waterfowl species could become the source of H5N1 infections in human. We found that the one of six viruses used in this study probably was a first antigenic shift virus in Indonesia. This study shows that the AI viruses isolated from birds around humans infected by H5N1 virus has specific characteristics namely the presence of several amino acid substitutions especially on the M1 and M2 proteins. The substitutions are similar in most of H5N1 human cases in Indonesia.

  5. Practices Surrounding Event Photos

    NARCIS (Netherlands)

    Vyas, Dhaval; Nijholt, Antinus; van der Veer, Gerrit C.; Kotzé, P.; Marsden, G.; Lindgaard, G.; Wesson, J.; Winckler, M.

    Sharing photos through mobile devices has a great potential for creating shared experiences of social events between co-located as well as remote participants. In order to design novel event sharing tools, we need to develop indepth understanding of current practices surrounding these so called

  6. Bacteriocin protein BacL1 of Enterococcus faecalis targets cell division loci and specifically recognizes L-Ala2-cross-bridged peptidoglycan.

    Science.gov (United States)

    Kurushima, Jun; Nakane, Daisuke; Nishizaka, Takayuki; Tomita, Haruyoshi

    2015-01-01

    Bacteriocin 41 (Bac41) is produced from clinical isolates of Enterococcus faecalis and consists of two extracellular proteins, BacL1 and BacA. We previously reported that BacL1 protein (595 amino acids, 64.5 kDa) is a bacteriolytic peptidoglycan D-isoglutamyl-L-lysine endopeptidase that induces cell lysis of E. faecalis when an accessory factor, BacA, is copresent. However, the target of BacL1 remains unknown. In this study, we investigated the targeting specificity of BacL1. Fluorescence microscopy analysis using fluorescent dye-conjugated recombinant protein demonstrated that BacL1 specifically localized at the cell division-associated site, including the equatorial ring, division septum, and nascent cell wall, on the cell surface of target E. faecalis cells. This specific targeting was dependent on the triple repeat of the SH3 domain located in the region from amino acid 329 to 590 of BacL1. Repression of cell growth due to the stationary state of the growth phase or to treatment with bacteriostatic antibiotics rescued bacteria from the bacteriolytic activity of BacL1 and BacA. The static growth state also abolished the binding and targeting of BacL1 to the cell division-associated site. Furthermore, the targeting of BacL1 was detectable among Gram-positive bacteria with an L-Ala-L-Ala-cross-bridging peptidoglycan, including E. faecalis, Streptococcus pyogenes, or Streptococcus pneumoniae, but not among bacteria with alternate peptidoglycan structures, such as Enterococcus faecium, Enterococcus hirae, Staphylococcus aureus, or Listeria monocytogenes. These data suggest that BacL1 specifically targets the L-Ala-L-Ala-cross-bridged peptidoglycan and potentially lyses the E. faecalis cells during cell division.

  7. Examination of Potential Overlap in Autism and Language Loci on Chromosomes 2, 7, and 13 in Two Independent Samples Ascertained for Specific Language Impairment

    OpenAIRE

    Bartlett, Christopher W.; Flax, Judy F.; Logue, Mark W.; Smith, Brett J.; Vieland, Veronica J.; Tallal, Paula; Brzustowicz, Linda M.

    2004-01-01

    Specific language impairment is a neurodevelopmental disorder characterized by impairments essentially restricted to the domain of language and language learning skills. This contrasts with autism, which is a pervasive developmental disorder defined by multiple impairments in language, social reciprocity, narrow interests and/or repetitive behaviors. Genetic linkage studies and family data suggest that the two disorders may have genetic components in common. Two samples, from Canada and the U...

  8. Recombinant protein expression by targeting pre-selected chromosomal loci

    Directory of Open Access Journals (Sweden)

    Krömer Wolfgang

    2009-12-01

    Full Text Available Abstract Background Recombinant protein expression in mammalian cells is mostly achieved by stable integration of transgenes into the chromosomal DNA of established cell lines. The chromosomal surroundings have strong influences on the expression of transgenes. The exploitation of defined loci by targeting expression constructs with different regulatory elements is an approach to design high level expression systems. Further, this allows to evaluate the impact of chromosomal surroundings on distinct vector constructs. Results We explored antibody expression upon targeting diverse expression constructs into previously tagged loci in CHO-K1 and HEK293 cells that exhibit high reporter gene expression. These loci were selected by random transfer of reporter cassettes and subsequent screening. Both, retroviral infection and plasmid transfection with eGFP or antibody expression cassettes were employed for tagging. The tagged cell clones were screened for expression and single copy integration. Cell clones producing > 20 pg/cell in 24 hours could be identified. Selected integration sites that had been flanked with heterologous recombinase target sites (FRTs were targeted by Flp recombinase mediated cassette exchange (RMCE. The results give proof of principle for consistent protein expression upon RMCE. Upon targeting antibody expression cassettes 90-100% of all resulting cell clones showed correct integration. Antibody production was found to be highly consistent within the individual cell clones as expected from their isogenic nature. However, the nature and orientation of expression control elements revealed to be critical. The impact of different promoters was examined with the tag-and-targeting approach. For each of the chosen promoters high expression sites were identified. However, each site supported the chosen promoters to a different extent, indicating that the strength of a particular promoter is dominantly defined by its chromosomal context

  9. The "Transport Specificity Ratio": a structure-function tool to search the protein fold for loci that control transition state stability in membrane transport catalysis

    Directory of Open Access Journals (Sweden)

    King Steven C

    2004-11-01

    Full Text Available Abstract Background In establishing structure-function relationships for membrane transport proteins, the interpretation of phenotypic changes can be problematic, owing to uncertainties in protein expression levels, sub-cellular localization, and protein-folding fidelity. A dual-label competitive transport assay called "Transport Specificity Ratio" (TSR analysis has been developed that is simple to perform, and circumvents the "expression problem," providing a reliable TSR phenotype (a constant for comparison to other transporters. Results Using the Escherichia coli GABA (4-aminobutyrate permease (GabP as a model carrier, it is demonstrated that the TSR phenotype is largely independent of assay conditions, exhibiting: (i indifference to the particular substrate concentrations used, (ii indifference to extreme changes (40-fold in transporter expression level, and within broad limits (iii indifference to assay duration. The theoretical underpinnings of TSR analysis predict all of the above observations, supporting that TSR has (i applicability in the analysis of membrane transport, and (ii particular utility in the face of incomplete information on protein expression levels and initial reaction rate intervals (e.g., in high-throughput screening situations. The TSR was used to identify gab permease (GabP variants that exhibit relative changes in catalytic specificity (kcat/Km for [14C]GABA (4-aminobutyrate versus [3H]NA (nipecotic acid. Conclusions The TSR phenotype is an easily measured constant that reflects innate molecular properties of the transition state, and provides a reliable index of the difference in catalytic specificity that a carrier exhibits toward a particular pair of substrates. A change in the TSR phenotype, called a Δ(TSR, represents a specificity shift attributable to underlying changes in the intrinsic substrate binding energy (ΔGb that translocation catalysts rely upon to decrease activation energy (. TSR analysis is

  10. Explaining preferences for home surroundings and locations

    Directory of Open Access Journals (Sweden)

    Hans Skifter Andersen

    2011-01-01

    Full Text Available This article is based on a survey carried out in Denmark that asked a random sample of the population about their preferences for home surroundings and locations. It shows that the characteristics of social surroundings are very important and can be divided into three independent dimensions: avoiding social nuisances, preferring social homogeneity and living close to one’s social network and place of origin. The study shows that most people have many detailed preferences, whereas some have very few. This confirms an earlier theory that some people are very connected to certain places with given characteristics and thus do not have priorities regarding home surroundings and locations. For others, mostly young people and singles, home is just a place to sleep and relax, whereas life is lived elsewhere. For this group, there are only preferences for location and there are few specific preferences for surroundings.

  11. Stringent and reproducible tetracycline-regulated transgene expression by site-specific insertion at chromosomal loci with pre-characterised induction characteristics

    Directory of Open Access Journals (Sweden)

    Papanastasiou Antigoni M

    2007-05-01

    Full Text Available Abstract Background The ability to regulate transgene expression has many applications, mostly concerning the analysis of gene function. Desirable induction characteristics, such as low un-induced expression, high induced expression and limited cellular heterogeneity, can be seriously impaired by chromosomal position effects at the site of transgene integration. Many clones may therefore need to be screened before one with optimal induction characteristics is identified. Furthermore, such screens must be repeated for each new transgene investigated, and comparisons between clones with different transgenes is complicated by their different integration sites. Results To circumvent these problems we have developed a "screen and insert" strategy in which clones carrying a transgene for a fluorescent reporter are first screened for those with optimal induction characteristics. Site-specific recombination (SSR is then be used repeatedly to insert any new transgene at the reporter transgene locus of such clones so that optimal induction characteristics are conferred upon it. Here we have tested in a human fibrosarcoma cell line (HT1080 two of many possible implementations of this approach. Clones (e.g. Rht14-10 in which a GFP reporter gene is very stringently regulated by the tetracycline (tet transactivator (tTA protein were first identified flow-cytometrically. Transgenes encoding luciferase, I-SceI endonuclease or Rad52 were then inserted by SSR at a LoxP site adjacent to the GFP gene resulting stringent tet-regulated transgene expression. In clone Rht14-10, increases in expression from essentially background levels (+tet to more than 104-fold above background (-tet were reproducibly detected after Cre-mediated insertion of either the luciferase or the I-SceI transgenes. Conclusion Although previous methods have made use of SSR to integrate transgenes at defined sites, none has effectively combined this with a pre-selection step to identify

  12. Clinical Application of Surrounding Puncture

    Institute of Scientific and Technical Information of China (English)

    GUO Yao-jie; HAN Chou-ping

    2003-01-01

    Surrounding puncture can stop pathogenic qi from spreading, consolidate the connection between local meridians and enrich local qi and blood, which can eventually supplement anti-pathogenic qi and remove pathogenic qi, and consequently remedy diseases. The author of this article summrized and analyzed the clinical application of surrounding puncture for the purpose of studying this technique and improving the therapeutic effect.

  13. Reduced surround inhibition in musicians.

    Science.gov (United States)

    Shin, Hae-Won; Kang, Suk Y; Hallett, Mark; Sohn, Young H

    2012-06-01

    To investigate whether surround inhibition (SI) in the motor system is altered in professional musicians, we performed a transcranial magnetic stimulation (TMS) study in 10 professional musicians and 15 age-matched healthy non-musicians. TMS was set to be triggered by self-initiated flexion of the index finger at different intervals ranging from 3 to 1,000 ms. Average motor evoked potential (MEP) amplitudes obtained from self-triggered TMS were normalized to average MEPs of the control TMS at rest and expressed as a percentage. Normalized MEP amplitudes of the abductor digiti minimi (ADM) muscles were compared between the musicians and non-musicians with the primary analysis being the intervals between 3 and 80 ms (during the movement). A mixed-design ANOVA revealed a significant difference in normalized ADM MEPs during the index finger flexion between groups, with less SI in the musicians. This study demonstrated that the functional operation of SI is less strong in musicians than non-musicians, perhaps due to practice of movement synergies involving both muscles. Reduced SI, however, could lead susceptible musicians to be prone to develop task-specific dystonia.

  14. Fine-mapping and initial characterization of QT interval loci in African Americans.

    Directory of Open Access Journals (Sweden)

    Christy L Avery

    Full Text Available The QT interval (QT is heritable and its prolongation is a risk factor for ventricular tachyarrhythmias and sudden death. Most genetic studies of QT have examined European ancestral populations; however, the increased genetic diversity in African Americans provides opportunities to narrow association signals and identify population-specific variants. We therefore evaluated 6,670 SNPs spanning eleven previously identified QT loci in 8,644 African American participants from two Population Architecture using Genomics and Epidemiology (PAGE studies: the Atherosclerosis Risk in Communities study and Women's Health Initiative Clinical Trial. Of the fifteen known independent QT variants at the eleven previously identified loci, six were significantly associated with QT in African American populations (P≤1.20×10(-4: ATP1B1, PLN1, KCNQ1, NDRG4, and two NOS1AP independent signals. We also identified three population-specific signals significantly associated with QT in African Americans (P≤1.37×10(-5: one at NOS1AP and two at ATP1B1. Linkage disequilibrium (LD patterns in African Americans assisted in narrowing the region likely to contain the functional variants for several loci. For example, African American LD patterns showed that 0 SNPs were in LD with NOS1AP signal rs12143842, compared with European LD patterns that indicated 87 SNPs, which spanned 114.2 Kb, were in LD with rs12143842. Finally, bioinformatic-based characterization of the nine African American signals pointed to functional candidates located exclusively within non-coding regions, including predicted binding sites for transcription factors such as TBX5, which has been implicated in cardiac structure and conductance. In this detailed evaluation of QT loci, we identified several African Americans SNPs that better define the association with QT and successfully narrowed intervals surrounding established loci. These results demonstrate that the same loci influence variation in QT

  15. 孕妇血浆中胎儿游离核酸Y染色体STR复合扩增的应用%Application of Multiple PCR of 17 Y-Chromosome Specific STR Loci in Maternal Plasma

    Institute of Scientific and Technical Information of China (English)

    荣媛; 高嘉嘉; 姜新强; 涂建成; 郑芳

    2012-01-01

    目的:探讨利用孕妇血浆中游离胎儿DNA通过复合扩增Y染色体上的STR进行胎儿性别鉴定及其应用在产前无创性亲子鉴定中的可能性.方法:收集23例12-28孕周的孕妇外周血以及血浆,同时收集胎儿羊水标本以及可疑父亲的外周血标本,提取DNA,利用ABI Identifiler以及ABI Yfiler扩增系统复合扩增常染色体以及Y染色体上的STR位点,扩增产物经ABI 3130基因测序仪分析,用GeneMapper ID 3.2软件分析.结果:23例孕妇中,有16例孕妇经羊水Identifiler系统验证为男性胎儿,该16例孕男胎的孕妇血浆DNA的Y染色体STR位点扩增成功率100%,扩增出位点数目5-12个不等;并将其分型结果与羊水标本相比较,结果均一致;同时将其与可疑父亲的Y染色体STR位点分型结果相比较,在9例经ABI identifiler验证为非父子关系的案例中有8例可以成功排除其父子关系.结论:利用位于Y染色体上的STR位点进行多位点复合扩增可以明显提高胎儿性别鉴定的准确率,同时将其应用于产前无创性亲子鉴定中,可用于亲缘关系的初步排除.%Objective: To develop a reliable method for determination of fetal gender from maternal plasma by multiple PCR of Y-chromosome specific STR and to discuss its preliminary application in the noninvasive prenatal paternity testing. Methods: Cell-free DNA was isolated from 23 samples of maternal plasma and amplified using ABI ampFLSTR Yfiler kits. Gender of fetuses was confirmed by amnionic fluid. Results: In the sixteen cases of male fetuses, all cases were successfully amplified between five and twelve fetal loci. All the amplified fetal alleles matched the alleles of amnionic fluid. Of nine non-paternity father/child pairs which has been previously confirmed by using ampFLSTR Identifiler kit, eight cases were successfully excluded. Conclusion: ABI ampFLSTR Yfiler was found to be fully reliable as it amplified Y-chromosome in all cases of male fetuses

  16. Visual surround suppression in schizophrenia

    Directory of Open Access Journals (Sweden)

    Marc Samuel Tibber

    2013-02-01

    Full Text Available Compared to unaffected observers patients with schizophrenia show characteristic differences in visual perception, including a reduced susceptibility to the influence of context on judgements of contrast - a manifestation of weaker surround suppression. To examine the generality of this phenomenon we measured the ability of 24 individuals with schizophrenia to judge the luminance, contrast, orientation and size of targets embedded in contextual surrounds that would typically influence the target’s appearance. Individuals with schizophrenia demonstrated weaker surround suppression compared to matched controls for stimuli defined by contrast or size, but not for those defined by luminance or orientation. As perceived luminance is thought to be regulated at the earliest stages of visual processing our findings are consistent with a suppression deficit that is predominantly cortical in origin. In addition, we propose that preserved orientation surround suppression in schizophrenia may reflect the sparing of broadly tuned mechanisms of suppression. We attempt to reconcile these data with findings from previous studies.

  17. Educational Success and Surrounding Culture

    Science.gov (United States)

    Walters, Garrison

    2016-01-01

    The curriculum, instruction, and services we provide in schools, colleges, and universities matter a lot, but if we continue to ignore our students' "surrounding culture," progress toward a more educated nation will continue to be disappointing.

  18. Educational Success and Surrounding Culture

    Science.gov (United States)

    Walters, Garrison

    2016-01-01

    The curriculum, instruction, and services we provide in schools, colleges, and universities matter a lot, but if we continue to ignore our students' "surrounding culture," progress toward a more educated nation will continue to be disappointing.

  19. Multichannel spatial surround sound system

    Institute of Scientific and Technical Information of China (English)

    RAO Dan; XIE Bosun

    2004-01-01

    Based on the consideration of being compatible with 5.1 channel horizontal surround sound system, a spatial surround sound system is proposed. Theoretical and experimental results show that the system has a wide listening area. It can not only recreate stable image in the front and rear direction, but also eliminate the defect of poor lateral image of 5.1 channel system. The system can be used to reproduce special 3D sound effect and the spaciousness of hall.

  20. Persistent Confusion and Controversy Surrounding Gene Patents

    Science.gov (United States)

    Guerrini, Christi J.; Majumder, Mary A.; McGuire, Amy L.

    2016-01-01

    There is persistent confusion and controversy surrounding basic issues of patent law relevant to the genomics industry. Uncertainty and conflict can lead to the adoption of inefficient practices and exposure to liability. The development of patent-specific educational resources for industry members, as well as the prompt resolution of patentability rules unsettled by recent U.S. Supreme Court decisions, are therefore urgently needed. PMID:26849516

  1. Complex Loci in human and mouse genomes.

    Science.gov (United States)

    Engström, Pär G; Suzuki, Harukazu; Ninomiya, Noriko; Akalin, Altuna; Sessa, Luca; Lavorgna, Giovanni; Brozzi, Alessandro; Luzi, Lucilla; Tan, Sin Lam; Yang, Liang; Kunarso, Galih; Ng, Edwin Lian-Chong; Batalov, Serge; Wahlestedt, Claes; Kai, Chikatoshi; Kawai, Jun; Carninci, Piero; Hayashizaki, Yoshihide; Wells, Christine; Bajic, Vladimir B; Orlando, Valerio; Reid, James F; Lenhard, Boris; Lipovich, Leonard

    2006-04-01

    Mammalian genomes harbor a larger than expected number of complex loci, in which multiple genes are coupled by shared transcribed regions in antisense orientation and/or by bidirectional core promoters. To determine the incidence, functional significance, and evolutionary context of mammalian complex loci, we identified and characterized 5,248 cis-antisense pairs, 1,638 bidirectional promoters, and 1,153 chains of multiple cis-antisense and/or bidirectionally promoted pairs from 36,606 mouse transcriptional units (TUs), along with 6,141 cis-antisense pairs, 2,113 bidirectional promoters, and 1,480 chains from 42,887 human TUs. In both human and mouse, 25% of TUs resided in cis-antisense pairs, only 17% of which were conserved between the two organisms, indicating frequent species specificity of antisense gene arrangements. A sampling approach indicated that over 40% of all TUs might actually be in cis-antisense pairs, and that only a minority of these arrangements are likely to be conserved between human and mouse. Bidirectional promoters were characterized by variable transcriptional start sites and an identifiable midpoint at which overall sequence composition changed strand and the direction of transcriptional initiation switched. In microarray data covering a wide range of mouse tissues, genes in cis-antisense and bidirectionally promoted arrangement showed a higher probability of being coordinately expressed than random pairs of genes. In a case study on homeotic loci, we observed extensive transcription of nonconserved sequences on the noncoding strand, implying that the presence rather than the sequence of these transcripts is of functional importance. Complex loci are ubiquitous, host numerous nonconserved gene structures and lineage-specific exonification events, and may have a cis-regulatory impact on the member genes.

  2. Complex Loci in human and mouse genomes.

    Directory of Open Access Journals (Sweden)

    Pär G Engström

    2006-04-01

    Full Text Available Mammalian genomes harbor a larger than expected number of complex loci, in which multiple genes are coupled by shared transcribed regions in antisense orientation and/or by bidirectional core promoters. To determine the incidence, functional significance, and evolutionary context of mammalian complex loci, we identified and characterized 5,248 cis-antisense pairs, 1,638 bidirectional promoters, and 1,153 chains of multiple cis-antisense and/or bidirectionally promoted pairs from 36,606 mouse transcriptional units (TUs, along with 6,141 cis-antisense pairs, 2,113 bidirectional promoters, and 1,480 chains from 42,887 human TUs. In both human and mouse, 25% of TUs resided in cis-antisense pairs, only 17% of which were conserved between the two organisms, indicating frequent species specificity of antisense gene arrangements. A sampling approach indicated that over 40% of all TUs might actually be in cis-antisense pairs, and that only a minority of these arrangements are likely to be conserved between human and mouse. Bidirectional promoters were characterized by variable transcriptional start sites and an identifiable midpoint at which overall sequence composition changed strand and the direction of transcriptional initiation switched. In microarray data covering a wide range of mouse tissues, genes in cis-antisense and bidirectionally promoted arrangement showed a higher probability of being coordinately expressed than random pairs of genes. In a case study on homeotic loci, we observed extensive transcription of nonconserved sequences on the noncoding strand, implying that the presence rather than the sequence of these transcripts is of functional importance. Complex loci are ubiquitous, host numerous nonconserved gene structures and lineage-specific exonification events, and may have a cis-regulatory impact on the member genes.

  3. Schubert varieties and degeneracy loci

    CERN Document Server

    Fulton, William

    1998-01-01

    Schubert varieties and degeneracy loci have a long history in mathematics, starting from questions about loci of matrices with given ranks. These notes, from a summer school in Thurnau, aim to give an introduction to these topics, and to describe recent progress on these problems. There are interesting interactions with the algebra of symmetric functions and combinatorics, as well as the geometry of flag manifolds and intersection theory and algebraic geometry.

  4. Library Spirit and Genius Loci

    DEFF Research Database (Denmark)

    Dahlkild, Nan

    2009-01-01

    The architecture and design of Nyborg Public Library in the light of the concepts "Library Spirit" and "Genius Loci", related to contemporary social and cultural movements, the development of the early welfare state and the "Scandinavian Style".......The architecture and design of Nyborg Public Library in the light of the concepts "Library Spirit" and "Genius Loci", related to contemporary social and cultural movements, the development of the early welfare state and the "Scandinavian Style"....

  5. Visual Surround Suppression in Schizophrenia

    Science.gov (United States)

    Tibber, Marc S.; Anderson, Elaine J.; Bobin, Tracy; Antonova, Elena; Seabright, Alice; Wright, Bernice; Carlin, Patricia; Shergill, Sukhwinder S.; Dakin, Steven C.

    2013-01-01

    Compared to unaffected observers patients with schizophrenia (SZ) show characteristic differences in visual perception, including a reduced susceptibility to the influence of context on judgments of contrast – a manifestation of weaker surround suppression (SS). To examine the generality of this phenomenon we measured the ability of 24 individuals with SZ to judge the luminance, contrast, orientation, and size of targets embedded in contextual surrounds that would typically influence the target’s appearance. Individuals with SZ demonstrated weaker SS compared to matched controls for stimuli defined by contrast or size, but not for those defined by luminance or orientation. As perceived luminance is thought to be regulated at the earliest stages of visual processing our findings are consistent with a suppression deficit that is predominantly cortical in origin. In addition, we propose that preserved orientation SS in SZ may reflect the sparing of broadly tuned mechanisms of suppression. We attempt to reconcile these data with findings from previous studies. PMID:23450069

  6. Explaining preferences for home surroundings and locations

    DEFF Research Database (Denmark)

    Andersen, Hans Skifter

    2011-01-01

    : avoiding social nuisances, preferring social homogeneity and living close to one’s social network and place of origin. The study shows that most people have many detailed preferences, whereas some have very few. This confirms an earlier theory that some people are very connected to certain places...... with given characteristics and thus do not have priorities regarding home surroundings and locations. For others, mostly young people and singles, home is just a place to sleep and relax, whereas life is lived elsewhere. For this group, there are only preferences for location and there are few specific...

  7. Origins of amino acid transporter loci in trypanosomatid parasites

    Directory of Open Access Journals (Sweden)

    Jackson Andrew P

    2007-02-01

    Full Text Available Abstract Background Large amino acid transporter gene families were identified from the genome sequences of three parasitic protists, Trypanosoma brucei, Trypanosoma cruzi and Leishmania major. These genes encode molecular sensors of the external host environment for trypanosomatid cells and are crucial to modulation of gene expression as the parasite passes through different life stages. This study provides a comprehensive phylogenetic account of the origins of these genes, redefining each locus according to a positional criterion, through the integration of phyletic identity with comparative gene order information. Results Each locus was individually specified by its surrounding gene order and associated with homologs showing the same position ('homoeologs' in other species, where available. Bayesian and maximum likelihood phylogenies were in general agreement on systematic relationships and confirmed several 'orthology sets' of genes retained since divergence from the common ancestor. Reconciliation analysis quantified the scale of duplication and gene loss, as well as identifying further apparent orthology sets, which lacked conservation of genomic position. These instances suggested substantial genomic restructuring or transposition. Other analyses identified clear instances of evolutionary rate changes post-duplication, the effects of concerted evolution within tandem gene arrays and gene conversion events between syntenic loci. Conclusion Despite their importance to cell function and parasite development, the repertoires of AAT loci in trypanosomatid parasites are relatively fluid in both complement and gene dosage. Some loci are ubiquitous and, after an ancient origin through transposition, originated through descent from the ancestral trypanosomatid. However, reconciliation analysis demonstrated that unilateral expansions of gene number through tandem gene duplication, transposition of gene duplicates to otherwise well conserved genomic

  8. Binaural Rendering in MPEG Surround

    Directory of Open Access Journals (Sweden)

    Kristofer Kjörling

    2008-04-01

    Full Text Available This paper describes novel methods for evoking a multichannel audio experience over stereo headphones. In contrast to the conventional convolution-based approach where, for example, five input channels are filtered using ten head-related transfer functions, the current approach is based on a parametric representation of the multichannel signal, along with either a parametric representation of the head-related transfer functions or a reduced set of head-related transfer functions. An audio scene with multiple virtual sound sources is represented by a mono or a stereo downmix signal of all sound source signals, accompanied by certain statistical (spatial properties. These statistical properties of the sound sources are either combined with statistical properties of head-related transfer functions to estimate “binaural parameters” that represent the perceptually relevant aspects of the auditory scene or used to create a limited set of combined head-related transfer functions that can be applied directly on the downmix signal. Subsequently, a binaural rendering stage reinstates the statistical properties of the sound sources by applying the estimated binaural parameters or the reduced set of combined head-related transfer functions directly on the downmix. If combined with parametric multichannel audio coders such as MPEG Surround, the proposed methods are advantageous over conventional methods in terms of perceived quality and computational complexity.

  9. Binaural Rendering in MPEG Surround

    Science.gov (United States)

    Breebaart, Jeroen; Villemoes, Lars; Kjörling, Kristofer

    2008-12-01

    This paper describes novel methods for evoking a multichannel audio experience over stereo headphones. In contrast to the conventional convolution-based approach where, for example, five input channels are filtered using ten head-related transfer functions, the current approach is based on a parametric representation of the multichannel signal, along with either a parametric representation of the head-related transfer functions or a reduced set of head-related transfer functions. An audio scene with multiple virtual sound sources is represented by a mono or a stereo downmix signal of all sound source signals, accompanied by certain statistical (spatial) properties. These statistical properties of the sound sources are either combined with statistical properties of head-related transfer functions to estimate "binaural parameters" that represent the perceptually relevant aspects of the auditory scene or used to create a limited set of combined head-related transfer functions that can be applied directly on the downmix signal. Subsequently, a binaural rendering stage reinstates the statistical properties of the sound sources by applying the estimated binaural parameters or the reduced set of combined head-related transfer functions directly on the downmix. If combined with parametric multichannel audio coders such as MPEG Surround, the proposed methods are advantageous over conventional methods in terms of perceived quality and computational complexity.

  10. Poisson modules and degeneracy loci

    CERN Document Server

    Gualtieri, Marco

    2012-01-01

    In this paper, we study the interplay between modules and sub-objects in holomorphic Poisson geometry. In particular, we define a new notion of "residue" for a Poisson module, analogous to the Poincar\\'e residue of a meromorphic volume form. Of particular interest is the interaction between the residues of the canonical line bundle of a Poisson manifold and its degeneracy loci---where the rank of the Poisson structure drops. As an application, we provide new evidence in favour of Bondal's conjecture that the rank \\leq 2k locus of a Fano Poisson manifold always has dimension \\geq 2k+1. In particular, we show that the conjecture holds for Fano fourfolds. We also apply our techniques to a family of Poisson structures defined by Fe\\u{\\i}gin and Odesski\\u{\\i}, where the degeneracy loci are given by the secant varieties of elliptic normal curves.

  11. Physiologic characterization of type 2 diabetes-related loci

    DEFF Research Database (Denmark)

    Grarup, Niels; Sparsø, Thomas; Hansen, Torben

    2010-01-01

    of these variants influence pancreatic ß-cell function. However, risk alleles in five loci seem to have a primary impact on insulin sensitivity. Investigations of more detailed physiologic phenotypes, such as the insulin response to intravenous glucose or the incretion hormones, are now emerging and give...... indications of more specific pathologic mechanisms for diabetes-related risk variants. Such studies have shed light on the function of some loci but also underlined the complex nature of disease mechanism. In the future, sequencing-based discovery of low-frequency variants with higher impact on intermediate...

  12. High-Density Genotyping of Immune Loci in Koreans and Europeans Identifies Eight New Rheumatoid Arthritis Risk Loci

    Science.gov (United States)

    Kim, Kwangwoo; Bang, So-Young; Lee, Hye-Soon; Cho, Soo-Kyung; Choi, Chan-Bum; Sung, Yoon-Kyoung; Kim, Tae-Hwan; Jun, Jae-Bum; Yoo, Dae Hyun; Kang, Young Mo; Kim, Seong-Kyu; Suh, Chang-Hee; Shim, Seung-Cheol; Lee, Shin-Seok; Lee, Jisoo; Chung, Won Tae; Choe, Jung-Yoon; Shin, Hyoung Doo; Lee, Jong-Young; Han, Bok-Ghee; Nath, Swapan K.; Eyre, Steve; Bowes, John; Pappas, Dimitrios A.; Kremer, Joel M.; Gonzalez-Gay, Miguel A; Rodriguez-Rodriguez, Luis; Ärlestig, Lisbeth; Okada, Yukinori; Diogo, Dorothée; Liao, Katherine P.; Karlson, Elizabeth W.; Raychaudhuri, Soumya; Rantapää-Dahlqvist, Solbritt; Martin, Javier; Klareskog, Lars; Padyukov, Leonid; Gregersen, Peter K.; Worthington, Jane; Greenberg, Jeffrey D.; Plenge, Robert M.; Bae, Sang-Cheol

    2015-01-01

    Objective A highly polygenic etiology and high degree of allele-sharing between ancestries have been well-elucidated in genetic studies of rheumatoid arthritis. Recently, the high-density genotyping array Immunochip for immune disease loci identified 14 new rheumatoid arthritis risk loci among individuals of European ancestry. Here, we aimed to identify new rheumatoid arthritis risk loci using Korean-specific Immunochip data. Methods We analyzed Korean rheumatoid arthritis case-control samples using the Immunochip and GWAS array to search for new risk alleles of rheumatoid arthritis with anti-citrullinated peptide antibodies. To increase power, we performed a meta-analysis of Korean data with previously published European Immunochip and GWAS data, for a total sample size of 9,299 Korean and 45,790 European case-control samples. Results We identified 8 new rheumatoid arthritis susceptibility loci (TNFSF4, LBH, EOMES, ETS1–FLI1, COG6, RAD51B, UBASH3A and SYNGR1) that passed a genome-wide significance threshold (p<5×10−8), with evidence for three independent risk alleles at 1q25/TNFSF4. The risk alleles from the 7 new loci except for the TNFSF4 locus (monomorphic in Koreans), together with risk alleles from previously established RA risk loci, exhibited a high correlation of effect sizes between ancestries. Further, we refined the number of SNPs that represent potentially causal variants through a trans-ethnic comparison of densely genotyped SNPs. Conclusion This study demonstrates the advantage of dense-mapping and trans-ancestral analysis for identification of potentially causal SNPs. In addition, our findings support the importance of T cells in the pathogenesis and the fact of frequent overlap of risk loci among diverse autoimmune diseases. PMID:24532676

  13. High-density genotyping of immune loci in Koreans and Europeans identifies eight new rheumatoid arthritis risk loci.

    Science.gov (United States)

    Kim, Kwangwoo; Bang, So-Young; Lee, Hye-Soon; Cho, Soo-Kyung; Choi, Chan-Bum; Sung, Yoon-Kyoung; Kim, Tae-Hwan; Jun, Jae-Bum; Yoo, Dae Hyun; Kang, Young Mo; Kim, Seong-Kyu; Suh, Chang-Hee; Shim, Seung-Cheol; Lee, Shin-Seok; Lee, Jisoo; Chung, Won Tae; Choe, Jung-Yoon; Shin, Hyoung Doo; Lee, Jong-Young; Han, Bok-Ghee; Nath, Swapan K; Eyre, Steve; Bowes, John; Pappas, Dimitrios A; Kremer, Joel M; Gonzalez-Gay, Miguel A; Rodriguez-Rodriguez, Luis; Ärlestig, Lisbeth; Okada, Yukinori; Diogo, Dorothée; Liao, Katherine P; Karlson, Elizabeth W; Raychaudhuri, Soumya; Rantapää-Dahlqvist, Solbritt; Martin, Javier; Klareskog, Lars; Padyukov, Leonid; Gregersen, Peter K; Worthington, Jane; Greenberg, Jeffrey D; Plenge, Robert M; Bae, Sang-Cheol

    2015-03-01

    A highly polygenic aetiology and high degree of allele-sharing between ancestries have been well elucidated in genetic studies of rheumatoid arthritis. Recently, the high-density genotyping array Immunochip for immune disease loci identified 14 new rheumatoid arthritis risk loci among individuals of European ancestry. Here, we aimed to identify new rheumatoid arthritis risk loci using Korean-specific Immunochip data. We analysed Korean rheumatoid arthritis case-control samples using the Immunochip and genome-wide association studies (GWAS) array to search for new risk alleles of rheumatoid arthritis with anticitrullinated peptide antibodies. To increase power, we performed a meta-analysis of Korean data with previously published European Immunochip and GWAS data for a total sample size of 9299 Korean and 45,790 European case-control samples. We identified eight new rheumatoid arthritis susceptibility loci (TNFSF4, LBH, EOMES, ETS1-FLI1, COG6, RAD51B, UBASH3A and SYNGR1) that passed a genome-wide significance threshold (p<5×10(-8)), with evidence for three independent risk alleles at 1q25/TNFSF4. The risk alleles from the seven new loci except for the TNFSF4 locus (monomorphic in Koreans), together with risk alleles from previously established RA risk loci, exhibited a high correlation of effect sizes between ancestries. Further, we refined the number of single nucleotide polymorphisms (SNPs) that represent potentially causal variants through a trans-ethnic comparison of densely genotyped SNPs. This study demonstrates the advantage of dense-mapping and trans-ancestral analysis for identification of potentially causal SNPs. In addition, our findings support the importance of T cells in the pathogenesis and the fact of frequent overlap of risk loci among diverse autoimmune diseases. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  14. Colocalization of Multiple DNA Loci: A Physical Mechanism

    Science.gov (United States)

    Bianco, Valentino; Scialdone, Antonio; Nicodemi, Mario

    2012-01-01

    A variety of important cellular processes require, for functional purposes, the colocalization of multiple DNA loci at specific time points. In most cases, the physical mechanisms responsible for bringing them in close proximity are still elusive. Here we show that the interaction of DNA loci with a concentration of diffusing molecular factors can induce spontaneously their colocalization, through a mechanism based on a thermodynamic phase transition. We consider up to four DNA loci and different valencies for diffusing molecular factors. In particular, our analysis illustrates that a variety of nontrivial stable spatial configurations is allowed in the system, depending on the details of the molecular factor/DNA binding-sites interaction. Finally, we discuss as a case study an application of our model to the pairing of X chromosome at X inactivation, one of the best-known examples of DNA colocalization. We also speculate on the possible links between X colocalization and inactivation. PMID:23200056

  15. Black hole solutions surrounded by perfect fluid in Rastall theory

    Science.gov (United States)

    Heydarzade, Y.; Darabi, F.

    2017-08-01

    In this work, we obtain uncharged∖charged Kiselev-like black holes as a new class of black hole solutions surrounded by perfect fluid in the context of Rastall theory. Then, we study the specific cases of the uncharged∖charged black holes surrounded by regular matter like dust and radiation, or exotic matter like quintessence, cosmological constant and phantom fields. By comparing the Kiselev-like black hole solutions in Rastall theory with the Kiselev black hole solutions in GR, we find an effective perfect fluid behavior for the black hole's surrounding field. It is shown that the corresponding effective perfect fluid has interesting characteristic features depending on the different ranges of the parameters in Rastall theory. For instance, Kiselev-like black holes surrounded by regular matter in Rastall theory may be considered as Kiselev black holes surrounded by exotic matter in GR, or Kiselev-like black holes surrounded by exotic matter in Rastall theory may be considered as Kiselev black holes surrounded by regular matter in GR.

  16. High-throughput identification of informative nuclear loci for shallow-scale phylogenetics and phylogeography.

    Science.gov (United States)

    Lemmon, Alan R; Lemmon, Emily Moriarty

    2012-10-01

    par with mitochondrial loci commonly used in phylogeography. Specifically, we estimated that ~7% of loci in the chorus frog genome are >3% divergent within species; this translates to a prediction of approximately 50,000 single-copy loci in the genome with >3% divergence. Moreover, successful amplification of many loci at deeper phylogenetic levels indicates that the RRL approach represents an efficient method for rapid identification of informative loci for both phylogenetics and phylogeography. We conclude by making recommendations for minimizing the cost and maximizing the efficiency of locus identification for future studies in this field.

  17. Unmasking risk loci: DNA methylation illuminates the biology of cancer predisposition: analyzing DNA methylation of transcriptional enhancers reveals missed regulatory links between cancer risk loci and genes.

    Science.gov (United States)

    Aran, Dvir; Hellman, Asaf

    2014-02-01

    Paradoxically, DNA sequence polymorphisms in cancer risk loci rarely correlate with the expression of cancer genes. Therefore, the molecular mechanism underlying an individual's susceptibility to cancer has remained largely unknown. However, recent evaluations of the correlations between DNA methylation and gene expression levels across healthy and cancerous genomes have revealed enrichment of disease-related DNA methylation variations within disease-associated risk loci. Moreover, it appears that transcriptional enhancers embedded in cancer risk loci often contain DNA methylation sites that closely define the expression of prominent cancer genes, despite the lack of significant correlations between gene expression levels and the surrounding disease-associated polymorphic sequences. We suggest that DNA methylation variations may obscure the effect of co-residing risk sequence alleles. Analysis of enhancer methylation data may help to reveal the regulatory circuits underlying predisposition to cancers and other common diseases.

  18. Regulatory Issues Surrounding Merchant Interconnection

    Energy Technology Data Exchange (ETDEWEB)

    Kuijlaars, Kees-Jan; Zwart, Gijsbert [Office for Energy Regulation (DTe), The Hague (Netherlands)

    2003-11-01

    We discussed various issues concerning the regulatory perspective on private investment in interconnectors. One might claim that leaving investment in transmission infrastructure to competing market parties is more efficient than relying on regulated investment only (especially in the case of long (DC) lines connecting previously unconnected parts of the grids, so that externalities from e.g. loop flows do not play a significant role). We considered that some aspects of interconnection might reduce these market benefits. In particular, the large fixed costs of interconnection construction may lead to significant under investment (due to both first mover monopoly power and the fact that part of generation cost efficiencies realised by interconnection are not captured by the investor itself, and remain external to the investment decision). Second, merchant ownership restricts future opportunities for adaptation of regulation, as would be required e.g. for introduction of potentially more sophisticated methods of congestion management or market splitting. Some of the disadvantages of merchant investment may be mitigated however by a suitable regulatory framework, and we discussed some views in this direction. The issues we discussed are not intended to give a complete framework, and detailed regulation will certainly involve many more specific requirements. Areas we did not touch upon include e.g. the treatment of deep connection costs, rules for operation and maintenance of the line, and impact on availability of capacity on other interconnections.

  19. Fine-mapping inflammatory bowel disease loci to single-variant resolution

    DEFF Research Database (Denmark)

    Huang, Hailiang; Fang, Ming; Jostins, Luke

    2017-01-01

    Inflammatory bowel diseases are chronic gastrointestinal inflammatory disorders that affect millions of people worldwide. Genome-wide association studies have identified 200 inflammatory bowel disease-associated loci, but few have been conclusively resolved to specific functional variants. Here w...

  20. The "Genius Loci" of Prague

    DEFF Research Database (Denmark)

    Laursen, Bjørn

    2015-01-01

    The Bohemian culture, with Prague as a centre, has over centuries turned out to be exorbitant aesthetically fruitful surroundings, combining excellent craftsmanship, science and art innovatively in this area, in spite of the dominating historical position of being suppressed. This article opens...... embryology 4) The unique mentality of the Czech population 5) Combined multidimensional innovative aesthetics...

  1. Meta-analysis of Genome-Wide Association Studies Identifies Novel Loci Associated With Optic Disc Morphology.

    Science.gov (United States)

    Springelkamp, Henriët; Mishra, Aniket; Hysi, Pirro G; Gharahkhani, Puya; Höhn, René; Khor, Chiea-Chuen; Cooke Bailey, Jessica N; Luo, Xiaoyan; Ramdas, Wishal D; Vithana, Eranga; Koh, Victor; Yazar, Seyhan; Xu, Liang; Forward, Hannah; Kearns, Lisa S; Amin, Najaf; Iglesias, Adriana I; Sim, Kar-Seng; van Leeuwen, Elisabeth M; Demirkan, Ayse; van der Lee, Sven; Loon, Seng-Chee; Rivadeneira, Fernando; Nag, Abhishek; Sanfilippo, Paul G; Schillert, Arne; de Jong, Paulus T V M; Oostra, Ben A; Uitterlinden, André G; Hofman, Albert; Zhou, Tiger; Burdon, Kathryn P; Spector, Timothy D; Lackner, Karl J; Saw, Seang-Mei; Vingerling, Johannes R; Teo, Yik-Ying; Pasquale, Louis R; Wolfs, Roger C W; Lemij, Hans G; Tai, E-Shyong; Jonas, Jost B; Cheng, Ching-Yu; Aung, Tin; Jansonius, Nomdo M; Klaver, Caroline C W; Craig, Jamie E; Young, Terri L; Haines, Jonathan L; MacGregor, Stuart; Mackey, David A; Pfeiffer, Norbert; Wong, Tien-Yin; Wiggs, Janey L; Hewitt, Alex W; van Duijn, Cornelia M; Hammond, Christopher J

    2015-03-01

    Primary open-angle glaucoma is the most common optic neuropathy and an important cause of irreversible blindness worldwide. The optic nerve head or optic disc is divided in two parts: a central cup (without nerve fibers) surrounded by the neuroretinal rim (containing axons of the retinal ganglion cells). The International Glaucoma Genetics Consortium conducted a meta-analysis of genome-wide association studies consisting of 17,248 individuals of European ancestry and 6,841 individuals of Asian ancestry. The outcomes of the genome-wide association studies were disc area and cup area. These specific measurements describe optic nerve morphology in another way than the vertical cup-disc ratio, which is a clinically used measurement, and may shed light on new glaucoma mechanisms. We identified 10 new loci associated with disc area (CDC42BPA, F5, DIRC3, RARB, ABI3BP, DCAF4L2, ELP4, TMTC2, NR2F2, and HORMAD2) and another 10 new loci associated with cup area (DHRS3, TRIB2, EFEMP1, FLNB, FAM101, DDHD1, ASB7, KPNB1, BCAS3, and TRIOBP). The new genes participate in a number of pathways and future work is likely to identify more functions related to the pathogenesis of glaucoma. © 2015 Wiley Periodicals, Inc.

  2. Contour detection by surround suppression of texture

    NARCIS (Netherlands)

    Petkov, Nicolai; Tavares, JMRS; Jorge, RMN

    2007-01-01

    Based on a keynote lecture at Complmage 2006, Coimbra, Oct. 20-21, 2006, an overview is given of our activities in modelling and using surround inhibition for contour detection. The effect of suppression of a line or edge stimulus by similar surrounding stimuli is known from visual perception studie

  3. Isolation and characterization of microsatellite loci in the whale shark (Rhincodon typus)

    Science.gov (United States)

    Ramirez-Macias, D.; Shaw, K.; Ward, R.; Galvan-Magana, F.; Vazquez-Juarez, R.

    2009-01-01

    In preparation for a study on population structure of the whale shark (Rhincodon typus), nine species-specific polymorphic microsatellite DNA markers were developed. An initial screening of 50 individuals from Holbox Island, Mexico found all nine loci to be polymorphic, with two to 17 alleles observed per locus. Observed and expected heterozygosity per locus ranged from 0.200 to 0.826 and from 0.213 to 0.857, respectively. Neither statistically significant deviations from Hardy–Weinberg expectations nor statistically significant linkage disequilibrium between loci were observed. These microsatellite loci appear suitable for examining population structure, kinship assessment and other applications.

  4. Agroforestry practice in villages surrounding Nyamure former ...

    African Journals Online (AJOL)

    cntaganda

    Key words: Agroforestry, fuel wood, tree products, woodlot, forest plantation. INTRODUCTION ... The study area included three administrative cells in the surroundings of Nyamure ..... Table 6: Distance and time spent on firewood collection.

  5. Spare PRELI gene loci: failsafe chromosome insurance?

    Directory of Open Access Journals (Sweden)

    Wenbin Ma

    Full Text Available BACKGROUND: LEA (late embryogenesis abundant proteins encode conserved N-terminal mitochondrial signal domains and C-terminal (A/TAEKAK motif repeats, long-presumed to confer cell resistance to stress and death cues. This prompted the hypothesis that LEA proteins are central to mitochondria mechanisms that connect bioenergetics with cell responses to stress and death signaling. In support of this hypothesis, recent studies have demonstrated that mammalian LEA protein PRELI can act as a biochemical hub, which upholds mitochondria energy metabolism, while concomitantly promoting B cell resistance to stress and induced death. Hence, it is important to define in vivo the physiological relevance of PRELI expression. METHODS AND FINDINGS: Given the ubiquitous PRELI expression during mouse development, embryo lethality could be anticipated. Thus, conditional gene targeting was engineered by insertion of flanking loxP (flox/Cre recognition sites on PRELI chromosome 13 (Chr 13 locus to abort its expression in a tissue-specific manner. After obtaining mouse lines with homozygous PRELI floxed alleles (PRELI(f/f, the animals were crossed with CD19-driven Cre-recombinase transgenic mice to investigate whether PRELI inactivation could affect B-lymphocyte physiology and survival. Mice with homozygous B cell-specific PRELI deletion (CD19-Cre/Chr13 PRELI(-/- bred normally and did not show any signs of morbidity. Histopathology and flow cytometry analyses revealed that cell lineage identity, morphology, and viability were indistinguishable between wild type CD19-Cre/Chr13 PRELI(+/+ and CD19-Cre/Chr13 PRELI(-/- deficient mice. Furthermore, B cell PRELI gene expression seemed unaffected by Chr13 PRELI gene targeting. However, identification of additional PRELI loci in mouse Chr1 and Chr5 provided an explanation for the paradox between LEA-dependent cytoprotection and the seemingly futile consequences of Chr 13 PRELI gene inactivation. Importantly, PRELI expression

  6. Surround-Masking Affects Visual Estimation Ability

    Science.gov (United States)

    Jastrzebski, Nicola R.; Hugrass, Laila E.; Crewther, Sheila G.; Crewther, David P.

    2017-01-01

    Visual estimation of numerosity involves the discrimination of magnitude between two distributions or perceptual sets that vary in number of elements. How performance on such estimation depends on peripheral sensory stimulation is unclear, even in typically developing adults. Here, we varied the central and surround contrast of stimuli that comprised a visual estimation task in order to determine whether mechanisms involved with the removal of unessential visual input functionally contributes toward number acuity. The visual estimation judgments of typically developed adults were significantly impaired for high but not low contrast surround stimulus conditions. The center and surround contrasts of the stimuli also differentially affected the accuracy of numerosity estimation depending on whether fewer or more dots were presented. Remarkably, observers demonstrated the highest mean percentage accuracy across stimulus conditions in the discrimination of more elements when the surround contrast was low and the background luminance of the central region containing the elements was dark (black center). Conversely, accuracy was severely impaired during the discrimination of fewer elements when the surround contrast was high and the background luminance of the central region was mid level (gray center). These findings suggest that estimation ability is functionally related to the quality of low-order filtration of unessential visual information. These surround masking results may help understanding of the poor visual estimation ability commonly observed in developmental dyscalculia.

  7. Genes and longevity: a genetic-demographic approach reveals sex- and age-specific gene effects not shown by the case-control approach (APOE and HSP70.1 loci).

    Science.gov (United States)

    Dato, S; Carotenuto, L; De Benedictis, G

    2007-02-01

    Association analyses between gene variability and human longevity carried out by comparing gene frequencies between population samples of different ages (case/control design) may provide information on genes and pathways playing a role in modulating survival at old ages. However, by dealing with cross-sectional data, the gene-frequency (GF) approach ignores cohort effects in population mortality changes. The genetic-demographic (GD) approach adds demographic information to genetic data and allows the estimation of hazard rates and survival functions for candidate alleles and genotypes. Thus mortality changes in the cohort to which the cross-sectional sample belongs are taken into account. In this work, we applied the GD method to a dataset relevant to two genes, APOE and HSP70.1, previously shown to be related to longevity by the GF method. We show that the GD method reveals sex- and age-specific allelic effects not shown by the GF analysis. In addition, we provide an algorithm for the implementation of a non-parametric GD analysis.

  8. Designing of an artificial neural network model to evaluate the association of three combined Y-specific microsatellite loci on the actual and predicted postthaw motility in crossbred bull semen.

    Science.gov (United States)

    Deb, Rajib; Singh, Umesh; Raja, Thirvvothur Venkatesan; Kumar, Sushil; Tyagi, Shrikant; Alyethodi, Rafeeque R; Alex, Rani; Sengar, Gyanendra; Sharma, Sheetal

    2015-06-01

    The freezing of bull semen significantly hamper the motility of sperm which reduces the conception rate in dairy cattle. The prediction of postthaw motility (PTM) before freezing will be useful to take the decision on discarding or freezing of the germplasm. The artificial neural network (ANN) methodology found to be useful in prediction and classification problems related to animal science, and hence, the present study was undertaken to compare the efficiency of ANN in prediction of PTM on the basis of the number of ejaculates, volume, and concentration of sperms. The combined effect of Y-specific microsatellite alleles on the actual and predicted PTM was also studied. The results revealed that the prediction accuracy of PTM based on the semen quality parameters was comparatively lower because of higher variability in the data set. The ANN gave better prediction accuracy (34.88%) than the multiple regression analysis models (32.04%). The root mean square error was lower for ANN (8.4353) than that in the multiple regression analysis (8.6168). The haplotype or combined effect of microsatellite alleles on actual and predicted PTM was found to be highly significant (P < 0.01). On the basis of results, it was concluded that the ANN methodology can be used for prediction of PTM in crossbred bulls.

  9. Outlier loci detect intraspecific biodiversity amongst spring and autumn spawning herring across local scales

    DEFF Research Database (Denmark)

    Bekkevold, Dorte; Gross, Riho; Arula, Timo

    2016-01-01

    analyses reveal clear genetic differences between ecotypes and hence support reproductive isolation. Loci showing non-neutral behaviour, so-called outlier loci, show convergence between autumn spawning herring from demographically disjoint populations, potentially reflecting selective processes associated...... with autumn spawning ecotypes. The abundance and exploitation of the two ecotypes have varied strongly over space and time in the Baltic Sea, where autumn spawners have faced strong depression for decades. The results therefore have practical implications by highlighting the need for specific management...

  10. Obesity susceptibility loci and uncontrolled eating, emotional eating and cognitive restraint behaviors in men and women

    OpenAIRE

    Cornelis, Marilyn C.; Rimm, Eric B; Curhan, Gary C.; Kraft, Peter; Hunter, David J; Hu, Frank B; Van Dam, Rob M.

    2013-01-01

    Objective: Many confirmed genetic loci for obesity are expressed in regions of the brain that regulate energy intake and reward-seeking behavior. Whether these loci contribute to the development of specific eating behaviors has not been investigated. We examined the relationship between a genetic susceptibility to obesity and cognitive restraint, uncontrolled and emotional eating. Design and Methods Eating behavior and body mass index (BMI) were determined by questionnaires for 1471 men and 2...

  11. High density genetic mapping identifies new susceptibility loci for rheumatoid arthritis

    Science.gov (United States)

    Eyre, Steve; Bowes, John; Diogo, Dorothée; Lee, Annette; Barton, Anne; Martin, Paul; Zhernakova, Alexandra; Stahl, Eli; Viatte, Sebastien; McAllister, Kate; Amos, Christopher I.; Padyukov, Leonid; Toes, Rene E.M.; Huizinga, Tom W.J.; Wijmenga, Cisca; Trynka, Gosia; Franke, Lude; Westra, Harm-Jan; Alfredsson, Lars; Hu, Xinli; Sandor, Cynthia; de Bakker, Paul I.W.; Davila, Sonia; Khor, Chiea Chuen; Heng, Khai Koon; Andrews, Robert; Edkins, Sarah; Hunt, Sarah E; Langford, Cordelia; Symmons, Deborah; Concannon, Pat; Onengut-Gumuscu, Suna; Rich, Stephen S; Deloukas, Panos; Gonzalez-Gay, Miguel A.; Rodriguez-Rodriguez, Luis; Ärlsetig, Lisbeth; Martin, Javier; Rantapää-Dahlqvist, Solbritt; Plenge, Robert; Raychaudhuri, Soumya; Klareskog, Lars; Gregersen, Peter K; Worthington, Jane

    2012-01-01

    Summary Using the Immunochip custom single nucleotide polymorphism (SNP) array, designed for dense genotyping of 186 genome wide association study (GWAS) confirmed loci we analysed 11,475 rheumatoid arthritis cases of European ancestry and 15,870 controls for 129,464 markers. The data were combined in meta-analysis with GWAS data from additional independent cases (n=2,363) and controls (n=17,872). We identified fourteen novel loci; nine were associated with rheumatoid arthritis overall and 5 specifically in anti-citrillunated peptide antibody positive disease, bringing the number of confirmed European ancestry rheumatoid arthritis loci to 46. We refined the peak of association to a single gene for 19 loci, identified secondary independent effects at six loci and association to low frequency variants (minor allele frequency <0.05) at 4 loci. Bioinformatic analysis of the data generated strong hypotheses for the causal SNP at seven loci. This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations. PMID:23143596

  12. Smart Chips for Smart Surroundings - 4S

    NARCIS (Netherlands)

    Schuler, Eberhard; König, Ralf; Becker, Jürgen; Rauwerda, Gerard; Burgwal, van de Marcel; Smit, Gerard J.M.; Cardoso, João M.P.; Hübner, Michael

    2011-01-01

    The overall mission of the 4S project (Smart Chips for Smart Surroundings) was to define and develop efficient flexible, reconfigurable core building blocks, including the supporting tools, for future Ambient System Devices. Reconfigurability offers the needed flexibility and adaptability, it provid

  13. Balancing selection maintains polymorphisms at neurogenetic loci in field experiments.

    Science.gov (United States)

    Lonn, Eija; Koskela, Esa; Mappes, Tapio; Mokkonen, Mikael; Sims, Angela M; Watts, Phillip C

    2017-04-04

    Most variation in behavior has a genetic basis, but the processes determining the level of diversity at behavioral loci are largely unknown for natural populations. Expression of arginine vasopressin receptor 1a (Avpr1a) and oxytocin receptor (Oxtr) in specific regions of the brain regulates diverse social and reproductive behaviors in mammals, including humans. That these genes have important fitness consequences and that natural populations contain extensive diversity at these loci implies the action of balancing selection. In Myodes glareolus, Avpr1a and Oxtr each contain a polymorphic microsatellite locus located in their 5' regulatory region (the regulatory region-associated microsatellite, RRAM) that likely regulates gene expression. To test the hypothesis that balancing selection maintains diversity at behavioral loci, we released artificially bred females and males with different RRAM allele lengths into field enclosures that differed in population density. The length of Avpr1a and Oxtr RRAMs was associated with reproductive success, but population density and the sex interacted to determine the optimal genotype. In general, longer Avpr1a RRAMs were more beneficial for males, and shorter RRAMs were more beneficial for females; the opposite was true for Oxtr RRAMs. Moreover, Avpr1a RRAM allele length is correlated with the reproductive success of the sexes during different phases of reproduction; for males, RRAM length correlated with the numbers of newborn offspring, but for females selection was evident on the number of weaned offspring. This report of density-dependence and sexual antagonism acting on loci within the arginine vasopressin-oxytocin pathway explains how genetic diversity at Avpr1a and Oxtr could be maintained in natural populations.

  14. Inhibition of the dorsal premotor cortex does not repair surround inhibition in writer's cramp patients.

    Science.gov (United States)

    Veugen, Lidwien C; Hoffland, Britt S; Stegeman, Dick F; van de Warrenburg, Bart P

    2013-03-01

    Writer's cramp is a task-specific form of focal dystonia, characterized by abnormal movements and postures of the hand and arm during writing. Two consistent abnormalities in its pathophysiology are a loss of surround inhibition and overactivity of the dorsal premotor cortex (PMd). This study aimed to assess a possible link between these two phenomena by investigating whether PMd inhibition leads to an improvement of surround inhibition, in parallel with previously demonstrated writing improvement. Fifteen writer's cramp patients and ten controls performed a simple motor hand task during which surround inhibition was measured using transcranial magnetic stimulation. Motor cortical excitability was measured of the active and surround muscles at three phases of the task. Surround inhibition and writing performance were assessed before and after PMd inhibitory continuous theta burst stimulation. In contrast to healthy controls, patients did not show inhibition of the abductor digiti minimi muscle during movement initiation of the first dorsal interosseus muscle, confirming the loss of surround inhibition. PMd inhibition led to an improvement of writing speed in writer's cramp patients. However, in both groups, no changes in surround inhibition were observed. The results confirm a role for the PMd in the pathophysiology of writer's cramp. We show that PMd inhibition does not lead to restoration of the surround inhibition defect in writer's cramp, despite the improvement in writing. This questions the involvement of the PMd in the loss of surround inhibition, and perhaps also the direct link between surround inhibition and dystonia.

  15. The Interstellar Cloud Surrounding the Solar System

    Science.gov (United States)

    Frisch, P. C.

    Ultraviolet spectral data of nearby stars indicate that the cloud surrounding the solar system has an average neutral density n(HI)~0.1 cm-3, temperature ~6800 K, and turbulence ~1.7 km/s. Comparisons between the anomalous cosmic ray data and ultraviolet data suggest that the electron density is in the range n(e-)~0.22 to 0.44 cm-3. This cloud is flowing past the Sun from a position centered in the Norma-Lupis region. The cloud properties are consistent with interstellar gas which originated as material evaporated from the surfaces of embedded clouds in the Scorpius-Centaurus Association, and which was then displaced towards the Sun by a supernova event about 4 Myrs ago. The Sun and surrounding cloud velocities are nearly perpendicular in space, and this cloud is sweeping past the Sun. The morphology of this cloud can be reconstructed by assuming that the cloud moves in a direction parallel to the surface normal. With this assumption, the Sun entered the surrounding cloud 2000 to 8000 years ago, and is now about 0.05 to 0.16 pc from the cloud surface. Prior to its recent entry into the surrounding cloud complex, the Sun was embedded in a region of space with average density lower than 0.0002 cm-3. If a denser cloud velocity component seen towards alpha Cen A,B is real, it will encounter the solar system within 50,000 yr. The nearby magnetic field seen upwind has a spatial orientation that is parallel to the cloud surface. The nearby star Sirius is viewed through the wake of the solar system, but this direction also samples the hypothetical cloud interface. Comparisons of anomalous cosmic ray and interstellar absorption line data suggest that trace elements in the surrounding cloud are in ionization equilibrium. Data towards nearby white dwarfs indicate partial helium ionization, N(N(HI)(/N(HeI)>~13.7, which is consistent with pickup ion data within the solar system if less than 40% hydrogen ionization occurs in the heliopause region. However, the white dwarfs may

  16. DNA polymorphism at the casein loci in sheep.

    Science.gov (United States)

    Di Gregorio, P; Rando, A; Pieragostini, E; Masina, P

    1991-01-01

    By using seven endonucleases and four bovine cDNA probes specific for alpha S1-, alpha S2-, beta-, and kappa-casein genes, nine restriction fragment length polymorphisms (RFLPs) have been found in the sheep orthologous DNA regions. In contrast to the low level of variation observed at the protein level, these DNA polymorphisms determine a high level of heterozygosity and, therefore, represent useful tools for genetic analyses since they can also be obtained without the need for gene expression. In fact, informative matings suggest that in sheep, as in cattle, the four loci are linked.

  17. Quantifying missing heritability at known GWAS loci.

    Directory of Open Access Journals (Sweden)

    Alexander Gusev

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

  18. Identification of -SiC surrounded by relatable surrounding diamond medium using weak Raman surface phonons

    Indian Academy of Sciences (India)

    Mohan Kumar Kuntumalla; Harish Ojha; Vadali Venkata Satya Siva Srikanth

    2013-11-01

    It is difficult to detect -SiC using micro-Raman scattering, if it is surrounded by carbon medium. Here, -SiC is identified in the presence of a relatable surrounding diamond medium using subtle, but discernible Raman surface phonons. In this study, diamond/-SiC nanocomposite thin film system is considered in which nanosized -SiC crystallites are surrounded by a relatable nanodiamond medium that leads to the appearance of a weak Raman surface phonon band at about 855 cm-1. Change in the nature of the surrounding material structure and its volume content when relatable, will affect the resultant Raman response of -SiC phase as seen in the present case of diamond/-SiC nanocomposite thin films.

  19. 52 Genetic Loci Influencing Myocardial Mass

    Science.gov (United States)

    van der Harst, Pim; van Setten, Jessica; Verweij, Niek; Vogler, Georg; Franke, Lude; Maurano, Matthew T.; Wang, Xinchen; Leach, Irene Mateo; Eijgelsheim, Mark; Sotoodehnia, Nona; Hayward, Caroline; Sorice, Rossella; Meirelles, Osorio; Lyytikäinen, Leo-Pekka; Polašek, Ozren; Tanaka, Toshiko; Arking, Dan E.; Ulivi, Sheila; Trompet, Stella; Müller-Nurasyid, Martina; Smith, Albert V.; Dörr, Marcus; Kerr, Kathleen F.; Magnani, Jared W.; Fabiola Del Greco, M.; Zhang, Weihua; Nolte, Ilja M.; Silva, Claudia T.; Padmanabhan, Sandosh; Tragante, Vinicius; Esko, Tõnu; Abecasis, Gonçalo R.; Adriaens, Michiel E.; Andersen, Karl; Barnett, Phil; Bis, Joshua C.; Bodmer, Rolf; Buckley, Brendan M.; Campbell, Harry; Cannon, Megan V.; Chakravarti, Aravinda; Chen, Lin Y.; Delitala, Alessandro; Devereux, Richard B.; Doevendans, Pieter A.; Dominiczak, Anna F.; Ferrucci, Luigi; Ford, Ian; Gieger, Christian; Harris, Tamara B.; Haugen, Eric; Heinig, Matthias; Hernandez, Dena G.; Hillege, Hans L.; Hirschhorn, Joel N.; Hofman, Albert; Hubner, Norbert; Hwang, Shih-Jen; Iorio, Annamaria; Kähönen, Mika; Kellis, Manolis; Kolcic, Ivana; Kooner, Ishminder K.; Kooner, Jaspal S.; Kors, Jan A.; Lakatta, Edward G.; Lage, Kasper; Launer, Lenore J.; Levy, Daniel; Lundby, Alicia; Macfarlane, Peter W.; May, Dalit; Meitinger, Thomas; Metspalu, Andres; Nappo, Stefania; Naitza, Silvia; Neph, Shane; Nord, Alex S.; Nutile, Teresa; Okin, Peter M.; Olsen, Jesper V.; Oostra, Ben A.; Penninger, Josef M.; Pennacchio, Len A.; Pers, Tune H.; Perz, Siegfried; Peters, Annette; Pinto, Yigal M.; Pfeufer, Arne; Pilia, Maria Grazia; Pramstaller, Peter P.; Prins, Bram P.; Raitakari, Olli T.; Raychaudhuri, Soumya; Rice, Ken M.; Rossin, Elizabeth J.; Rotter, Jerome I.; Schafer, Sebastian; Schlessinger, David; Schmidt, Carsten O.; Sehmi, Jobanpreet; Silljé, Herman H.W.; Sinagra, Gianfranco; Sinner, Moritz F.; Slowikowski, Kamil; Soliman, Elsayed Z.; Spector, Timothy D.; Spiering, Wilko; Stamatoyannopoulos, John A.; Stolk, Ronald P.; Strauch, Konstantin; Tan, Sian-Tsung; Tarasov, Kirill V.; Trinh, Bosco; Uitterlinden, Andre G.; van den Boogaard, Malou; van Duijn, Cornelia M.; van Gilst, Wiek H.; Viikari, Jorma S.; Visscher, Peter M.; Vitart, Veronique; Völker, Uwe; Waldenberger, Melanie; Weichenberger, Christian X.; Westra, Harm-Jan; Wijmenga, Cisca; Wolffenbuttel, Bruce H.; Yang, Jian; Bezzina, Connie R.; Munroe, Patricia B.; Snieder, Harold; Wright, Alan F.; Rudan, Igor; Boyer, Laurie A.; Asselbergs, Folkert W.; van Veldhuisen, Dirk J.; Stricker, Bruno H.; Psaty, Bruce M.; Ciullo, Marina; Sanna, Serena; Lehtimäki, Terho; Wilson, James F.; Bandinelli, Stefania; Alonso, Alvaro; Gasparini, Paolo; Jukema, J. Wouter; Kääb, Stefan; Gudnason, Vilmundur; Felix, Stephan B.; Heckbert, Susan R.; de Boer, Rudolf A.; Newton-Cheh, Christopher; Hicks, Andrew A.; Chambers, John C.; Jamshidi, Yalda; Visel, Axel; Christoffels, Vincent M.; Isaacs, Aaron; Samani, Nilesh J.; de Bakker, Paul I.W.

    2017-01-01

    BACKGROUND Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death. OBJECTIVES This meta-analysis sought to gain insights into the genetic determinants of myocardial mass. METHODS We carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment. RESULTS We identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 × 10−8. These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus. We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo. CONCLUSIONS Taken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets. PMID:27659466

  20. Interval Mapping of Multiple Quantitative Trait Loci

    NARCIS (Netherlands)

    Jansen, Ritsert C.

    1993-01-01

    The interval mapping method is widely used for the mapping of quantitative trait loci (QTLs) in segregating generations derived from crosses between inbred lines. The efficiency of detecting and the accuracy of mapping multiple QTLs by using genetic markers are much increased by employing multiple Q

  1. Microsatellite loci for population and parentage analysis in the Amazon River dolphin (Inia geoffrensis de Blainville, 1817).

    Science.gov (United States)

    Gravena, Waleska; Hrbek, Tomas; DA Silva, Vera M S; Astolfi-Filho, Spartaco; Farias, Izeni P

    2009-03-01

    We developed specific primers for microsatellite DNA regions for the Amazon River dolphin or boto Inia geoffrensis, for use in population and conservation genetic studies. We also tested their transferability for two other species, Pontoporia blainvillei (sister taxon of I. geoffrensis) and Sotalia guianensis. A total of 12 microsatellite loci were polymorphic for the boto. An additional 25 microsatellite loci previously isolated from other cetacean species were also tested in the boto. The 26 polymorphic microsatellite loci indicate they will be excellent markers for studies of population structure and kinship relations of the boto.

  2. Characterization of microsatellite loci for the littorine snail Bembicium vittatum.

    Science.gov (United States)

    Kennington, W J; Lukehurst, S S; Johnson, M S

    2008-11-01

    We describe the isolation and development of 17 polymorphic microsatellite loci for the intertidal snail Bembicium vittatum (Gastropoda: Littorinidae). The loci were tested in 46 individuals from a single population situated near the centre of the species distribution. No evidence of linkage disequilibrium was detected between any pair of loci. However, two loci showed significant departures from Hardy-Weinberg expectations. The number of alleles per locus ranged from two to 15. © 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd.

  3. Characterization and Exploitation of CRISPR Loci in Bifidobacterium longum

    Directory of Open Access Journals (Sweden)

    Claudio Hidalgo-Cantabrana

    2017-09-01

    Full Text Available Diverse CRISPR-Cas systems provide adaptive immunity in many bacteria and most archaea, via a DNA-encoded, RNA-mediated, nucleic-acid targeting mechanism. Over time, CRISPR loci expand via iterative uptake of invasive DNA sequences into the CRISPR array during the adaptation process. These genetic vaccination cards thus provide insights into the exposure of strains to phages and plasmids in space and time, revealing the historical predatory exposure of a strain. These genetic loci thus constitute a unique basis for genotyping of strains, with potential of resolution at the strain-level. Here, we investigate the occurrence and diversity of CRISPR-Cas systems in the genomes of various Bifidobacterium longum strains across three sub-species. Specifically, we analyzed the genomic content of 66 genomes belonging to B. longum subsp. longum, B. longum subsp. infantis and B. longum subsp. suis, and identified 25 strains that carry 29 total CRISPR-Cas systems. We identify various Type I and Type II CRISPR-Cas systems that are widespread in this species, notably I-C, I-E, and II-C. Noteworthy, Type I-C systems showed extended CRISPR arrays, with extensive spacer diversity. We show how these hypervariable loci can be used to gain insights into strain origin, evolution and phylogeny, and can provide discriminatory sequences to distinguish even clonal isolates. By investigating CRISPR spacer sequences, we reveal their origin and implicate phages and prophages as drivers of CRISPR immunity expansion in this species, with redundant targeting of select prophages. Analysis of CRISPR spacer origin also revealed novel PAM sequences. Our results suggest that CRISPR-Cas immune systems are instrumental in mounting diversified viral resistance in B. longum, and show that these sequences are useful for typing across three subspecies.

  4. Blood pressure loci identified with a gene-centric array.

    Science.gov (United States)

    Johnson, Toby; Gaunt, Tom R; Newhouse, Stephen J; Padmanabhan, Sandosh; Tomaszewski, Maciej; Kumari, Meena; Morris, Richard W; Tzoulaki, Ioanna; O'Brien, Eoin T; Poulter, Neil R; Sever, Peter; Shields, Denis C; Thom, Simon; Wannamethee, Sasiwarang G; Whincup, Peter H; Brown, Morris J; Connell, John M; Dobson, Richard J; Howard, Philip J; Mein, Charles A; Onipinla, Abiodun; Shaw-Hawkins, Sue; Zhang, Yun; Davey Smith, George; Day, Ian N M; Lawlor, Debbie A; Goodall, Alison H; Fowkes, F Gerald; Abecasis, Gonçalo R; Elliott, Paul; Gateva, Vesela; Braund, Peter S; Burton, Paul R; Nelson, Christopher P; Tobin, Martin D; van der Harst, Pim; Glorioso, Nicola; Neuvrith, Hani; Salvi, Erika; Staessen, Jan A; Stucchi, Andrea; Devos, Nabila; Jeunemaitre, Xavier; Plouin, Pierre-François; Tichet, Jean; Juhanson, Peeter; Org, Elin; Putku, Margus; Sõber, Siim; Veldre, Gudrun; Viigimaa, Margus; Levinsson, Anna; Rosengren, Annika; Thelle, Dag S; Hastie, Claire E; Hedner, Thomas; Lee, Wai K; Melander, Olle; Wahlstrand, Björn; Hardy, Rebecca; Wong, Andrew; Cooper, Jackie A; Palmen, Jutta; Chen, Li; Stewart, Alexandre F R; Wells, George A; Westra, Harm-Jan; Wolfs, Marcel G M; Clarke, Robert; Franzosi, Maria Grazia; Goel, Anuj; Hamsten, Anders; Lathrop, Mark; Peden, John F; Seedorf, Udo; Watkins, Hugh; Ouwehand, Willem H; Sambrook, Jennifer; Stephens, Jonathan; Casas, Juan-Pablo; Drenos, Fotios; Holmes, Michael V; Kivimaki, Mika; Shah, Sonia; Shah, Tina; Talmud, Philippa J; Whittaker, John; Wallace, Chris; Delles, Christian; Laan, Maris; Kuh, Diana; Humphries, Steve E; Nyberg, Fredrik; Cusi, Daniele; Roberts, Robert; Newton-Cheh, Christopher; Franke, Lude; Stanton, Alice V; Dominiczak, Anna F; Farrall, Martin; Hingorani, Aroon D; Samani, Nilesh J; Caulfield, Mark J; Munroe, Patricia B

    2011-12-09

    Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples. We followed up four SNPs associated with BP at our p < 8.56 × 10(-7) study-specific significance threshold and six suggestively associated SNPs in a further 59,349 individuals. We identified and replicated a SNP at LSP1/TNNT3, a SNP at MTHFR-NPPB independent (r(2) = 0.33) of previous reports, and replicated SNPs at AGT and ATP2B1 reported previously. An analysis of combined discovery and follow-up data identified SNPs significantly associated with BP at p < 8.56 × 10(-7) at four further loci (NPR3, HFE, NOS3, and SOX6). The high number of discoveries made with modest genotyping effort can be attributed to using a large-scale yet targeted genotyping array and to the development of a weighting scheme that maximized power when meta-analyzing results from samples ascertained with extreme phenotypes, in combination with results from nonascertained or population samples. Chromatin immunoprecipitation and transcript expression data highlight potential gene regulatory mechanisms at the MTHFR and NOS3 loci. These results provide candidates for further study to help dissect mechanisms affecting BP and highlight the utility of studying SNPs and samples that are independent of those studied previously even when the sample size is smaller than that in previous studies.

  5. Alterations at chromosome 17 loci in peripheral nerve sheath tumors

    Energy Technology Data Exchange (ETDEWEB)

    Lothe, R.A.; Slettan, A.; Saeter, G. [Norwegian Radium Hospital, Oslo (Norway)] [and others

    1995-01-01

    Little is known about the molecular genetic changes in malignant peripheral nerve sheath tumors (MPNST). Inactivation of the TP53 gene in l7p has been reported in a few tumors. The MPNST is one of the manifestations of neurofibromatosis 1 (NF1), suggesting that the NF1 gene in 17q might be important. We present a study of 15 neurofibromas and MPNST from nine individuals. Seven patients had NF1 and six of these developed MPNST. Genetic alterations at nine polymorphic loci on chromosome 17 were examined. Allelic imbalance was detected only in the malignant tumors from NF1 patients (4/6). Complete loss of heterozygosity of 17q loci was found in three of these tumors, all including loci within the NF1 gene. Two of the malignant tumors also showed deletions on 17p. No mutations were detected within exon 5-8 of the TP53 in any of the MPNST, and none of them were TP53 protein-positive using immunostaining with mono- and polyclonal antibodies against TP53. The numbers of chromosome 17 present in each tumor were evaluated by use of fluorescence in situ hybridization (FISH) on interphase nuclei with a centromere-specific probe. A deviation from the disomic status of chromosome 17 was observed in two of the MPNST from NF1 patients. These results support the hypothesis of inactivation of both NF1 gene alleles during development of MPNST in patients with NF1. In contrast to other reports, we did not find evidence for a homozygous mutated condition of the TP53 gene in the same tumors. Finally, FISH analysis was in accordance with the DNA analysis in the deduction of the numbers of chromosome 17 in these tumors. 29 refs., 3 figs., 2 tabs.

  6. Microsatellite loci for genetic mapping in the turkey (Meleagris gallopavo).

    Science.gov (United States)

    Reed, K M; Chaves, L D; Hall, M K; Knutson, T P; Rowe, J A; Torgerson, A J

    2003-11-01

    New microsatellite loci for the turkey (Meleagris gallopavo) were developed from two small insert DNA libraries. Polymorphism at these new loci was examined in domestic birds and two resource populations designed for genetic linkage mapping. The majority of loci (152 of 168) was polymorphic in domestic turkeys and informative in two mapping resource populations and thus will be useful for genetic linkage mapping.

  7. Characterizing the Microenvironment Surrounding Phosphorylated Protein Sites

    Institute of Scientific and Technical Information of China (English)

    Shi-Cai Fan; Xue-Gong Zhang

    2005-01-01

    Protein phosphorylation plays an important role in various cellular processes. Due to its high complexity, the mechanism needs to be further studied. In the last few years, many methods have been contributed to this field, but almost all of them investigated the mechanism based on protein sequences around protein sites. In this study, we implement an exploration by characterizing the microenvironment surrounding phosphorylated protein sites with a modified shell model, and obtain some significant properties by the rank-sum test, such as the lack of some classes of residues, atoms, and secondary structures. Furthermore, we find that the depletion of some properties affects protein phosphorylation remarkably. Our results suggest that it is a meaningful direction to explore the mechanism of protein phosphorylation from microenvironment and we expect further findings along with the increasing size of phosphorylation and protein structure data.

  8. Opportunity's Surroundings After Sol 1820 Drive

    Science.gov (United States)

    2009-01-01

    NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this full-circle view of the rover's surroundings during the 1,820th to 1,822nd Martian days, or sols, of Opportunity's surface mission (March 7 to 9, 2009). South is at the center; north at both ends. The rover had driven 20.6 meters toward the northwest on Sol 1820 before beginning to take the frames in this view. Tracks from that drive recede southwestward. For scale, the distance between the parallel wheel tracks is about 1 meter (about 40 inches). The terrain in this portion of Mars' Meridiani Planum region includes dark-toned sand ripples and small exposures of lighter-toned bedrock. This view is presented as a cylindrical projection with geometric seam correction.

  9. Exploiting Surrounding Text for Retrieving Web Images

    Directory of Open Access Journals (Sweden)

    S. A. Noah

    2008-01-01

    Full Text Available Web documents contain useful textual information that can be exploited for describing images. Research had been focused on representing images by means of its content (low level description such as color, shape and texture, little research had been directed to exploiting such textual information. The aim of this research was to systematically exploit the textual content of HTML documents for automatically indexing and ranking of images embedded in web documents. A heuristic approach for locating and assigning weight surrounding web images and a modified tf.idf weighting scheme was proposed. Precision-recall measures of evaluation had been conducted for ten queries and promising results had been achieved. The proposed approach showed slightly better precision measure as compared to a popular search engine with an average of 0.63 and 0.55 relative precision measures respectively.

  10. The genetics of murine Hox loci: TAMERE, STRING, and PANTHERE to engineer chromosome variants.

    Science.gov (United States)

    Tschopp, Patrick; Duboule, Denis

    2014-01-01

    Following their duplications at the base of the vertebrate clade, Hox gene clusters underwent remarkable sub- and neo-functionalization events. Many of these evolutionary innovations can be associated with changes in the transcriptional regulation of their genes, where an intricate relationship between the structure of the gene cluster and the architecture of the surrounding genomic landscape is at play. Here, we report on a portfolio of in vivo genome engineering strategies in mice, which have been used to probe and decipher the genetic and molecular underpinnings of the complex regulatory mechanisms implemented at these loci.

  11. Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics

    DEFF Research Database (Denmark)

    Garcia-Closas, M.; Hall, P.; Nevanlinna, H.

    2008-01-01

    A three-stage genome-wide association study recently identified single nucleotide polymorphisms ( SNPs) in five loci ( fibroblast growth receptor 2 ( FGFR2), trinucleotide repeat containing 9 ( TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte- specific protein 1 ( LSP1...

  12. Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease

    NARCIS (Netherlands)

    Rivas, Manuel A.; Beaudoin, Melissa; Gardet, Agnes; Stevens, Christine; Sharma, Yashoda; Zhang, Clarence K.; Boucher, Gabrielle; Ripke, Stephan; Ellinghaus, David; Burtt, Noel; Fennell, Tim; Kirby, Andrew; Latiano, Anna; Goyette, Philippe; Green, Todd; Halfvarson, Jonas; Haritunians, Talin; Korn, Joshua M.; Kuruvilla, Finny; Lagace, Caroline; Neale, Benjamin; Lo, Ken Sin; Schumm, Phil; Torkvist, Leif; Dubinsky, Marla C.; Brant, Steven R.; Silverberg, Mark S.; Duerr, Richard H.; Altshuler, David; Gabriel, Stacey; Lettre, Guillaume; Franke, Andre; D'Amato, Mauro; McGovern, Dermot P. B.; Cho, Judy H.; Rioux, John D.; Xavier, Ramnik J.; Daly, Mark J.

    2011-01-01

    More than 1,000 susceptibility loci have been identified through genome-wide association studies (GWAS) of common variants; however, the specific genes and full allelic spectrum of causal variants underlying these findings have not yet been defined. Here we used pooled next-generation sequencing to

  13. 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...

  14. GLANET: genomic loci annotation and enrichment tool.

    Science.gov (United States)

    Otlu, Burçak; Firtina, Can; Keles, Sündüz; Tastan, Oznur

    2017-09-15

    Genomic studies identify genomic loci representing genetic variations, transcription factor (TF) occupancy, or histone modification through next generation sequencing (NGS) technologies. Interpreting these loci requires evaluating them with known genomic and epigenomic annotations. We present GLANET as a comprehensive annotation and enrichment analysis tool which implements a sampling-based enrichment test that accounts for GC content and/or mappability biases, jointly or separately. GLANET annotates and performs enrichment analysis on these loci with a rich library. We introduce and perform novel data-driven computational experiments for assessing the power and Type-I error of its enrichment procedure which show that GLANET has attained high statistical power and well-controlled Type-I error rate. As a key feature, users can easily extend its library with new gene sets and genomic intervals. Other key features include assessment of impact of single nucleotide variants (SNPs) on TF binding sites and regulation based pathway enrichment analysis. GLANET can be run using its GUI or on command line. GLANET's source code is available at https://github.com/burcakotlu/GLANET . Tutorials are provided at https://glanet.readthedocs.org . burcak@ceng.metu.edu.tr or oznur.tastan@cs.bilkent.edu.tr. Supplementary data are available at Bioinformatics online.

  15. Effects of Genetic Loci Associated with Central Obesity on Adipocyte Lipolysis.

    Science.gov (United States)

    Strawbridge, Rona J; Laumen, Helmut; Hamsten, Anders; Breier, Michaela; Grallert, Harald; Hauner, Hans; Arner, Peter; Dahlman, Ingrid

    2016-01-01

    Numerous genetic loci have been associated with measures of central fat accumulation, such as waist-to-hip ratio adjusted for body mass index (WHRadjBMI). However the mechanisms by which genetic variations influence obesity remain largely elusive. Lipolysis is a key process for regulation of lipid storage in adipocytes, thus is implicated in obesity and its metabolic complications. Here, genetic variants at 36 WHRadjBMI-associated loci were examined for their influence on abdominal subcutaneous adipocyte lipolysis. Fasting subcutaneous adipose tissue biopsies were collected from 789 volunteers (587 women and 202 men, body mass index (BMI) range 17.7-62.3 kg/m2). We quantified subcutaneous adipocyte lipolysis, both spontaneous and stimulated by the catecholamine isoprenaline or a cyclic AMP analogue. DNA was extracted from peripheral blood mononuclear cells and genotyping of SNPs associated with WHRadjBMI conducted. The effects on adipocyte lipolysis measures were assessed for SNPs individually and combined in a SNP score. The WHRadjBMI-associated loci CMIP, PLXND1, VEGFA and ZNRF3-KREMEN1 demonstrated nominal associations with spontaneous and/or stimulated lipolysis. Candidate genes in these loci have been reported to influence NFκB-signaling, fat cell size and Wnt signalling, all of which may influence lipolysis. This report provides evidence for specific WHRadjBMI-associated loci as candidates to modulate adipocyte lipolysis. Additionally, our data suggests that genetically increased central fat accumulation is unlikely to be a major cause of altered lipolysis in abdominal adipocytes.

  16. Quantitative assay for TALEN activity at endogenous genomic loci

    Directory of Open Access Journals (Sweden)

    Yu Hisano

    2013-02-01

    Artificially designed nucleases such as zinc-finger nucleases (ZFNs and transcription activator-like effector nucleases (TALENs can induce a targeted DNA double-strand break at the specific target genomic locus, leading to the frameshift-mediated gene disruption. However, the assays for their activity on the endogenous genomic loci remain limited. Herein, we describe a versatile modified lacZ assay to detect frameshifts in the nuclease target site. Short fragments of the genome DNA at the target or putative off-target loci were amplified from the genomic DNA of TALEN-treated or control embryos, and were inserted into the lacZα sequence for the conventional blue–white selection. The frequency of the frameshifts in the fragment can be estimated from the numbers of blue and white colonies. Insertions and/or deletions were easily determined by sequencing the plasmid DNAs recovered from the positive colonies. Our technique should offer broad application to the artificial nucleases for genome editing in various types of model organisms.

  17. The lithosphere-asthenosphere Italy and surroundings

    CERN Document Server

    Panza, G F; Chimera, G; Pontevivo, A; Raykova, R

    2003-01-01

    The velocity-depth distribution of the lithosphere-asthenosphere in the Italian region and surroundings is imaged, with a lateral resolution of about 100 km, by surface wave velocity tomography and non-linear inversion. Maps of the Moho depth, of the thickness of the lithosphere and of the shear-wave velocities, down to depths of 200 km and more, are constructed. A mantle wedge, identified in the uppermost mantle along the Apennines and the Calabrian Arc, underlies the principal recent volcanoes, and partial melting can be relevant in this part of the uppermost mantle. In Calabria a lithospheric doubling is seen, in connection with the subduction of the Ionian lithosphere. The asthenosphere is shallow in the Southern Tyrrhenian Sea. High velocity bodies, cutting the asthenosphere, outline the Adria-lonian subduction in the Tyrrhenian Sea and the deep-reaching lithospheric root in the Western Alps. Less deep lithospheric roots are seen in the Central Apennines. The lithosphere-asthenosphere properties delineat...

  18. The lithosphere-asthenosphere: Italy and surroundings

    Institute of Scientific and Technical Information of China (English)

    GiulianoF.Panza; AntonellaPontevivo; GiordanoChimera; RenetaRaykova; AbdelkrimAoudia

    2003-01-01

    The velocity-depth distribution of the lithosphere-asthenosphere in the Italian region and surroundings is imaged, with a lateral resolution of about 100 km, by sur-face wave velocity tomography and non-linear inversion.Maps of the Moho depth, of the thickness of the lithos-phere and of the shear-wave velocities, down to depths of 200 km and more, are constructed. A mantle wedge, iden-tified in the uppermost mantle along the Apennines and the Calabrian Arc, underlies the prmctpat recent votca-noes, and partial melting can be relevant in this part of the uppermost mantle. In Calabria, a lithospheric dou-bling is seen, in connection with the subduction of the Ionian lithosphere. The asthenosphere is shallow in the Southern Tyrrhenian Sea. High velocity bodies, cutting the asthenosphere, outline the Adria-lonian subduction in the Tyrrhenian Sea and the deep-reaching lithospheric root in the Western Alps. Less deep lithospheric roots are seen in the Central Apennines. The lithosphere-asthenos-phere properties delineate a differentiation between the northern and the southern sectors of the Adriatic Sea,likely attesting the fragmentation of Adria.

  19. Preliminary design of surrounding heliostat fields

    Energy Technology Data Exchange (ETDEWEB)

    Collado, Francisco J. [Zaragoza University, Dpto. de Ingenieria Mecanica, CPS-B, Maria de Luna 3, 50018 Zaragoza (Spain)

    2009-05-15

    Recently, the author has shown elsewhere a simplified model that allows quick evaluations of the annual overall energy collected by a surrounding heliostat field. This model is the combination of an analytical flux density function produced by a heliostat, developed by the own author, and an optimized mirror density distribution developed by University of Houston for the Solar One Project. As main conclusion of this previous work, it was recognized that such pseudo-continuous simplified model should not substitute much more accurate discrete evaluations, which manage thousands of individual heliostat coordinates. Here in this work, the difficulty of generating a preliminary discrete layout of a large number of heliostats is addressed. The main novelty is the direct definition of thousands of heliostat coordinates through basically two parameters i.e. a simplified blocking factor and an additional security distance. Such procedure, which was formerly theoretically suggested by the author, is put into practice here, showing examples and commenting their problems and advantages. Getting a previous set of thousands of heliostat coordinates would be a major first step in the complex process of designing solar power tower (SPT). (author)

  20. Association analysis of genomic loci important for grain weight control in elite common wheat varieties cultivated with variable water and fertiliser supply.

    Directory of Open Access Journals (Sweden)

    Kunpu Zhang

    Full Text Available Grain weight, an essential yield component, is under strong genetic control and markedly influenced by the environment. Here, by genome-wide association analysis with a panel of 94 elite common wheat varieties, 37 loci were found significantly associated with thousand-grain weight (TGW in one or more environments differing in water and fertiliser levels. Five loci were stably associated with TGW under all 12 environments examined. Their elite alleles had positive effects on TGW. Four, two, three, and two loci were consistently associated with TGW in the irrigated and fertilised (IF, rainfed (RF, reduced nitrogen (RN, and reduced phosphorus (RP environments. The elite alleles of the IF-specific loci enhanced TGW under well-resourced conditions, whereas those of the RF-, RN-, or RP-specific loci conferred tolerance to the TGW decrease when irrigation, nitrogen, or phosphorus were reduced. Moreover, the elite alleles of the environment-independent and -specific loci often acted additively to enhance TGW. Four additional loci were found associated with TGW in specific locations, one of which was shown to contribute to the TGW difference between two experimental sites. Further analysis of 14 associated loci revealed that nine affected both grain length and width, whereas the remaining loci influenced either grain length or width, indicating that these loci control grain weight by regulating kernel size. Finally, the elite allele of Xpsp3152 frequently co-segregated with the larger grain haplotype of TaGW2-6A, suggesting probable genetic and functional linkages between Xpsp3152 and GW2 that are important for grain weight control in cereal plants. Our study provides new knowledge on TGW control in elite common wheat lines, which may aid the improvement of wheat grain weight trait in further research.

  1. A revised nomenclature for transcribed human endogenous retroviral loci

    Directory of Open Access Journals (Sweden)

    Mayer Jens

    2011-05-01

    Full Text Available Abstract Background Endogenous retroviruses (ERVs and ERV-like sequences comprise 8% of the human genome. A hitherto unknown proportion of ERV loci are transcribed and thus contribute to the human transcriptome. A small proportion of these loci encode functional proteins. As the role of ERVs in normal and diseased biological processes is not yet established, transcribed ERV loci are of particular interest. As more transcribed ERV loci are likely to be identified in the near future, the development of a systematic nomenclature is important to ensure that all information on each locus can be easily retrieved. Results Here we present a revised nomenclature of transcribed human endogenous retroviral loci that sorts loci into groups based on Repbase classifications. Each symbol is of the format ERV + group symbol + unique number. Group symbols are based on a mixture of Repbase designations and well-supported symbols used in the literature. The presented guidelines will allow newly identified loci to be easily incorporated into the scheme. Conclusions The naming system will be employed by the HUGO Gene Nomenclature Committee for naming transcribed human ERV loci. We hope that the system will contribute to clarifying a certain aspect of a sometimes confusing nomenclature for human endogenous retroviruses. The presented system may also be employed for naming transcribed loci of human non-ERV repeat loci.

  2. Evaluation of 16 loci to examine the cross-species utility of single nucleotide polymorphism arrays.

    Science.gov (United States)

    Sechi, T; Coltman, D W; Kijas, J W

    2010-04-01

    Large collections of single nucleotide polymorphisms (SNPs) have recently been identified from a number of livestock genomes. This raises the possibility that SNP arrays might be useful for analysis in related species for which few genetic markers are currently available. To address the likely success of such an approach, the aim of this study was to examine the threshold number and position of flanking mutations which act to prevent genotype calls being produced. Sequence diversity was measured across 16 loci containing SNPs known either to work successfully between species or fail between species. In pairwise comparisons between domestic and wild sheep, sequence divergence surrounding working SNP assays was significantly lower than that surrounding non-functional assays. In addition, the location of flanking mismatches tended to be closer to the target SNP in loci that failed to generate genotype calls across species. The magnitude of sequence divergence observed for both working and non-functional assays was compared with the divergence separating domestic sheep from European Mouflon, African Barbary, goat and cattle. The results suggest that the utility of SNP arrays for analysis of shared polymorphism will be restricted to closely related pairs of species. Analysis across more divergent species will, however, be successful for other objectives, such as the identification of the ancestral state of SNPs.

  3. Are nuclear loci ideal for barcoding plants? A case study of genetic delimitation of two sister species using multiple loci and multiple intraspecific individuals

    Institute of Scientific and Technical Information of China (English)

    Qian WANG; Qiu-Shi YU; Jian-Quan LIU

    2011-01-01

    Considerable debate remains as to which DNA region should be used to barcode plants. Several different chloroplast (cp) DNA regions (rbcL, matK, and trnH-psbA) and nuclear ribosomal internal transcribed regions (ITS) have been suggested as suitable barcodes in plants. Recently, low-copy nuclear loci were also suggested to be potentially ideal barcode regions. The aim of the present study was to test the effectiveness of these proposed DNA fragments and five additional low-copy loci (CHS, DETl, COPl, PGICl, and RPS2; comprising both coding and non-coding regions) in barcoding closely related species. We examined the divergences within and between two species of Pugioniun (Brassicaceae). We failed to find any interspecific variation from three cpDNA fragments with which to discriminate the two species. However, a single base mutation in the internal transcribed spacer (ITS) could discriminate between the two species consistently. We found more variations among all individuals of the two species using each of the other five low-copy nuclear loci. However, only alleles from one locus (DET1) of the five low-copy loci related to flowering regulations was able to distinguish the sampled individuals into two species. We failed to amplify the corresponding fragments out of Brassicaceae using the designed DETl primers. We further discussed the discrimination power of different loci due to incomplete lineage sorting, gene flow, and species-specific evolution. Our results highlight the possibility of using the nuclear ITS as a core or complementary fragment to barcode recent diverged species.

  4. A taxonomy of bacterial microcompartment loci constructed by a novel scoring method.

    Directory of Open Access Journals (Sweden)

    Seth D Axen

    2014-10-01

    Full Text Available Bacterial microcompartments (BMCs are proteinaceous organelles involved in both autotrophic and heterotrophic metabolism. All BMCs share homologous shell proteins but differ in their complement of enzymes; these are typically encoded adjacent to shell protein genes in genetic loci, or operons. To enable the identification and prediction of functional (subtypes of BMCs, we developed LoClass, an algorithm that finds putative BMC loci and inventories, weights, and compares their constituent pfam domains to construct a locus similarity network and predict locus (subtypes. In addition to using LoClass to analyze sequences in the Non-redundant Protein Database, we compared predicted BMC loci found in seven candidate bacterial phyla (six from single-cell genomic studies to the LoClass taxonomy. Together, these analyses resulted in the identification of 23 different types of BMCs encoded in 30 distinct locus (subtypes found in 23 bacterial phyla. These include the two carboxysome types and a divergent set of metabolosomes, BMCs that share a common catalytic core and process distinct substrates via specific signature enzymes. Furthermore, many Candidate BMCs were found that lack one or more core metabolosome components, including one that is predicted to represent an entirely new paradigm for BMC-associated metabolism, joining the carboxysome and metabolosome. By placing these results in a phylogenetic context, we provide a framework for understanding the horizontal transfer of these loci, a starting point for studies aimed at understanding the evolution of BMCs. This comprehensive taxonomy of BMC loci, based on their constituent protein domains, foregrounds the functional diversity of BMCs and provides a reference for interpreting the role of BMC gene clusters encoded in isolate, single cell, and metagenomic data. Many loci encode ancillary functions such as transporters or genes for cofactor assembly; this expanded vocabulary of BMC-related functions

  5. Impacts of Artificial Reefs on Surrounding Ecosystems

    Science.gov (United States)

    Manoukian, Sarine

    Artificial reefs are becoming a popular biological and management component in shallow water environments characterized by soft seabed, representing both important marine habitats and tools to manage coastal fisheries and resources. An artificial reef in the marine environment acts as an open system with exchange of material and energy, altering the physical and biological characteristics of the surrounding area. Reef stability will depend on the balance of scour, settlement, and burial resulting from ocean conditions over time. Because of the unstable nature of sediments, they require a detailed and systematic investigation. Acoustic systems like high-frequency multibeam sonar are efficient tools in monitoring the environmental evolution around artificial reefs, whereas water turbidity can limit visual dive and ROV inspections. A high-frequency multibeam echo sounder offers the potential of detecting fine-scale distribution of reef units, providing an unprecedented level of resolution, coverage, and spatial definition. How do artificial reefs change over time in relation to the coastal processes? How accurately does multibeam technology map different typologies of artificial modules of known size and shape? How do artificial reefs affect fish school behavior? What are the limitations of multibeam technology for investigating fish school distribution as well as spatial and temporal changes? This study addresses the above questions and presents results of a new approach for artificial reef seafloor mapping over time, based upon an integrated analysis of multibeam swath bathymetry data and geoscientific information (backscatter data analysis, SCUBA observations, physical oceanographic data, and previous findings on the geology and sedimentation processes, integrated with unpublished data) from Senigallia artificial reef, northwestern Adriatic Sea (Italy) and St. Petersburg Beach Reef, west-central Florida continental shelf. A new approach for observation of fish

  6. Fine mapping of quantitative trait loci using linkage disequilibria with closely linked marker loci

    NARCIS (Netherlands)

    Meuwissen, T.H.E.; Goddard, M.E.

    2000-01-01

    A multimarker linkage disequilibrium mapping method was developed for the fine mapping of quantitative trait loci (QTL) using a dense marker map. The method compares the expected covariances between haplotype effects given a postulated QTL position to the covariances that are found in the data. The

  7. Novel genetic loci associated with hippocampal volume

    Science.gov (United States)

    Hibar, Derrek P.; Adams, Hieab H. H.; Jahanshad, Neda; Chauhan, Ganesh; Stein, Jason L.; Hofer, Edith; Renteria, Miguel E.; Bis, Joshua C.; Arias-Vasquez, Alejandro; Ikram, M. Kamran; Desrivières, Sylvane; Vernooij, Meike W.; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S.; Armstrong, Nicola J.; Athanasiu, Lavinia; Axelsson, Tomas; Beecham, Ashley H.; Beiser, Alexa; Bernard, Manon; Blanton, Susan H.; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brickman, Adam M.; Carmichael, Owen; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Chouraki, Vincent; Cuellar-Partida, Gabriel; Crivello, Fabrice; Den Braber, Anouk; Doan, Nhat Trung; Ehrlich, Stefan; Giddaluru, Sudheer; Goldman, Aaron L.; Gottesman, Rebecca F.; Grimm, Oliver; Griswold, Michael E.; Guadalupe, Tulio; Gutman, Boris A.; Hass, Johanna; Haukvik, Unn K.; Hoehn, David; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Jørgensen, Kjetil N.; Karbalai, Nazanin; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Liewald, David C. M.; Lopez, Lorna M.; Luciano, Michelle; Macare, Christine; Marquand, Andre F.; Matarin, Mar; Mather, Karen A.; Mattheisen, Manuel; McKay, David R.; Milaneschi, Yuri; Muñoz Maniega, Susana; Nho, Kwangsik; Nugent, Allison C.; Nyquist, Paul; Loohuis, Loes M. Olde; Oosterlaan, Jaap; Papmeyer, Martina; Pirpamer, Lukas; Pütz, Benno; Ramasamy, Adaikalavan; Richards, Jennifer S.; Risacher, Shannon L.; Roiz-Santiañez, Roberto; Rommelse, Nanda; Ropele, Stefan; Rose, Emma J.; Royle, Natalie A.; Rundek, Tatjana; Sämann, Philipp G.; Saremi, Arvin; Satizabal, Claudia L.; Schmaal, Lianne; Schork, Andrew J.; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V.; Sprooten, Emma; Strike, Lachlan T.; Teumer, Alexander; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Trompet, Stella; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Lee, Sven J.; Van der Meer, Dennis; Van Donkelaar, Marjolein M. J.; Van Eijk, Kristel R.; Van Erp, Theo G. M.; Van Rooij, Daan; Walton, Esther; Westlye, Lars T.; Whelan, Christopher D.; Windham, Beverly G.; Winkler, Anderson M.; Wittfeld, Katharina; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Yanek, Lisa R.; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P.; Agartz, Ingrid; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A.; Arepalli, Sampath; Assareh, Amelia A.; Barral, Sandra; Bastin, Mark E.; Becker, Diane M.; Becker, James T.; Bennett, David A.; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I.; Brodaty, Henry; Brouwer, Rachel M.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Bulayeva, Kazima B.; Cahn, Wiepke; Calhoun, Vince D.; Cannon, Dara M.; Cavalleri, Gianpiero L.; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R.; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E.; Czisch, Michael; Dale, Anders M.; Davies, Gareth E.; De Craen, Anton J. M.; De Geus, Eco J. C.; De Jager, Philip L.; De Zubicaray, Greig I.; Deary, Ian J.; Debette, Stéphanie; DeCarli, Charles; Delanty, Norman; Depondt, Chantal; DeStefano, Anita; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C.; Duggirala, Ravi; Dyer, Thomas D.; Enzinger, Christian; Erk, Susanne; Espeseth, Thomas; Fedko, Iryna O.; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E.; Fleischman, Debra A.; Ford, Ian; Fornage, Myriam; Foroud, Tatiana M.; Fox, Peter T.; Francks, Clyde; Fukunaga, Masaki; Gibbs, J. Raphael; Glahn, David C.; Gollub, Randy L.; Göring, Harald H. H.; Green, Robert C.; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Håberg, Asta K.; Hansell, Narelle K.; Hardy, John; Hartman, Catharina A.; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G.; Heslenfeld, Dirk J.; Ho, Beng-Choon; Hoekstra, Pieter J.; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Huentelman, Matthew; Pol, Hilleke E. Hulshoff; Ikeda, Masashi; Jack Jr, Clifford R.; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G.; Jukema, J. Wouter; Kahn, René S.; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L.; Lopez, Oscar L.; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S.; McDonald, Colm; McIntosh, Andrew M.; McMahon, Francis J.; McMahon, Katie L.; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W.; Morris, Derek W.; Mosley, Thomas H.; Mühleisen, Thomas W.; Müller-Myhsok, Bertram; Nalls, Michael A.; Nauck, Matthias; Nichols, Thomas E.; Niessen, Wiro J.; Nöthen, Markus M.; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L.; Ophoff, Roel A.; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W. J. H.; Pike, G. Bruce; Potkin, Steven G.; Psaty, Bruce M.; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L.; Romanczuk-Seiferth, Nina; Rotter, Jerome I.; Ryten, Mina; Sacco, Ralph L.; Sachdev, Perminder S.; Saykin, Andrew J.; Schmidt, Reinhold; Schmidt, Helena; Schofield, Peter R.; Sigursson, Sigurdur; Simmons, Andrew; Singleton, Andrew; Sisodiya, Sanjay M.; Smith, Colin; Smoller, Jordan W.; Soininen, Hilkka; Steen, Vidar M.; Stott, David J.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Tsolaki, Magda; Tzourio, Christophe; Uitterlinden, Andre G.; Hernández, Maria C. Valdés; Van der Brug, Marcel; van der Lugt, Aad; van der Wee, Nic J. A.; Van Haren, Neeltje E. M.; van 't Ent, Dennis; Van Tol, Marie-Jose; Vardarajan, Badri N.; Vellas, Bruno; Veltman, Dick J.; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M.; Wassink, Thomas H.; Weale, Michael E.; Weinberger, Daniel R.; Weiner, Michael W.; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y.; Wright, Clinton B.; Zielke, Ronald H.; Zonderman, Alan B.; Martin, Nicholas G.; Van Duijn, Cornelia M.; Wright, Margaret J.; Longstreth, W. T.; Schumann, Gunter; Grabe, Hans J.; Franke, Barbara; Launer, Lenore J.; Medland, Sarah E.; Seshadri, Sudha; Thompson, Paul M.; Ikram, M. Arfan

    2017-01-01

    The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg=−0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness. PMID:28098162

  8. Perpetual points and periodic perpetual loci in maps

    Science.gov (United States)

    Dudkowski, Dawid; Prasad, Awadhesh; Kapitaniak, Tomasz

    2016-10-01

    We introduce the concepts of perpetual points and periodic perpetual loci in discrete-time systems (maps). The occurrence and analysis of these points/loci are shown and basic examples are considered. We discuss the potential usage and properties of the introduced concepts. The comparison of perpetual points and loci in discrete-time and continuous-time systems is presented. The discussed methods can be widely applied in other dynamical systems.

  9. Paths to selection on life history loci in different natural environments across the native range of Arabidopsis thaliana

    NARCIS (Netherlands)

    Fournier-Level, A.; Wilczek, A.M.; Cooper, M.D.; Roe, J.L.; Anderson, J.; Eaton, D.; Moyers, B.T.; Petipas, R.H.; Schaeffer, R.N.; Pieper, B.; Reymond, M.; Koornneef, M.; Welch, S.M.; Remington, D.L.; Schmitt, J.

    2013-01-01

    Selection on quantitative trait loci (QTL) may vary among natural environments due to differences in the genetic architecture of traits, environment-specific allelic effects or changes in the direction and magnitude of selection on specific traits. To dissect the environmental differences in selecti

  10. Paths to selection on life history loci in different natural environments across the native range of Arabidopsis thaliana

    NARCIS (Netherlands)

    Fournier-Level, A.; Wilczek, A.M.; Cooper, M.D.; Roe, J.L.; Anderson, J.; Eaton, D.; Moyers, B.T.; Petipas, R.H.; Schaeffer, R.N.; Pieper, B.; Reymond, M.; Koornneef, M.; Welch, S.M.; Remington, D.L.; Schmitt, J.

    2013-01-01

    Selection on quantitative trait loci (QTL) may vary among natural environments due to differences in the genetic architecture of traits, environment-specific allelic effects or changes in the direction and magnitude of selection on specific traits. To dissect the environmental differences in selecti

  11. Multiple loci are associated with white blood cell phenotypes.

    Directory of Open Access Journals (Sweden)

    Michael A Nalls

    2011-06-01

    Full Text Available White blood cell (WBC count is a common clinical measure from complete blood count assays, and it varies widely among healthy individuals. Total WBC count and its constituent subtypes have been shown to be moderately heritable, with the heritability estimates varying across cell types. We studied 19,509 subjects from seven cohorts in a discovery analysis, and 11,823 subjects from ten cohorts for replication analyses, to determine genetic factors influencing variability within the normal hematological range for total WBC count and five WBC subtype measures. Cohort specific data was supplied by the CHARGE, HeamGen, and INGI consortia, as well as independent collaborative studies. We identified and replicated ten associations with total WBC count and five WBC subtypes at seven different genomic loci (total WBC count-6p21 in the HLA region, 17q21 near ORMDL3, and CSF3; neutrophil count-17q21; basophil count- 3p21 near RPN1 and C3orf27; lymphocyte count-6p21, 19p13 at EPS15L1; monocyte count-2q31 at ITGA4, 3q21, 8q24 an intergenic region, 9q31 near EDG2, including three previously reported associations and seven novel associations. To investigate functional relationships among variants contributing to variability in the six WBC traits, we utilized gene expression- and pathways-based analyses. We implemented gene-clustering algorithms to evaluate functional connectivity among implicated loci and showed functional relationships across cell types. Gene expression data from whole blood was utilized to show that significant biological consequences can be extracted from our genome-wide analyses, with effect estimates for significant loci from the meta-analyses being highly corellated with the proximal gene expression. In addition, collaborative efforts between the groups contributing to this study and related studies conducted by the COGENT and RIKEN groups allowed for the examination of effect homogeneity for genome-wide significant associations across

  12. The mating type-like loci of Candida glabrata.

    Science.gov (United States)

    Yáñez-Carrillo, Patricia; Robledo-Márquez, Karina A; Ramírez-Zavaleta, Candy Y; De Las Peñas, Alejandro; Castaño, Irene

    2014-01-01

    Candida glabrata, a haploid and opportunistic fungal pathogen that has not known sexual cycle, has conserved the majority of the genes required for mating and cell type identity. The C. glabrata genome contains three mating-type-like loci called MTL1, MTL2 and MTL3. The three loci encode putative transcription factors, a1, α1 and α2 that regulate cell type identity and sexual reproduction in other fungi like the closely related Saccharomyces cerevisiae. MTL1 can contain either a or α information. MTL2, which contains a information and MTL3 with α information, are relatively close to two telomeres. MTL1 and MTL2 are transcriptionally active, while MTL3 is subject to an incomplete silencing nucleated at the telomere that depends on the silencing proteins Sir2, Sir3, Sir4, yKu70/80, Rif1, Rap1 and Sum1. C. glabrata does not seem to maintain cell type identity, as cell type-specific genes are expressed regardless of the type (or even absence) of mating information. These data highlight important differences in the control of mating and cell type identity between the non-pathogenic yeast S. cerevisiae and C. glabrata, which might explain the absence of a sexual cycle in C. glabrata. The fact that C. glabrata has conserved the vast majority of the genes involved in mating might suggest that some of these genes perhaps have been rewired to control other processes important for the survival inside the host as a commensal or as a human pathogen. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012). Copyright © 2013 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

  13. lociNGS: a lightweight alternative for assessing suitability of next-generation loci for evolutionary analysis.

    Directory of Open Access Journals (Sweden)

    Sarah M Hird

    Full Text Available Genomic enrichment methods and next-generation sequencing produce uneven coverage for the portions of the genome (the loci they target; this information is essential for ascertaining the suitability of each locus for further analysis. lociNGS is a user-friendly accessory program that takes multi-FASTA formatted loci, next-generation sequence alignments and demographic data as input and collates, displays and outputs information about the data. Summary information includes the parameters coverage per locus, coverage per individual and number of polymorphic sites, among others. The program can output the raw sequences used to call loci from next-generation sequencing data. lociNGS also reformats subsets of loci in three commonly used formats for multi-locus phylogeographic and population genetics analyses - NEXUS, IMa2 and Migrate. lociNGS is available at https://github.com/SHird/lociNGS and is dependent on installation of MongoDB (freely available at http://www.mongodb.org/downloads. lociNGS is written in Python and is supported on MacOSX and Unix; it is distributed under a GNU General Public License.

  14. Impact of surrounding tissue on conductance measurement of coronary and peripheral lumen area.

    Science.gov (United States)

    Won Choi, Hyo; Jansen, Benjamin; Zhang, Zhen-Du; Kassab, Ghassan S

    2012-11-07

    Parallel conductance (electric current flow through surrounding tissue) is an important determinant of accurate measurements of arterial lumen diameter, using the conductance method. The present study is focused on the role of non-uniform geometrical/electrical configurations of surrounding tissue, which are a primary source of electric current leakage. Computational models were constructed to simulate the conductance catheter measurement with two different excitation electrodes spacings (i.e. 12 and 20 mm for coronary and peripheral sizing, respectively) for different vessel-tissue configurations: (i) blood vessel fully embedded in muscle tissue, (ii) blood vessel superficially embedded in muscle tissue, and (iii) blood vessel superficially embedded in muscle tissue with fat covering half of the arterial vessel (anterior portion). The simulations suggest that the parallel conductance and accuracy of measurement is dependent on the inhomogeneous/anisotropic configuration of surrounding tissue, including the asymmetric dimension and anisotropy in electrical conductivity of surrounding tissue. Specifically, the measurement was shown to be accurate as long as the vessel was superficial, regardless of the considerable total surrounding tissue dimension for coronary or peripheral arteries. Moreover, it was shown that the unfavourable impact of parallel conductance on the accuracy of conductance catheter measurement is decreased by the combination of a lower transverse electrical conductivity of surrounding muscle tissue, a smaller electrode spacing and a larger lumen diameter. The present findings confirm that the conductance catheter technique provides an accurate platform for sizing of clinically relevant (i.e. superficial and diseased) arteries.

  15. Activation of int-1 and int-2 loci in GRf mammary tumors.

    Science.gov (United States)

    Gray, D A; Jackson, D P; Percy, D H; Morris, V L

    1986-10-30

    The Mtv-2 locus is known to be associated with a high mammary tumor incidence (97%) and early development of mammary tumors (3-13 months) in GR mice. However, it was not previously known whether the provirus which resides at the Mtv-2 locus is tumorigenic in and of itself or whether reintegration of proviruses generated from Mtv-2 is required for tumorigenesis. Foster-nursing GR mice on C57/BL mice eliminates the milk-borne source of GR virus, and allows the study of Mtv-2 derived proviruses alone. Using this approach, we have tested predictions which follow from the "positional" versus "reintegrational" models of tumorigenesis. Specifically, we have examined tumors from primary foster-nursed (GRf) mice to determine if MMTV proviruses derived from Mtv-2 were scattered randomly throughout the genome or were clustered in the vicinity of the int-1 and int-2 loci, which are thought to be associated with mammary tumorigenesis. It was found that the majority of spontaneous GRf mammary tumors that were tested have MMTV proviral integrations in either or both of the int-1 and int-2 loci and have transcription of either or both of the int loci. Tumors induced by Mtv-2, therefore, appear to have arisen via a mechanism similar to the activation of the int loci by exogenous (milk-borne) MMTV proviruses.

  16. Characterization of three loci for homologous gene targeting and transgene expression.

    Science.gov (United States)

    Eyquem, Justin; Poirot, Laurent; Galetto, Roman; Scharenberg, Andrew M; Smith, Julianne

    2013-08-01

    Integrative gene transfer is widely used for bioproduction, drug screening, and therapeutic applications but usual viral methods lead to random and multicopy insertions, contribute to unstable transgene expression and can disturb endogenous gene expression. Homologous targeting of an expression cassette using rare-cutting endonucleases is a potential solution; however the number of studied loci remains limited. Furthermore, the behavior and performance of various types of gene cassettes following gene targeting is poorly defined. Here we have evaluated three loci for gene targeting, including one locus compatible with the proposed Safe Harbor criteria for human translational applications. Using optimized conditions for homologous gene targeting, reporter genes under the control of different promoters were efficiently inserted at each locus in both sense and antisense orientations. Sustainable expression was achieved at all three loci without detectable disturbance of flanking gene expression. However, the promoter, the integration locus and the cassette orientation have a strong impact on transgene expression. Finally, single targeted integrations exhibited greatly improved transgene expression stability versus multicopy or random integration. Taken together, our data suggest a potential set of loci for site-specific transgene integration, suitable for a variety of biotechnological applications.

  17. Alzheimer disease susceptibility loci: evidence for a protein network under natural selection.

    Science.gov (United States)

    Raj, Towfique; Shulman, Joshua M; Keenan, Brendan T; Chibnik, Lori B; Evans, Denis A; Bennett, David A; Stranger, Barbara E; De Jager, Philip L

    2012-04-06

    Recent genome-wide association studies have identified a number of susceptibility loci for Alzheimer disease (AD). To understand the functional consequences and potential interactions of the associated loci, we explored large-scale data sets interrogating the human genome for evidence of positive natural selection. Our findings provide significant evidence for signatures of recent positive selection acting on several haplotypes carrying AD susceptibility alleles; interestingly, the genes found in these selected haplotypes can be assembled, independently, into a molecular complex via a protein-protein interaction (PPI) network approach. These results suggest a possible coevolution of genes encoding physically-interacting proteins that underlie AD susceptibility and are coexpressed in different tissues. In particular, PICALM, BIN1, CD2AP, and EPHA1 are interconnected through multiple interacting proteins and appear to have coordinated evidence of selection in the same human population, suggesting that they may be involved in the execution of a shared molecular function. This observation may be AD-specific, as the 12 loci associated with Parkinson disease do not demonstrate excess evidence of natural selection. The context for selection is probably unrelated to AD itself; it is likely that these genes interact in another context, such as in immune cells, where we observe cis-regulatory effects at several of the selected AD loci. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  18. Mapping Quantitative Trait Loci in Yeast.

    Science.gov (United States)

    Liti, Gianni; Warringer, Jonas; Blomberg, Anders

    2017-08-01

    Natural Saccharomyces strains isolated from the wild differ quantitatively in molecular and organismal phenotypes. Quantitative trait loci (QTL) mapping is a powerful approach for identifying sequence variants that alter gene function. In yeast, QTL mapping has been used in designed crosses to map functional polymorphisms. This approach, outlined here, is often the first step in understanding the molecular basis of quantitative traits. New large-scale sequencing surveys have the potential to directly associate genotypes with organismal phenotypes, providing a broader catalog of causative genetic variants. Additional analysis of intermediate phenotypes (e.g., RNA, protein, or metabolite levels) can produce a multilayered and integrated view of individual variation, producing a high-resolution view of the genotype-phenotype map. © 2017 Cold Spring Harbor Laboratory Press.

  19. Issues surrounding health claims for barley.

    Science.gov (United States)

    Ames, Nancy P; Rhymer, Camille R

    2008-06-01

    Government-approved health claims support dietary intervention as a safe and practical approach to improving consumer health and provide industry with regulatory guidelines for food product labels. Claims already allowed in the United States, United Kingdom, Sweden, and The Netherlands for reducing cholesterol through consumption of oat or barley soluble fiber provide a basis for review, but each country may have different criteria for assessing clinical evidence for a physiological effect. For example, the FDA-approved barley health claim was based on a petition that included 39 animal model studies and 11 human clinical trials. Since then, more studies have been published, but with few exceptions, clinical data continue to demonstrate that the consumption of barley products is effective for lowering total and LDL cholesterol. More research is needed to fully understand the mechanism of cholesterol reduction and the role of beta-glucan molecular weight, viscosity, and solubility. In an assessment of the physiological efficacy of a dietary intervention, consideration should also be given to the potential impact of physical and thermal food-processing treatments and genotypic variation in the barley source. New barley cultivars have been generated specifically for food use, possessing increased beta-glucan, desirable starch composition profiles, and improved milling/processing traits. These advances in barley production, coupled with the establishment of a government-regulated health claim for barley beta-glucan, will stimulate new processing opportunities for barley foods and provide consumers with reliable, healthy food choices.

  20. Discovery and refinement of loci associated with lipid levels

    NARCIS (Netherlands)

    Willer, Cristen J; Schmidt, Ellen M; Sengupta, Sebanti; Peloso, Gina M; Gustafsson, Stefan; Kanoni, Stavroula; Ganna, Andrea; Chen, Jin; Buchkovich, Martin L; Mora, Samia; Beckmann, Jacques S; Bragg-Gresham, Jennifer L; Chang, Hsing-Yi; Demirkan, Ayşe; Den Hertog, Heleen M; Do, Ron; Donnelly, Louise A; Ehret, Georg B; Esko, Tõnu; Feitosa, Mary F; Ferreira, Teresa; Fischer, Krista; Fontanillas, Pierre; Fraser, Ross M; Freitag, Daniel F; Gurdasani, Deepti; Heikkilä, Kauko; Hyppönen, Elina; Isaacs, Aaron; Jackson, Anne U; Johansson, Asa; Johnson, Toby; Kaakinen, Marika; Kettunen, Johannes; Kleber, Marcus E; Li, Xiaohui; Luan, Jian'an; Lyytikäinen, Leo-Pekka; Magnusson, Patrik K E; Mangino, Massimo; Mihailov, Evelin; Montasser, May E; Müller-Nurasyid, Martina; Nolte, Ilja M; O'Connell, Jeffrey R; Palmer, Cameron D; Perola, Markus; Petersen, Ann-Kristin; Sanna, Serena; Saxena, Richa; Service, Susan K; Shah, Sonia; Shungin, Dmitry; Sidore, Carlo; Song, Ci; Strawbridge, Rona J; Surakka, Ida; Tanaka, Toshiko; Teslovich, Tanya M; Thorleifsson, Gudmar; Van den Herik, Evita G; Voight, Benjamin F; Volcik, Kelly A; Waite, Lindsay L; Wong, Andrew; Wu, Ying; Zhang, Weihua; Absher, Devin; Asiki, Gershim; Barroso, Inês; Been, Latonya F; Bolton, Jennifer L; Bonnycastle, Lori L; Brambilla, Paolo; Burnett, Mary S; Cesana, Giancarlo; Dimitriou, Maria; Doney, Alex S F; Döring, Angela; Elliott, Paul; Epstein, Stephen E; Eyjolfsson, Gudmundur Ingi; Gigante, Bruna; Goodarzi, Mark O; Grallert, Harald; Gravito, Martha L; Groves, Christopher J; Hallmans, Göran; Hartikainen, Anna-Liisa; Hayward, Caroline; Hernandez, Dena; Hicks, Andrew A; Holm, Hilma; Hung, Yi-Jen; Illig, Thomas; Jones, Michelle R; Kaleebu, Pontiano; Kastelein, John J P; Khaw, Kay-Tee; Kim, Eric; Klopp, Norman; Komulainen, Pirjo; Kumari, Meena; Langenberg, Claudia; Lehtimäki, Terho; Lin, Shih-Yi; Lindström, Jaana; Loos, Ruth J F; Mach, François; McArdle, Wendy L; Meisinger, Christa; Mitchell, Braxton D; Müller, Gabrielle; Nagaraja, Ramaiah; Narisu, Narisu; Nieminen, Tuomo V M; Nsubuga, Rebecca N; Olafsson, Isleifur; Ong, Ken K; Palotie, Aarno; Papamarkou, Theodore; Pomilla, Cristina; Pouta, Anneli; Rader, Daniel J; Reilly, Muredach P; Ridker, Paul M; Rivadeneira, Fernando; Rudan, Igor; Ruokonen, Aimo; Samani, Nilesh; Scharnagl, Hubert; Seeley, Janet; Silander, Kaisa; Stancáková, Alena; Stirrups, Kathleen; Swift, Amy J; Tiret, Laurence; Uitterlinden, Andre G; van Pelt, L Joost; Vedantam, Sailaja; Wainwright, Nicholas; Wijmenga, Cisca; Wild, Sarah H; Willemsen, Gonneke; Wilsgaard, Tom; Wilson, James F; Young, Elizabeth H; Zhao, Jing Hua; Adair, Linda S; Arveiler, Dominique; Assimes, Themistocles L; Bandinelli, Stefania; Bennett, Franklyn; Bochud, Murielle; Boehm, Bernhard O; Boomsma, Dorret I; Borecki, Ingrid B; Bornstein, Stefan R; Bovet, Pascal; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chambers, John C; Chen, Yii-Der Ida; Collins, Francis S; Cooper, Richard S; Danesh, John; Dedoussis, George; de Faire, Ulf; Feranil, Alan B; Ferrières, Jean; Ferrucci, Luigi; Freimer, Nelson B; Gieger, Christian; Groop, Leif C; Gudnason, Vilmundur; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B; Hingorani, Aroon; Hirschhorn, Joel N; Hofman, Albert; Hovingh, G Kees; Hsiung, Chao Agnes; Humphries, Steve E; Hunt, Steven C; Hveem, Kristian; Iribarren, Carlos; Järvelin, Marjo-Riitta; Jula, Antti; Kähönen, Mika; Kaprio, Jaakko; Kesäniemi, Antero; Kivimaki, Mika; Kooner, Jaspal S; Koudstaal, Peter J; Krauss, Ronald M; Kuh, Diana; Kuusisto, Johanna; Kyvik, Kirsten O; Laakso, Markku; Lakka, Timo A; Lind, Lars; Lindgren, Cecilia M; Martin, Nicholas G; März, Winfried; McCarthy, Mark I; McKenzie, Colin A; Meneton, Pierre; Metspalu, Andres; Moilanen, Leena; Morris, Andrew D; Munroe, Patricia B; Njølstad, Inger; Pedersen, Nancy L; Power, Chris; Pramstaller, Peter P; Price, Jackie F; Psaty, Bruce M; Quertermous, Thomas; Rauramaa, Rainer; Saleheen, Danish; Salomaa, Veikko; Sanghera, Dharambir K; Saramies, Jouko; Schwarz, Peter E H; Sheu, Wayne H-H; Shuldiner, Alan R; Siegbahn, Agneta; Spector, Tim D; Stefansson, Kari; Strachan, David P; Tayo, Bamidele O; Tremoli, Elena; Tuomilehto, Jaakko; Uusitupa, Matti; van Duijn, Cornelia M; Vollenweider, Peter; Wallentin, Lars; Wareham, Nicholas J; Whitfield, John B; Wolffenbuttel, Bruce H R; Ordovas, Jose M; Boerwinkle, Eric; Palmer, Colin N A; Thorsteinsdottir, Unnur; Chasman, Daniel I; Rotter, Jerome I; Franks, Paul W; Ripatti, Samuli; Cupples, L Adrienne; Sandhu, Manjinder S; Rich, Stephen S; Boehnke, Michael; Deloukas, Panos; Kathiresan, Sekar; Mohlke, Karen L; Ingelsson, Erik; Abecasis, Gonçalo R

    2013-01-01

    Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individual

  1. Subanalytic Bundles and Tubular Neighbourhoods of Zero-Loci

    Indian Academy of Sciences (India)

    Vishwambhar Pati

    2003-08-01

    We introduce the natural and fairly general notion of a subanalytic bundle (with a finite dimensional vector space of sections) on a subanalytic subset of a real analytic manifold , and prove that when is compact, there is a Baire subset of sections in whose zero-loci in have tubular neighbourhoods, homeomorphic to the restriction of the given bundle to these zero-loci.

  2. Study design for the identification of loci affecting human longevity

    NARCIS (Netherlands)

    Heijmans, B.T.; Kluft, C.; Bots, M.L.; Lagaay, A.M.; Brand, A.; Grobbee, D.E.; Knook, D.L.; Slagboom, P.E.

    1996-01-01

    The genetic component of human longevity is estimated at 30%. Which genes are involved in determining human longevity, however, is largely unknown. Genes that may affect human survival are susceptibility loci for major age related pathologies. Many studies are being performed to identify such loci f

  3. Discovery and refinement of loci associated with lipid levels

    NARCIS (Netherlands)

    Willer, Cristen J; Schmidt, Ellen M; Sengupta, Sebanti; Peloso, Gina M; Gustafsson, Stefan; Kanoni, Stavroula; Ganna, Andrea; Chen, Jin; Buchkovich, Martin L; Mora, Samia; Beckmann, Jacques S; Bragg-Gresham, Jennifer L; Chang, Hsing-Yi; Demirkan, Ayşe; Den Hertog, Heleen M; Do, Ron; Donnelly, Louise A; Ehret, Georg B; Esko, Tõnu; Feitosa, Mary F; Ferreira, Teresa; Fischer, Krista; Fontanillas, Pierre; Fraser, Ross M; Freitag, Daniel F; Gurdasani, Deepti; Heikkilä, Kauko; Hyppönen, Elina; Isaacs, Aaron; Jackson, Anne U; Johansson, Asa; Johnson, Toby; Kaakinen, Marika; Kettunen, Johannes; Kleber, Marcus E; Li, Xiaohui; Luan, Jian'an; Lyytikäinen, Leo-Pekka; Magnusson, Patrik K E; Mangino, Massimo; Mihailov, Evelin; Montasser, May E; Müller-Nurasyid, Martina; Nolte, Ilja M; O'Connell, Jeffrey R; Palmer, Cameron D; Perola, Markus; Petersen, Ann-Kristin; Sanna, Serena; Saxena, Richa; Service, Susan K; Shah, Sonia; Shungin, Dmitry; Sidore, Carlo; Song, Ci; Strawbridge, Rona J; Surakka, Ida; Tanaka, Toshiko; Teslovich, Tanya M; Thorleifsson, Gudmar; Van den Herik, Evita G; Voight, Benjamin F; Volcik, Kelly A; Waite, Lindsay L; Wong, Andrew; Wu, Ying; Zhang, Weihua; Absher, Devin; Asiki, Gershim; Barroso, Inês; Been, Latonya F; Bolton, Jennifer L; Bonnycastle, Lori L; Brambilla, Paolo; Burnett, Mary S; Cesana, Giancarlo; Dimitriou, Maria; Doney, Alex S F; Döring, Angela; Elliott, Paul; Epstein, Stephen E; Eyjolfsson, Gudmundur Ingi; Gigante, Bruna; Goodarzi, Mark O; Grallert, Harald; Gravito, Martha L; Groves, Christopher J; Hallmans, Göran; Hartikainen, Anna-Liisa; Hayward, Caroline; Hernandez, Dena; Hicks, Andrew A; Holm, Hilma; Hung, Yi-Jen; Illig, Thomas; Jones, Michelle R; Kaleebu, Pontiano; Kastelein, John J P; Khaw, Kay-Tee; Kim, Eric; Klopp, Norman; Komulainen, Pirjo; Kumari, Meena; Langenberg, Claudia; Lehtimäki, Terho; Lin, Shih-Yi; Lindström, Jaana; Loos, Ruth J F; Mach, François; McArdle, Wendy L; Meisinger, Christa; Mitchell, Braxton D; Müller, Gabrielle; Nagaraja, Ramaiah; Narisu, Narisu; Nieminen, Tuomo V M; Nsubuga, Rebecca N; Olafsson, Isleifur; Ong, Ken K; Palotie, Aarno; Papamarkou, Theodore; Pomilla, Cristina; Pouta, Anneli; Rader, Daniel J; Reilly, Muredach P; Ridker, Paul M; Rivadeneira, Fernando; Rudan, Igor; Ruokonen, Aimo; Samani, Nilesh; Scharnagl, Hubert; Seeley, Janet; Silander, Kaisa; Stancáková, Alena; Stirrups, Kathleen; Swift, Amy J; Tiret, Laurence; Uitterlinden, Andre G; van Pelt, L Joost; Vedantam, Sailaja; Wainwright, Nicholas; Wijmenga, Cisca; Wild, Sarah H; Willemsen, Gonneke; Wilsgaard, Tom; Wilson, James F; Young, Elizabeth H; Zhao, Jing Hua; Adair, Linda S; Arveiler, Dominique; Assimes, Themistocles L; Bandinelli, Stefania; Bennett, Franklyn; Bochud, Murielle; Boehm, Bernhard O; Boomsma, Dorret I; Borecki, Ingrid B; Bornstein, Stefan R; Bovet, Pascal; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chambers, John C; Chen, Yii-Der Ida; Collins, Francis S; Cooper, Richard S; Danesh, John; Dedoussis, George; de Faire, Ulf; Feranil, Alan B; Ferrières, Jean; Ferrucci, Luigi; Freimer, Nelson B; Gieger, Christian; Groop, Leif C; Gudnason, Vilmundur; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B; Hingorani, Aroon; Hirschhorn, Joel N; Hofman, Albert; Hovingh, G Kees; Hsiung, Chao Agnes; Humphries, Steve E; Hunt, Steven C; Hveem, Kristian; Iribarren, Carlos; Järvelin, Marjo-Riitta; Jula, Antti; Kähönen, Mika; Kaprio, Jaakko; Kesäniemi, Antero; Kivimaki, Mika; Kooner, Jaspal S; Koudstaal, Peter J; Krauss, Ronald M; Kuh, Diana; Kuusisto, Johanna; Kyvik, Kirsten O; Laakso, Markku; Lakka, Timo A; Lind, Lars; Lindgren, Cecilia M; Martin, Nicholas G; März, Winfried; McCarthy, Mark I; McKenzie, Colin A; Meneton, Pierre; Metspalu, Andres; Moilanen, Leena; Morris, Andrew D; Munroe, Patricia B; Njølstad, Inger; Pedersen, Nancy L; Power, Chris; Pramstaller, Peter P; Price, Jackie F; Psaty, Bruce M; Quertermous, Thomas; Rauramaa, Rainer; Saleheen, Danish; Salomaa, Veikko; Sanghera, Dharambir K; Saramies, Jouko; Schwarz, Peter E H; Sheu, Wayne H-H; Shuldiner, Alan R; Siegbahn, Agneta; Spector, Tim D; Stefansson, Kari; Strachan, David P; Tayo, Bamidele O; Tremoli, Elena; Tuomilehto, Jaakko; Uusitupa, Matti; van Duijn, Cornelia M; Vollenweider, Peter; Wallentin, Lars; Wareham, Nicholas J; Whitfield, John B; Wolffenbuttel, Bruce H R; Ordovas, Jose M; Boerwinkle, Eric; Palmer, Colin N A; Thorsteinsdottir, Unnur; Chasman, Daniel I; Rotter, Jerome I; Franks, Paul W; Ripatti, Samuli; Cupples, L Adrienne; Sandhu, Manjinder S; Rich, Stephen S; Boehnke, Michael; Deloukas, Panos; Kathiresan, Sekar; Mohlke, Karen L; Ingelsson, Erik; Abecasis, Gonçalo R

    2013-01-01

    Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577

  4. Discovery and refinement of loci associated with lipid levels

    DEFF Research Database (Denmark)

    Willer, C. J.; Schmidt, E. M.; Sengupta, S.

    2013-01-01

    Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individ...

  5. Dynamics of CRISPR Loci in Microevolutionary Process of Yersinia pestis Strains

    Science.gov (United States)

    Barros, Maria Paloma S.; França, Camila T.; Lins, Rosanny Holanda F. B.; Santos, Milena Danda V.; Silva, Ednaldo J.; Oliveira, Maria Betânia M.; Silveira-Filho, Vladimir M.; Rezende, Antônio M.; Balbino, Valdir Q.; Leal-Balbino, Tereza Cristina

    2014-01-01

    The potential use of CRISPR loci genotyping to elucidate population dynamics and microevolution of 146 Yersinia pestis strains from different biovars and locations was investigated in this work. The majority of strains from the Orientalis biovar presented specific spacer arrays, allowing for the establishment of a CRISPR signature for their respective isolates. Twenty-one new spacers were found in the Y. pestis strains from plague foci in Brazil. Ninety-three (64%) strains were grouped in the G1 genotype, whereas the others were distributed in 35 genotypes. This study allowed observing a microevolutionary process in a group of Y. pestis isolated from Brazil. We also identified specific genotypes of Y. pestis that were important for the establishment of the bacteria in plague foci in Brazil. The data have provided supporting evidence for the diversity and dynamics of CRISPR loci present in the genome of Y. pestis strains from plague foci in Brazil. PMID:25265542

  6. Development of eighteen microsatellite loci in walleye (Sander vitreus)

    Science.gov (United States)

    Coykendall, Dolly K.; Morrison, Cheryl L.; Stott, Wendylee; Springmann, Marcus J.

    2014-01-01

    A suite of tri- and tetra-nucleotide microsatellite loci were developed for walleye (Sander vitreus) from 454 pyrosequencing data. Eighteen of the 50 primer sets tested amplified consistently in 35 walleye from two lakes on Isle Royale, Lake Superior: Chickenbone Lake and Whittlesey Lake. The loci displayed moderate levels of allelic diversity (average 5.5 alleles/locus) and heterozygosity (average 35.8 %). Levels of genetic diversity were sufficient to produce unique multi-locus genotypes and detect phylogeographic structuring as individuals assigned back to their population of origin. Cross-species amplification within S. canadensis(sauger) was successful for 15 loci, and 11 loci were diagnostic to species. The loci characterized here will be useful for detecting fine-scale spatial structuring, resolving the taxonomic status of Sander species and sub-species, and detecting walleye/sauger hybrids.

  7. Meta-analysis identifies seven susceptibility loci involved in the atopic march

    OpenAIRE

    Marenholz, I.; Esparza-Gordillo, J.; Rueschendorf, F; Bauerfeind, A; Strachan, D. P.; Spycher, B.D.; Baurecht, H; Margaritte-Jeannin, P.; Saeaef, A.; Kerkhof, M; Ege, M.; Baltic, S.; Matheson, M. C.; Li,J.; Michel, S.

    2015-01-01

    Eczema often precedes the development of asthma in a disease course called the 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs93577...

  8. THE CLASSIFICATION OF THE SURROUNDINGS OF COAL MINING ROADWAYS

    Institute of Scientific and Technical Information of China (English)

    邹喜正; 侯朝炯; 李华祥

    1996-01-01

    This introduces the calculation of opaper the deformationg .the Surroundings of coaowaysand the divisi of surroundings into 5 levels by means or !fuzzy integral assess mairrx, wnlcnserves-asthe scientific basis for selecting supporting pattern of roadways and determining the, pa-rameters of support.

  9. DNA barcodes from four loci provide poor resolution of taxonomic groups in the genus Crataegus.

    Science.gov (United States)

    Zarrei, Mehdi; Talent, Nadia; Kuzmina, Maria; Lee, Jeanette; Lund, Jensen; Shipley, Paul R; Stefanović, Saša; Dickinson, Timothy A

    2015-04-28

    DNA barcodes can facilitate identification of organisms especially when morphological characters are limited or unobservable. To what extent this potential is realized in specific groups of plants remains to be determined. Libraries of barcode sequences from well-studied authoritatively identified plants represented by herbarium voucher specimens are needed in order for DNA barcodes to serve their intended purpose, where this is possible, and to understand the reasons behind their failure to do so, when this occurs. We evaluated four loci, widely regarded as universal DNA barcodes for plants, for their utility in hawthorn species identification. Three plastid regions, matK, rbcLa and psbA-trnH, and the internal transcribed spacer 2 (ITS2) of nuclear ribosomal DNA discriminate only some of the species of Crataegus that can be recognized on the basis of their morphology etc. This is, in part, because in Rosaceae tribe Maleae most individual plastid loci yield relatively little taxonomic resolution and, in part, because the effects of allopolyploidization have not been eliminated by concerted evolution of the ITS regions. Although individual plastid markers provided generally poor resolution of taxonomic groups in Crataegus, a few species were notable exceptions. In contrast, analyses of concatenated sequences of the 3 plastid barcode loci plus 11 additional plastid loci gave a well-resolved maternal phylogeny. In the ITS2 tree, different individuals of some species formed groups with taxonomically unrelated species. This is a sign of lineage sorting due to incomplete concerted evolution in ITS2. Incongruence between the ITS2 and plastid trees is best explained by hybridization between different lineages within the genus. In aggregate, limited between-species variation in plastid loci, hybridization and a lack of concerted evolution in ITS2 all combine to limit the utility of standard barcoding markers in Crataegus. These results have implications for authentication

  10. MicNeSs: genotyping microsatellite loci from a collection of (NGS) reads.

    Science.gov (United States)

    Suez, Marie; Behdenna, Abdelkader; Brouillet, Sophie; Graça, Paula; Higuet, Dominique; Achaz, Guillaume

    2016-03-01

    Microsatellites are widely used in population genetics to uncover recent evolutionary events. They are typically genotyped using capillary sequencer, which capacity is usually limited to 9, at most 12 loci for each run, and which analysis is a tedious task that is performed by hand. With the rise of next-generation sequencing (NGS), a much larger number of loci and individuals are available from sequencing: for example, on a single run of a GS Junior, 28 loci from 96 individuals are sequenced with a 30X cover. We have developed an algorithm to automatically and efficiently genotype microsatellites from a collection of reads sorted by individual (e.g. specific PCR amplifications of a locus or a collection of reads that encompass a locus of interest). As the sequencing and the PCR amplification introduce artefactual insertions or deletions, the set of reads from a single microsatellite allele shows several length variants. The algorithm infers, without alignment, the true unknown allele(s) of each individual from the observed distributions of microsatellites length of all individuals. MicNeSs, a python implementation of the algorithm, can be used to genotype any microsatellite locus from any organism and has been tested on 454 pyrosequencing data of several loci from fruit flies (a model species) and red deers (a nonmodel species). Without any parallelization, it automatically genotypes 22 loci from 441 individuals in 11 hours on a standard computer. The comparison of MicNeSs inferences to the standard method shows an excellent agreement, with some differences illustrating the pros and cons of both methods.

  11. CASFISH: CRISPR/Cas9-mediated in situ labeling of genomic loci in fixed cells.

    Science.gov (United States)

    Deng, Wulan; Shi, Xinghua; Tjian, Robert; Lionnet, Timothée; Singer, Robert H

    2015-09-22

    Direct visualization of genomic loci in the 3D nucleus is important for understanding the spatial organization of the genome and its association with gene expression. Various DNA FISH methods have been developed in the past decades, all involving denaturing dsDNA and hybridizing fluorescent nucleic acid probes. Here we report a novel approach that uses in vitro constituted nuclease-deficient clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated caspase 9 (Cas9) complexes as probes to label sequence-specific genomic loci fluorescently without global DNA denaturation (Cas9-mediated fluorescence in situ hybridization, CASFISH). Using fluorescently labeled nuclease-deficient Cas9 (dCas9) protein assembled with various single-guide RNA (sgRNA), we demonstrated rapid and robust labeling of repetitive DNA elements in pericentromere, centromere, G-rich telomere, and coding gene loci. Assembling dCas9 with an array of sgRNAs tiling arbitrary target loci, we were able to visualize nonrepetitive genomic sequences. The dCas9/sgRNA binary complex is stable and binds its target DNA with high affinity, allowing sequential or simultaneous probing of multiple targets. CASFISH assays using differently colored dCas9/sgRNA complexes allow multicolor labeling of target loci in cells. In addition, the CASFISH assay is remarkably rapid under optimal conditions and is applicable for detection in primary tissue sections. This rapid, robust, less disruptive, and cost-effective technology adds a valuable tool for basic research and genetic diagnosis.

  12. Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations.

    Directory of Open Access Journals (Sweden)

    Ayşe Demirkan

    Full Text Available Phospho- and sphingolipids are crucial cellular and intracellular compounds. These lipids are required for active transport, a number of enzymatic processes, membrane formation, and cell signalling. Disruption of their metabolism leads to several diseases, with diverse neurological, psychiatric, and metabolic consequences. A large number of phospholipid and sphingolipid species can be detected and measured in human plasma. We conducted a meta-analysis of five European family-based genome-wide association studies (N = 4034 on plasma levels of 24 sphingomyelins (SPM, 9 ceramides (CER, 57 phosphatidylcholines (PC, 20 lysophosphatidylcholines (LPC, 27 phosphatidylethanolamines (PE, and 16 PE-based plasmalogens (PLPE, as well as their proportions in each major class. This effort yielded 25 genome-wide significant loci for phospholipids (smallest P-value = 9.88×10(-204 and 10 loci for sphingolipids (smallest P-value = 3.10×10(-57. After a correction for multiple comparisons (P-value<2.2×10(-9, we observed four novel loci significantly associated with phospholipids (PAQR9, AGPAT1, PKD2L1, PDXDC1 and two with sphingolipids (PLD2 and APOE explaining up to 3.1% of the variance. Further analysis of the top findings with respect to within class molar proportions uncovered three additional loci for phospholipids (PNLIPRP2, PCDH20, and ABDH3 suggesting their involvement in either fatty acid elongation/saturation processes or fatty acid specific turnover mechanisms. Among those, 14 loci (KCNH7, AGPAT1, PNLIPRP2, SYT9, FADS1-2-3, DLG2, APOA1, ELOVL2, CDK17, LIPC, PDXDC1, PLD2, LASS4, and APOE mapped into the glycerophospholipid and 12 loci (ILKAP, ITGA9, AGPAT1, FADS1-2-3, APOA1, PCDH20, LIPC, PDXDC1, SGPP1, APOE, LASS4, and PLD2 to the sphingolipid pathways. In large meta-analyses, associations between FADS1-2-3 and carotid intima media thickness, AGPAT1 and type 2 diabetes, and APOA1 and coronary artery disease were observed. In conclusion, our

  13. EXPRESSION OF GENETIC LOCI IN THE PERIPHERAL BLOOD MONONUCLEAR FRACTION FROM PATIENTS WITH PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    M. I. Kogan

    2012-01-01

    Full Text Available The early diagnosis and radical treatment of aggressive prostate cancers (PC is an effective way of improving survival and quality of life in patients. To develop mini-invasive tests is one of the ways of solving the problem. The cells of a peripheral blood mononuclear fraction in the expression patterns of their genetic loci reflect the presence or absence of cancers, including information on therapeutic effectiveness. RT-PRC was used to study the relative expression of 15 genetic loci in a chromosome and one locus of mitochondrial DNA in the cells of the peripheral blood mononuclear fraction in patients with PC or benign prostate hyperplasia and in healthy men. The genetic locus patterns whose change may be of informative value for differential diagnosis in patients with different stages of PC were revealed. The authors studied the relationship and showed the prognostic role and non-relationship of the altered transcriptional activity of loci in the TP53, GSTP1, and IL10 genes in PC to the changes in prostate-specific antigen the level with 90 % specificity and 93 % specificity.

  14. EXPRESSION OF GENETIC LOCI IN THE PERIPHERAL BLOOD MONONUCLEAR FRACTION FROM PATIENTS WITH PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    M. I. Kogan

    2014-08-01

    Full Text Available The early diagnosis and radical treatment of aggressive prostate cancers (PC is an effective way of improving survival and quality of life in patients. To develop mini-invasive tests is one of the ways of solving the problem. The cells of a peripheral blood mononuclear fraction in the expression patterns of their genetic loci reflect the presence or absence of cancers, including information on therapeutic effectiveness. RT-PRC was used to study the relative expression of 15 genetic loci in a chromosome and one locus of mitochondrial DNA in the cells of the peripheral blood mononuclear fraction in patients with PC or benign prostate hyperplasia and in healthy men. The genetic locus patterns whose change may be of informative value for differential diagnosis in patients with different stages of PC were revealed. The authors studied the relationship and showed the prognostic role and non-relationship of the altered transcriptional activity of loci in the TP53, GSTP1, and IL10 genes in PC to the changes in prostate-specific antigen the level with 90 % specificity and 93 % specificity.

  15. A genome-wide SNP scan accelerates trait-regulatory genomic loci identification in chickpea

    Science.gov (United States)

    Kujur, Alice; Bajaj, Deepak; Upadhyaya, Hari D.; Das, Shouvik; Ranjan, Rajeev; Shree, Tanima; Saxena, Maneesha S.; Badoni, Saurabh; Kumar, Vinod; Tripathi, Shailesh; Gowda, C.L.L.; Sharma, Shivali; Singh, Sube; Tyagi, Akhilesh K.; Parida, Swarup K.

    2015-01-01

    We identified 44844 high-quality SNPs by sequencing 92 diverse chickpea accessions belonging to a seed and pod trait-specific association panel using reference genome- and de novo-based GBS (genotyping-by-sequencing) assays. A GWAS (genome-wide association study) in an association panel of 211, including the 92 sequenced accessions, identified 22 major genomic loci showing significant association (explaining 23–47% phenotypic variation) with pod and seed number/plant and 100-seed weight. Eighteen trait-regulatory major genomic loci underlying 13 robust QTLs were validated and mapped on an intra-specific genetic linkage map by QTL mapping. A combinatorial approach of GWAS, QTL mapping and gene haplotype-specific LD mapping and transcript profiling uncovered one superior haplotype and favourable natural allelic variants in the upstream regulatory region of a CesA-type cellulose synthase (Ca_Kabuli_CesA3) gene regulating high pod and seed number/plant (explaining 47% phenotypic variation) in chickpea. The up-regulation of this superior gene haplotype correlated with increased transcript expression of Ca_Kabuli_CesA3 gene in the pollen and pod of high pod/seed number accession, resulting in higher cellulose accumulation for normal pollen and pollen tube growth. A rapid combinatorial genome-wide SNP genotyping-based approach has potential to dissect complex quantitative agronomic traits and delineate trait-regulatory genomic loci (candidate genes) for genetic enhancement in crop plants, including chickpea. PMID:26058368

  16. The structural feature surrounding glycated lysine residues in human hemoglobin.

    Science.gov (United States)

    Ito, Shigenori; Nakahari, Takashi; Yamamoto, Daisuke

    2011-06-01

    Complications derived from diabetes mellitus are caused by nonenzymatic protein glycation at the specific sites. LC/MS/MS was performed for the identification of the tryptic peptides of glycated hemoglobins using glyceraldehyde. After the identification of the glycation or non-glycation site, computer analysis of the structure surrounding the sites was carried out using PDB data (1BZ0). Five glycated lysine residues (Lys-16(α), -56(α), -8(β), -82(β), and -144(β)) and four non-glycated lysine residues (Lys-7(α), -40(α), -99(α), and -132(β)) were identified. The non-glycated lysine residues, Lys-7(α), -40(α), and -132(β), are most likely to form electrostatic interactions with the β carboxyl group of Asp-74(α), C-terminal His-146(β), and Glu-7(β) by virtue of their proximity, which is 2.67-2.91 Å (N-O). Additionally, there are histidine residues within 4.55-7.38 Å (N-N) around eight sites except for Lys-7(α). We conclude that the following factors seem to be necessary for glycation of lysine residues: (i) the apparent absence of aspartate or glutamate residues to inhibit the glycation reaction by forming an electrostatic interaction, (ii) the presence of histidine residues for acid-base catalysis of the Amadori rearrangement, and (iii) the presence of an amino acid residue capable of stabilizing a phosphate during proton transfer.

  17. Association mapping of partitioning loci in barley

    Directory of Open Access Journals (Sweden)

    Mackay Ian J

    2008-02-01

    Full Text Available Abstract Background Association mapping, initially developed in human disease genetics, is now being applied to plant species. The model species Arabidopsis provided some of the first examples of association mapping in plants, identifying previously cloned flowering time genes, despite high population sub-structure. More recently, association genetics has been applied to barley, where breeding activity has resulted in a high degree of population sub-structure. A major genotypic division within barley is that between winter- and spring-sown varieties, which differ in their requirement for vernalization to promote subsequent flowering. To date, all attempts to validate association genetics in barley by identifying major flowering time loci that control vernalization requirement (VRN-H1 and VRN-H2 have failed. Here, we validate the use of association genetics in barley by identifying VRN-H1 and VRN-H2, despite their prominent role in determining population sub-structure. Results By taking barley as a typical inbreeding crop, and seasonal growth habit as a major partitioning phenotype, we develop an association mapping approach which successfully identifies VRN-H1 and VRN-H2, the underlying loci largely responsible for this agronomic division. We find a combination of Structured Association followed by Genomic Control to correct for population structure and inflation of the test statistic, resolved significant associations only with VRN-H1 and the VRN-H2 candidate genes, as well as two genes closely linked to VRN-H1 (HvCSFs1 and HvPHYC. Conclusion We show that, after employing appropriate statistical methods to correct for population sub-structure, the genome-wide partitioning effect of allelic status at VRN-H1 and VRN-H2 does not result in the high levels of spurious association expected to occur in highly structured samples. Furthermore, we demonstrate that both VRN-H1 and the candidate VRN-H2 genes can be identified using association mapping

  18. A method for rapid and simultaneous mapping of genetic loci and introgression sizes in nematode species.

    Science.gov (United States)

    Yan, Cheung; Bi, Yu; Yin, Da; Zhao, Zhongying

    2012-01-01

    Caenorhabditis briggsae is emerging as an attractive model organism not only in studying comparative biology against C. elegans, but also in developing novel experimentation avenues. In particular, recent identification of a new Caenorhabditis species, C. sp.9 with which it can mate and produce viable progeny provides an opportunity for studying the genetics of hybrid incompatibilities (HI) between the two. Mapping of a specific HI locus demands repeated backcrossing to get hold of the specific genomic region underlying an observed phenotype. To facilitate mapping of HI loci between C. briggsae and C. sp.9, an efficient mapping method and a genetic map ideally consisting of dominant markers are required for systematic introgression of genomic fragments between the two species. We developed a fast and cost-effective method for high throughput mapping of dominant loci with resolution up to 1 million bps in C. briggsae. The method takes advantage of the introgression between C. briggsae and C. sp.9 followed by PCR genotyping using C. briggsae specific primers. Importantly, the mapping results can not only serve as an effective way for estimating the chromosomal position of a genetic locus in C. briggsae, but also provides size information for the introgression fragment in an otherwise C. sp.9 background. In addition, it also helps generate introgression line as a side-product that is invaluable for the subsequent mapping of HI loci. The method will greatly facilitate the construction of a genetic map consisting of dominant markers and pave the way for systematic isolation of HI loci between C. briggsae and C. sp.9 which has so far not been attempted between nematode species. The method is designed for mapping of a dominant allele, but can be easily adapted for mapping of any other type of alleles in any other species if introgression between a sister species pair is feasible.

  19. Genetic loci for retinal arteriolar microcirculation.

    Science.gov (United States)

    Sim, Xueling; Jensen, Richard A; Ikram, M Kamran; Cotch, Mary Frances; Li, Xiaohui; MacGregor, Stuart; Xie, Jing; Smith, Albert Vernon; Boerwinkle, Eric; Mitchell, Paul; Klein, Ronald; Klein, Barbara E K; Glazer, Nicole L; Lumley, Thomas; McKnight, Barbara; Psaty, Bruce M; de Jong, Paulus T V M; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G; van Duijn, Cornelia M; Aspelund, Thor; Eiriksdottir, Gudny; Harris, Tamara B; Jonasson, Fridbert; Launer, Lenore J; Attia, John; Baird, Paul N; Harrap, Stephen; Holliday, Elizabeth G; Inouye, Michael; Rochtchina, Elena; Scott, Rodney J; Viswanathan, Ananth; Li, Guo; Smith, Nicholas L; Wiggins, Kerri L; Kuo, Jane Z; Taylor, Kent D; Hewitt, Alex W; Martin, Nicholas G; Montgomery, Grant W; Sun, Cong; Young, Terri L; Mackey, David A; van Zuydam, Natalie R; Doney, Alex S F; Palmer, Colin N A; Morris, Andrew D; Rotter, Jerome I; Tai, E Shyong; Gudnason, Vilmundur; Vingerling, Johannes R; Siscovick, David S; Wang, Jie Jin; Wong, Tien Y

    2013-01-01

    Narrow arterioles in the retina have been shown to predict hypertension as well as other vascular diseases, likely through an increase in the peripheral resistance of the microcirculatory flow. In this study, we performed a genome-wide association study in 18,722 unrelated individuals of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium and the Blue Mountain Eye Study, to identify genetic determinants associated with variations in retinal arteriolar caliber. Retinal vascular calibers were measured on digitized retinal photographs using a standardized protocol. One variant (rs2194025 on chromosome 5q14 near the myocyte enhancer factor 2C MEF2C gene) was associated with retinal arteriolar caliber in the meta-analysis of the discovery cohorts at genome-wide significance of P-value <5×10(-8). This variant was replicated in an additional 3,939 individuals of European ancestry from the Australian Twins Study and Multi-Ethnic Study of Atherosclerosis (rs2194025, P-value = 2.11×10(-12) in combined meta-analysis of discovery and replication cohorts). In independent studies of modest sample sizes, no significant association was found between this variant and clinical outcomes including coronary artery disease, stroke, myocardial infarction or hypertension. In conclusion, we found one novel loci which underlie genetic variation in microvasculature which may be relevant to vascular disease. The relevance of these findings to clinical outcomes remains to be determined.

  20. Genetic loci for retinal arteriolar microcirculation.

    Directory of Open Access Journals (Sweden)

    Xueling Sim

    Full Text Available Narrow arterioles in the retina have been shown to predict hypertension as well as other vascular diseases, likely through an increase in the peripheral resistance of the microcirculatory flow. In this study, we performed a genome-wide association study in 18,722 unrelated individuals of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium and the Blue Mountain Eye Study, to identify genetic determinants associated with variations in retinal arteriolar caliber. Retinal vascular calibers were measured on digitized retinal photographs using a standardized protocol. One variant (rs2194025 on chromosome 5q14 near the myocyte enhancer factor 2C MEF2C gene was associated with retinal arteriolar caliber in the meta-analysis of the discovery cohorts at genome-wide significance of P-value <5×10(-8. This variant was replicated in an additional 3,939 individuals of European ancestry from the Australian Twins Study and Multi-Ethnic Study of Atherosclerosis (rs2194025, P-value = 2.11×10(-12 in combined meta-analysis of discovery and replication cohorts. In independent studies of modest sample sizes, no significant association was found between this variant and clinical outcomes including coronary artery disease, stroke, myocardial infarction or hypertension. In conclusion, we found one novel loci which underlie genetic variation in microvasculature which may be relevant to vascular disease. The relevance of these findings to clinical outcomes remains to be determined.

  1. Surround suppression and sparse coding in visual and barrel cortices

    Directory of Open Access Journals (Sweden)

    Robert N S Sachdev

    2012-07-01

    Full Text Available During natural vision the entire retina is stimulated. Likewise, during natural tactile behaviors, spatially extensive regions of the somatosensory surface are co-activated. The large spatial extent of naturalistic stimulation means that surround suppression, a phenomenon whose neural mechanisms remain a matter of debate, must arise during natural behavior. To identify common neural motifs that might instantiate surround suppression across modalities, we review models of surround suppression and compare the evidence supporting the competing ideas that surround suppression has either cortical or sub-cortical origins in visual and barrel cortex. In the visual system there is general agreement lateral inhibitory mechanisms contribute to surround suppression, but little direct experimental evidence that intracortical inhibition plays a major role. Two intracellular recording studies of V1, one using naturalistic stimuli (Haider et al., 2010, the other sinusoidal gratings (Ozeki et al., 2009, sought to identify the causes of reduced activity in V1 with increasing stimulus size, a hallmark of surround suppression. The former attributed this effect to increased inhibition, the latter to largely balanced withdrawal of excitation and inhibition. In rodent primary somatosensory barrel cortex, multi-whisker responses are generally weaker than single whisker responses, suggesting multi-whisker stimulation engages similar surround suppressive mechanisms. The origins of suppression in S1 remain elusive: studies have implicated brainstem lateral/internuclear interactions and both thalamic and cortical inhibition. Although the anatomical organization and instantiation of surround suppression in the visual and somatosensory systems differ, we consider the idea that one common function of surround suppression, in both modalities, is to remove the statistical redundancies associated with natural stimuli by increasing the sparseness or selectivity of sensory

  2. Three new loci for determining x chromosome inactivation patterns

    DEFF Research Database (Denmark)

    Bertelsen, Birgitte; Tümer, Zeynep; Ravn, Kirstine

    2011-01-01

    on two differentially methylated restriction enzyme sites (HpaII) and a polymorphic repeat located within this locus. Although highly informative, this locus is not always sufficient to evaluate the X-inactivation status in X-linked disorders. We have identified three new loci that can be used...... to determine XCI patterns in a methylation-sensitive PCR-based assay. All three loci contain polymorphic repeats and a methylation-sensitive restriction enzyme (HpaII) site, methylation of which was shown to correlate with XCI. DNA from 60 females was used to estimate the heterozygosity of these new loci...

  3. Polymorphic microsatellite loci for the crimson snapper (Lutjanus erythropterus).

    Science.gov (United States)

    Liu, L; Lin, L; Li, C H; Xu, S N; Liu, Y; Zhou, Y B

    2014-07-24

    We isolated and characterized 22 polymorphic microsatellite loci in Lutjanus erythropterus using a (GT)13-enriched genomic library. We found between 2 and 8 alleles per locus, with a mean of 4.85. The observed and expected heterozygosities ranged from 0.065 to 0.867 and from 0.085 to 0.832, respectively, with means of 0.461 and 0.529, respectively. Allele frequencies in three loci were found to deviate from Hardy-Weinberg equilibrium. Evidence for null alleles was found for three loci. These markers will be useful for distinguishing released captive-bred L. erythropterus individuals from wild individuals.

  4. Novel loci and pathways significantly associated with longevity

    DEFF Research Database (Denmark)

    Zeng, Yi; Nie, Chao; Min, Junxia

    2016-01-01

    Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han...... Chinese with a sample size 2.7 times the largest previously published GWAS on centenarians. We identified 11 independent loci associated with longevity replicated in Southern-Northern regions of China, including two novel loci (rs2069837-IL6; rs2440012-ANKRD20A9P) with genome-wide significance...

  5. A Genome-wide Association Analysis of a Broad Psychosis Phenotype Identifies Three Loci for Further Investigation

    NARCIS (Netherlands)

    Bramon, Elvira; Pirinen, Matti; Strange, Amy; Lin, Kuang; Freeman, Colin; Bellenguez, Celine; Su, Zhan; Band, Gavin; Pearson, Richard; Vukcevic, Damjan; Langford, Cordelia; Deloukas, Panos; Hunt, Sarah; Gray, Emma; Dronov, Serge; Potter, Simon C.; Tashakkori-Ghanbaria, Avazeh; Edkins, Sarah; Bumpstead, Suzannah J.; Arranz, Maria J.; Bakker, Steven; Bender, Stephan; Bruggeman, Richard; Cahn, Wiepke; Chandler, David; Collier, David A.; Crespo-Facorro, Benedicto; Dazzan, Paola; de Haan, Lieuwe; di Forti, Marta; Dragovic, Milan; Giegling, Ina; Hall, Jeremy; Iyegbe, Conrad; Jablensky, Assen; Kahn, Rene S.; Kalaydjieva, Luba; Kravariti, Eugenia; Lawrie, Stephen; Lins-Zen, Don H.; Mata, Ignacio; McDonald, Colm; McIntosh, Andrew; Myin-Germeys, Inez; Ophoff, Roel A.; Pariante, Carmine M.; Paunio, Tiina; Picchioni, Marco; Ripke, Stephan; Rujescu, Dan; Sauer, Heinrich; Shaikh, Madiha; Sussmann, Jessika; Suvisaari, Jaana; Tosato, Sarah; Toulopoulou, Timothea; Van Os, Jim; Walshe, Muriel; Weisbrod, Matthias; Whalley, Heather; Wiersma, Durk; Blackwell, Jenefer M.; Brown, Matthew A.; Casas, Juan P.; Corvin, Aiden; Duncanson, Audrey; Jankowski, Janusz A. Z.; Markus, Hugh S.; Mathew, Christopher G.; Palmer, Colin N. A.; Plomin, Robert; Rautanen, Anna; Sawcer, Stephen J.; Trembath, Richard C.; Wood, Nicholas W.; Barroso, Ines; Peltonen, Leena; Lewis, Cathryn M.; Murray, Robin M.; Donnelly, Peter; Powell, John; Spencer, Chris C. A.

    2014-01-01

    Background: Genome-wide association studies (GWAS) have identified several loci associated with schizophrenia and/or bipolar disorder. We performed a GWAS of psychosis as a broad syndrome rather than within specific diagnostic categories. Methods: 1239 cases with schizophrenia, schizoaffective disor

  6. Association of age-of-onset groups with GWAS significant schizophrenia and bipolar disorder loci in Romanian bipolar I patients.

    Science.gov (United States)

    Grigoroiu-Serbanescu, Maria; Diaconu, Carmen C; Heilmann-Heimbach, Stefanie; Neagu, Ana Iulia; Becker, Tim

    2015-12-30

    We investigated the influence of the age-of-onset (AO) on the association of 45 loci conferring risk for bipolar disorder (BP) and schizophrenia with BP-type-I in a Romanian sample (461 patients, 436 controls). The AO-analysis implicated the EGFR gene, as well as loci in other genes, in the AO variation of BP-type-I and revealed for the first time the link between BP-type-I and risk variants considered specific to schizophrenia (polymorphisms in MMP16/RIPK2 and CNNM2 genes).

  7. A nondegenerate code of deleterious variants in Mendelian loci contributes to complex disease risk.

    Science.gov (United States)

    Blair, David R; Lyttle, Christopher S; Mortensen, Jonathan M; Bearden, Charles F; Jensen, Anders Boeck; Khiabanian, Hossein; Melamed, Rachel; Rabadan, Raul; Bernstam, Elmer V; Brunak, Søren; Jensen, Lars Juhl; Nicolae, Dan; Shah, Nigam H; Grossman, Robert L; Cox, Nancy J; White, Kevin P; Rzhetsky, Andrey

    2013-09-26

    Although countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. By mining the medical records of over 110 million patients, we examine the extent to which Mendelian variation contributes to complex disease risk. We detect thousands of associations between Mendelian and complex diseases, revealing a nondegenerate, phenotypic code that links each complex disorder to a unique collection of Mendelian loci. Using genome-wide association results, we demonstrate that common variants associated with complex diseases are enriched in the genes indicated by this "Mendelian code." Finally, we detect hundreds of comorbidity associations among Mendelian disorders, and we use probabilistic genetic modeling to demonstrate that Mendelian variants likely contribute nonadditively to the risk for a subset of complex diseases. Overall, this study illustrates a complementary approach for mapping complex disease loci and provides unique predictions concerning the etiologies of specific diseases. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. A Non-Degenerate Code of Deleterious Variants in Mendelian Loci Contributes to Complex Disease Risk

    Science.gov (United States)

    Blair, David R.; Lyttle, Christopher S.; Mortensen, Jonathan M.; Bearden, Charles F.; Jensen, Anders Boeck; Khiabanian, Hossein; Melamed, Rachel; Rabadan, Raul; Bernstam, Elmer V.; Brunak, Søren; Jensen, Lars Juhl; Nicolae, Dan; Shah, Nigam H.; Grossman, Robert L.; Cox, Nancy J.; White, Kevin P.; Rzhetsky, Andrey

    2013-01-01

    Summary Whereas countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. Here, we examine the extent to which Mendelian variation contributes to complex disease risk by mining the medical records of over 110 million patients. We detect thousands of associations between Mendelian and complex diseases, revealing a non-degenerate, phenotypic code that links each complex disorder to a unique collection of Mendelian loci. Using genome-wide association results, we demonstrate that common variants associated with complex diseases are enriched in the genes indicated by this “Mendelian code.” Finally, we detect hundreds of comorbidity associations among Mendelian disorders, and we use probabilistic genetic modeling to demonstrate that Mendelian variants likely contribute non-additively to the risk for a subset of complex diseases. Overall, this study illustrates a complementary approach for mapping complex disease loci and provides unique predictions concerning the etiologies of specific diseases. PMID:24074861

  9. Differential effect of allorecognition loci on phenotype in Hydractinia symbiolongicarpus (Cnidaria: Hydrozoa).

    Science.gov (United States)

    Powell, Anahid E; Nicotra, Matthew L; Moreno, Maria A; Lakkis, Fadi G; Dellaporta, Stephen L; Buss, Leo W

    2007-12-01

    The allorecognition complex of Hydractinia symbiolongicarpus is a chromosomal interval containing two loci, alr1 and alr2, that controls fusion between genetically distinct colonies. Recombination between these two loci has been associated with a heterogeneous class of phenotypes called transitory fusion. A large-scale backcross was performed to generate a population of colonies (N = 106) with recombination breakpoints within the allorecognition complex. Two distinct forms of transitory fusion were correlated with reciprocal recombination products, suggesting that alr1 and alr2 contributed differentially to the allorecognition response. Specifically, type I transitory fusion is associated with rapid and persistent separation of allogeneic tissues, whereas type II transitory fusion generates a patchwork of continuously fusing and separating tissues.

  10. Quantitative Trait Loci (QTLs mapping for growth traits in the mouse: A review

    Directory of Open Access Journals (Sweden)

    Medrano Juan F

    2001-03-01

    Full Text Available Abstract The attainment of a specific mature body size is one of the most fundamental differences among species of mammals. Moreover, body size seems to be the central factor underlying differences in traits such as growth rate, energy metabolism and body composition. An important proportion of this variability is of genetic origin. The goal of the genetic analysis of animal growth is to understand its "genetic architecture", that is the number and position of loci affecting the trait, the magnitude of their effects, allele frequencies and types of gene action. In this review, the different strategies developed to identify and characterize genes involved in the regulation of growth in the mouse are described, with emphasis on the methods developed to map loci contributing to the regulation of quantitative traits (QTLs.

  11. Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci

    DEFF Research Database (Denmark)

    Gaulton, Kyle J; Ferreira, Teresa; Lee, Yeji

    2015-01-01

    We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct...... signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping...... implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele...

  12. Surrounding Moving Obstacle Detection for Autonomous Driving Using Stereo Vision

    Directory of Open Access Journals (Sweden)

    Hao Sun

    2013-06-01

    Full Text Available Detection and tracking surrounding moving obstacles such as vehicles and pedestrians are crucial for the safety of mobile robotics and autonomous vehicles. This is especially the case in urban driving scenarios. This paper presents a novel framework for surrounding moving obstacles detection using binocular stereo vision. The contributions of our work are threefold. Firstly, a multiview feature matching scheme is presented for simultaneous stereo correspondence and motion correspondence searching. Secondly, the multiview geometry constraint derived from the relative camera positions in pairs of consecutive stereo views is exploited for surrounding moving obstacles detection. Thirdly, an adaptive particle filter is proposed for tracking of multiple moving obstacles in surrounding areas. Experimental results from real‐world driving sequences demonstrate the effectiveness and robustness of the proposed framework.

  13. Surrounding Moving Obstacle Detection for Autonomous Driving Using Stereo Vision

    Directory of Open Access Journals (Sweden)

    Hao Sun

    2013-06-01

    Full Text Available Detection and tracking surrounding moving obstacles such as vehicles and pedestrians are crucial for the safety of mobile robotics and autonomous vehicles. This is especially the case in urban driving scenarios. This paper presents a novel framework for surrounding moving obstacles detection using binocular stereo vision. The contributions of our work are threefold. Firstly, a multiview feature matching scheme is presented for simultaneous stereo correspondence and motion correspondence searching. Secondly, the multiview geometry constraint derived from the relative camera positions in pairs of consecutive stereo views is exploited for surrounding moving obstacles detection. Thirdly, an adaptive particle filter is proposed for tracking of multiple moving obstacles in surrounding areas. Experimental results from real-world driving sequences demonstrate the effectiveness and robustness of the proposed framework.

  14. Traditional Indian custOInS surrounding birth

    African Journals Online (AJOL)

    traditional custOIns surrounding birth in Indian culture. ... conception, pregnancy, birth and the early months ofparenthood. .... house attended by a traditional birth attendant of a ..... Spiritual components play a dominant role in traditional.

  15. Glow phenomenon surrounding the vertical stabilizer and OMS pods

    Science.gov (United States)

    1994-01-01

    This 35mm frame, photographed as the Space Shuttle Columbia was orbiting Earth during a 'night' pass, documents the glow phenomenon surrounding the vertical stabilizer and the Orbital Maneuvering System (OMS) pods of the spacecraft.

  16. High-Resolution Genome-Wide Linkage Mapping Identifies Susceptibility Loci for BMI in the Chinese Population

    DEFF Research Database (Denmark)

    Zhang, Dong Feng; Pang, Zengchang; Li, Shuxia

    2012-01-01

    The genetic loci affecting the commonly used BMI have been intensively investigated using linkage approaches in multiple populations. This study aims at performing the first genome-wide linkage scan on BMI in the Chinese population in mainland China with hypothesis that heterogeneity in genetic...... in western countries. Multiple loci showing suggestive linkage were found on chromosome 1 (lod score 2.38 at 242 cM), chromosome 8 (2.48 at 95 cM), and chromosome 14 (2.2 at 89.4 cM). The strong linkage identified in the Chinese subjects that is consistent with that found in populations of European origin...... could suggest the existence of evolutionarily preserved genetic mechanisms for BMI whereas the multiple suggestive loci could represent genetic effect from gene-environment interaction as a result of population-specific environmental adaptation....

  17. pilS loci in Neisseria gonorrhoeae are transcriptionally active

    Science.gov (United States)

    Wachter, Jenny; Masters, Thao L.; Wachter, Shaun; Mason, Joanna

    2015-01-01

    Piliation is an important virulence determinant for Neisseria gonorrhoeae. PilE polypeptide is the major protein subunit in the pilus organelle and engages in extensive antigenic variation due to recombination between pilE and a pilS locus. pilS were so-named as they are believed to be transcriptionally silent, in contrast to the pilE locus. In this study, we demonstrate the presence of a small, pil-specific RNA species. Through using a series of pilE deletion mutants, we show by Northern blotting and quantitative reverse transcriptase PCR analysis (qRT-PCR), that these smaller RNA species are not derived from the primary pilE transcript following some processing events, but rather, arose through transcription of the pilS loci. Small transcriptome analysis, in conjunction with analysis of pilS recombinants, identified both sense and anti-sense RNAs originating from most, but not all, of the pilS gene copies. Focusing on the MS11 pilS6 locus, we identified by site-directed mutagenesis a sense promoter located immediately upstream of pilS6 copy 2, as well as an anti-sense promoter immediately downstream of pilS6 copy 1. Whole transcriptome analysis also revealed the presence of pil-specific sRNA in both gonococci and meningococci. Overall, this study reveals an added layer of complexity to the pilE/pilS recombination scheme by demonstrating pil-specific transcription within genes that were previously thought to be transcriptionally silent. PMID:25701734

  18. Surrounding Moving Obstacle Detection for Autonomous Driving Using Stereo Vision

    OpenAIRE

    Hao Sun; Huanxin Zou; Shilin Zhou; Cheng Wang; Naser El-Sheimy

    2013-01-01

    Detection and tracking surrounding moving obstacles such as vehicles and pedestrians are crucial for the safety of mobile robotics and autonomous vehicles. This is especially the case in urban driving scenarios. This paper presents a novel framework for surrounding moving obstacles detection using binocular stereo vision. The contributions of our work are threefold. Firstly, a multiview feature matching scheme is presented for simultaneous stereo correspondence and motion correspondence searc...

  19. Quantitative trait loci underlying milk production traits in sheep.

    Science.gov (United States)

    Gutiérrez-Gil, B; El-Zarei, M F; Alvarez, L; Bayón, Y; de la Fuente, L F; San Primitivo, F; Arranz, J-J

    2009-08-01

    Improvement of milk production traits in dairy sheep is required to increase the competitiveness of the industry and to maintain the production of high quality cheese in regions of Mediterranean countries with less favourable conditions. Additional improvement over classical selection could be reached if genes with significant effects on the relevant traits were specifically targeted by selection. However, so far, few studies have been undertaken to detect quantitative trait loci (QTL) in dairy sheep. In this study, we present a complete genome scan performed in a commercial population of Spanish Churra sheep to identify chromosomal regions associated with phenotypic variation observed in milk production traits. Eleven half-sib families, including a total of 1213 ewes, were analysed following a daughter design. Genome-wise multi-marker regression analysis revealed a genome-wise significant QTL for milk protein percentage on chromosome 3. Eight other regions, localized on chromosomes 1, 2, 20, 23 and 25, showed suggestive significant linkage associations with some of the analysed traits. To our knowledge, this study represents the first complete genome scan for milk production traits reported in dairy sheep. The experiment described here shows that analysis of commercial dairy sheep populations has the potential to increase our understanding of the genetic determinants of complex production-related traits.

  20. Liver expression quantitative trait loci: a foundation for pharmacogenomic research

    Directory of Open Access Journals (Sweden)

    Dylan eGlubb

    2012-08-01

    Full Text Available Expression quantitative trait loci (eQTL analysis can provide insights into the genetic regulation of gene expression at a genomic level and this information is proving extremely useful in many different areas of research. As a consequence of the role of the liver in drug metabolism and disposition, the study of eQTLs in primary human liver tissue could provide a foundation for pharmacogenomics. Thus far, four genome-wide eQTL studies have been performed using human livers. Many liver eQTLs have been found to be reproducible and a proportion of these may be specific to the liver. Already these data have been used to interpret and inform clinic genome-wide association studies, providing potential mechanistic evidence for clinical associations and identifying genes which may impact on clinical phenotypes. However, the utility of liver eQTL data has not yet been fully explored or realized in pharmacogenomics. As further liver eQTL research is undertaken, the genetic regulation of gene expression will become much better characterized and this knowledge will create a rational basis for the prospective pharmacogenomic study of many drugs.

  1. Comparative analysis of methods for detecting interacting loci

    Directory of Open Access Journals (Sweden)

    Yuan Xiguo

    2011-07-01

    Full Text Available Abstract Background Interactions among genetic loci are believed to play an important role in disease risk. While many methods have been proposed for detecting such interactions, their relative performance remains largely unclear, mainly because different data sources, detection performance criteria, and experimental protocols were used in the papers introducing these methods and in subsequent studies. Moreover, there have been very few studies strictly focused on comparison of existing methods. Given the importance of detecting gene-gene and gene-environment interactions, a rigorous, comprehensive comparison of performance and limitations of available interaction detection methods is warranted. Results We report a comparison of eight representative methods, of which seven were specifically designed to detect interactions among single nucleotide polymorphisms (SNPs, with the last a popular main-effect testing method used as a baseline for performance evaluation. The selected methods, multifactor dimensionality reduction (MDR, full interaction model (FIM, information gain (IG, Bayesian epistasis association mapping (BEAM, SNP harvester (SH, maximum entropy conditional probability modeling (MECPM, logistic regression with an interaction term (LRIT, and logistic regression (LR were compared on a large number of simulated data sets, each, consistent with complex disease models, embedding multiple sets of interacting SNPs, under different interaction models. The assessment criteria included several relevant detection power measures, family-wise type I error rate, and computational complexity. There are several important results from this study. First, while some SNPs in interactions with strong effects are successfully detected, most of the methods miss many interacting SNPs at an acceptable rate of false positives. In this study, the best-performing method was MECPM. Second, the statistical significance assessment criteria, used by some of the

  2. Evidence for heterozygote instability in microsatellite loci in house wrens.

    Science.gov (United States)

    Masters, Brian S; Johnson, L Scott; Johnson, Bonnie G P; Brubaker, Jessica L; Sakaluk, Scott K; Thompson, Charles F

    2011-02-23

    Microsatellite loci have high mutation rates and high levels of allelic variation, but the factors influencing their mutation rate are not well understood. The proposal that heterozygosity may increase mutation rates has profound implications for understanding the evolution of microsatellite loci, but currently has limited empirical support. We examined 20 microsatellite mutations identified in an analysis of 12 260 meiotic events across three loci in two populations of a songbird, the house wren (Troglodytes aedon). We found that for an allele of a given length, mutation was significantly more likely when there was a relatively large difference in size between the allele and its homologue (i.e. a large 'allele span'). Our results support the proposal of heterozygote instability at microsatellite loci.

  3. CHARACTERIZATION OF MICROSATELLITE LOCI IN SCHOENOPLECTUS AMERICANUS (CYPERACEAE)

    Science.gov (United States)

    Schoenoplectus americanus is a model organism for studying ecological and ecosystem responses of salt marsh plant communities to global climate change. Here we characterize 16 microsatellite loci in S. americanus to facilitate studies on the genetic basis of phenotypic responses...

  4. Subsequent yield loci of 5754O aluminum alloy sheet

    Institute of Scientific and Technical Information of China (English)

    WANG Hai-bo; WAN Min; WU Xiang-dong; YAN Yu

    2009-01-01

    Complex loading paths were realized with cruciform specimens and biaxial loading testing machine. Experimental method for determining the subsequent yield locus of sheet metal was established. With this method, the subsequent yield loci of 5754O aluminum alloy sheet were obtained under complex loading paths. Theoretical subsequent yield loci based on Yld2000-2d yield criterion and three kinds of hardening modes were calculated and compared with the experimental results. The results show that the theoretical subsequent yield loci based on mixed hardening mode describe the experimental subsequent yield loci well, whereas isotropic hardening mode, which is widely used in sheet metal forming fields, predicts values larger than the experimental results. Kinematic hardening mode predicts values smaller than the experimental results and its errors are the largest.

  5. "Tilt" in color space: Hue changes induced by chromatic surrounds.

    Science.gov (United States)

    Klauke, Susanne; Wachtler, Thomas

    2015-01-01

    The perceived color of a chromatic stimulus is influenced by the chromaticity of its surround. To investigate these influences along the dimension of hue, we measured hue changes induced in stimuli of different hues by isoluminant chromatic surrounds. Generally, induced hue changes were directed in color space away from the hue of the inducing surround and depended on the magnitude on the hue difference between stimulus and surround. With increasing difference in hue between stimulus and surround, induced hue changes increased up to a maximum and then decreased for larger differences. This qualitative pattern was similar for different inducers, but quantitatively, induction was weaker along some directions in cone-opponent color space than along other directions. The strongest induction effects were found along an oblique, blue-yellow axis that corresponds to the daylight axis. The overall pattern of the induction effect shows similarities to the well-known tilt effect, where shifts in perceived angle of oriented stimuli are induced by oriented surrounds. This suggests analogous neural representations and similar mechanisms of contextual processing for different visual features such as orientation and color.

  6. Control of Formation of Lithological Reservoirs by Surrounding Mudstone

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Taking the Jiyang depression as an example, this paper discusses the control of the formation of lithological reservoir by surrounding rocks by integrated application of geological analysis, physical simulation, and the analysis of oil & gas accumulation mechanism. Geological statistical shows that the major burial depth and interval of lithological reservoirs in the Jiyang depression are related to the hydrocarbon generation in and expulsion from the Lower Tertiary source rocks and the time of the formation of most lithological reservoirs coincides with the peak of hydrocarbon generation and expulsion. The lithological traps located in the center of effective source rocks are propitious to high oil saturation than those located on the margin of effective source rocks. The hydrocarbon charge degree of the lithological reservoir has a positive correlation with the intensity of hydrocarbon expulsion from surrounding source rocks.Geological analyses and NMR experiments also show that the oil saturation of surrounding source rocks control the hydrocarbon potential of lithological traps, and a critical value for oil saturation of surrounding mudstone is required, that is, when the oil saturation of surrounding mudstone is lower than this critical value, no oil and gas accumulate in the lithological trap. The control of surrounding mudstone on the oil-bearing properties of lithological reservoirs is also analyzed by the mechanisms of hydrocarbon generation and expulsion as well as accumulation.

  7. Discovery and Refinement of Loci Associated with Lipid Levels

    Science.gov (United States)

    Peloso, Gina M.; Gustafsson, Stefan; Kanoni, Stavroula; Ganna, Andrea; Chen, Jin; Buchkovich, Martin L.; Mora, Samia; Beckmann, Jacques S.; Bragg-Gresham, Jennifer L.; Chang, Hsing-Yi; Demirkan, Ayşe; Den Hertog, Heleen M.; Do, Ron; Donnelly, Louise A.; Ehret, Georg B.; Esko, Tõnu; Feitosa, Mary F.; Ferreira, Teresa; Fischer, Krista; Fontanillas, Pierre; Fraser, Ross M.; Freitag, Daniel F.; Gurdasani, Deepti; Heikkilä, Kauko; Hyppönen, Elina; Isaacs, Aaron; Jackson, Anne U.; Johansson, Åsa; Johnson, Toby; Kaakinen, Marika; Kettunen, Johannes; Kleber, Marcus E.; Li, Xiaohui; Luan, Jian’an; Lyytikäinen, Leo-Pekka; Magnusson, Patrik K.E.; Mangino, Massimo; Mihailov, Evelin; Montasser, May E.; Müller-Nurasyid, Martina; Nolte, Ilja M.; O’Connell, Jeffrey R.; Palmer, Cameron D.; Perola, Markus; Petersen, Ann-Kristin; Sanna, Serena; Saxena, Richa; Service, Susan K.; Shah, Sonia; Shungin, Dmitry; Sidore, Carlo; Song, Ci; Strawbridge, Rona J.; Surakka, Ida; Tanaka, Toshiko; Teslovich, Tanya M.; Thorleifsson, Gudmar; Van den Herik, Evita G.; Voight, Benjamin F.; Volcik, Kelly A.; Waite, Lindsay L.; Wong, Andrew; Wu, Ying; Zhang, Weihua; Absher, Devin; Asiki, Gershim; Barroso, Inês; Been, Latonya F.; Bolton, Jennifer L.; Bonnycastle, Lori L; Brambilla, Paolo; Burnett, Mary S.; Cesana, Giancarlo; Dimitriou, Maria; Doney, Alex S.F.; Döring, Angela; Elliott, Paul; Epstein, Stephen E.; Ingi Eyjolfsson, Gudmundur; Gigante, Bruna; Goodarzi, Mark O.; Grallert, Harald; Gravito, Martha L.; Groves, Christopher J.; Hallmans, Göran; Hartikainen, Anna-Liisa; Hayward, Caroline; Hernandez, Dena; Hicks, Andrew A.; Holm, Hilma; Hung, Yi-Jen; Illig, Thomas; Jones, Michelle R.; Kaleebu, Pontiano; Kastelein, John J.P.; Khaw, Kay-Tee; Kim, Eric; Klopp, Norman; Komulainen, Pirjo; Kumari, Meena; Langenberg, Claudia; Lehtimäki, Terho; Lin, Shih-Yi; Lindström, Jaana; Loos, Ruth J.F.; Mach, François; McArdle, Wendy L; Meisinger, Christa; Mitchell, Braxton D.; Müller, Gabrielle; Nagaraja, Ramaiah; Narisu, Narisu; Nieminen, Tuomo V.M.; Nsubuga, Rebecca N.; Olafsson, Isleifur; Ong, Ken K.; Palotie, Aarno; Papamarkou, Theodore; Pomilla, Cristina; Pouta, Anneli; Rader, Daniel J.; Reilly, Muredach P.; Ridker, Paul M.; Rivadeneira, Fernando; Rudan, Igor; Ruokonen, Aimo; Samani, Nilesh; Scharnagl, Hubert; Seeley, Janet; Silander, Kaisa; Stančáková, Alena; Stirrups, Kathleen; Swift, Amy J.; Tiret, Laurence; Uitterlinden, Andre G.; van Pelt, L. Joost; Vedantam, Sailaja; Wainwright, Nicholas; Wijmenga, Cisca; Wild, Sarah H.; Willemsen, Gonneke; Wilsgaard, Tom; Wilson, James F.; Young, Elizabeth H.; Zhao, Jing Hua; Adair, Linda S.; Arveiler, Dominique; Assimes, Themistocles L.; Bandinelli, Stefania; Bennett, Franklyn; Bochud, Murielle; Boehm, Bernhard O.; Boomsma, Dorret I.; Borecki, Ingrid B.; Bornstein, Stefan R.; Bovet, Pascal; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chambers, John C.; Chen, Yii-Der Ida; Collins, Francis S.; Cooper, Richard S.; Danesh, John; Dedoussis, George; de Faire, Ulf; Feranil, Alan B.; Ferrières, Jean; Ferrucci, Luigi; Freimer, Nelson B.; Gieger, Christian; Groop, Leif C.; Gudnason, Vilmundur; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B.; Hingorani, Aroon; Hirschhorn, Joel N.; Hofman, Albert; Hovingh, G. Kees; Hsiung, Chao Agnes; Humphries, Steve E.; Hunt, Steven C.; Hveem, Kristian; Iribarren, Carlos; Järvelin, Marjo-Riitta; Jula, Antti; Kähönen, Mika; Kaprio, Jaakko; Kesäniemi, Antero; Kivimaki, Mika; Kooner, Jaspal S.; Koudstaal, Peter J.; Krauss, Ronald M.; Kuh, Diana; Kuusisto, Johanna; Kyvik, Kirsten O.; Laakso, Markku; Lakka, Timo A.; Lind, Lars; Lindgren, Cecilia M.; Martin, Nicholas G.; März, Winfried; McCarthy, Mark I.; McKenzie, Colin A.; Meneton, Pierre; Metspalu, Andres; Moilanen, Leena; Morris, Andrew D.; Munroe, Patricia B.; Njølstad, Inger; Pedersen, Nancy L.; Power, Chris; Pramstaller, Peter P.; Price, Jackie F.; Psaty, Bruce M.; Quertermous, Thomas; Rauramaa, Rainer; Saleheen, Danish; Salomaa, Veikko; Sanghera, Dharambir K.; Saramies, Jouko; Schwarz, Peter E.H.; Sheu, Wayne H-H; Shuldiner, Alan R.; Siegbahn, Agneta; Spector, Tim D.; Stefansson, Kari; Strachan, David P.; Tayo, Bamidele O.; Tremoli, Elena; Tuomilehto, Jaakko; Uusitupa, Matti; van Duijn, Cornelia M.; Vollenweider, Peter; Wallentin, Lars; Wareham, Nicholas J.; Whitfield, John B.; Wolffenbuttel, Bruce H.R.; Ordovas, Jose M.; Boerwinkle, Eric; Palmer, Colin N.A.; Thorsteinsdottir, Unnur; Chasman, Daniel I.; Rotter, Jerome I.; Franks, Paul W.; Ripatti, Samuli; Cupples, L. Adrienne; Sandhu, Manjinder S.; Rich, Stephen S.

    2013-01-01

    Low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, and total cholesterol are heritable, modifiable, risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,578 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5×10−8, including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian, and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipids are often associated with cardiovascular and metabolic traits including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio, and body mass index. Our results illustrate the value of genetic data from individuals of diverse ancestries and provide insights into biological mechanisms regulating blood lipids to guide future genetic, biological, and therapeutic research. PMID:24097068

  8. Regulation of alternative splicing in human obesity loci.

    Science.gov (United States)

    Kaminska, Dorota; Käkelä, Pirjo; Nikkola, Elina; Venesmaa, Sari; Ilves, Imre; Herzig, Karl-Heinz; Kolehmainen, Marjukka; Karhunen, Leila; Kuusisto, Johanna; Gylling, Helena; Pajukanta, Päivi; Laakso, Markku; Pihlajamäki, Jussi

    2016-10-01

    Multiple obesity susceptibility loci have been identified by genome-wide association studies, yet the mechanisms by which these loci influence obesity remain unclear. Alternative splicing could contribute to obesity by regulating the transcriptomic and proteomic diversity of genes in these loci. Based on a database search, 72 of the 136 genes at the 13 obesity loci encoded multiple protein isoforms. Thus, alternative splicing of these genes in adipose tissue samples was analyzed from the Metabolic Syndrome in Men population-based study and from two weight loss intervention studies (surgical and very low calorie diet). Alternative splicing was confirmed in 11 genes with PCR capillary electrophoresis in human subcutaneous adipose tissue. Interestingly, differential splicing of TRA2B, BAG6, and MSH5 was observed between lean individuals with normoglycemia and overweight individuals with type 2 diabetes. Of these genes, we detected fat depot-dependent splicing of TRA2B and BAG6 and weight loss-induced regulation of MSH5 splicing in the intervention studies. Finally, body mass index was a major determinant of TRA2B, BAG6, and MSH5 splicing in the combined data. This study provides evidence for alternative splicing in obesity loci, suggesting that alternative splicing at least in part mediates the obesity-associated risk in these loci. © 2016 The Obesity Society.

  9. Creation and maintenance of variation in allorecognition loci

    Directory of Open Access Journals (Sweden)

    Marie Louise Nydam

    2011-12-01

    Full Text Available Allorecognition is the ability of an organism to differentiate self or close relatives from unrelated individuals. Effective allorecognition systems are critical to the survival of organisms; they prevent inbreeding, protect against pathogens, and facilitate fusions between close relatives. Where the loci governing allorecognition outcomes have been identified, the corresponding proteins often exhibit exceptional polymorphism. Two important questions about this polymorphism remain unresolved: how is it created, and how is it maintained. Studies on the evolution of polymorphism in allorecognition loci have traditionally been restricted to the Major Histocompatibility Complex (MHC. But because the genetic bases of several allorecognition systems have now been identified, including alr2 in Hydractinia, FuHC in Botryllus, the het (vic loci in fungi, lagB1 and lagC1 in Dictyostelium, and self-incompatibility (SI loci in several plant families, we are now poised to achieve a clearer understanding of how these loci evolve. In this review, we summarize what is currently know about the evolution of allorecognition loci, highlight open questions, and suggest future directions.

  10. Physical Modeling of Dynamic Coupling between Chromosomal Loci.

    Science.gov (United States)

    Lampo, Thomas J; Kennard, Andrew S; Spakowitz, Andrew J

    2016-01-19

    The motion of chromosomal DNA is essential to many biological processes, including segregation, transcriptional regulation, recombination, and packaging. Physical understanding of these processes would be dramatically enhanced through predictive, quantitative modeling of chromosome dynamics of multiple loci. Using a polymer dynamics framework, we develop a prediction for the correlation in the velocities of two loci on a single chromosome or otherwise connected by chromatin. These predictions reveal that the signature of correlated motion between two loci can be identified by varying the lag time between locus position measurements. In general, this theory predicts that as the lag time interval increases, the dual-loci dynamic behavior transitions from being completely uncorrelated to behaving as an effective single locus. This transition corresponds to the timescale of the stress communication between loci through the intervening segment. This relatively simple framework makes quantitative predictions based on a single timescale fit parameter that can be directly compared to the in vivo motion of fluorescently labeled chromosome loci. Furthermore, this theoretical framework enables the detection of dynamically coupled chromosome regions from the signature of their correlated motion.

  11. Escherichia coli Chromosomal Loci Segregate from Midcell with Universal Dynamics.

    Science.gov (United States)

    Cass, Julie A; Kuwada, Nathan J; Traxler, Beth; Wiggins, Paul A

    2016-06-21

    The structure of the Escherichia coli chromosome is inherently dynamic over the duration of the cell cycle. Genetic loci undergo both stochastic motion around their initial positions and directed motion to opposite poles of the rod-shaped cell during segregation. We developed a quantitative method to characterize cell-cycle dynamics of the E. coli chromosome to probe the chromosomal steady-state mobility and segregation process. By tracking fluorescently labeled chromosomal loci in thousands of cells throughout the entire cell cycle, our method allows for the statistical analysis of locus position and motion, the step-size distribution for movement during segregation, and the locus drift velocity. The robust statistics of our detailed analysis of the wild-type E. coli nucleoid allow us to observe loci moving toward midcell before segregation occurs, consistent with a replication factory model. Then, as segregation initiates, we perform a detailed characterization of the average segregation velocity of loci. Contrary to origin-centric models of segregation, which predict distinct dynamics for oriC-proximal versus oriC-distal loci, we find that the dynamics of loci were universal and independent of genetic position.

  12. Association mapping of loci controlling genetic and environmental interaction of soybean flowering time under various photo-thermal conditions.

    Science.gov (United States)

    Mao, Tingting; Li, Jinyu; Wen, Zixiang; Wu, Tingting; Wu, Cunxiang; Sun, Shi; Jiang, Bingjun; Hou, Wensheng; Li, Wenbin; Song, Qijian; Wang, Dechun; Han, Tianfu

    2017-05-26

    Soybean (Glycine max (L.) Merr.) is a short day plant. Its flowering and maturity time are controlled by genetic and environmental factors, as well the interaction between the two factors. Previous studies have shown that both genetic and environmental factors, mainly photoperiod and temperature, control flowering time of soybean. Additionally, these studies have reported gene × gene and gene × environment interactions on flowering time. However, the effects of quantitative trait loci (QTL) in response to photoperiod and temperature have not been well evaluated. The objectives of the current study were to identify the effects of loci associated with flowering time under different photo-thermal conditions and to understand the effects of interaction between loci and environment on soybean flowering. Different photoperiod and temperature combinations were obtained by adjusting sowing dates (spring sowing and summer sowing) or day-length (12 h, 16 h). Association mapping was performed on 91 soybean cultivars from different maturity groups (MG000-VIII) using 172 SSR markers and 5107 SNPs from the Illumina SoySNP6K iSelectBeadChip. The effects of the interaction between QTL and environments on flowering time were also analysed using the QTXNetwork. Large-effect loci were detected on Gm 11, Gm 16 and Gm 20 as in previous reports. Most loci associated with flowering time are sensitive to photo-thermal conditions. Number of loci associated with flowering time was more under the long day (LD) than under the short day (SD) condition. The variation of flowering time among the soybean cultivars mostly resulted from the epistasis × environment and additive × environment interactions. Among the three candidate loci, i.e. Gm04_4497001 (near GmCOL3a), Gm16_30766209 (near GmFT2a and GmFT2b) and Gm19_47514601 (E3 or GmPhyA3), the Gm04_4497001 may be the key locus interacting with other loci for controlling soybean flowering time. The effects of loci associated

  13. Forest Fragments Surrounded by Sugar Cane Are More Inhospitable to Terrestrial Amphibian Abundance Than Fragments Surrounded by Pasture

    Directory of Open Access Journals (Sweden)

    Paula Eveline Ribeiro D’Anunciação

    2013-01-01

    Full Text Available In recent years, there has been increasing interest in matrix-type influence on forest fragments. Terrestrial amphibians are good bioindicators for this kind of research because of low vagility and high philopatry. This study compared richness, abundance, and species composition of terrestrial amphibians through pitfall traps in two sets of semideciduous seasonal forest fragments in southeastern Brazil, according to the predominant surrounding matrix (sugar cane and pasture. There were no differences in richness, but fragments surrounded by sugar cane had the lowest abundance of amphibians, whereas fragments surrounded by pastures had greater abundance. The most abundant species, Rhinella ornata, showed no biometric differences between fragment groups but like many other amphibians sampled showed very low numbers of individuals in fragments dominated by sugar cane fields. Our data indicate that the sugar cane matrix negatively influences the community of amphibians present in fragments surrounded by this type of land use.

  14. Migraine increases centre-surround suppression for drifting visual stimuli.

    Directory of Open Access Journals (Sweden)

    Josephine Battista

    Full Text Available BACKGROUND: The pathophysiology of migraine is incompletely understood, but evidence points to hyper-responsivity of cortical neurons being a key feature. The basis of hyper-responsiveness is not clear, with an excitability imbalance potentially arising from either reduced inhibition or increased excitation. In this study, we measure centre-surround contrast suppression in people with migraine as a perceptual analogue of the interplay between inhibition and excitation in cortical areas responsible for vision. We predicted that reduced inhibitory function in migraine would reduce perceptual surround suppression. Recent models of neuronal surround suppression incorporate excitatory feedback that drives surround inhibition. Consequently, an increase in excitation predicts an increase in perceptual surround suppression. METHODS AND FINDINGS: Twenty-six people with migraine and twenty approximately age- and gender-matched non-headache controls participated. The perceived contrast of a central sinusoidal grating patch (4 c/deg stationary grating, or 2 c/deg drifting at 2 deg/sec, 40% contrast was measured in the presence and absence of a 95% contrast annular grating (same orientation, spatial frequency, and drift rate. For the static grating, similar surround suppression strength was present in control and migraine groups with the presence of the surround resulting in the central patch appearing to be 72% and 65% of its true contrast for control and migraine groups respectively (t(44 = 0.81, p = 0.42. For the drifting stimulus, the migraine group showed significantly increased surround suppression (t(44 = 2.86, p<0.01, with perceived contrast being on average 53% of actual contrast for the migraine group and 68% for non-headache controls. CONCLUSIONS: In between migraines, when asymptomatic, visual surround suppression for drifting stimuli is greater in individuals with migraine than in controls. The data provides evidence for a

  15. Transancestral fine-mapping of four type 2 diabetes susceptibility loci highlights potential causal regulatory mechanisms

    Science.gov (United States)

    Horikoshi, Momoko; Pasquali, Lorenzo; Wiltshire, Steven; Huyghe, Jeroen R.; Mahajan, Anubha; Asimit, Jennifer L.; Ferreira, Teresa; Locke, Adam E.; Robertson, Neil R.; Wang, Xu; Sim, Xueling; Fujita, Hayato; Hara, Kazuo; Young, Robin; Zhang, Weihua; Choi, Sungkyoung; Chen, Han; Kaur, Ismeet; Takeuchi, Fumihiko; Fontanillas, Pierre; Thuillier, Dorothée; Yengo, Loic; Below, Jennifer E.; Tam, Claudia H.T.; Wu, Ying; Abecasis, Gonçalo; Altshuler, David; Bell, Graeme I.; Blangero, John; Burtt, Noél P.; Duggirala, Ravindranath; Florez, Jose C.; Hanis, Craig L.; Seielstad, Mark; Atzmon, Gil; Chan, Juliana C.N.; Ma, Ronald C.W.; Froguel, Philippe; Wilson, James G.; Bharadwaj, Dwaipayan; Dupuis, Josee; Meigs, James B.; Cho, Yoon Shin; Park, Taesung; Kooner, Jaspal S.; Chambers, John C.; Saleheen, Danish; Kadowaki, Takashi; Tai, E. Shyong; Mohlke, Karen L.; Cox, Nancy J.; Ferrer, Jorge; Zeggini, Eleftheria; Kato, Norihiro; Teo, Yik Ying; Boehnke, Michael; McCarthy, Mark I.; Morris, Andrew P.

    2016-01-01

    To gain insight into potential regulatory mechanisms through which the effects of variants at four established type 2 diabetes (T2D) susceptibility loci (CDKAL1, CDKN2A-B, IGF2BP2 and KCNQ1) are mediated, we undertook transancestral fine-mapping in 22 086 cases and 42 539 controls of East Asian, European, South Asian, African American and Mexican American descent. Through high-density imputation and conditional analyses, we identified seven distinct association signals at these four loci, each with allelic effects on T2D susceptibility that were homogenous across ancestry groups. By leveraging differences in the structure of linkage disequilibrium between diverse populations, and increased sample size, we localised the variants most likely to drive each distinct association signal. We demonstrated that integration of these genetic fine-mapping data with genomic annotation can highlight potential causal regulatory elements in T2D-relevant tissues. These analyses provide insight into the mechanisms through which T2D association signals are mediated, and suggest future routes to understanding the biology of specific disease susceptibility loci. PMID:26911676

  16. Mutations of microsatellite autosomal loci in paternity investigations of the Southern Poland population.

    Science.gov (United States)

    Wojtas, Marta; Piniewska, Danuta; Polańska, Nina; Stawowiak, Agnieszka; Sanak, Marek

    2013-05-01

    In this study, germline mutations were analyzed for 26,040 parent-child allelic transfers among subjects referred to paternity testing and originating from the Slavonic population of the Southern Poland. Mutation rates were estimated for 15 autosomal microsatellite loci: D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and FGA. There were 35 mutation events observed at 11 from 15 analyzed loci. No mutations were found at TH01, D2S1338, D19S433 and TPOX loci. The mutation rate estimate was 0.0019 [0.0012-0.0028 95% CI] for paternal and 0.0004 [0.0002-0.0009] for maternal meiosis, while 25% mutations remained unassigned. The locus-specific mutation rate ranged from 0.0000 [0.0000-0.0014] to 0.0046 [0.0022-0.0087]. Mutations observed in male germlines were more frequent than in female germlines.

  17. Genetic polymorphism of six DNA loci in six population groups of India.

    Science.gov (United States)

    Ahmad, Shazia; Seshadri, M

    2007-08-01

    The genetic profile based on autosomal markers, four microsatellite DNA markers (D8S315, FES, D8S592, and D2S1328) and two minisatellite DNA markers (TPMT and PDGFA), were analyzed in six endogamous populations to examine the effect of geographic and linguistic affiliation on the genetic affinities among the groups. The six populations are from three different states of India and are linguistically different. Marathas from western India speak Marathi, an Indo-European language. Arayas, Muslims, Ezhavas, and Nairs from Kerala state of South India speak Malayalam, and Iyers from Tamil Nadu state speak Tamil. Genomic DNA was extracted from peripheral blood samples of random, normal, healthy individuals. Locus-specific PCR amplification was carried out, followed by electrophoresis of the amplicons and genotyping. All the loci were highly polymorphic and followed Hardy-Weinberg equilibrium, except for loci D8S315 and PDGFA in Iyers and Marathas, respectively. All six loci had high heterozygosity (average heterozygosity ranged from 0.73 to 0.76) and high polymorphism information content (0.57-0.90). The extent of gene differentiation among the six populations (G(ST) = 0.030) was greater than that for four Kerala populations (G(ST) = 0.011), suggesting proximity between the four Kerala populations. This result conforms with the cultural and linguistic background of the populations. The extent of diversity found among the populations probably resulted from the strict endogamous practices that they follow.

  18. Identification of nine new susceptibility loci for testicular cancer, including variants near DAZL and PRDM14

    Science.gov (United States)

    Ruark, Elise; Seal, Sheila; McDonald, Heather; Zhang, Feng; Elliot, Anna; Lau, KingWai; Perdeaux, Elizabeth; Rapley, Elizabeth; Eeles, Rosalind; Peto, Julian; Kote-Jarai, Zsofia; Muir, Kenneth; Nsengimana, Jeremie; Shipley, Janet; Bishop, D. Timothy; Stratton, Michael R; Easton, Douglas F; Huddart, Robert A; Rahman, Nazneen; Turnbull, Clare

    2013-01-01

    Testicular germ cell tumor (TGCT) is the most common cancer in young men and is notable for its high familial risks1,2. To date, six loci associated with TGCT have been reported3-7. From GWAS analysis of 307,291 SNPs in 986 cases and 4,946 controls, we selected for follow-up 694 SNPs, which we genotyped in a further 1,064 TGCT cases and 10,082 controls from the UK. We identified SNPs at nine new loci showing association with TGCT (P<5×10−8), at 1q22, 1q24.1, 3p24.3, 4q24, 5q31.1, 8q13.3, 16q12.1, 17q22 and 21q22.3, which together account for an additional 4-6% of the familial risk of TGCT. The loci include genes plausibly related to TGCT development. PRDM14, at 8q13.3, is essential for early germ cell specification8 whilst DAZL, at 3p24.3, is required for regulation of germ cell development9. Furthermore, PITX1, at 5q31.1 regulates TERT expression, and is the third TGCT locus implicated in telomerase regulation10. PMID:23666240

  19. Experiments on the Microenvironment and Breathing of a Person in Isothermal and Stratified Surroundings

    DEFF Research Database (Denmark)

    Nielsen, Peter V.; Jensen, Rasmus Lund; Litewnicki, Michal;

    2009-01-01

    This study investigates the characteristics of human exhalation. Experiments are performed on a breathing thermal manikin in a test room. The manikin is heated, and an artificial lung is used to generate varying air flows with specific flow rates and temperatures for breathing. Smoke visualisation...... is used to show the formation, movement and disappearance of the exhalation jets from both nose and mouth. The exhalation of breathing without ventilation in the room, and with stratified surroundings (displacement ventilation) is analysed....

  20. Enrichment of putative PAX8 target genes at serous epithelial ovarian cancer susceptibility loci.

    Science.gov (United States)

    Kar, Siddhartha P; Adler, Emily; Tyrer, Jonathan; Hazelett, Dennis; Anton-Culver, Hoda; Bandera, Elisa V; Beckmann, Matthias W; Berchuck, Andrew; Bogdanova, Natalia; Brinton, Louise; Butzow, Ralf; Campbell, Ian; Carty, Karen; Chang-Claude, Jenny; Cook, Linda S; Cramer, Daniel W; Cunningham, Julie M; Dansonka-Mieszkowska, Agnieszka; Doherty, Jennifer Anne; Dörk, Thilo; Dürst, Matthias; Eccles, Diana; Fasching, Peter A; Flanagan, James; Gentry-Maharaj, Aleksandra; Glasspool, Rosalind; Goode, Ellen L; Goodman, Marc T; Gronwald, Jacek; Heitz, Florian; Hildebrandt, Michelle A T; Høgdall, Estrid; Høgdall, Claus K; Huntsman, David G; Jensen, Allan; Karlan, Beth Y; Kelemen, Linda E; Kiemeney, Lambertus A; Kjaer, Susanne K; Kupryjanczyk, Jolanta; Lambrechts, Diether; Levine, Douglas A; Li, Qiyuan; Lissowska, Jolanta; Lu, Karen H; Lubiński, Jan; Massuger, Leon F A G; McGuire, Valerie; McNeish, Iain; Menon, Usha; Modugno, Francesmary; Monteiro, Alvaro N; Moysich, Kirsten B; Ness, Roberta B; Nevanlinna, Heli; Paul, James; Pearce, Celeste L; Pejovic, Tanja; Permuth, Jennifer B; Phelan, Catherine; Pike, Malcolm C; Poole, Elizabeth M; Ramus, Susan J; Risch, Harvey A; Rossing, Mary Anne; Salvesen, Helga B; Schildkraut, Joellen M; Sellers, Thomas A; Sherman, Mark; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa; Terry, Kathryn L; Tworoger, Shelley S; Walsh, Christine; Wentzensen, Nicolas; Whittemore, Alice S; Wu, Anna H; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Freedman, Matthew L; Gayther, Simon A; Pharoah, Paul D P; Lawrenson, Kate

    2017-02-14

    Genome-wide association studies (GWAS) have identified 18 loci associated with serous ovarian cancer (SOC) susceptibility but the biological mechanisms driving these findings remain poorly characterised. Germline cancer risk loci may be enriched for target genes of transcription factors (TFs) critical to somatic tumorigenesis. All 615 TF-target sets from the Molecular Signatures Database were evaluated using gene set enrichment analysis (GSEA) and three GWAS for SOC risk: discovery (2196 cases/4396 controls), replication (7035 cases/21 693 controls; independent from discovery), and combined (9627 cases/30 845 controls; including additional individuals). The PAX8-target gene set was ranked 1/615 in the discovery (PGSEA<0.001; FDR=0.21), 7/615 in the replication (PGSEA=0.004; FDR=0.37), and 1/615 in the combined (PGSEA<0.001; FDR=0.21) studies. Adding other genes reported to interact with PAX8 in the literature to the PAX8-target set and applying an alternative to GSEA, interval enrichment, further confirmed this association (P=0.006). Fifteen of the 157 genes from this expanded PAX8 pathway were near eight loci associated with SOC risk at P<10(-5) (including six with P<5 × 10(-8)). The pathway was also associated with differential gene expression after shRNA-mediated silencing of PAX8 in HeyA8 (PGSEA=0.025) and IGROV1 (PGSEA=0.004) SOC cells and several PAX8 targets near SOC risk loci demonstrated in vitro transcriptomic perturbation. Putative PAX8 target genes are enriched for common SOC risk variants. This finding from our agnostic evaluation is of particular interest given that PAX8 is well-established as a specific marker for the cell of origin of SOC.

  1. Genome-wide interaction-based association analysis identified multiple new susceptibility Loci for common diseases.

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2011-03-01

    Full Text Available Genome-wide interaction-based association (GWIBA analysis has the potential to identify novel susceptibility loci. These interaction effects could be missed with the prevailing approaches in genome-wide association studies (GWAS. However, no convincing loci have been discovered exclusively from GWIBA methods, and the intensive computation involved is a major barrier for application. Here, we developed a fast, multi-thread/parallel program named "pair-wise interaction-based association mapping" (PIAM for exhaustive two-locus searches. With this program, we performed a complete GWIBA analysis on seven diseases with stringent control for false positives, and we validated the results for three of these diseases. We identified one pair-wise interaction between a previously identified locus, C1orf106, and one new locus, TEC, that was specific for Crohn's disease, with a Bonferroni corrected P < 0.05 (P = 0.039. This interaction was replicated with a pair of proxy linked loci (P = 0.013 on an independent dataset. Five other interactions had corrected P < 0.5. We identified the allelic effect of a locus close to SLC7A13 for coronary artery disease. This was replicated with a linked locus on an independent dataset (P = 1.09 × 10⁻⁷. Through a local validation analysis that evaluated association signals, rather than locus-based associations, we found that several other regions showed association/interaction signals with nominal P < 0.05. In conclusion, this study demonstrated that the GWIBA approach was successful for identifying novel loci, and the results provide new insights into the genetic architecture of common diseases. In addition, our PIAM program was capable of handling very large GWAS datasets that are likely to be produced in the future.

  2. Transferability and Fine Mapping of genome-wide associated loci for lipids in African Americans

    Directory of Open Access Journals (Sweden)

    Adeyemo Adebowale

    2012-09-01

    Full Text Available Abstract Background A recent, large genome-wide association study (GWAS of European ancestry individuals has identified multiple genetic variants influencing serum lipids. Studies of the transferability of these associations to African Americans remain few, an important limitation given interethnic differences in serum lipids and the disproportionate burden of lipid-associated metabolic diseases among African Americans. Methods We attempted to evaluate the transferability of 95 lipid-associated loci recently identified in European ancestry individuals to 887 non-diabetic, unrelated African Americans from a population-based sample in the Washington, DC area. Additionally, we took advantage of the generally reduced linkage disequilibrium among African ancestry populations in comparison to European ancestry populations to fine-map replicated GWAS signals. Results We successfully replicated reported associations for 10 loci (CILP2/SF4, STARD3, LPL, CYP7A1, DOCK7/ANGPTL3, APOE, SORT1, IRS1, CETP, and UBASH3B. Through trans-ethnic fine-mapping, we were able to reduce associated regions around 75% of the loci that replicated. Conclusions Between this study and previous work in African Americans, 40 of the 95 loci reported in a large GWAS of European ancestry individuals also influence lipid levels in African Americans. While there is now evidence that the lipid-influencing role of a number of genetic variants is observed in both European and African ancestry populations, the still considerable lack of concordance highlights the importance of continued ancestry-specific studies to elucidate the genetic underpinnings of these traits.

  3. Genomic study in Mexicans identifies a new locus for triglycerides and refines European lipid loci

    Science.gov (United States)

    Weissglas-Volkov, Daphna; Aguilar-Salinas, Carlos A.; Nikkola, Elina; Deere, Kerry A.; Cruz-Bautista, Ivette; Arellano-Campos, Olimpia; Muñoz-Hernandez, Linda Liliana; Gomez-Munguia, Lizeth; Ordoñez-Sánchez, Maria Luisa; Reddy, Prasad MV Linga; Lusis, Aldons J.; Matikainen, Niina; Taskinen, Marja-Riitta; Riba, Laura; Cantor, Rita M.; Sinsheimer, Janet S.; Tusie-Luna, Teresa; Pajukanta, Päivi

    2013-01-01

    Background The Mexican population and others with Amerindian heritage exhibit a substantial predisposition to dyslipidemias and coronary heart disease. Yet, these populations remain underinvestigated by genomic studies, and to date, no genome-wide association (GWA) studies have been reported for lipids in these rapidly expanding populations. Methods and Findings We performed a two-stage GWA study for hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) in Mexicans (n=4,361) and identified a novel Mexican-specific genome-wide significant locus for serum triglycerides (TGs) near the Niemann-Pick type C1 protein (NPC1) gene (P=2.43×10−08). Furthermore, three European loci for TGs (APOA5, GCKR, and LPL) and four loci for HDL-C (ABCA1, CETP, LIPC and LOC55908) reached genome-wide significance in Mexicans. We utilized cross-ethnic mapping to narrow three European TG GWA loci, APOA5, MLXIPL, and CILP2 that were wide and contained multiple candidate variants in the European scan. At the APOA5 locus, this reduced the most likely susceptibility variants to one, rs964184. Importantly, our functional analysis demonstrated a direct link between rs964184 and postprandial serum apoAV protein levels, supporting rs964184 as the causative variant underlying the European and Mexican GWA signal. Overall, 52 of the 100 reported associations from European lipid GWA meta-analysis generalized to Mexicans. However, in 82 of the 100 European GWA loci, a different variant other than the European lead/best-proxy variant had the strongest regional evidence of association in Mexicans. Conclusions This first Mexican GWA study of lipids identified a novel GWA locus for high TG levels; utilized the inter-population heterogeneity to significantly restrict three previously known European GWA signals; and surveyed whether the European lipid GWA SNPs extend to the Mexican population. PMID:23505323

  4. Multiple loci associated with renal function in African Americans.

    Directory of Open Access Journals (Sweden)

    Daniel Shriner

    Full Text Available The incidence of chronic kidney disease varies by ethnic group in the USA, with African Americans displaying a two-fold higher rate than European Americans. One of the two defining variables underlying staging of chronic kidney disease is the glomerular filtration rate. Meta-analysis in individuals of European ancestry has identified 23 genetic loci associated with the estimated glomerular filtration rate (eGFR. We conducted a follow-up study of these 23 genetic loci using a population-based sample of 1,018 unrelated admixed African Americans. We included in our follow-up study two variants in APOL1 associated with end-stage kidney disease discovered by admixture mapping in admixed African Americans. To address confounding due to admixture, we estimated local ancestry at each marker and global ancestry. We performed regression analysis stratified by local ancestry and combined the resulting regression estimates across ancestry strata using an inverse variance-weighted fixed effects model. We found that 11 of the 24 loci were significantly associated with eGFR in our sample. The effect size estimates were not significantly different between the subgroups of individuals with two copies of African ancestry vs. two copies of European ancestry for any of the 11 loci. In contrast, allele frequencies were significantly different at 10 of the 11 loci. Collectively, the 11 loci, including four secondary signals revealed by conditional analyses, explained 14.2% of the phenotypic variance in eGFR, in contrast to the 1.4% explained by the 24 loci in individuals of European ancestry. Our findings provide insight into the genetic basis of variation in renal function among admixed African Americans.

  5. Diversity of nuclear short tandem repeat loci in representative sample of North-eastern Bosnian and Herzegovina population

    Directory of Open Access Journals (Sweden)

    Hadžiavdić Vesna

    2012-01-01

    Full Text Available Diversity of nuclear microsatellite markers were analyzed in a reference sample of the population of northeast Bosnia and Herzegovina. 437 samples taken from unrelated individuals were processed and three samples of paternity proof were shown. Detection effectiveness profile of the research, points to a valid choice of method of extraction, amplification and genotyping short tandem repeat (STR loci with PowerPlextm16 kit. Genetic analysis of allelic variants of the 15 STR loci PowerPlextm16 kit detected 17 samples determined as rare allelic variants or microvariants. Samples were divided into 15 different allelic variants at 7 different loci, and are: in locus D7S820, D16S539, D3S1358, D18S51, PENTA D, PENTA E and in locus vWA. Genetic analysis of mutations in cases of paternity determined three examples of single-step mutations in the loci FGA, Penta D and D3S1358. Genetic analysis of observed STR loci detected three allelic variant of genotype combination 7/10/11.3 in locus D7S820 Type II. Population genetic analysis of STR loci in a representative sample of the population of northeast Bosnia and Herzegovina included the application of the assessment tests of within-population genetic diversity and interpopulation diversity, as well as genetic differentiation between populations: North-eastern Bosnia and Herzegovina (BH and BH general reference, then the Croatian population, Macedonian, Serbian and Slovenian. Based on the result analysis of specific forensic parameters, it can be assumed that the most informative marker is PENTA E for population genetic analysis and forensic testing in the population of northeast Bosnia and Herzegovina. Research results fit regional STR database of this part of Europe.

  6. Unmasking Novel Loci for Internal Phosphorus Utilization Efficiency in Rice Germplasm through Genome-Wide Association Analysis

    Science.gov (United States)

    Wissuwa, Matthias; Kondo, Katsuhiko; Fukuda, Takuya; Mori, Asako; Rose, Michael T.; Pariasca-Tanaka, Juan; Kretzschmar, Tobias; Haefele, Stephan M.; Rose, Terry J.

    2015-01-01

    Depletion of non-renewable rock phosphate reserves and phosphorus (P) fertilizer price increases has renewed interest in breeding P-efficient varieties. Internal P utilization efficiency (PUE) is of prime interest because there has been no progress to date in breeding for high PUE. We characterized the genotypic variation for PUE present within the rice gene pool by using a hydroponic system that assured equal plant P uptake, followed by mapping of loci controlling PUE via Genome-Wide Association Studies (GWAS). Loci associated with PUE were mapped on chromosomes 1, 4, 11 and 12. The highest PUE was associated with a minor indica-specific haplotype on chromosome 1 and a rare aus-specific haplotype on chromosome 11. Comparative variant and expression analysis for genes contained within the chromosome 1 haplotype identified high priority candidate genes. Differences in coding regions and expression patterns between genotypes of contrasting haplotypes, suggested functional alterations for two predicted nucleic acid-interacting proteins that are likely causative for the observed differences in PUE. The loci reported here are the first identified for PUE in any crop that is not confounded by differential P uptake among genotypes. Importantly, modern rice varieties lacked haplotypes associated with superior PUE, and would thus benefit from targeted introgressions of these loci from traditional donors to improve plant growth in phosphorus-limited cropping systems. PMID:25923470

  7. 3D Room Visualization on Android Based Mobile Device (with Philips™’ Surround Sound Music Player

    Directory of Open Access Journals (Sweden)

    Durio Etgar

    2012-12-01

    Full Text Available This project’s specifically purposed as a demo application, so anyone can get the experience of a surround audio room without having to physically involved to it, with a main idea of generating a 3D surround sound room scenery coupled with surround sound in a handier package, namely, a “Virtual Listen Room”. Virtual Listen Room set a foundation of an innovative visualization that later will be developed and released as one of way of portable advertisement. This application was built inside of Android environment. Android device had been chosen as the implementation target, since it leaves massive development spaces and mostly contains essential components needed on this project, including graphic processor unit (GPU.  Graphic manipulation can be done using an embedded programming interface called OpenGL ES, which is planted in all Android devices generally. Further, Android has a Accelerometer Sensor that is needed to be coupled with scene to produce a dynamic movement of the camera. Surround sound effect can be reached with a decoder from Phillips called MPEG Surround Sound Decoder. To sum the whole project, we got an application with sensor-dynamic 3D room visualization coupled with Philips’ Surround Sound Music Player. We can manipulate several room’s properties; Subwoofer location, Room light, and how many speakers inside it, the application itself works well despite facing several performance problems before, later to be solved. [Keywords : Android,Visualization,Open GL; ES; 3D; Surround Sensor

  8. 6.1 channel general planar surround sound system

    Institute of Scientific and Technical Information of China (English)

    XIE Bosun

    2001-01-01

    A new 6.1 channel surround sound system and its two signal mixing methods are proposed. Theoretical and experimental results show that the system is able to recreate 360°sound image in horizontal plane. Especially, compared with current 5.1 channel system, lateral and rear image of the new system is improved obviously. Therefore it is suitable to be used as a general surround sound system. It is also proved that, the new system is fully compatible with 5.1 channel system, and current methods are available to record 6.1 channel signals.

  9. Linking disadvantaged housing areas to the surrounding city

    DEFF Research Database (Denmark)

    Stender, Marie

    Several disadvantaged social housing areas in Denmark are currently undergo-ing thorough physical refurbishments, aiming to integrate them better with the surrounding city. The ambition is to attract new users and residents by opening up the borders of the area and establish attractive, new...... that especially eve-ryday-route strategies adding new public functions within the area can pave the way for integration with the surroundings. The applicability of such strategies is however highly dependent on the context, location and existing image of the ar-ea. Social distance may sustain though physical...

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

    Science.gov (United States)

    Maisano Delser, Pierpaolo; Fuselli, Silvia

    2013-05-01

    Understanding the role of inheritance in individual variation in drug response is the focus of pharmacogenetics (PGx). A key part of this understanding is quantifying the role of genetic ancestry in this phenotypic outcome. To provide insight into the relationship between ethnicity and drug response, this study first infers the global distribution of PGx variation and defines its structure. Second, the study evaluates if geographic population structure stems from all PGx loci in general, or if structure is caused by specific genes. Lastly, we identify the genetic variants contributing the greatest proportion of such structure. Our study describes the global genetic structure of PGx loci across the 52 populations of the Human Genome Diversity Cell-Line Panel, the most inclusive set of human populations freely available for studies on human genetic variation. By analysing genetic variation at 1,001 single nucleotide polymorphisms (SNPs) involved in biotransformation of exogenous substances, we describe the between-populations PGx variation, as well geographical groupings of diversity. In addition, with discriminant analysis of principal component (DAPC), we infer how many and which groups of populations are supported by PGx variation, and identify which SNPs actually contribute to the PGx structure between such groups. Our results show that intergenic, synonymous and non-synonymous SNPs show similar levels of genetic variation across the globe. Conversely, loci coding for Cytochrome P450s (mainly metabolizing exogenous substances) show significantly higher levels of genetic diversity between populations than the other gene categories. Overall, genetic variation at PGx loci correlates with geographic distances between populations, and the apportionment of genetic variation is similar to that observed for the rest of the genome. In other words, the pattern of PGx variation has been mainly shaped by the demographic history of our species, as in the case of most of our

  11. Genetic polymorphism of milk protein loci in Argentinian Holstein cattle

    Directory of Open Access Journals (Sweden)

    Bonvillani Adriana Gloria

    2000-01-01

    Full Text Available Some alleles of milk protein loci are associated with superior cheese production characteristics. The genetic polymorphism of the milk protein loci alphas1-casein, beta-casein, k-casein and beta-lactoglobulin was examined in Argentinian Holstein cattle. Samples from 12 herds of four regions of Córdoba were analyzed by starch gel electrophoresis. The chi² test was used to assess whether the populations were in Hardy-Weinberg equilibrium. Genotypic diversity was analyzed by the Shannon-Weaver index. The observed genotypic frequencies were analyzed by Hedrick's genetic identity and the genetic distance of Balakrishnan and Sanghvi. The allelic and genotypic frequencies were similar to those of other Holstein populations. The genotypic frequencies of the alphas1-casein and beta-casein loci were in equilibrium, whereas in some populations the k-casein and beta-lactoglobulin loci were not. According to the Shannon-Weaver index the total genetic diversity within each herd was greater than 96%. The high values of identity agreed with the low genetic distances among populations. We conclude that there is extensive genetic homogeneity in Holstein cattle in Córdoba Province and that it would be feasible to select for B alleles at the k-casein and b-lactoglobulin loci in order to improve the quality of milk available for cheese manufacturing.

  12. Isolation and characterization of the bovine microsatellite loci.

    Science.gov (United States)

    Chung, H Y; Kim, T H; Choi, B H; Jang, G W; Lee, J W; Lee, K T; Ha, J M

    2006-12-01

    Microsatellite loci were isolated using five repetitive probes for Korean native cattle. Eleven microsatellite loci were developed based on a biotin hybrid capture method, and enrichment of the genomic libraries (AAAT, TG, AG, T, and TGC repeats) was performed using Sau3AI adapters. The isolated markers were tested in two half-sib Korean cattle families and four imported breeds (Angus, Limousine, Holstein, and Shorthorn). Nine informative microsatellite loci were observed, and two microsatellite loci were revealed as monomorphic in Korean cattle. In the imported breeds, however, all of the markers were informative. In total, 213 alleles were obtained at the 11 loci across five breeds, and the average number of alleles found per locus, considering all populations, was 4.26. Heterozygosity was 0.71 (expected) and 0.57 (observed). The range of the polymorphic information content for the markers in all cattle populations was 0.43-0.69. Eleven percent of genetic variation was attributed to differentiation between populations as determined by the mean F (ST) values. The remaining 89% corresponded to differences among individuals. The isolated markers may be used to identify and classify the local breeds on a molecular basis.

  13. Plasmodium genetic loci linked to host cytokine and chemokine responses.

    Science.gov (United States)

    Pattaradilokrat, S; Li, J; Wu, J; Qi, Y; Eastman, R T; Zilversmit, M; Nair, S C; Huaman, M C; Quinones, M; Jiang, H; Li, N; Zhu, J; Zhao, K; Kaneko, O; Long, C A; Su, X-z

    2014-01-01

    Both host and parasite factors contribute to disease severity of malaria infection; however, the molecular mechanisms responsible for the disease and the host-parasite interactions involved remain largely unresolved. To investigate the effects of parasite factors on host immune responses and pathogenesis, we measured levels of plasma cytokines/chemokines (CCs) and growth rates in mice infected with two Plasmodium yoelii strains having different virulence phenotypes and in progeny from a genetic cross of the two parasites. Quantitative trait loci (QTL) analysis linked levels of many CCs, particularly IL-1β, IP-10, IFN-γ, MCP-1 and MIG, and early parasite growth rate to loci on multiple parasite chromosomes, including chromosomes 7, 9, 10, 12 and 13. Comparison of the genome sequences spanning the mapped loci revealed various candidate genes. The loci on chromosomes 7 and 13 had significant (P<0.005) additive effects on IL-1β, IL-5 and IP-10 responses, and the chromosome 9 and 12 loci had significant (P=0.017) interaction. Infection of knockout mice showed critical roles of MCP-1 and IL-10 in parasitemia control and host mortality. These results provide important information for a better understanding of malaria pathogenesis and can be used to examine the role of these factors in human malaria infection.

  14. Sexual dimorphisms in genetic loci linked to body fat distribution

    Science.gov (United States)

    Pulit, Sara L.; Karaderi, Tugce

    2017-01-01

    Obesity is a chronic condition associated with increased morbidity and mortality and is a risk factor for a number of other diseases including type 2 diabetes and cardiovascular disease. Obesity confers an enormous, costly burden on both individuals and public health more broadly. Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes. Body fat distribution is distinct from overall obesity in measurement, but studies of body fat distribution can yield insights into the risk factors for and causes of overall obesity. Sexual dimorphism in body fat distribution is present throughout life. Though sexual dimorphism is subtle in early stages of life, it is attenuated in puberty and during menopause. This phenomenon could be, at least in part, due to the influence of sex hormones on the trait. Findings from recent large genome-wide association studies (GWAS) for various measures of body fat distribution (including waist-to-hip ratio, hip or waist circumference, trunk fat percentage and the ratio of android and gynoid fat percentage) emphasize the strong sexual dimorphism in the genetic regulation of fat distribution traits. Importantly, sexual dimorphism is not observed for overall obesity (as assessed by body mass index or total fat percentage). Notably, the genetic loci associated with body fat distribution, which show sexual dimorphism, are located near genes that are expressed in adipose tissues and/or adipose cells. Considering the epidemiological and genetic evidence, sexual dimorphism is a prominent feature of body fat distribution. Research that specifically focuses on sexual dimorphism in fat distribution can provide novel insights into human physiology and into the development of obesity and its comorbidities, as well as yield biological clues that will aid in the improvement of disease prevention and treatment. PMID:28073971

  15. Conserved generation of short products at piRNA loci

    Directory of Open Access Journals (Sweden)

    Khorshid Mohsen

    2011-01-01

    Full Text Available Abstract Background The piRNA pathway operates in animal germ lines to ensure genome integrity through retrotransposon silencing. The Piwi protein-associated small RNAs (piRNAs guide Piwi proteins to retrotransposon transcripts, which are degraded and thereby post-transcriptionally silenced through a ping-pong amplification process. Cleavage of the retrotransposon transcript defines at the same time the 5' end of a secondary piRNA that will in turn guide a Piwi protein to a primary piRNA precursor, thereby amplifying primary piRNAs. Although several studies provided evidence that this mechanism is conserved among metazoa, how the process is initiated and what enzymatic activities are responsible for generating the primary and secondary piRNAs are not entirely clear. Results Here we analyzed small RNAs from three mammalian species, seeking to gain further insight into the mechanisms responsible for the piRNA amplification loop. We found that in all these species piRNA-directed targeting is accompanied by the generation of short sequences that have a very precisely defined length, 19 nucleotides, and a specific spatial relationship with the guide piRNAs. Conclusions This suggests that the processing of the 5' product of piRNA-guided cleavage occurs while the piRNA target is engaged by the Piwi protein. Although they are not stabilized through methylation of their 3' ends, the 19-mers are abundant not only in testes lysates but also in immunoprecipitates of Miwi and Mili proteins. They will enable more accurate identification of piRNA loci in deep sequencing data sets.

  16. Ecological mechanisms linking protected areas to surrounding lands.

    Science.gov (United States)

    Hansen, Andrew J; DeFries, Ruth

    2007-06-01

    Land use is expanding and intensifying in the unprotected lands surrounding many of the world's protected areas. The influence of this land use change on ecological processes is poorly understood. The goal of this paper is to draw on ecological theory to provide a synthetic framework for understanding how land use change around protected areas may alter ecological processes and biodiversity within protected areas and to provide a basis for identifying scientifically based management alternatives. We first present a conceptual model of protected areas embedded within larger ecosystems that often include surrounding human land use. Drawing on case studies in this Invited Feature, we then explore a comprehensive set of ecological mechanisms by which land use on surrounding lands may influence ecological processes and biodiversity within reserves. These mechanisms involve changes in ecosystem size, with implications for minimum dynamic area, species-area effect, and trophic structure; altered flows of materials and disturbances into and out of reserves; effects on crucial habitats for seasonal and migration movements and population source/sink dynamics; and exposure to humans through hunting, poaching, exotics species, and disease. These ecological mechanisms provide a basis for assessing the vulnerability of protected areas to land use. They also suggest criteria for designing regional management to sustain protected areas in the context of surrounding human land use. These design criteria include maximizing the area of functional habitats, identifying and maintaining ecological process zones, maintaining key migration and source habitats, and managing human proximity and edge effects.

  17. Metrizamide demonstration of the subarachnoid space surrounding the Gasserian ganglion

    Energy Technology Data Exchange (ETDEWEB)

    Christmann, D.; Babin, E.

    1980-05-01

    The chance opacification of the subarachnoid space surrounding the Gasserian ganglion, observed during metrizamide basal cisternography, is reported. This is compared to similar demonstrations of the optic subarachnoid space. Such infrequently observed images should be known because they may be related to the occurrence of trigeminal neuralgia.

  18. Orientation-tuned surround suppression in mouse visual cortex

    NARCIS (Netherlands)

    Self, Matthew W; Lorteije, Jeannette A M; Vangeneugden, Joris; van Beest, Enny H; Grigore, Mihaela E; Levelt, Christiaan N; Heimel, J.A.; Roelfsema, Pieter R

    2014-01-01

    The firing rates of neurons in primary visual cortex (V1) are suppressed by large stimuli, an effect known as surround suppression. In cats and monkeys, the strength of suppression is sensitive to orientation; responses to regions containing uniform orientations are more suppressed than those contai

  19. Challenges Surrounding the Education of Children with Chronic Diseases

    Science.gov (United States)

    Gordon, Maria, Ed.

    2016-01-01

    While governing bodies have mandated that all students have the right to an education, with disabled students treated to the same rights and opportunities as non-disabled students, policymakers do not always agree on what all-inclusive education should look like. "Challenges Surrounding the Education of Children with Chronic Diseases"…

  20. Military installation sequestered more carbon than surrounding areas

    Science.gov (United States)

    Zhao, S.; Liu, S.; Li, Z.; Sohl, T.

    2008-12-01

    Land use activities greatly affect the temporal trends and spatial patterns of regional land-atmospheric exchange of carbon. Military installations generally have drastically different land management strategies from surrounding areas, and the carbon consequences have never been quantified and assessed. Here, we used the General Ensemble Biogeochemical Modeling System (GEMS) to simulate and compare ecosystem carbon dynamics between Fort Benning and surrounding areas from 1992 to 2050. GEMS was driven by unique combinations of spatial and temporal dynamics of major driving forces, such as climate, soil properties, nitrogen deposition, and land use and land cover changes (predicted by FOREcasting SCEnarios of land cover change (FORE-SCE)). Our results indicated that the military installation sequestered more carbon than surrounding areas (0.77 vs. 0.16 Mg C ha-1 y-1 averaged from 1992 to 2007). Differences in land use activities were the primary cause behind the difference in carbon sequestration rates. From 1992 to 2007, no urban/residential expansion occurred at the installation, and transitional barren (primarily caused by forest harvesting) slightly increased from 0 to 0.2%. In contrast, urban land increased from 5.6 to 7.6% and transitional barren increased from 0.1 to 0.7% in the surrounding areas. Live biomass accumulation accounted for most of the carbon sink in both Fort Benning and surrounding areas (0.75 vs. 0.15 Mg C ha-1 y-1), while soil organic carbon accumulation was small (0.02 vs. 0.01 Mg C ha- 1 y-1), suggesting biomass removal caused by urbanization and harvesting resulted in much less carbon sequestration in surrounding areas. Fort Benning is likely to sequester more carbon in the future, although the rate of carbon sequestered per year will gradually reduce. The future carbon source/sink strength in the surrounding areas varied greatly, from a small sink to a strong source, depending on the path of land use change (e.g., increase of clear

  1. Development of polymorphic microsatellite loci for conservation genetic studies of the coral reef fish Centropyge bicolor.

    Science.gov (United States)

    Herrera, M; Saenz-Agudelo, P; Nanninga, G B; Berumen, M L

    2015-09-01

    A total of 23 novel polymorphic microsatellite marker loci were developed for the angelfish Centropyge bicolor through 454 sequencing, and further tested on two spatially separated populations (90 individuals each) from Kimbe Bay in Papua New Guinea. The mean ± s.e. number of alleles per locus was 14·65 ± 1·05, and mean ± s.e. observed (HO ) and expected (HE ) heterozygosity frequencies were 0·676 ± 0·021 and 0·749 ± 0·018, respectively. The markers reported here constitute the first specific set for this genus and will be useful for future conservation genetic studies in the Indo-Pacific region.

  2. Advancing genetic theory and application by metabolic quantitative trait loci analysis.

    Science.gov (United States)

    Kliebenstein, Danielj

    2009-06-01

    This review describes recent advances in the analysis of metabolism using quantitative genetics. It focuses on how recent metabolic quantitative trait loci (QTL) studies enhance our understanding of the genetic architecture underlying naturally variable phenotypes and the impact of this fundamental research on agriculture, specifically crop breeding. In particular, the role of whole-genome duplications in generating quantitative genetic variation within a species is highlighted and the potential uses of this phenomenon presented. Additionally, the review describes how new observations from metabolic QTL mapping analyses are helping to shape and expand the concepts of genetic epistasis.

  3. A global analysis of Y-chromosomal haplotype diversity for 23 STR loci

    OpenAIRE

    Purps, J.; Siegert, S.; Willuweit, S.; Nagy, M.; C. Alves; Salazar, R.; Angustia, S.M.T.; Santos,L.H.; Anslinger, K.; Bayer, B.; Ayub, Q.; Wei, W; Xue, Y.; Tyler-Smith, C; Bafalluy, M.B.

    2014-01-01

    In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129 different\\ud populations in 51 countries. These chromosomes were typed for 23 short-tandem repeat (STR) loci\\ud (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439,\\ud DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643)\\ud and using the PowerPlex Y23 System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic\\ud spectra of...

  4. Genetic polymorphism of 15 STR loci in El Salvador.

    Science.gov (United States)

    Muñoz, Pablo; Pinto de Erazo, Eugenia Leticia; Baeza, Carlos; Arroyo-Pardo, Eduardo; López-Parra, Ana Maria

    2015-09-01

    The aim of this study was to estimate the allelic frequencies of the 15 short tandem repeat (STR) loci included in AmpFlSTRIdentifiler PCR Amplification Kit. Biological samples were obtained from 109 unrelated individuals from El Salvador. Allelic frequencies and forensic parameters were calculated. All loci showed no departure from Hardy-Weinberg equilibrium after Bonferroni correction. The obtained frequencies were compared with other previously reported population data. The multidimensional scaling plot and the neighbor-joining phylogeny supported a high native Mesoamerican contribution.

  5. Strategie di spazializzazione dei contenuti nel GeniusLoci Digitale

    Directory of Open Access Journals (Sweden)

    Davide Gasperi

    2013-07-01

    Full Text Available GeniusLoci Digitale is a software architecture of virtual tour that integrates various multimedia technologies (3D computer graphics, panoramas, dynamic maps, movies, pictures to represent the identity of places. The designer is interested in reproducing virtually complex aspects that define a context, which means the effect of meaning that distinguishes one place. GeniusLoci Digitale is in fact an architecture that evolves in search of a reproductive and communicative function which is recognizable to extend its development to the Open Source community.

  6. 52 Genetic Loci Influencing Myocardial Mass

    DEFF Research Database (Denmark)

    van der Harst, Pim; van Setten, Jessica; Verweij, Niek

    2016-01-01

    BACKGROUND: Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect......, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially...

  7. Confirmation of novel type 1 diabetes risk loci in families

    DEFF Research Database (Denmark)

    Cooper, J D; Howson, J M M; Smyth, D

    2012-01-01

    Over 50 regions of the genome have been associated with type 1 diabetes risk, mainly using large case/control collections. In a recent genome-wide association (GWA) study, 18 novel susceptibility loci were identified and replicated, including replication evidence from 2,319 families. Here, we......, the Type 1 Diabetes Genetics Consortium (T1DGC), aimed to exclude the possibility that any of the 18 loci were false-positives due to population stratification by significantly increasing the statistical power of our family study....

  8. Improving DNA data exchange: validation studies on a single 6 dye STR kit with 24 loci.

    Science.gov (United States)

    Martín, Pablo; de Simón, Lourdes Fernández; Luque, Gracia; Farfán, María José; Alonso, Antonio

    2014-11-01

    The idea of developing a new multiplex STR amplification system was conceived in 2011 as an effective way to implement the new European standard set (ESS) of 12 STR markers adopted by The Council of the European Union in 2009 while maintaining an effective compatibility and information exchange with the historical DNA profiles contained in the Spanish national DNA database (around 200,000 DNA profiles) mainly based on the 13 CODIS core STR loci plus D19S433 and D2S1338 markers. With this goal in mind we proposed to test and validate a single STR amplification system for simultaneous analysis of 21 STR markers covering both CODIS and ESS core STR loci plus three additional markers (D19S433, D2S1338, and SE33) also contained in commonly used STR kits and national DNA databases. In 2012, we started the first beta-testing with a 6-dye STR kit prototype containing 24 loci (now known as the GlobalFiler™ PCR Amplification Kit) developed by Life Technologies in response to the CODIS Core Loci Working Group's recommendation to expand the CODIS Core Loci. This prototype included our proposal of 21 autosomal STR markers and two Y-chromosome markers (DYS391 and Y-indel) and maximizes concordance with established databases and previously analyzed samples by maintaining primer sequences of previous Identifiler(®)/NGM SElect™ kits for the 21 STR markers except for TPOX. This paper describes the validation studies conducted with the first commercial available 6-dye STR kit for casework using a 3500 genetic analyzer for fragment detection that included the analysis of the following parameters and aspects: analytical threshold, sensitivity & stochastic threshold, heterozygous balance, stutter threshold, precision and accuracy, repeatability and reproducibility, genotype concordance, DNA mixtures, species specificity, and stability studies with case type samples. The studies demonstrated that the GlobalFiler™ system provided equivalent overall performance to previous forensic

  9. Surface position, not signaling from surrounding maternal tissues, specifies aleurone epidermal cell fate in maize.

    Science.gov (United States)

    Gruis, Darren Fred; Guo, Hena; Selinger, David; Tian, Qing; Olsen, Odd-Arne

    2006-07-01

    Maize (Zea mays) endosperm consists of an epidermal-like surface layer of aleurone cells, an underlying body of starchy endosperm cells, and a basal layer of transfer cells. To determine whether surrounding maternal tissues perform a role in specifying endosperm cell fates, a maize endosperm organ culture technique was established whereby the developing endosperm is completely removed from surrounding maternal tissues. Using cell type-specific fluorescence markers, we show that aleurone cell fate specification occurs exclusively in response to surface position and does not require specific, continued maternal signal input. The starchy endosperm and aleurone cell fates are freely interchangeable throughout the lifespan of the endosperm, with internalized aleurone cells converting to starchy endosperm cells and with starchy endosperm cells that become positioned at the surface converting to aleurone cells. In contrast to aleurone and starchy endosperm cells, transfer cells fail to develop in in vitro-grown endosperm, supporting earlier indications that maternal tissue interaction is required to fully differentiate this cell type. Several parameters confirm that the maize endosperm organ cultures described herein retain the main developmental features of in planta endosperm, including fidelity of aleurone mutant phenotypes, temporal and spatial control of cell type-specific fluorescent markers, specificity of cell type transcripts, and control of mitotic cell divisions.

  10. Genome-wide association study of alcohol dependence: significant findings in African- and European-Americans including novel risk loci

    Science.gov (United States)

    Gelernter, J; Kranzler, HR; Sherva, R; Almasy, L; Koesterer, R; Smith, AH; Anton, R; Preuss, UW; Ridinger, M; Rujescu, D; Wodarz, N; Zill, P; Zhao, H; Farrer, LA

    2014-01-01

    We report a GWAS of alcohol dependence (AD) in European-American (EA) and African-American (AA) populations, with replication in independent samples of EAs, AAs and Germans. Our sample for discovery and replication was 16 087 subjects, the largest sample for AD GWAS to date. Numerous genome-wide significant (GWS) associations were identified, many novel. Most associations were population specific, but in several cases were GWS in EAs and AAs for different SNPs at the same locus, showing biological convergence across populations. We confirmed well-known risk loci mapped to alcohol-metabolizing enzyme genes, notably ADH1B (EAs: Arg48His, P = 1.17 × 10−31; AAs: Arg369Cys, P = 6.33 × 10−17) and ADH1C in AAs (Thr151Thr, P = 4.94 × 10−10), and identified novel risk loci mapping to the ADH gene cluster on chromosome 4 and extending centromerically beyond it to include GWS associations at LOC100507053 in AAs (P = 2.63 × 10−11), PDLIM5 in EAs (P = 2.01 × 10−8), and METAP in AAs (P = 3.35 × 10−8). We also identified a novel GWS association (1.17 × 10−10) mapped to chromosome 2 at rs1437396, between MTIF2 and CCDC88A, across all of the EA and AA cohorts, with supportive gene expression evidence, and population-specific GWS for markers on chromosomes 5, 9 and 19. Several of the novel associations implicate direct involvement of, or interaction with, genes previously identified as schizophrenia risk loci. Confirmation of known AD risk loci supports the overall validity of the study; the novel loci are worthy of genetic and biological follow-up. The findings support a convergence of risk genes (but not necessarily risk alleles) between populations, and, to a lesser extent, between psychiatric traits. PMID:24166409

  11. Confronting, Confirming, and Dispelling Myths Surrounding ERP-in-the-Cloud

    DEFF Research Database (Denmark)

    Beaulieu, Tanya; C. Martin, Todd; Sarker, Saonee;

    2015-01-01

    understanding about the true challenges related to ERP cloud computing, it is important to examine these myths in an effort to dispel or support them. In this paper, we attempt to achieve that. Specifically, we explore eight myths related to cloud-based ERP systems through a study involving in-depth interviews......Although cloud computing is still in its infancy, it is rapidly becoming one of the most used buzzwords in the IS/IT field and ERP-systems are one of the fastest growing SaaS cloud applications. However, given the relative newness of ERP cloud computing, and the lack of empirical research...... on the topic, there is substantial uncertainty surrounding the benefits and challenges of ERP cloud computing. Consequently, as often is the case with new technologies, popular myths surrounding the technology are used to make adoption and implementation decisions. As a first step toward providing an informed...

  12. Functional characterization of polysaccharide utilization loci in the marine Bacteroidetes 'Gramella forsetii' KT0803.

    Science.gov (United States)

    Kabisch, Antje; Otto, Andreas; König, Sten; Becher, Dörte; Albrecht, Dirk; Schüler, Margarete; Teeling, Hanno; Amann, Rudolf I; Schweder, Thomas

    2014-07-01

    Members of the phylum Bacteroidetes are abundant in many marine ecosystems and are known to have a pivotal role in the mineralization of complex organic substrates such as polysaccharides and proteins. We studied the decomposition of the algal glycans laminarin and alginate by 'Gramella forsetii' KT0803, a bacteroidetal isolate from North Sea surface waters. A combined application of isotope labeling, subcellular protein fractionation and quantitative proteomics revealed two large polysaccharide utilization loci (PULs) that were specifically induced, one by alginate and the other by laminarin. These regulons comprised genes of surface-exposed proteins such as oligomer transporters, substrate-binding proteins, carbohydrate-active enzymes and hypothetical proteins. Besides, several glycan-specific TonB-dependent receptors and SusD-like substrate-binding proteins were expressed also in the absence of polysaccharide substrates, suggesting an anticipatory sensing function. Genes for the utilization of the beta-1,3-glucan laminarin were found to be co-regulated with genes for glucose and alpha-1,4-glucan utilization, which was not the case for the non-glucan alginate. Strong syntenies of the PULs of 'G. forsetii' with similar loci in other Bacteroidetes indicate that the specific response mechanisms of 'G. forsetii' to changes in polysaccharide availability likely apply to other Bacteroidetes. Our results can thus contribute to an improved understanding of the ecological niches of marine Bacteroidetes and their roles in the polysaccharide decomposition part of carbon cycling in marine ecosystems.

  13. Role of vapBC toxin-antitoxin loci in the thermal stress response of Sulfolobus solfataricus.

    Science.gov (United States)

    Cooper, Charlotte R; Daugherty, Amanda J; Tachdjian, Sabrina; Blum, Paul H; Kelly, Robert M

    2009-02-01

    TA (toxin-antitoxin) loci are ubiquitous in prokaryotic micro-organisms, including archaea, yet their physiological function is largely unknown. For example, preliminary reports have suggested that TA loci are microbial stress-response elements, although it was recently shown that knocking out all known chromosomally located TA loci in Escherichia coli did not have an impact on survival under certain types of stress. The hyperthermophilic crenarchaeon Sulfolobus solfataricus encodes at least 26 vapBC (where vap is virulence-associated protein) family TA loci in its genome. VapCs are PIN (PilT N-terminus) domain proteins with putative ribonuclease activity, while VapBs are proteolytically labile proteins, which purportedly function to silence VapCs when associated as a cognate pair. Global transcriptional analysis of S. solfataricus heat-shock-response dynamics (temperature shift from 80 to 90 degrees C) revealed that several vapBC genes were triggered by the thermal shift, suggesting a role in heat-shock-response. Indeed, knocking out a specific vapBC locus in S. solfataricus substantially changed the transcriptome and, in one case, rendered the crenarchaeon heat-shock-labile. These findings indicate that more work needs to be done to determine the role of VapBCs in S. solfataricus and other thermophilic archaea, especially with respect to post-transcriptional regulation.

  14. Role of vapBC toxin–antitoxin loci in the thermal stress response of Sulfolobus solfataricus

    Science.gov (United States)

    Cooper, Charlotte R.; Daugherty, Amanda J.; Tachdjian, Sabrina; Blum, Paul H.; Kelly, Robert M.

    2010-01-01

    TA (toxin–antitoxin) loci are ubiquitous in prokaryotic microorganisms, including archaea, yet their physiological function is largely unknown. For example, preliminary reports have suggested that TA loci are microbial stress-response elements, although it was recently shown that knocking out all known chromosomally located TA loci in Escherichia coli did not have an impact on survival under certain types of stress. The hyperthermophilic crenarchaeon Sulfolobus solfataricus encodes at least 26 vapBC (where vap is virulence-associated protein) family TA loci in its genome. VapCs are PIN (PilT N-terminus) domain proteins with putative ribonuclease activity, while VapBs are proteolytically labile proteins, which purportedly function to silence VapCs when associated as a cognate pair. Global transcriptional analysis of S. solfataricus heat-shock-response dynamics (temperature shift from 80 to 90°C) revealed that several vapBC genes were triggered by the thermal shift, suggesting a role in heat-shock-response. Indeed, knocking out a specific vapBC locus in S. solfataricus substantially changed the transcriptome and, in one case, rendered the crenarchaeon heat-shock-labile. These findings indicate that more work needs to be done to determine the role of VapBCs in S. solfataricus and other thermophilic archaea, especially with respect to post-transcriptional regulation. PMID:19143615

  15. Inheritance mode of microsatellite loci and their use for kinship analysis in the Pacific oyster (Crassostrea gigas)

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Five full-sib families of the Pacific oyster (Crassostrea gigas) larvae were used to study the mode of inheritance at eight microsatellite loci, and the feasibility of these markers for kinship estimate was also examined. All eight microsatellite loci were compatible with Mendelian inheritance. Neither evidence of sex-linked barriers to transmission nor evidence of major barriers to fertilization between gametes from the parents was shown. Three of the eight loci showed the presence of null alleles in four families, demonstrating the need to conduct comprehensive species-specific inheritance studies for microsatellite loci used in population genetic studies. Although the null allele heterozygotes were considered as homozygotes in the calculation of genetic distance, offspring from five full-sib families were unambiguously discriminated in the neighbor-joining dendrogram. This result indicates that the microsatellite markers may be capable of discriminating between related and unrelated oyster larvae in the absence of pedigree information, and is applicable to the investigation of the effective number of parents contributing to the hatchery population of the Pacific oyster.

  16. Genome-wide search for segregation distortion loci associated with the expression of complex traits in Populus tomentosa

    Institute of Scientific and Technical Information of China (English)

    Zhang De-qiang; Zhang Zhi-yi; Yang Kai

    2007-01-01

    Segregation distortion of molecular markers has been reported in a broad range of organisms. It has been detected in an interspecific BC1 Populus pedigree established by controlled crossing between clone "LM50" (Populus tomentosa) and its hybrid clone "TB01" (P. tomentosa×P. bolleana). The study with a total of 150 AFLP markers (approximately 18.9% of the total loci)exhibited significant deviation from the Mendelian ratio (1:1) (p<0.01). Twenty-five percent of the markers were mapped on the parental specific genetic linkage maps of clones "LM50" and "TB01" with a pseudo-test-cross mapping strategy. Twelve linkage groups had markers with skewed segregation ratios, but the major regions were on linkage groups TLG2, TLG4 and TLG6 in the linkage map of clone "LM50". We also analyzed the association between distorted loci and expression of complex traits with Mapmaker/QTL software. A total of 16 putative QTLs affecting 12 traits were identified in the distorted regions on seven linkage groups.Therefore we could detect the distribution of skewed loci along the entire genome and identify the association between quantitative traits and segregation loci via genetic mapping in an interspecific BC1 P. tomentosa family. Furthermore, the genetic nature and possible causes of these segregation distortions for differentiation between female and male parents were also discussed.

  17. Nine Loci for Ocular Axial Length Identified through Genome-wide Association Studies, Including Shared Loci with Refractive Error

    OpenAIRE

    Cheng, Ching-Yu; Schache, Maria; Ikram, M. Kamran; Young, Terri L.; Guggenheim, Jeremy A.; Vitart, Veronique; MacGregor, Stuart; Verhoeven, Virginie J.M.; Barathi, Veluchamy A.; Liao, Jiemin; Hysi, Pirro G.; Bailey-Wilson, Joan E.; St. Pourcain, Beate; Kemp, John P.; McMahon, George

    2013-01-01

    Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LA...

  18. Dynamics of two-component membranes surrounded by viscoelastic media.

    Science.gov (United States)

    Komura, Shigeyuki; Yasuda, Kento; Okamoto, Ryuichi

    2015-11-01

    We discuss the dynamics of two-component fluid membranes which are surrounded by viscoelastic media. We assume that membrane-embedded proteins can diffuse laterally and induce a local membrane curvature. The mean squared displacement of a tagged membrane segment is obtained as a generalized Einstein relation. When the elasticity of the surrounding media obeys a power-law behavior in frequency, an anomalous diffusion of the membrane segment is predicted. We also consider the situation where the proteins generate active non-equilibrium forces. The generalized Einstein relation is further modified by an effective temperature that depends on the force dipole energy. The obtained generalized Einstein relations are useful for membrane microrheology experiments.

  19. Study on Temperature Fieldof Surrounding Rock with BEM

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The authors analyzed the characteristic of surrounding rock temperature field around a drifting face, setup its mathematic model, and got its numerical result with the boundary element method(BEM). To calculate in-tra-domain integral, it was transformed into boundary integration with the DRM method. Using the similitude the-ory, the dimensionless differential equation was educed. Finally, the authors calculated two drifting faces of San-hejian Coal Mine using the computer software developed by authors based on the above principium, and got the dis-tribution characteristic of surrounding rock temperature field around a drifting face and the periodic variation intemperature with its periodic moving forward. Comparing the calculated heat dissipating-capacity of surroundingrock with the measured data shows that the computer software is proper.

  20. Experimental Study of Deformation of Surrounding Rock with Infrared Radiation

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yong-jun; AN Li-qian; REN Run-hou; FAN Shi-min; MA Nian-jie; LI Jian-hui; JI Yuan-ming

    2005-01-01

    According to the practical conditions of coal roadway in Changcun Coal Mine of Lu'an Mining Group, the deformation of rock surrounding roadway was experimentally studied by means of thermal infrared (TIR) imaging system in the process of confined compressions. It is found that the model surface TIR temperature (TIRT) changes with the increase of load. Furthermore, TIRT changes non-synchronously in different ranges such as the roof, floor, wall, corners and bolted ranges. The TIRT is higher in the location of stress concentration and bolted ranges than that in the location of stress relaxation and broken ranges. The interaction ranges of bolt and rock are determined preliminarily according to the corresponding relationship of TIRT fields and the strain fields of the surrounding rock. The new method of TIR image processing has been proved to be effective for the study of bolt support and observation of roadway stability under mine pressure.

  1. High resolution bathymetry of China seas and their surroundings

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Based on the oceanic lithospheric flexure and the worldwide bathymetric data ETOPO5, the high resolu tion bathymetry of the China seas and their surroundings is computed from altimeter derived gravity anomalies. The new bathymetry obtained by this study is higher resolution and accuracy than the widely used ETOPO5 data, mean while it shows clearly the seafioor, the tectonic characteristics and the geodynamical processes in the China seas.

  2. Thermodynamic stability of black holes surrounded by quintessence

    OpenAIRE

    Ma, Meng-Sen; Zhao, Ren; Ma, Ya-Qin

    2016-01-01

    We study the thermodynamic stabilities of uncharged and charged black holes surrounded by quintessence (BHQ) by means of effective thermodynamic quantities. When the state parameter of quintessence $\\omega_q$ is appropriately chosen, the structures of BHQ are something like that of black holes in de Sitter space. Constructing the effective first law of thermodynamics in two different ways, we can derive the effective thermodynamic quantities of BHQ. Especially, these effective thermodynamic q...

  3. Hidden History: A Mobile Application for Discovering Surrounding Landscapes

    OpenAIRE

    2016-01-01

    This thesis work describes the design, development and evaluation of a mobile application called Hidden History. This application lets users discover and explore three types of landscapes (Historic, Scenic and Cultural) using three different modes of discovery (Route, Explore and Tour). Before designing Hidden History, the feature set of other applications that help users explore surrounding landscapes were identified and analyzed. Hidden History was then designed to implement the best fea...

  4. Treatment of Postherpetic Neuralgia by Surround Needling with Electric Stimulation

    Institute of Scientific and Technical Information of China (English)

    FAN Jin; YANG Qin-hua

    2005-01-01

    运用电针围刺法治疗带状疱疹后遗神经痛29例,获得较好疗效,总有效率为93.1%.%Twenty-nine cases of postherpetic neuralgia of herpes zoster were treated by the surround needling with electric stimulation, and the better therapeutic effect was obtained, the total effective rate was 93.1%.

  5. Belief and Attitudes surrounding Childhood Autism in Ghana

    OpenAIRE

    2012-01-01

    Autism is a life-long invisible impairment with an unknown etiology. Current literature shows an increase in the diagnosis of autism worldwide. This qualitative study explores the attitudes and beliefs which surround childhood autism in Ghana. In-depth interviews were conducted with four (4) parents whose children have autism and three (3) key informants; a Religious Leader, a Health Worker and an Administrator of a Special school in Accra, Ghana. A semi-structured interview guide was used fo...

  6. A permeability barrier surrounds taste buds in lingual epithelia.

    Science.gov (United States)

    Dando, Robin; Pereira, Elizabeth; Kurian, Mani; Barro-Soria, Rene; Chaudhari, Nirupa; Roper, Stephen D

    2015-01-01

    Epithelial tissues are characterized by specialized cell-cell junctions, typically localized to the apical regions of cells. These junctions are formed by interacting membrane proteins and by cytoskeletal and extracellular matrix components. Within the lingual epithelium, tight junctions join the apical tips of the gustatory sensory cells in taste buds. These junctions constitute a selective barrier that limits penetration of chemosensory stimuli into taste buds (Michlig et al. J Comp Neurol 502: 1003-1011, 2007). We tested the ability of chemical compounds to permeate into sensory end organs in the lingual epithelium. Our findings reveal a robust barrier that surrounds the entire body of taste buds, not limited to the apical tight junctions. This barrier prevents penetration of many, but not all, compounds, whether they are applied topically, injected into the parenchyma of the tongue, or circulating in the blood supply, into taste buds. Enzymatic treatments indicate that this barrier likely includes glycosaminoglycans, as it was disrupted by chondroitinase but, less effectively, by proteases. The barrier surrounding taste buds could also be disrupted by brief treatment of lingual tissue samples with DMSO. Brief exposure of lingual slices to DMSO did not affect the ability of taste buds within the slice to respond to chemical stimulation. The existence of a highly impermeable barrier surrounding taste buds and methods to break through this barrier may be relevant to basic research and to clinical treatments of taste.

  7. THE DESIGN OF DYNAMIC SIMULATION SYSTEM ON EARTHQUAKE SURROUNDINGS

    Institute of Scientific and Technical Information of China (English)

    沈毅力; 杨云; 李天石

    2003-01-01

    Objective To design a system that can simulate earthquake surroundings. In the surroundings, people can be familiar with the omen, strong shock and aftershock of earthquake, thus make right choices and get away when the disaster occurs. Methods The system consists of an electro-hydraulic servo system, a whole-information sound system and some lighting device; By using the adaptive inverse control method and LMS algorithms, the inverse model (I.e. The controller) is convergent rapidly; The software based on LabVIEW makes the parameters can be modified easily; There is a double closed-loop structure in the system: an analog closed-loop and a digital closed-loop, and their parameters can be inspected in real time. Results The system is of very high reliability, and the desired vibration signal can be tracked exactly by output. Conclusion Earthquake surroundings is simulated vividly. Through the system, people can be familiar with earthquake phenomena, and know lots of knowledge of earthquake.

  8. Tissue reaction surrounding miniscrews for orthodontic anchorage: An animal experiment

    Directory of Open Access Journals (Sweden)

    Stephanie Shih-Hsuan Chen

    2012-03-01

    Results and conclusions: (1 Tissue surrounding roots damaged by a miniscrew showed a significant inflammatory response. (2 Root resorption was occasionally observed after 3 weeks following insertion of a miniscrew even if the miniscrew was not in direct contact with the root. (3 Root repair was noted with a cementoblast lining along the resorption surface at as early as 3 weeks after miniscrew insertion. Alveolar bone filled in the lesion when the root damage was large so that the contour of the alveolar bone followed that of the damaged root, with the width of the periodontal ligament space being maintained. (4 Stable miniscrews were mainly those which did not contact adjacent roots, and for which the surrounding tissue showed only a small inflammatory response with some extent of direct bone contact around the miniscrew. On the contrary, most of the failed miniscrews were those which had direct contact with adjacent roots, and which exhibited severe tissue inflammation and were covered by thick layers of soft tissue. Failure was detected 3 weeks after insertion. Surprisingly, the epithelial lining surrounding the miniscrews might not have spontaneously resolved 6 weeks after screw removal. Persistent infection in the sinus tract was noted, and this would require attention.

  9. 3D Room Visualization on Android Based Mobile Device (with Philips™’ Surround Sound Music Player

    Directory of Open Access Journals (Sweden)

    Durio Etgar

    2013-01-01

    Full Text Available This project’s specifically purposed as a demo application, so anyone can get the experience of a surround audio room without having to physically involved to it, with a main idea of generating a 3D surround sound room scenery coupled with surround sound in a handier package, namely, a “Virtual Listen Room”. Virtual Listen Room set a foundation of an innovative visualization that later will be developed and released as one of way of portable advertisement. This application was built inside of Android environment. Android device had been chosen as the implementation target, since it leaves massive development spaces and mostly contains essential components needed on this project, including graphic processor unit (GPU. Graphic manipulation can be done using an embedded programming interface called OpenGL ES, which is planted in all Android devices generally. Further, Android has a Accelerometer Sensor that is needed to be coupled with scene to produce a dynamic movement of the camera. Surround sound effect can be reached with a decoder from Phillips called MPEG Surround Sound Decoder. To sum the whole project, we got an application with sensor-dynamic 3D room visualization coupled with Philips’ Surround Sound Music Player. We can manipulate several room’s properties; Subwoofer location, Room light, and how many speakers inside it, the application itself works well despite facing several performance problems before, later to be solved.

  10. Microsatellite loci for the invasive colonial hydrozoan Cordylophora caspia

    Science.gov (United States)

    Cordylophora caspia, a colonial hydrozoan native to the Ponto-Caspian region, has become a common invader of both fresh and brackish water ecosystems of North America and Europe. Here we describe 11 polymorphic microsatellite loci for this species. Preliminary analyses indicate ...

  11. Genetic mapping of quantitative trait loci (QTLs) with effects on ...

    African Journals Online (AJOL)

    SERVER

    2008-02-05

    Feb 5, 2008 ... 2Department of Crop Protection and Environmental Biology, ... identify genetic loci associated with the expression of resistance to FTh. ... indicated that resistance to FTh may be controlled by ... population or to pyramid resistance into new populations. .... environment and human health (Eigenbrode and.

  12. Combined effects of multiple linked loci on pairwise sibling tests.

    Science.gov (United States)

    Tamura, Tomonori; Osawa, Motoki; Kakimoto, Yu; Ochiai, Eriko; Suzuki, Takanori; Nakamura, Takashi

    2017-01-01

    The advanced multiplex STR system, PowerPlex Fusion, includes four linked locus pairs. The conventional Identifiler system has one pair of linked loci. Therefore, sibling tests conducted using the advanced system might be more affected by linkage than those conducted using the conventional system. This study simulated single and combined effects of the four linked locus pairs on pairwise sibling tests. Simulated genotypes of 100,000 pairs of full siblings and nonrelatives were constructed according to allele frequencies of the Japanese population. The single linkage effect was evaluated for simulated genotype data by calculating both the likelihood ratio accounting for the linkage between two loci and the likelihood ratio ignoring the linkage. The combined effect was obtained by multiplication of the respective single effects. Furthermore, we investigated the possibility that ignoring the linkage affects subject classification by introducing a scale of the likelihood ratio into sibling tests. The single effect in the Identifiler analysis was 0.645-1.746 times if the linkage was ignored. Overestimations and underestimations were predictable from the identical-by-state status at two linked loci. The combined effect in the PowerPlex Fusion analysis was 0.217-7.390 times. Ignoring the linkage rarely caused a false conclusive or inconclusive result, even from PowerPlex Fusion analysis. Application of the advanced system improved sibling tests considerably. The additional examined loci were more beneficial than the adverse effect of the linkage derived from the four linked locus pairs.

  13. Linkage relationships of 19 enzyme Loci in maize.

    Science.gov (United States)

    Goodman, M M; Stuber, C W; Newton, K; Weissinger, H H

    1980-11-01

    Linkage relationships of 19 enzyme loci have been examined. The chromosomal locations of eight of these loci are formally reported for the first time in this paper. These localizations should assist in the construction of additional useful chromosome marker stocks, especially since several of these enzyme loci lie in regions that were previously poorly mapped. Six loci are on the long arm of chromosome 1. The arrangement is (centromere)-Mdh4-mmm-Pgm1-Adh1-Phi-Gdh1, with about 46% recombination between Mdh4 and Gdh1.-Linkage studies with a2 and pr have resulted in the localization of four enzyme genes to chromosome 5 with arrangement Pgm2-Mdh5-Got3-a2-(centromere)-pr-Got2. Pgm2 lies approximately 35 map units distal to a2 in a previously unmapped region of the short arm of 5, beyond ameiotic.-Approximately 23% recombination was observed between Mdh4 and Pgm1 on chromosome 1, while 17% recombination occurred between Mdh5 and Pgm2 on chromosome 5. Similarly, linkages between Idh1 and Mdh1, about 22 map units apart on chromosome 8, and between Mdh2 and Idh2, less than 5 map units apart on chromosome 6, were observed. Thus, segments of chromosomes 1 and 5 and segments of 6 and 8 may represent duplications on nonhomologous chromosomes.

  14. A multigene phylogeny of the Dothideomycetes using four nuclear loci

    NARCIS (Netherlands)

    Schoch, C.; Shoemaker, R.A.; Seifert, K.; Hambleton, S.; Spatafora, J.W.; Crous, P.W.

    2006-01-01

    We present an expanded multigene phylogeny of the Dothideomycetes. The final data matrix consisted of four loci (nuc SSU rDNA, nuc LSU rDNA, TEF1, RPB2) for 96 taxa, representing five of the seven orders in the current classification of Dothideomycetes and several outgroup taxa representative of the

  15. Failure Loci of Suction Caisson Foundations Under Combined Loading Conditions

    Institute of Scientific and Technical Information of China (English)

    WANG Dong; JIN Xia

    2008-01-01

    Suction caissons are widely used to support offshore fixed platforms in coastal areas. The loadings transferred to suction caissons include the eccentric lateral force induced by waves and self weight of the platform structure. However, under this kind of combined loading conditions, the failure mechanism of caissons with shallow embedment depths is quite different from conventional deep foundations or onshore shallow footings. The behaviour of caissons subjected to combined loadings may be described with the "failure locus" in force resultant spaces. Here the failure loci of smooth caissons are studied by use of finite element approach, with the embedment ratio of caissons varying in the range of 0.25~1.0 and eccentricity ratio of horizontal loadings in 0~10. The platform settlement and tilt limits are involved into determination of failure loci, thus the platforms can avoid significant displacements for the combined loadings located inside the failure locus. Three families of loading paths are used to map out the locus. It is found that the shape of failure loci depends on 3 non-dimensional parameters, and the failure locus of a given caisson changes gradually from the elliptical curve to hooked curve with increasing shear strength of soil. The lateral capacity of short caissons may be enhanced by vertical forces, compared with the maximum lateral capacity of long caissons occurring at the vertical force being zero. The critical embedment ratios partitioning elliptical and hooked loci are proposed.

  16. Novel Associations of Nonstructural Loci with Paraoxonase Activity

    Directory of Open Access Journals (Sweden)

    Ellen E. Quillen

    2012-01-01

    Full Text Available The high-density-lipoprotein-(HDL- associated esterase paraoxonase 1 (PON1 is a likely contributor to the antioxidant and antiatherosclerotic capabilities of HDL. Two nonsynonymous mutations in the structural gene, PON1, have been associated with variation in activity levels, but substantial interindividual differences remain unexplained and are greatest for substrates other than the eponymous paraoxon. PON1 activity levels were measured for three substrates—organophosphate paraoxon, arylester phenyl acetate, and lactone dihydrocoumarin—in 767 Mexican American individuals from San Antonio, Texas. Genetic influences on activity levels for each substrate were evaluated by association with approximately one million single nucleotide polymorphism (SNPs while conditioning on PON1 genotypes. Significant associations were detected at five loci including regions on chromosomes 4 and 17 known to be associated with atherosclerosis and lipoprotein regulation and loci on chromosome 3 that regulate ubiquitous transcription factors. These loci explain 7.8% of variation in PON1 activity with lactone as a substrate, 5.6% with the arylester, and 3.0% with paraoxon. In light of the potential importance of PON1 in preventing cardiovascular disease/events, these novel loci merit further investigation.

  17. Geometry of Brill-Noether loci on Prym varieties

    CERN Document Server

    Hoering, Andreas

    2011-01-01

    Given the Prym variety of an \\'etale double cover one can define analogues of the classical Brill-Noether loci on Jacobians of curves. Recent work by Lahoz and Naranjo shows that the Brill-Noether locus V^2 completely determines the covering. In this paper we describe the singular locus and the irreducible components of V^2.

  18. A multigene phylogeny of the Dothideomycetes using four nuclear loci

    NARCIS (Netherlands)

    Schoch, C.L.; Shoemaker, R.A.; Seifert, K.A.; Hambleton, S.; Spatafora, J.W.; Crous, P.W.

    2006-01-01

    We present an expanded multigene phylogeny of the Dothideomycetes. The final data matrix consisted of four loci (nuc SSU rDNA, nuc LSU rDNA, TEF1, RPB2) for 96 taxa, representing five of the seven orders in the current classification of Dothideomycetes and several outgroup taxa representative of the

  19. Hidden landscapes: the metropolitan garden and the genius loci

    NARCIS (Netherlands)

    De wit, S.I.

    2014-01-01

    This thesis aims at the landscape architecture of the enclosed garden as an expression of the genius loci: definition, analysis, typology and transformation. The process of metropolisation tends to eliminate, or at least hide, the underlying landscape. The research addresses the question of how the

  20. STR data for the 13 CODIS loci in Singapore Malays.

    Science.gov (United States)

    Ang, H C; Sornarajah, R; Lim, S E S; Syn, C K C; Tan-Siew, W F; Chow, S T; Budowle, Bruce

    2005-03-10

    Allele frequencies for the 13 CODIS (Combined DNA Index System, USA) STR loci included in the AmpFISTR Profiler Plus and AmpFISTR Cofiler kits (Applied Biosystems, Foster City, USA) were determined in a sample of 197 unrelated Malays in Singapore.

  1. Overdominant quantitative trait loci for yield and fitness in tomato.

    Science.gov (United States)

    Semel, Yaniv; Nissenbaum, Jonathan; Menda, Naama; Zinder, Michael; Krieger, Uri; Issman, Noa; Pleban, Tzili; Lippman, Zachary; Gur, Amit; Zamir, Dani

    2006-08-29

    Heterosis, or hybrid vigor, is a major genetic force that contributes to world food production. The genetic basis of heterosis is not clear, and the importance of loci with overdominant (ODO) effects is debated. One problem has been the use of whole-genome segregating populations, where interactions often mask the effects of individual loci. To assess the contribution of ODO to heterosis in the absence of epistasis, we carried out quantitative genetic and phenotypic analyses on a population of tomato (Solanum lycopersicum) introgression lines (ILs), which carry single marker-defined chromosome segments from the distantly related wild species Solanum pennellii. The ILs revealed 841 quantitative trait loci (QTL) for 35 diverse traits measured in the field on homozygous and heterozygous plants. ILs showing greater reproductive fitness were characterized by the prevalence of ODO QTL, which were virtually absent for the nonreproductive traits. ODO can result from true ODO due to allelic interactions of a single gene or from pseudoODO that involves linked loci with dominant alleles in repulsion. The fact that we detected dominant and recessive QTL for all phenotypic categories but ODO only for the reproductive traits indicates that pseudoODO due to random linkage is unlikely to explain heterosis in the ILs. Thus, we favor the true ODO model involving a single functional Mendelian locus. We propose that the alliance of ODO QTL with higher reproductive fitness was selected for in evolution and was domesticated by man to improve yields of crop plants.

  2. Blood Pressure Loci Identified with a Gene-Centric Array

    NARCIS (Netherlands)

    Johnson, Toby; Gaunt, Tom R.; Newhouse, Stephen J.; Padmanabhan, Sandosh; Tomaszewski, Maciej; Kumari, Meena; Morris, Richard W.; Tzoulaki, Ioanna; O'Brien, Eoin T.; Poulter, Neil R.; Sever, Peter; Shields, Denis C.; Thom, Simon; Wannamethee, Sasiwarang G.; Whincup, Peter H.; Brown, Morris J.; Connell, John M.; Dobson, Richard J.; Howard, Philip J.; Mein, Charles A.; Onipinla, Abiodun; Shaw-Hawkins, Sue; Zhang, Yun; Smith, George Davey; Day, Ian N. M.; Lawlor, Debbie A.; Goodall, Alison H.; Fowkes, F. Gerald; Abecasis, Goncalo R.; Elliott, Paul; Gateva, Vesela; Braund, Peter S.; Burton, Paul R.; Nelson, Christopher P.; Tobin, Martin D.; van der Harst, Pim; Glorioso, Nicola; Neuvrith, Hani; Salvi, Erika; Staessen, Jan A.; Stucchi, Andrea; Devos, Nabila; Jeunemaitre, Xavier; Plouin, Pierre-Francois; Tichet, Jean; Juhanson, Peeter; Org, Elin; Putku, Margus; Sober, Siim; Veldre, Gudrun; Viigimaa, Margus; Levinsson, Anna; Rosengren, Annika; Thelle, Dag S.; Hastie, Claire E.; Hedner, Thomas; Lee, Wai K.; Melander, Olle; Wahlstrand, Bjoern; Hardy, Rebecca; Wong, Andrew; Cooper, Jackie A.; Palmen, Jutta; Chen, Li; Stewart, Alexandre F. R.; Wells, George A.; Westra, Harm-Jan; Wolfs, Marcel G. M.; Clarke, Robert; Franzosi, Maria Grazia; Goel, Anuj; Hamsten, Anders; Lathrop, Mark; Peden, John F.; Seedorf, Udo; Watkins, Hugh; Ouwehand, Willem H.; Sambrook, Jennifer; Stephens, Jonathan; Casas, Juan-Pablo; Drenos, Fotios; Holmes, Michael V.; Kivimaki, Mika; Shah, Sonia; Shah, Tina; Talmud, Philippa J.; Whittaker, John; Wallace, Chris; Delles, Christian; Laan, Mans; Kuh, Diana; Humphries, Steve E.; Nyberg, Fredrik; Cusi, Daniele; Roberts, Robert; Newton-Cheh, Christopher; Franke, Lude; Stanton, Alice V.; Dominiczak, Anna F.; Farrall, Martin; Hingorani, Aroon D.; Samani, Nilesh J.; Caulfield, Mark J.; Munroe, Patricia B.

    2011-01-01

    Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a

  3. Blood Pressure Loci Identified with a Gene-Centric Array

    NARCIS (Netherlands)

    Johnson, Toby; Gaunt, Tom R.; Newhouse, Stephen J.; Padmanabhan, Sandosh; Tomaszewski, Maciej; Kumari, Meena; Morris, Richard W.; Tzoulaki, Ioanna; O'Brien, Eoin T.; Poulter, Neil R.; Sever, Peter; Shields, Denis C.; Thom, Simon; Wannamethee, Sasiwarang G.; Whincup, Peter H.; Brown, Morris J.; Connell, John M.; Dobson, Richard J.; Howard, Philip J.; Mein, Charles A.; Onipinla, Abiodun; Shaw-Hawkins, Sue; Zhang, Yun; Smith, George Davey; Day, Ian N. M.; Lawlor, Debbie A.; Goodall, Alison H.; Fowkes, F. Gerald; Abecasis, Goncalo R.; Elliott, Paul; Gateva, Vesela; Braund, Peter S.; Burton, Paul R.; Nelson, Christopher P.; Tobin, Martin D.; van der Harst, Pim; Glorioso, Nicola; Neuvrith, Hani; Salvi, Erika; Staessen, Jan A.; Stucchi, Andrea; Devos, Nabila; Jeunemaitre, Xavier; Plouin, Pierre-Francois; Tichet, Jean; Juhanson, Peeter; Org, Elin; Putku, Margus; Sober, Siim; Veldre, Gudrun; Viigimaa, Margus; Levinsson, Anna; Rosengren, Annika; Thelle, Dag S.; Hastie, Claire E.; Hedner, Thomas; Lee, Wai K.; Melander, Olle; Wahlstrand, Bjoern; Hardy, Rebecca; Wong, Andrew; Cooper, Jackie A.; Palmen, Jutta; Chen, Li; Stewart, Alexandre F. R.; Wells, George A.; Westra, Harm-Jan; Wolfs, Marcel G. M.; Clarke, Robert; Franzosi, Maria Grazia; Goel, Anuj; Hamsten, Anders; Lathrop, Mark; Peden, John F.; Seedorf, Udo; Watkins, Hugh; Ouwehand, Willem H.; Sambrook, Jennifer; Stephens, Jonathan; Casas, Juan-Pablo; Drenos, Fotios; Holmes, Michael V.; Kivimaki, Mika; Shah, Sonia; Shah, Tina; Talmud, Philippa J.; Whittaker, John; Wallace, Chris; Delles, Christian; Laan, Mans; Kuh, Diana; Humphries, Steve E.; Nyberg, Fredrik; Cusi, Daniele; Roberts, Robert; Newton-Cheh, Christopher; Franke, Lude; Stanton, Alice V.; Dominiczak, Anna F.; Farrall, Martin; Hingorani, Aroon D.; Samani, Nilesh J.; Caulfield, Mark J.; Munroe, Patricia B.

    2011-01-01

    Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a besp

  4. Quantitative trait loci associated with anthracnose resistance in sorghum

    Science.gov (United States)

    With an aim to develop a durable resistance to the fungal disease anthracnose, two unique genetic sources of resistance were selected to create genetic mapping populations to identify regions of the sorghum genome that encode anthracnose resistance. A series of quantitative trait loci were identifi...

  5. Ancient conservation of trinucleotide microsatellite loci in polistine wasps

    DEFF Research Database (Denmark)

    Ezenwa, V O; Peters, J M; Zhu, Y

    1998-01-01

    Microsatellites have proven to be very useful genetic markers for studies of kinship, parentage, and gene mapping. If microsatellites are conserved among species, then those developed for one species can be used on related species, which would save the time and effort of developing new loci. We e...

  6. Association between the Igk and Igh immunoglobulin loci mediated by the 3' Igk enhancer induces 'decontraction' of the Igh locus in pre-B cells.

    Science.gov (United States)

    Hewitt, Susannah L; Farmer, Deborah; Marszalek, Katarzyna; Cadera, Emily; Liang, Hong-Erh; Xu, Yang; Schlissel, Mark S; Skok, Jane A

    2008-04-01

    Variable-(diversity)-joining (V(D)J) recombination at loci encoding the immunoglobulin heavy chain (Igh) and immunoglobulin light chain (Igk) takes place sequentially during successive stages in B cell development. Using three-dimensional DNA fluorescence in situ hybridization, here we identify a lineage-specific and stage-specific interchromosomal association between these two loci that marks the transition between Igh and Igk recombination. Colocalization occurred between pericentromerically located alleles in pre-B cells and was mediated by the 3' Igk enhancer. Deletion of this regulatory element prevented association of the Igh and Igk loci, inhibited pericentromeric recruitment and locus 'decontraction' of an Igh allele, and resulted in greater distal rearrangement of the gene encoding the variable heavy-chain region. Our data indicate involvement of the Igk locus and its 3' enhancer in directing the Igh locus to a repressive nuclear subcompartment and inducing the Igh locus to decontract.

  7. GlyRα2, not GlyRα3, modulates the receptive field surround of OFF retinal ganglion cells.

    Science.gov (United States)

    Zhang, Chi; Nobles, Regina D; McCall, Maureen A

    2015-01-01

    Receptive fields (RFs) of most retinal ganglion cells (RGCs) consist of an excitatory center and suppressive surround. The RF center arises from the summation of excitatory bipolar cell glutamatergic inputs, whereas the surround arises from lateral inhibitory inputs. In the retina, both gamma amino butyric acid (GABA) and glycine are inhibitory neurotransmitters. A clear role for GABAergic inhibition modulating the RGC RF surround has been demonstrated across species. Glycinergic inhibition is more commonly associated with RF center modulation, although there is some evidence that it may contribute to the RF surround. The synaptic glycinergic chloride channels are formed by three homomeric β and two homomeric α subunits that can be glycine receptor (GlyR) α1, α2, α3, or α4. GlyRα composition is responsible for currents with distinct decay kinetics. Their expression within the inner plexiform laminae and neuronal subtypes also differ. We studied the role of GlyR subunit selective modulation of RGC RF surrounds, using mice lacking GlyRα2 (Glra2 -/-), GlyRα3 (Glra3 -/-), or both (Glra2/3 -/-). We chose this molecular genetic approach instead of pharmacological manipulation because there are no subunit selective antagonists and strychnine blocks all GlyRs. Comparisons of annulus-evoked responses among wild type (WT) and GlyRα knockouts (Glra2 -/-, Glra3 -/- and Glra2/3 -/-) show that GlyRα2 inhibition enhances RF surround suppression and post-stimulus excitation in only WT OFF RGCs. Similarities in the responses in Glra2 -/- and Glra2/3 -/- RGCs verify these conclusions. Based on previous and current data, we propose that GlyRα2-mediated input uses a crossover inhibitory circuit. Further, we suggest that GlyRα2 modulates the OFF RGC RF center and surround independently. In summary, our results define a selective GlyR subunit-specific control of RF surround suppression in OFF RGCs.

  8. Regulation of the rate of beta-galactosidase synthese by the Bgs and Bgt loci in the mouse.

    Science.gov (United States)

    Berger, F G; Paigen, K

    1978-08-10

    We have developed an assay for the in vivo rate of beta-galactosidase synthesis in mouse tissues to assess the mechanism by which the Bgs and Bgt loci regulate activity levels of this enzyme. Genetically determined differences in liver and kidney beta-galactosidase content reflect equivalent differences in specific rates of enzyme synthesis. We conclude that Bgs and Bgt regulate beta-galactosidase activity by controlling the rate of synthesis of the beta-galactosidase molecule.

  9. Twenty-eight divergent polysaccharide loci specifying within and amongst strain capsule diversity in three strains of Bacteroides fragilis

    DEFF Research Database (Denmark)

    Patrick, S.; Blakely, G.W.; Houston, S.

    2010-01-01

    including a putative Wzx flippase and Wzy polymerase, was confirmed in all three strains, despite a lack of cross-reactivity between NCTC 9343 and 638R surface polysaccharide-specific antibodies by immunolabelling and microscopy. Genomic comparisons revealed an exceptional level of polysaccharide...... restriction and modification systems that act to prevent acquisition of foreign DNA. The level of amongst strain diversity in polysaccharide biosynthesis loci is unprecedented....

  10. Characterizing leader sequences of CRISPR loci

    DEFF Research Database (Denmark)

    Alkhnbashi, Omer; Shah, Shiraz Ali; Garrett, Roger Antony

    2016-01-01

    The CRISPR-Cas system is an adaptive immune system in many archaea and bacteria, which provides resistance against invading genetic elements. The first phase of CRISPR-Cas immunity is called adaptation, in which small DNA fragments are excised from genetic elements and are inserted into a CRISPR...... array generally adjacent to its so called leader sequence at one end of the array. It has been shown that transcription initiation and adaptation signals of the CRISPR array are located within the leader. However, apart from promoters, there is very little knowledge of sequence or structural motifs...... sequences by focusing on the consensus repeat of the adjacent CRISPR array and weak upstream conservation signals. We applied our tool to the analysis of a comprehensive genomic database and identified several characteristic properties of leader sequences specific to archaea and bacteria, ranging from...

  11. Influence analysis in quantitative trait loci detection.

    Science.gov (United States)

    Dou, Xiaoling; Kuriki, Satoshi; Maeno, Akiteru; Takada, Toyoyuki; Shiroishi, Toshihiko

    2014-07-01

    This paper presents systematic methods for the detection of influential individuals that affect the log odds (LOD) score curve. We derive general formulas of influence functions for profile likelihoods and introduce them into two standard quantitative trait locus detection methods-the interval mapping method and single marker analysis. Besides influence analysis on specific LOD scores, we also develop influence analysis methods on the shape of the LOD score curves. A simulation-based method is proposed to assess the significance of the influence of the individuals. These methods are shown useful in the influence analysis of a real dataset of an experimental population from an F2 mouse cross. By receiver operating characteristic analysis, we confirm that the proposed methods show better performance than existing diagnostics.

  12. Identification of chloroplast genome loci suitable for high-resolution phylogeographic studies of Colocasia esculenta (L.) Schott (Araceae) and closely related taxa.

    Science.gov (United States)

    Ahmed, Ibrar; Matthews, Peter J; Biggs, Patrick J; Naeem, Muhammad; McLenachan, Patricia A; Lockhart, Peter J

    2013-09-01

    Recently, we reported the chloroplast genome-wide association of oligonucleotide repeats, indels and nucleotide substitutions in aroid chloroplast genomes. We hypothesized that the distribution of oligonucleotide repeat sequences in a single representative genome can be used to identify mutational hotspots and loci suitable for population genetic, phylogenetic and phylogeographic studies. Using information on the location of oligonucleotide repeats in the chloroplast genome of taro (Colocasia esculenta), we designed 30 primer pairs to amplify and sequence polymorphic loci. The primers have been tested in a range of intra-specific to intergeneric comparisons, including ten taro samples (Colocasia esculenta) from diverse geographical locations, four other Colocasia species (C. affinis, C. fallax, C. formosana, C. gigantea) and three other aroid genera (represented by Remusatia vivipara, Alocasia brisbanensis and Amorphophallus konjac). Multiple sequence alignments for the intra-specific comparison revealed nucleotide substitutions (point mutations) at all 30 loci and microsatellite polymorphisms at 14 loci. The primer pairs reported here reveal levels of genetic variation suitable for high-resolution phylogeographic and evolutionary studies of taro and other closely related aroids. Our results confirm that information on repeat distribution can be used to identify loci suitable for such studies, and we expect that this approach can be used in other plant groups.

  13. Evaluating the Performance of Fine-Mapping Strategies at Common Variant GWAS Loci.

    Directory of Open Access Journals (Sweden)

    Martijn van de Bunt

    Full Text Available The growing availability of high-quality genomic annotation has increased the potential for mechanistic insights when the specific variants driving common genome-wide association signals are accurately localized. A range of fine-mapping strategies have been advocated, and specific successes reported, but the overall performance of such approaches, in the face of the extensive linkage disequilibrium that characterizes the human genome, is not well understood. Using simulations based on sequence data from the 1000 Genomes Project, we quantify the extent to which fine-mapping, here conducted using an approximate Bayesian approach, can be expected to lead to useful improvements in causal variant localization. We show that resolution is highly variable between loci, and that performance is severely degraded as the statistical power to detect association is reduced. We confirm that, where causal variants are shared between ancestry groups, further improvements in performance can be obtained in a trans-ethnic fine-mapping design. Finally, using empirical data from a recently published genome-wide association study for ankylosing spondylitis, we provide empirical confirmation of the behaviour of the approximate Bayesian approach and demonstrate that seven of twenty-six loci can be fine-mapped to fewer than ten variants.

  14. A unique epigenetic signature is associated with active DNA replication loci in human embryonic stem cells.

    Science.gov (United States)

    Li, Bing; Su, Trent; Ferrari, Roberto; Li, Jing-Yu; Kurdistani, Siavash K

    2014-02-01

    The cellular epigenetic landscape changes as pluripotent stem cells differentiate to somatic cells or when differentiated cells transform to a cancerous state. These epigenetic changes are commonly correlated with differences in gene expression. Whether active DNA replication is also associated with distinct chromatin environments in these developmentally and phenotypically diverse cell types has not been known. Here, we used BrdU-seq to map active DNA replication loci in human embryonic stem cells (hESCs), normal primary fibroblasts and a cancer cell line, and correlated these maps to the epigenome. In all cell lines, the majority of BrdU peaks were enriched in euchromatin and at DNA repetitive elements, especially at microsatellite repeats, and coincided with previously determined replication origins. The most prominent BrdU peaks were shared between all cells but a sizable fraction of the peaks were specific to each cell type and associated with cell type-specific genes. Surprisingly, the BrdU peaks that were common to all cell lines were associated with H3K18ac, H3K56ac, and H4K20me1 histone marks only in hESCs but not in normal fibroblasts or cancer cells. Depletion of the histone acetyltransferases for H3K18 and H3K56 dramatically decreased the number and intensity of BrdU peaks in hESCs. Our data reveal a unique epigenetic signature that distinguishes active replication loci in hESCs from normal somatic or malignant cells.

  15. Tight genetic linkage of prezygotic barrier loci creates a multifunctional speciation island in Petunia.

    Science.gov (United States)

    Hermann, Katrin; Klahre, Ulrich; Moser, Michel; Sheehan, Hester; Mandel, Therese; Kuhlemeier, Cris

    2013-05-20

    Most flowering plants depend on animal vectors for pollination and seed dispersal. Differential pollinator preferences lead to premating isolation and thus reduced gene flow between interbreeding plant populations. Sets of floral traits, adapted to attract specific pollinator guilds, are called pollination syndromes. Shifts in pollination syndromes have occurred surprisingly frequently, considering that they must involve coordinated changes in multiple genes affecting multiple floral traits. Although the identification of individual genes specifying single pollination syndrome traits is in progress in many species, little is known about the genetic architecture of coadapted pollination syndrome traits and how they are embedded within the genome. Here we describe the tight genetic linkage of loci specifying five major pollination syndrome traits in the genus Petunia: visible color, UV absorption, floral scent production, pistil length, and stamen length. Comparison with other Solanaceae indicates that, in P. exserta and P. axillaris, loci specifying these floral traits have specifically become clustered into a multifunctional "speciation island". Such an arrangement promotes linkage disequilibrium and avoids the dissolution of pollination syndromes by recombination. We suggest that tight genetic linkage provides a mechanism for rapid switches between distinct pollination syndromes in response to changes in pollinator availabilities. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Two sex-chromosome-linked microsatellite loci show geographic variance among North American Ostrinia nubilalis

    Directory of Open Access Journals (Sweden)

    Brad S. Coates

    2003-09-01

    Full Text Available PCR-based O. nubilalis population and pedigree analysis indicated female specificity of a (GAAAATn microsatellite, and male specificity of a CAYCARCGTCACTAA repeat unit marker. These loci were respectively named Ostrinia nubilalis W-chromosome 1 (ONW1 and O. nubilalis Z-chromosome 1 (ONZ1. Intact repeats of three, four, or five GAAAAT units are present among ONW1 alleles, and biallelic variation exists at the ONZ1 locus. Screening of 493 male at ONZ1 and 448 heterogametic females at ONZ1 and ONW1 loci from eleven North American sample sites was used to construct genotypic data. Analysis of molecular variance (AMOVA and F-statistics indicated no female haplotype or male ONZ1 allele frequency differentiation between voltinism ecotypes. Four subpopulations from northern latitudes, Minnesota and South Dakota, showed the absence of a single female haplotype, a significant deviation of ONZ1 data from Hardy-Weinberg expectation, and low-level geographic divergence from other subpopulations. Low ONZ1 and ONW1 allele diversity could be attributed either to large repeat unit sizes, low repeat number, reduced effective population (Ne size of sex chromosomes, or the result of recent O. nubilalis introduction and population expansion, but likely could not be due to inbreeding. These sequences have been deposited in GenBank AF442958, and AY102618 to AY102620.

  17. Thousands of microsatellite loci from the venomous coralsnake (Micrurus fulvius) and variability of select loci across populations and related species

    Science.gov (United States)

    Castoe, Todd A.; Streicher, Jeffrey W.; Meik, Jesse M.; Ingrasci, Matthew J.; Poole, Alexander W.; de Koning, A.P. Jason; Campbell, Jonathan A.; Parkinson, Christopher L.; Smith, Eric N.; Pollock, David D.

    2012-01-01

    Studies of population genetics increasingly use next-generation DNA sequencing to identify microsatellite loci in non-model organisms. There are, however, relatively few studies that validate the feasibility of transitioning from marker development to experimental application across populations and species. North American coralsnakes of the Micrurus fulvius species complex occur in the United States and Mexico, and little is known about their population structure and phylogenetic relationships. This absence of information and population genetics markers is particularly concerning because they are highly venomous and have important implications on human health. To alleviate this problem in coralsnakes, we investigated the feasibility of using 454 shotgun sequences for microsatellite marker development. First, a genomic shotgun library from a single individual was sequenced (~7.74 megabases; 26,831 reads) to identify potentially amplifiable microsatellite loci (PALs). We then hierarchically sampled 76 individuals from throughout the geographic distribution of the species complex and examined whether PALs were amplifiable and polymorphic. Approximately half of the loci tested were readily amplifiable from all individuals, and 80% of the loci tested for variation were variable and thus informative as population genetic markers. To evaluate the repetitive landscape characteristics across multiple snakes, we also compared microsatellite content between the coralsnake and two other previously sampled snakes, the venomous copperhead (Agkistrodon contortrix) and Burmese python (Python molurus). PMID:22938699

  18. Thousands of microsatellite loci from the venomous coralsnake Micrurus fulvius and variability of select loci across populations and related species.

    Science.gov (United States)

    Castoe, Todd A; Streicher, Jeffrey W; Meik, Jesse M; Ingrasci, Matthew J; Poole, Alexander W; de Koning, A P Jason; Campbell, Jonathan A; Parkinson, Christopher L; Smith, Eric N; Pollock, David D

    2012-11-01

    Studies of population genetics increasingly use next-generation DNA sequencing to identify microsatellite loci in nonmodel organisms. There are, however, relatively few studies that validate the feasibility of transitioning from marker development to experimental application across populations and species. North American coralsnakes of the Micrurus fulvius species complex occur in the United States and Mexico, and little is known about their population structure and phylogenetic relationships. This absence of information and population genetics markers is particularly concerning because they are highly venomous and have important implications on human health. To alleviate this problem in coralsnakes, we investigated the feasibility of using 454 shotgun sequences for microsatellite marker development. First, a genomic shotgun library from a single individual was sequenced (approximately 7.74 megabases; 26,831 reads) to identify potentially amplifiable microsatellite loci (PALs). We then hierarchically sampled 76 individuals from throughout the geographic distribution of the species complex and examined whether PALs were amplifiable and polymorphic. Approximately half of the loci tested were readily amplifiable from all individuals, and 80% of the loci tested for variation were variable and thus informative as population genetic markers. To evaluate the repetitive landscape characteristics across multiple snakes, we also compared microsatellite content between the coralsnake and two other previously sampled snakes, the venomous copperhead (Agkistrodon contortrix) and Burmese python (Python molurus). © 2012 Blackwell Publishing Ltd.

  19. Genetic association studies in complex disease : Disentangling additional predisposing loci from associated neutral loci using a constrained - permutation approach

    NARCIS (Netherlands)

    Spijker, G T; Nolte, I.M.; Jansen, R.C.; te Meerman, G.J.

    2005-01-01

    In the process of genetically mapping a complex disease, the question may arise whether a certain polymorphism is the only causal variant in a region. A number of methods can answer this question, but unfortunately these methods are optimal for bi-allelic loci only. We wanted to develop a method tha

  20. Geometric-model-based segmentation of the prostate and surrounding structures for image-guided radiotherapy

    Science.gov (United States)

    Tang, Xiaoli; Jeong, Yongwon; Radke, Richard J.; Chen, George T. Y.

    2004-01-01

    We present a computer vision tool to improve the clinical outcome of patients undergoing radiation therapy for prostate cancer by improving irradiation technique. While intensity modulated radiotherapy (IMRT) allows one to irradiate a specific region in the body with high accuracy, it is still difficult to know exactly where to aim the radiation beam on every day of the 30~40 treatments that are necessary. This paper presents a geometric model-based technique to accurately segment the prostate and other surrounding structures in a daily serial CT image, compensating for daily motion and shape variation. We first acquire a collection of serial CT scans of patients undergoing external beam radiotherapy, and manual segmentation of the prostate and other nearby structures by radiation oncologists. Then we train shape and local appearance models for the structures of interest. When new images are available, an iterative algorithm is applied to locate the prostate and surrounding structures automatically. Our experimental results show that excellent matches can be given to the prostate and surrounding structure. Convergence is declared after 10 iterations. For 256 x 256 images, the mean distance between the hand-segmented contour and the automatically estimated contour is about 1.5 pixels (2.44 mm), with variance about 0.6 pixel (1.24 mm).

  1. Allele distribution and genetic diversity of VNTR loci in Salmonella enterica serotype Enteritidis isolates from different sources

    Directory of Open Access Journals (Sweden)

    Bartkus Joanne M

    2008-09-01

    . Enteritidis isolates from different sources were found. Polymorphism in most of the VNTR loci was more frequent among human S. Enteritidis isolates than isolates from chickens or eggs. Therefore, VNTR profiles of S. Enteritidis isolates from a specific source should be further evaluated as potential markers in epidemiologic investigations to trace S. Enteritidis to their probable source.

  2. Impacts of Instructor and Student Loci of Commitment on Biology Learning for Prospective Elementary School Teachers.

    Science.gov (United States)

    Moscovici, Hedy

    1998-01-01

    Explores the dynamics in the loci of commitment of several participants in a university-level biology course developed for elementary school teachers. Concentrates on two instructors with almost opposing loci of commitment. Contains 19 references. (DDR)

  3. Impacts of Instructor and Student Loci of Commitment on Biology Learning for Prospective Elementary School Teachers.

    Science.gov (United States)

    Moscovici, Hedy

    1998-01-01

    Explores the dynamics in the loci of commitment of several participants in a university-level biology course developed for elementary school teachers. Concentrates on two instructors with almost opposing loci of commitment. Contains 19 references. (DDR)

  4. rDNA Loci Evolution in the Genus Glechoma (Lamiaceae)

    Science.gov (United States)

    Jang, Tae-Soo; McCann, Jamie; Parker, John S.; Takayama, Koji; Hong, Suk-Pyo; Schneeweiss, Gerald M.

    2016-01-01

    Glechoma L. (Lamiaceae) is distributed in eastern Asia and Europe. Understanding chromosome evolution in Glechoma has been strongly hampered by its small chromosomes, constant karyotype and polyploidy. Here phylogenetic patterns and chromosomal variation in Glechoma species are considered, using genome sizes, chromosome mapping of 5S and 35S rDNAs by fluorescence in situ hybridisation (FISH), and phylogenetic analyses of internal transcribed spacers (nrITS) of 35S rDNA and 5S rDNA NTS sequences. Species and populations of Glechoma are tetraploid (2n = 36) with base chromosome number of x = 9. Four chromosomes carry pericentric 5S rDNA sites in their short arms in all the species. Two to four of these chromosomes also carry 35S rDNA in subterminal regions of the same arms. Two to four other chromosomes have 35S rDNA sites, all located subterminally within short arms; one individual possessed additional weak pericentric 35S rDNA signals on three other chromosomes. Five types of rDNA locus distribution have been defined on the basis of 35S rDNA variation, but none is species-specific, and most species have more than one type. Glechoma hederacea has four types. Genome size in Glechoma ranges from 0.80 to 0.94 pg (1C), with low levels of intrapopulational variation in all species. Phylogenetic analyses of ITS and NTS sequences distinguish three main clades coinciding with geographical distribution: European (G. hederacea–G. hirsuta), Chinese and Korean (G. longituba), and Japanese (G. grandis). The paper presents the first comparative cytogenetic analyses of Glechoma species including karyotype structure, rDNA location and number, and genome size interpreted in a phylogenetic context. The observed variation suggests that the genus is still in genomic flux. Genome size, but not rDNA loci number and distribution, provides a character for species delimitation which allows better inferences of interspecific relationships to be made, in the absence of well

  5. The loci recommended as universal barcodes for plants on the basis of floristic studies may not work with congeneric species as exemplified by DNA barcoding of Dendrobium species

    Directory of Open Access Journals (Sweden)

    Singh Hemant

    2012-01-01

    Full Text Available Abstract Background Based on the testing of several loci, predominantly against floristic backgrounds, individual or different combinations of loci have been suggested as possible universal DNA barcodes for plants. The present investigation was undertaken to check the applicability of the recommended locus/loci for congeneric species with Dendrobium species as an illustrative example. Results Six loci, matK, rbcL, rpoB, rpoC1, trnH-psbA spacer from the chloroplast genome and ITS, from the nuclear genome, were compared for their amplification, sequencing and species discrimination success rates among multiple accessions of 36 Dendrobium species. The trnH-psbA spacer could not be considered for analysis as good quality sequences were not obtained with its forward primer. Among the tested loci, ITS, recommended by some as a possible barcode for plants, provided 100% species identification. Another locus, matK, also recommended as a universal barcode for plants, resolved 80.56% species. ITS remained the best even when sequences of investigated loci of additional Dendrobium species available on the NCBI GenBank (93, 33, 20, 18 and 17 of ITS, matK, rbcL, rpoB and rpoC1, respectively were also considered for calculating the percent species resolution capabilities. The species discrimination of various combinations of the loci was also compared based on the 36 investigated species and additional 16 for which sequences of all the five loci were available on GenBank. Two-locus combination of matK+rbcL recommended by the Plant Working Group of Consortium for Barcoding of Life (CBOL could discriminate 86.11% of 36 species. The species discriminating ability of this barcode was reduced to 80.77% when additional sequences available on NCBI were included in the analysis. Among the recommended combinations, the barcode based on three loci - matK, rpoB and rpoC1- resolved maximum number of species. Conclusions Any recommended barcode based on the loci tested so

  6. Investigation of population structure in Gulf of Mexico Seepiophila jonesi (Polychaeta, Siboglinidae using cross-amplified microsatellite loci

    Directory of Open Access Journals (Sweden)

    Chunya Huang

    2016-08-01

    Full Text Available Background Vestimentiferan tubeworms are some of the most recognizable fauna found at deep-sea cold seeps, isolated environments where hydrocarbon rich fluids fuel biological communities. Several studies have investigated tubeworm population structure; however, much is still unknown about larval dispersal patterns at Gulf of Mexico (GoM seeps. As such, researchers have applied microsatellite markers as a measure for documenting the transport of vestimentiferan individuals. In the present study, we investigate the utility of microsatellites to be cross-amplified within the escarpiid clade of seep vestimentiferans, by determining if loci originally developed for Escarpia spp. could be amplified in the GoM seep tubeworm, Seepiophila jonesi. Additionally, we determine if cross-amplified loci can reliably uncover the same signatures of high gene flow seen in a previous investigation of S. jonesi. Methods Seventy-seven S. jonesi individuals were collected from eight seep sites across the upper Louisiana slope (<1,000 m in the GoM. Forty-eight microsatellite loci that were originally developed for Escarpia laminata (18 loci and Escarpia southwardae (30 loci were tested to determine if they were homologous and polymorphic in S. jonesi. Loci found to be both polymorphic and of high quality were used to test for significant population structuring in S. jonesi. Results Microsatellite pre-screening identified 13 (27% of the Escarpia loci were homologous and polymorphic in S. jonesi, revealing that microsatellites can be amplified within the escarpiid clade of vestimentiferans. Our findings uncovered low levels of heterozygosity and a lack of genetic differentiation amongst S. jonesi from various sites and regions, in line with previous investigations that employed species-specific polymorphic loci on S. jonesi individuals retrieved from both the same and different seep sites. The lack of genetic structure identified from these populations supports the

  7. INTERACTIONS OF THE INFRARED BUBBLE N4 WITH ITS SURROUNDINGS

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Hong-Li; Li, Jin-Zeng; Yuan, Jing-Hua; Huang, Maohai; Huang, Ya-Fang; Zhang, Si-Ju [National Astronomical Observatories, Chinese Academy of Sciences, 20A Datun Road, Chaoyang District, Beijing 100012 (China); Wu, Yuefang [Department of Astronomy, Peking University, 100871 Beijing (China); Liu, Tie [Korea Astronomy and Space Science Institute 776, Daedeokdae-ro, Yuseong-gu, Daejeon, 305-348 (Korea, Republic of); Dubner, G.; Paron, S.; Ortega, M. E. [1Instituto de Astronomía y Física del Espacio (IAFE, CONICET-UBA), CC 67, Suc. 28, 1428 Buenos Aires (Argentina); Molinari, Sergio [Istituto di Astrofisica e Planetologia Spaziali—IAPS, Istituto Nazionale di Astrofisica—INAF, via Fosso del Cavaliere 100, I-00133 Roma (Italy); Zavagno, Annie; Samal, Manash R., E-mail: hlliu@nao.cas.cn [Aix Marseille Universit, CNRS, LAM (Laboratoire d’Astrophysique de Marseille) UMR 7326, F-13388, Marseille (France)

    2016-02-10

    The physical mechanisms that induce the transformation of a certain mass of gas in new stars are far from being well understood. Infrared bubbles associated with H ii regions have been considered to be good samples for investigating triggered star formation. In this paper we report on the investigation of the dust properties of the infrared bubble N4 around the H ii region G11.898+0.747, analyzing its interaction with its surroundings and star formation histories therein, with the aim of determining the possibility of star formation triggered by the expansion of the bubble. Using Herschel PACS and SPIRE images with a wide wavelength coverage, we reveal the dust properties over the entire bubble. Meanwhile, we are able to identify six dust clumps surrounding the bubble, with a mean size of 0.50 pc, temperature of about 22 K, mean column density of 1.7 × 10{sup 22} cm{sup −2}, mean volume density of about 4.4 × 10{sup 4} cm{sup −3}, and a mean mass of 320 M{sub ⊙}. In addition, from PAH emission seen at 8 μm, free–free emission detected at 20 cm, and a probability density function in special regions, we could identify clear signatures of the influence of the H ii region on the surroundings. There are hints of star formation, though further investigation is required to demonstrate that N4 is the triggering source.

  8. On the environment surrounding close-in exoplanets

    Science.gov (United States)

    Vidotto, A. A.; Fares, R.; Jardine, M.; Moutou, C.; Donati, J.-F.

    2015-06-01

    Exoplanets in extremely close-in orbits are immersed in a local interplanetary medium (i.e. the stellar wind) much denser than the local conditions encountered around the Solar system planets. The environment surrounding these exoplanets also differs in terms of dynamics (slower stellar winds, but higher Keplerian velocities) and ambient magnetic fields (likely higher for host stars more active than the Sun). Here, we quantitatively investigate the nature of the interplanetary media surrounding the hot Jupiters HD 46375b, HD 73256b, HD 102195b, HD 130322b and HD 179949b. We simulate the three-dimensional winds of their host stars, in which we directly incorporate their observed surface magnetic fields. With that, we derive mass-loss rates (1.9-8.0 × 10-13 M⊙ yr-1) and the wind properties at the position of the hot Jupiters' orbits (temperature, velocity, magnetic field intensity and pressure). We show that these exoplanets' orbits are supermagnetosonic, indicating that bow shocks are formed surrounding these planets. Assuming planetary magnetic fields similar to Jupiter's, we estimate planetary magnetospheric sizes of 4.1-5.6 planetary radii. We also derive the exoplanetary radio emission released in the dissipation of the stellar wind energy. We find radio fluxes ranging from 0.02 to 0.13 mJy, which are challenging to be observed with present-day technology, but could be detectable with future higher sensitivity arrays (e.g. Square Kilometre Array). Radio emission from systems having closer hot Jupiters, such as from τ Boo b or HD 189733b, or from nearby planetary systems orbiting young stars, are likely to have higher radio fluxes, presenting better prospects for detecting exoplanetary radio emission.

  9. Genome-wide association study identifies shared risk loci common to two malignancies in golden retrievers.

    Directory of Open Access Journals (Sweden)

    Noriko Tonomura

    2015-02-01

    Full Text Available Dogs, with their breed-determined limited genetic background, are great models of human disease including cancer. Canine B-cell lymphoma and hemangiosarcoma are both malignancies of the hematologic system that are clinically and histologically similar to human B-cell non-Hodgkin lymphoma and angiosarcoma, respectively. Golden retrievers in the US show significantly elevated lifetime risk for both B-cell lymphoma (6% and hemangiosarcoma (20%. We conducted genome-wide association studies for hemangiosarcoma and B-cell lymphoma, identifying two shared predisposing loci. The two associated loci are located on chromosome 5, and together contribute ~20% of the risk of developing these cancers. Genome-wide p-values for the top SNP of each locus are 4.6×10-7 and 2.7×10-6, respectively. Whole genome resequencing of nine cases and controls followed by genotyping and detailed analysis identified three shared and one B-cell lymphoma specific risk haplotypes within the two loci, but no coding changes were associated with the risk haplotypes. Gene expression analysis of B-cell lymphoma tumors revealed that carrying the risk haplotypes at the first locus is associated with down-regulation of several nearby genes including the proximal gene TRPC6, a transient receptor Ca2+-channel involved in T-cell activation, among other functions. The shared risk haplotype in the second locus overlaps the vesicle transport and release gene STX8. Carrying the shared risk haplotype is associated with gene expression changes of 100 genes enriched for pathways involved in immune cell activation. Thus, the predisposing germ-line mutations in B-cell lymphoma and hemangiosarcoma appear to be regulatory, and affect pathways involved in T-cell mediated immune response in the tumor. This suggests that the interaction between the immune system and malignant cells plays a common role in the tumorigenesis of these relatively different cancers.

  10. Polymorphism at expressed DQ and DR loci in five common equine MHC haplotypes.

    Science.gov (United States)

    Miller, Donald; Tallmadge, Rebecca L; Binns, Matthew; Zhu, Baoli; Mohamoud, Yasmin Ali; Ahmed, Ayeda; Brooks, Samantha A; Antczak, Douglas F

    2017-03-01

    The polymorphism of major histocompatibility complex (MHC) class II DQ and DR genes in five common equine leukocyte antigen (ELA) haplotypes was determined through sequencing of mRNA transcripts isolated from lymphocytes of eight ELA homozygous horses. Ten expressed MHC class II genes were detected in horses of the ELA-A3 haplotype carried by the donor horses of the equine bacterial artificial chromosome (BAC) library and the reference genome sequence: four DR genes and six DQ genes. The other four ELA haplotypes contained at least eight expressed polymorphic MHC class II loci. Next generation sequencing (NGS) of genomic DNA of these four MHC haplotypes revealed stop codons in the DQA3 gene in the ELA-A2, ELA-A5, and ELA-A9 haplotypes. Few NGS reads were obtained for the other MHC class II genes that were not amplified in these horses. The amino acid sequences across haplotypes contained locus-specific residues, and the locus clusters produced by phylogenetic analysis were well supported. The MHC class II alleles within the five tested haplotypes were largely non-overlapping between haplotypes. The complement of equine MHC class II DQ and DR genes appears to be well conserved between haplotypes, in contrast to the recently described variation in class I gene loci between equine MHC haplotypes. The identification of allelic series of equine MHC class II loci will aid comparative studies of mammalian MHC conservation and evolution and may also help to interpret associations between the equine MHC class II region and diseases of the horse.

  11. Nonrandom Distribution of miRNAs Genes and Single Nucleotide Variants in Keratoconus Loci.

    Directory of Open Access Journals (Sweden)

    Dorota M Nowak

    Full Text Available Despite numerous studies, the causes of both development and progression of keratoconus remain elusive. Previous studies of this disorder focused mainly on one or two genetic factors only. However, in the analysis of such complex diseases all potential factors should be taken into consideration. The purpose of this study was a comprehensive analysis of known keratoconus loci to uncover genetic factors involved in this disease causation in the general population, which could be omitted in the original studies. In this investigation genomic data available in various databases and experimental own data were assessed. The lists of single nucleotide variants and miRNA genes localized in reported keratoconus loci were obtained from Ensembl and miRBase, respectively. The potential impact of nonsynonymous amino acid substitutions on protein structure and function was assessed with PolyPhen-2 and SIFT. For selected protein genes the ranking was made to choose those most promising for keratoconus development. Ranking results were based on topological features in the protein-protein interaction network. High specificity for the populations in which the causative sequence variants have been identified was found. In addition, the possibility of links between previously analyzed keratoconus loci was confirmed including miRNA-gene interactions. Identified number of genes associated with oxidative stress and inflammatory agents corroborated the hypothesis of their effect on the disease etiology. Distribution of the numerous sequences variants within both exons and mature miRNA which forces you to search for a broader look at the determinants of keratoconus. Our findings highlight the complexity of the keratoconus genetics.

  12. Allelic loss of the ING gene family loci is a frequent event in ameloblastoma.

    Science.gov (United States)

    Borkosky, Silvia S; Gunduz, Mehmet; Beder, Levent; Tsujigiwa, Hidetsugu; Tamamura, Ryo; Gunduz, Esra; Katase, Naoki; Rodriguez, Andrea P; Sasaki, Akira; Nagai, Noriyuki; Nagatsuka, Hitoshi

    2010-01-01

    Ameloblastoma is the most frequently encountered odontogenic tumor, characterized by a locally invasive behavior, frequent recurrences, and, although rare, metastatic capacity. Loss or inactivation of tumor suppressor genes (TSGs) allows cells to acquire neoplastic growth. The ING family proteins are tumor suppressors that physically and functionally interact with p53 to perform important roles in apoptosis, DNA repair, cell cycle regulation, and senescence. TP53 genetic alterations were reported to infrequently occur in ameloblastoma. Considering that other TSGs related to TP53 could be altered in this tumor, we focused our study on the ING family genes. We analyzed the loss of heterozygosity (LOH) status of the ING family (ING1-ING5) chromosomal loci in a group of ameloblastomas by microsatellite analysis, and correlated the ING LOH status with clinicopathological characteristics. By using specific microsatellite markers, high frequency of LOH was found at the loci of each ING gene family member (33.3-72.2%). A significant relationship was shown between LOH of D2S 140 (ING5 locus) and solid tumor type (p = 0.02). LOH of ING3MS (ING3 locus) was also high in solid type tumors, showing a near significant association. In addition, a notable tendency toward higher LOH for half of the markers was observed in recurrent cases. LOH of ING family genes appears as a common genetic alteration in solid ameloblastoma. The current study provides interesting novel information regarding the potential prognostic significance of the allelic loss of the ING gene family loci in ameloblastoma tumorigenesis.

  13. Nonrandom Distribution of miRNAs Genes and Single Nucleotide Variants in Keratoconus Loci.

    Science.gov (United States)

    Nowak, Dorota M; Gajecka, Marzena

    2015-01-01

    Despite numerous studies, the causes of both development and progression of keratoconus remain elusive. Previous studies of this disorder focused mainly on one or two genetic factors only. However, in the analysis of such complex diseases all potential factors should be taken into consideration. The purpose of this study was a comprehensive analysis of known keratoconus loci to uncover genetic factors involved in this disease causation in the general population, which could be omitted in the original studies. In this investigation genomic data available in various databases and experimental own data were assessed. The lists of single nucleotide variants and miRNA genes localized in reported keratoconus loci were obtained from Ensembl and miRBase, respectively. The potential impact of nonsynonymous amino acid substitutions on protein structure and function was assessed with PolyPhen-2 and SIFT. For selected protein genes the ranking was made to choose those most promising for keratoconus development. Ranking results were based on topological features in the protein-protein interaction network. High specificity for the populations in which the causative sequence variants have been identified was found. In addition, the possibility of links between previously analyzed keratoconus loci was confirmed including miRNA-gene interactions. Identified number of genes associated with oxidative stress and inflammatory agents corroborated the hypothesis of their effect on the disease etiology. Distribution of the numerous sequences variants within both exons and mature miRNA which forces you to search for a broader look at the determinants of keratoconus. Our findings highlight the complexity of the keratoconus genetics.

  14. Characterization of candidate genes in inflammatory bowel disease–associated risk loci

    Science.gov (United States)

    Peloquin, Joanna M.; Sartor, R. Balfour; Newberry, Rodney D.; McGovern, Dermot P.; Yajnik, Vijay; Lira, Sergio A.

    2016-01-01

    GWAS have linked SNPs to risk of inflammatory bowel disease (IBD), but a systematic characterization of disease-associated genes has been lacking. Prior studies utilized microarrays that did not capture many genes encoded within risk loci or defined expression quantitative trait loci (eQTLs) using peripheral blood, which is not the target tissue in IBD. To address these gaps, we sought to characterize the expression of IBD-associated risk genes in disease-relevant tissues and in the setting of active IBD. Terminal ileal (TI) and colonic mucosal tissues were obtained from patients with Crohn’s disease or ulcerative colitis and from healthy controls. We developed a NanoString code set to profile 678 genes within IBD risk loci. A subset of patients and controls were genotyped for IBD-associated risk SNPs. Analyses included differential expression and variance analysis, weighted gene coexpression network analysis, and eQTL analysis. We identified 116 genes that discriminate between healthy TI and colon samples and uncovered patterns in variance of gene expression that highlight heterogeneity of disease. We identified 107 coexpressed gene pairs for which transcriptional regulation is either conserved or reversed in an inflammation-independent or -dependent manner. We demonstrate that on average approximately 60% of disease-associated genes are differentially expressed in inflamed tissue. Last, we identified eQTLs with either genotype-only effects on expression or an interaction effect between genotype and inflammation. Our data reinforce tissue specificity of expression in disease-associated candidate genes, highlight genes and gene pairs that are regulated in disease-relevant tissue and inflammation, and provide a foundation to advance the understanding of IBD pathogenesis. PMID:27668286

  15. Transgenerational function of Tetrahymena Piwi protein Twi8p at distinctive noncoding RNA loci.

    Science.gov (United States)

    Farley, Brian M; Collins, Kathleen

    2017-04-01

    Transgenerational transmission of genome-regulatory epigenetic information can determine phenotypes in the progeny of sexual reproduction. Sequence specificity of transgenerational regulation derives from small RNAs assembled into Piwi-protein complexes. Known targets of transgenerational regulation are primarily transposons and transposon-derived sequences. Here, we extend the scope of Piwi-mediated transgenerational regulation to include unique noncoding RNA loci. Ciliates such as Tetrahymena have a phenotypically silent germline micronucleus and an expressed somatic macronucleus, which is differentiated anew from a germline genome copy in sexual reproduction. We show that the nuclear-localized Tetrahymena Piwi protein Twi8p shuttles from parental to zygotic macronuclei. Genetic elimination of Twi8p has no phenotype for cells in asexual growth. On the other hand, cells lacking Twi8p arrest in sexual reproduction with zygotic nuclei that retain the germline genome structure, without the DNA elimination and fragmentation required to generate a functional macronucleus. Twi8p-bound small RNAs originate from long-noncoding RNAs with a terminal hairpin, which become detectable in the absence of Twi8p. Curiously, the loci that generate Twi8p-bound small RNAs are essential for asexual cell growth, even though Twi8 RNPs are essential only in sexual reproduction. Our findings suggest the model that Twi8 RNPs act on silent germline chromosomes to permit their conversion to expressed macronuclear chromosomes. Overall this work reveals that a Piwi protein carrying small RNAs from long-noncoding RNA loci has transgenerational function in establishing zygotic nucleus competence for gene expression.

  16. Issues surrounding record keeping in district nursing practice.

    Science.gov (United States)

    Anderson, E E

    2000-07-01

    This article examines some aspects of nursing documentation following the publication of the document 'Guidelines for Records and Record Keeping' (UKCC, 1998). The importance of nursing documentation in patient care, in guiding practice and in providing information for members of the interprofessional healthcare team is highlighted. Record keeping forms an important part of the clinical governance initiative in terms of quality improvement and risk management. The issues surrounding the legal requirements of record keeping in district nursing practice are discussed. Suggestions are made for assessing the quality of nursing documentation by audit and research, in order to establish the suitability of using the present systems in the community setting.

  17. Induced radioactivity in a 4 MW target and its surroundings

    CERN Document Server

    Agosteo, Stefano; Otto, Thomas; Silari, Marco

    2003-01-01

    An important aspect of a future CERN Neutrino Factory is the material activation arising from a 2.2 GeV, 4 MW proton beam striking a mercury target. An estimation of the hadronic inelastic interactions and the production of residual nuclei in the target, the magnetic horn, the decay tunnel, the surrounding rock and a downstream dump was performed by the Monte Carlo hadronic cascade code FLUKA. The aim was both to assess the dose equivalent rate to be expected during maintenance work and to evaluate the amount of residual radioactivity, which will have to be disposed of after the facility has ceased operation.

  18. Mutual seismic interaction between tunnels and the surrounding granular soil

    Directory of Open Access Journals (Sweden)

    Mohamed Ahmed Abdel-Motaal

    2014-12-01

    Study results show that the maximum exerted straining actions in tunnel lining are directly proportional to the relative stiffness between tunnel and surrounding soil (lining thickness and soil shear modulus. Moreover, it is highly affected by the peak ground acceleration and the tunnel location (embedment depth. A comprehensive study is performed to show the effect of tunnel thickness and tunnel diameter on both the induced bending moment and lining deformation. In general, it is concluded that seismic analysis should be considered in regions subjected to peak ground acceleration greater than 0.15g.

  19. Problems Surrounding Probation In The South African Public Service

    Directory of Open Access Journals (Sweden)

    Z. Baloyi

    2006-11-01

    Full Text Available The aim of the study was to investigate problems surrounding probation periods in the South African Public Service. A qualitative study was conducted to determine the views of both probationers and supervisors managing the probation process. Data was gathered by means of focus groups and individual interviews. Nine key areas were identified as being problematic, viz. clarity regarding the purpose of probation, lack of proper guidelines, the duration of probation, rotation during probation, lack of training, poor management of probation, performance management, anxiety and stress, power and authority. Recommendations are made concerning possible interventions.

  20. A comparison of SNP and STR loci for delineating population structure and performing individual genetic assignment

    DEFF Research Database (Denmark)

    Glover, Kevin A.; Hansen, Michael Møller; Lien, Sigbjørn

    2010-01-01

    between SNP and STR data sets and variants thereof. The best 15 SNPs (30 alleles) gave a similar level of self-assignment to the best 4 STR loci (83 alleles), however, addition of further STR loci did not lead to a notable increase assignment whereas addition of up to 100 SNP loci increased assignment...

  1. The expected performance of single nucleotide polymorphism loci in paternity testing.

    Science.gov (United States)

    Ayres, Karen L

    2005-11-25

    We discuss the utility of single nucleotide polymorphism loci for full trio and mother-unavailable paternity testing cases, in the presence of population substructure and relatedness of putative and actual fathers. We focus primarily on the expected number of loci required to gain specified probabilities of mismatches, and report the expected proportion of paternity indices greater than three threshold values for these loci.

  2. Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

    NARCIS (Netherlands)

    Couch, Fergus J; Kuchenbaecker, Karoline B; Michailidou, Kyriaki; Mendoza-Fandino, Gustavo A; Nord, Silje; Lilyquist, Janna; Olswold, Curtis; Hallberg, Emily; Agata, Simona; Ahsan, Habibul; Aittomäki, Kristiina; Ambrosone, Christine; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Arun, Banu K; Arver, Brita; Barile, Monica; Barkardottir, Rosa B; Barrowdale, Daniel; Beckmann, Lars; Beckmann, Matthias W; Benitez, Javier; Blank, Stephanie V; Blomqvist, Carl; Bogdanova, Natalia V; Bojesen, Stig E; Bolla, Manjeet K; Bonanni, Bernardo; Brauch, Hiltrud; Brenner, Hermann; Burwinkel, Barbara; Buys, Saundra S; Caldes, Trinidad; Caligo, Maria A; Canzian, Federico; Carpenter, Jane; Chang-Claude, Jenny; Chanock, Stephen J; Chung, Wendy K; Claes, Kathleen B M; Cox, Angela; Cross, Simon S; Cunningham, Julie M; Czene, Kamila; Daly, Mary B; Damiola, Francesca; Darabi, Hatef; de la Hoya, Miguel; Devilee, Peter; Diez, Orland; Ding, Yuan C; Dolcetti, Riccardo; Domchek, Susan M; Dorfling, Cecilia M; Dos-Santos-Silva, Isabel; Dumont, Martine; Dunning, Alison M; Eccles, Diana M; Ehrencrona, Hans; Ekici, Arif B; Eliassen, Heather; Ellis, Steve; Fasching, Peter A; Figueroa, Jonine; Flesch-Janys, Dieter; Försti, Asta; Fostira, Florentia; Foulkes, William D; Friebel, Tara; Friedman, Eitan; Frost, Debra; Gabrielson, Marike; Gammon, Marilie D; Ganz, Patricia A; Gapstur, Susan M; Garber, Judy; Gaudet, Mia M; Gayther, Simon A; Gerdes, Anne-Marie; Ghoussaini, Maya; Giles, Graham G; Glendon, Gord; Godwin, Andrew K; Goldberg, Mark S; Goldgar, David E; González-Neira, Anna; Greene, Mark H; Gronwald, Jacek; Guénel, Pascal; Gunter, Marc; Haeberle, Lothar; Haiman, Christopher A; Hamann, Ute; Hansen, Thomas V O; Hart, Steven; Healey, Sue; Heikkinen, Tuomas; Henderson, Brian E; Herzog, Josef; Hogervorst, Frans B L; Hollestelle, Antoinette; Hooning, Maartje J; Hoover, Robert N; Hopper, John L; Humphreys, Keith; Hunter, David J; Huzarski, Tomasz; Imyanitov, Evgeny N; Isaacs, Claudine; Jakubowska, Anna; James, Paul; Janavicius, Ramunas; Jensen, Uffe Birk; John, Esther M; Jones, Michael; Kabisch, Maria; Kar, Siddhartha; Karlan, Beth Y; Khan, Sofia; Khaw, Kay-Tee; Kibriya, Muhammad G; Knight, Julia A; Ko, Yon-Dschun; Konstantopoulou, Irene; Kosma, Veli-Matti; Kristensen, Vessela; Kwong, Ava; Laitman, Yael; Lambrechts, Diether; Lazaro, Conxi; Lee, Eunjung; Le Marchand, Loic; Lester, Jenny; Lindblom, Annika; Lindor, Noralane; Lindstrom, Sara; Liu, Jianjun; Long, Jirong; Lubinski, Jan; Mai, Phuong L; Makalic, Enes; Malone, Kathleen E; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Marme, Frederik; Martens, John W M; McGuffog, Lesley; Meindl, Alfons; Miller, Austin; Milne, Roger L; Miron, Penelope; Montagna, Marco; Mazoyer, Sylvie; Mulligan, Anna M; Muranen, Taru A; Nathanson, Katherine L; Neuhausen, Susan L; Nevanlinna, Heli; Nordestgaard, Børge G; Nussbaum, Robert L; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I; Olson, Janet E; Osorio, Ana; Park, Sue K; Peeters, Petra H; Peissel, Bernard; Peterlongo, Paolo; Peto, Julian; Phelan, Catherine M; Pilarski, Robert; Poppe, Bruce; Pylkäs, Katri; Radice, Paolo; Rahman, Nazneen; Rantala, Johanna; Rappaport, Christine; Rennert, Gad; Richardson, Andrea; Robson, Mark; Romieu, Isabelle; Rudolph, Anja; Rutgers, Emiel J; Sanchez, Maria-Jose; Santella, Regina M; Sawyer, Elinor J; Schmidt, Daniel F; Schmidt, Marjanka K; Schmutzler, Rita K; Schumacher, Fredrick; Scott, Rodney; Senter, Leigha; Sharma, Priyanka; Simard, Jacques; Singer, Christian F; Sinilnikova, Olga M; Soucy, Penny; Southey, Melissa; Steinemann, Doris; Stenmark-Askmalm, Marie; Stoppa-Lyonnet, Dominique; Swerdlow, Anthony; Szabo, Csilla I; Tamimi, Rulla; Tapper, William; Teixeira, Manuel R; Teo, Soo-Hwang; Terry, Mary B; Thomassen, Mads; Thompson, Deborah; Tihomirova, Laima; Toland, Amanda E; Tollenaar, Robert A E M; Tomlinson, Ian; Truong, Thérèse; Tsimiklis, Helen; Teulé, Alex; Tumino, Rosario; Tung, Nadine; Turnbull, Clare; Ursin, Giski; van Deurzen, Carolien H M; van Rensburg, Elizabeth J; Varon-Mateeva, Raymonda; Wang, Zhaoming; Wang-Gohrke, Shan; Weiderpass, Elisabete; Weitzel, Jeffrey N; Whittemore, Alice; Wildiers, Hans; Winqvist, Robert; Yang, Xiaohong R; Yannoukakos, Drakoulis; Yao, Song; Zamora, M Pilar; Zheng, Wei; Hall, Per; Kraft, Peter; Vachon, Celine; Slager, Susan; Chenevix-Trench, Georgia; Pharoah, Paul D P; Monteiro, Alvaro A N; García-Closas, Montserrat; Easton, Douglas F; Antoniou, Antonis C

    2016-01-01

    Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, w

  3. Multi-ethnic fine-mapping of 14 central adiposity loci

    DEFF Research Database (Denmark)

    Liu, Ching-Ti; Buchkovich, Martin L; Winkler, Thomas W;

    2014-01-01

    The Genetic Investigation of Anthropometric Traits (GIANT) consortium identified 14 loci in European Ancestry (EA) individuals associated with waist-to-hip ratio (WHR) adjusted for body mass index. These loci are wide and narrowing the signals remains necessary. Twelve of 14 loci identified in GI...

  4. Isolation and characterization of microsatellite loci from the yellow-eyed penguin (Megadyptes antipodes).

    Science.gov (United States)

    Boessenkool, S; King, T M; Seddon, P J; Waters, J M

    2008-09-01

    Twelve microsatellite loci were isolated and characterized in the endangered yellow-eyed penguin (Megadyptes antipodes) using enriched genomic libraries. Polymorphic loci revealed two to eight alleles per locus and observed heterozygosity ranged from 0.21 to 0.77. These loci will be suitable for assessing current and historical patterns of genetic variability in yellow-eyed penguins.

  5. Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

    NARCIS (Netherlands)

    Couch, Fergus J; Kuchenbaecker, Karoline B; Michailidou, Kyriaki; Mendoza-Fandino, Gustavo A; Nord, Silje; Lilyquist, Janna; Olswold, Curtis; Hallberg, Emily; Agata, Simona; Ahsan, Habibul; Aittomäki, Kristiina; Ambrosone, Christine; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Arun, Banu K; Arver, Brita; Barile, Monica; Barkardottir, Rosa B; Barrowdale, Daniel; Beckmann, Lars; Beckmann, Matthias W; Benitez, Javier; Blank, Stephanie V; Blomqvist, Carl; Bogdanova, Natalia V; Bojesen, Stig E; Bolla, Manjeet K; Bonanni, Bernardo; Brauch, Hiltrud; Brenner, Hermann; Burwinkel, Barbara; Buys, Saundra S; Caldes, Trinidad; Caligo, Maria A; Canzian, Federico; Carpenter, Jane; Chang-Claude, Jenny; Chanock, Stephen J; Chung, Wendy K; Claes, Kathleen B M; Cox, Angela; Cross, Simon S; Cunningham, Julie M; Czene, Kamila; Daly, Mary B; Damiola, Francesca; Darabi, Hatef; de la Hoya, Miguel; Devilee, Peter; Diez, Orland; Ding, Yuan C; Dolcetti, Riccardo; Domchek, Susan M; Dorfling, Cecilia M; Dos-Santos-Silva, Isabel; Dumont, Martine; Dunning, Alison M; Eccles, Diana M; Ehrencrona, Hans; Ekici, Arif B; Eliassen, Heather; Ellis, Steve; Fasching, Peter A; Figueroa, Jonine; Flesch-Janys, Dieter; Försti, Asta; Fostira, Florentia; Foulkes, William D; Friebel, Tara; Friedman, Eitan; Frost, Debra; Gabrielson, Marike; Gammon, Marilie D; Ganz, Patricia A; Gapstur, Susan M; Garber, Judy; Gaudet, Mia M; Gayther, Simon A; Gerdes, Anne-Marie; Ghoussaini, Maya; Giles, Graham G; Glendon, Gord; Godwin, Andrew K; Goldberg, Mark S; Goldgar, David E; González-Neira, Anna; Greene, Mark H; Gronwald, Jacek; Guénel, Pascal; Gunter, Marc; Haeberle, Lothar; Haiman, Christopher A; Hamann, Ute; Hansen, Thomas V O; Hart, Steven; Healey, Sue; Heikkinen, Tuomas; Henderson, Brian E; Herzog, Josef; Hogervorst, Frans B L; Hollestelle, Antoinette; Hooning, Maartje J; Hoover, Robert N; Hopper, John L; Humphreys, Keith; Hunter, David J; Huzarski, Tomasz; Imyanitov, Evgeny N; Isaacs, Claudine; Jakubowska, Anna; James, Paul; Janavicius, Ramunas; Jensen, Uffe Birk; John, Esther M; Jones, Michael; Kabisch, Maria; Kar, Siddhartha; Karlan, Beth Y; Khan, Sofia; Khaw, Kay-Tee; Kibriya, Muhammad G; Knight, Julia A; Ko, Yon-Dschun; Konstantopoulou, Irene; Kosma, Veli-Matti; Kristensen, Vessela; Kwong, Ava; Laitman, Yael; Lambrechts, Diether; Lazaro, Conxi; Lee, Eunjung; Le Marchand, Loic; Lester, Jenny; Lindblom, Annika; Lindor, Noralane; Lindstrom, Sara; Liu, Jianjun; Long, Jirong; Lubinski, Jan; Mai, Phuong L; Makalic, Enes; Malone, Kathleen E; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Marme, Frederik; Martens, John W M; McGuffog, Lesley; Meindl, Alfons; Miller, Austin; Milne, Roger L; Miron, Penelope; Montagna, Marco; Mazoyer, Sylvie; Mulligan, Anna M; Muranen, Taru A; Nathanson, Katherine L; Neuhausen, Susan L; Nevanlinna, Heli; Nordestgaard, Børge G; Nussbaum, Robert L; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I; Olson, Janet E; Osorio, Ana; Park, Sue K; Peeters, Petra H; Peissel, Bernard; Peterlongo, Paolo; Peto, Julian; Phelan, Catherine M; Pilarski, Robert; Poppe, Bruce; Pylkäs, Katri; Radice, Paolo; Rahman, Nazneen; Rantala, Johanna; Rappaport, Christine; Rennert, Gad; Richardson, Andrea; Robson, Mark; Romieu, Isabelle; Rudolph, Anja; Rutgers, Emiel J; Sanchez, Maria-Jose; Santella, Regina M; Sawyer, Elinor J; Schmidt, Daniel F; Schmidt, Marjanka K; Schmutzler, Rita K; Schumacher, Fredrick; Scott, Rodney; Senter, Leigha; Sharma, Priyanka; Simard, Jacques; Singer, Christian F; Sinilnikova, Olga M; Soucy, Penny; Southey, Melissa; Steinemann, Doris; Stenmark-Askmalm, Marie; Stoppa-Lyonnet, Dominique; Swerdlow, Anthony; Szabo, Csilla I; Tamimi, Rulla; Tapper, William; Teixeira, Manuel R; Teo, Soo-Hwang; Terry, Mary B; Thomassen, Mads; Thompson, Deborah; Tihomirova, Laima; Toland, Amanda E; Tollenaar, Robert A E M; Tomlinson, Ian; Truong, Thérèse; Tsimiklis, Helen; Teulé, Alex; Tumino, Rosario; Tung, Nadine; Turnbull, Clare; Ursin, Giski; van Deurzen, Carolien H M; van Rensburg, Elizabeth J; Varon-Mateeva, Raymonda; Wang, Zhaoming; Wang-Gohrke, Shan; Weiderpass, Elisabete; Weitzel, Jeffrey N; Whittemore, Alice; Wildiers, Hans; Winqvist, Robert; Yang, Xiaohong R; Yannoukakos, Drakoulis; Yao, Song; Zamora, M Pilar; Zheng, Wei; Hall, Per; Kraft, Peter; Vachon, Celine; Slager, Susan; Chenevix-Trench, Georgia; Pharoah, Paul D P; Monteiro, Alvaro A N; García-Closas, Montserrat; Easton, Douglas F; Antoniou, Antonis C

    2016-01-01

    Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci,

  6. Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

    DEFF Research Database (Denmark)

    Couch, Fergus J; Kuchenbaecker, Karoline B; Michailidou, Kyriaki

    2016-01-01

    Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci...

  7. Accumulating mutations in series of haplotypes at the KIT and MITF loci are major determinants of white markings in Franches-Montagnes horses.

    Science.gov (United States)

    Haase, Bianca; Signer-Hasler, Heidi; Binns, Matthew M; Obexer-Ruff, Gabriela; Hauswirth, Regula; Bellone, Rebecca R; Burger, Dominik; Rieder, Stefan; Wade, Claire M; Leeb, Tosso

    2013-01-01

    Coat color and pattern variations in domestic animals are frequently inherited as simple monogenic traits, but a number are known to have a complex genetic basis. While the analysis of complex trait data remains a challenge in all species, we can use the reduced haplotypic diversity in domestic animal populations to gain insight into the genomic interactions underlying complex phenotypes. White face and leg markings are examples of complex traits in horses where little is known of the underlying genetics. In this study, Franches-Montagnes (FM) horses were scored for the occurrence of white facial and leg markings using a standardized scoring system. A genome-wide association study (GWAS) was performed for several white patterning traits in 1,077 FM horses. Seven quantitative trait loci (QTL) affecting the white marking score with p-values p≤10(-4) were identified. Three loci, MC1R and the known white spotting genes, KIT and MITF, were identified as the major loci underlying the extent of white patterning in this breed. Together, the seven loci explain 54% of the genetic variance in total white marking score, while MITF and KIT alone account for 26%. Although MITF and KIT are the major loci controlling white patterning, their influence varies according to the basic coat color of the horse and the specific body location of the white patterning. Fine mapping across the MITF and KIT loci was used to characterize haplotypes present. Phylogenetic relationships among haplotypes were calculated to assess their selective and evolutionary influences on the extent of white patterning. This novel approach shows that KIT and MITF act in an additive manner and that accumulating mutations at these loci progressively increase the extent of white markings.

  8. Interactions of the Infrared bubble N4 with the surroundings

    CERN Document Server

    Liu, Hong-Li; Wu, Yuefang; Yuan, Jing-Hua; Liu, Tie; Dubner, G; Paron, S; Ortega, M E; Molinari, Sergio; Huang, Maohai; Zavagno, Annie; Samal, Manash R; Huang, Ya-Fang; Zhang, Si-Ju

    2016-01-01

    The physical mechanisms that induce the transformation of a certain mass of gas in new stars are far from being well understood. Infrared bubbles associated with HII regions have been considered to be a good sample to investigate triggered star formation. In this paper we report on the investigation of the dust properties of the infrared bubble N4 around the HII region G11.898+0.747, analyzing its interaction with the surroundings and star formation histories therein, aiming at determining the possibility of star formation triggered by the expansion of the bubble. Using Herschel PACS and SPIRE images with a wide wavelength coverage, we reveal the dust properties over the entire bubble. Meanwhile, we are able to identify six dust clumps surrounding the bubble, with a mean size of 0.50 pc, temperature of about 22 K, mean column density of 1.7 $\\times10^{22}$ cm$^{-2}$, mean volume density of about 4.4 $\\times10^{4}$ cm$^{-3}$, and a mean mass of 320 $M_{\\odot}$. In addition, from PAH emission seen at 8 $\\mu$m, ...

  9. Radio observations of Supernova Remnants and the surrounding molecular gas

    CERN Document Server

    Dubner, G

    2011-01-01

    Supernova Remnants (SNRs) are believed to be the main source of Galactic cosmic rays (CR). The strong SNR shocks provide ideal acceleration sites for particles of at least 10^14 eV/nucleon. Radio continuum studies of SNRs carried out with good sensitivity and high angular resolution convey information about three main aspects of the SNRs: morphology, polarization and spectrum. Based on this information it is possible to localize sites of higher compression and particle acceleration as well as the orientation and degree of order of the magnetic fields, and in some cases even its intensity. All this information, when complemented with the study of the distribution and kinematics of the surrounding interstellar gas, results in a very useful dataset to investigate the role of SNRs as cosmic ray accelerators. In this presentation, I analyze the radio observations of SNRs and surrounding molecular clouds, showing the contribution of these studies to the understanding of the role of SNRs as factories of CRs.

  10. Triggered Star Formation Surrounding Wolf-Rayet Star HD 211853

    Science.gov (United States)

    Liu, Tie; Wu, Yuefang; Zhang, Huawei; Qin, Sheng-Li

    2012-05-01

    The environment surrounding Wolf-Rayet (W-R) star HD 211853 is studied in molecular, infrared, as well as radio, and H I emission. The molecular ring consists of well-separated cores, which have a volume density of 103 cm-3 and kinematic temperature ~20 K. Most of the cores are under gravitational collapse due to external pressure from the surrounding ionized gas. From the spectral energy distribution modeling toward the young stellar objects, the sequential star formation is revealed on a large scale in space spreading from the W-R star to the molecular ring. A small-scale sequential star formation is revealed toward core "A," which harbors a very young star cluster. Triggered star formations are thus suggested. The presence of the photodissociation region, the fragmentation of the molecular ring, the collapse of the cores, and the large-scale sequential star formation indicate that the "collect and collapse" process functions in this region. The star-forming activities in core "A" seem to be affected by the "radiation-driven implosion" process.

  11. On the environment surrounding close-in exoplanets

    CERN Document Server

    Vidotto, A A; Jardine, M; Moutou, C; Donati, J -F

    2015-01-01

    Exoplanets in extremely close-in orbits are immersed in a local interplanetary medium (i.e., the stellar wind) much denser than the local conditions encountered around the solar system planets. The environment surrounding these exoplanets also differs in terms of dynamics (slower stellar winds, but higher Keplerian velocities) and ambient magnetic fields (likely higher for host stars more active than the Sun). Here, we quantitatively investigate the nature of the interplanetary media surrounding the hot Jupiters HD46375b, HD73256b, HD102195b, HD130322b, HD179949b. We simulate the three-dimensional winds of their host stars, in which we directly incorporate their observed surface magnetic fields. With that, we derive mass-loss rates (1.9 to 8.0 $\\times 10^{-13} M_{\\odot}$/yr) and the wind properties at the position of the hot-Jupiters' orbits (temperature, velocity, magnetic field intensity and pressure). We show that these exoplanets' orbits are super-magnetosonic, indicating that bow shocks are formed surrou...

  12. Triggered star formation surrounding Wolf-Rayet star HD 211853

    CERN Document Server

    Liu, Tie; Zhang, Huawei; Qin, Sheng-Li

    2012-01-01

    The environment surrounding Wolf-Rayet star HD 211853 is studied in molecular emission, infrared emission, as well as radio and HI emission. The molecular ring consists of well-separated cores, which have a volume density of 10$^{3}$ cm$^{-3}$ and kinematic temperature $\\sim$20 K. Most of the cores are under gravitational collapse due to external pressure from the surrounding ionized gas. From SED modeling towards the young stellar objects (YSOs), sequential star formation is revealed on a large scale in space spreading from the Wolf-Rayet star to the molecular ring. A small scale sequential star formation is revealed towards core A, which harbors a very young star cluster. Triggered star formations is thus suggested. The presence of PDR, the fragmentation of the molecular ring, the collapse of the cores, the large scale sequential star formation indicate the "Collect and Collapse" process functions in this region. The star forming activities in core A seem to be affected by the "Radiation-Driven Implosion" (...

  13. TRIGGERED STAR FORMATION SURROUNDING WOLF-RAYET STAR HD 211853

    Energy Technology Data Exchange (ETDEWEB)

    Liu Tie; Wu Yuefang; Zhang Huawei [Department of Astronomy, Peking University, 100871 Beijing (China); Qin Shengli, E-mail: liutiepku@gmail.com [I. Physikalisches Institut, Universitaet zu Koeln, Zuelpicher Str. 77, 50937 Koeln (Germany)

    2012-05-20

    The environment surrounding Wolf-Rayet (W-R) star HD 211853 is studied in molecular, infrared, as well as radio, and H I emission. The molecular ring consists of well-separated cores, which have a volume density of 10{sup 3} cm{sup -3} and kinematic temperature {approx}20 K. Most of the cores are under gravitational collapse due to external pressure from the surrounding ionized gas. From the spectral energy distribution modeling toward the young stellar objects, the sequential star formation is revealed on a large scale in space spreading from the W-R star to the molecular ring. A small-scale sequential star formation is revealed toward core 'A', which harbors a very young star cluster. Triggered star formations are thus suggested. The presence of the photodissociation region, the fragmentation of the molecular ring, the collapse of the cores, and the large-scale sequential star formation indicate that the 'collect and collapse' process functions in this region. The star-forming activities in core 'A' seem to be affected by the 'radiation-driven implosion' process.

  14. Seven newly identified loci for autoimmune thyroid disease.

    Science.gov (United States)

    Cooper, Jason D; Simmonds, Matthew J; Walker, Neil M; Burren, Oliver; Brand, Oliver J; Guo, Hui; Wallace, Chris; Stevens, Helen; Coleman, Gillian; Franklyn, Jayne A; Todd, John A; Gough, Stephen C L

    2012-12-01

    Autoimmune thyroid disease (AITD), including Graves' disease (GD) and Hashimoto's thyroiditis (HT), is one of the most common of the immune-mediated diseases. To further investigate the genetic determinants of AITD, we conducted an association study using a custom-made single-nucleotide polymorphism (SNP) array, the ImmunoChip. The SNP array contains all known and genotype-able SNPs across 186 distinct susceptibility loci associated with one or more immune-mediated diseases. After stringent quality control, we analysed 103 875 common SNPs (minor allele frequency >0.05) in 2285 GD and 462 HT patients and 9364 controls. We found evidence for seven new AITD risk loci (P < 1.12 × 10(-6); a permutation test derived significance threshold), five at locations previously associated and two at locations awaiting confirmation, with other immune-mediated diseases.

  15. Informativeness of the CODIS STR loci for admixture analysis.

    Science.gov (United States)

    Barnholtz-Sloan, Jill S; Pfaff, Carrie L; Chakraborty, Ranajit; Long, Jeffrey C

    2005-11-01

    Population admixture (or ancestry) is used as an approach to gene discovery in complex diseases, particularly when the disease prevalence varies widely across geographic populations. Admixture analysis could be useful for forensics because an indication of a perpetrator's ancestry would narrow the pool of suspects for a particular crime. The purpose of this study was to use Fisher's information to identify informative sets of markers for admixture analysis. Using published founding population allele frequencies we test three marker sets for efficacy for estimating admixture: the FBI CODIS Core STR loci, the HGDP-CEPH Human Genome Diversity Cell Line Panel and the set of 39 ancestry informative SNPS from the Shriver lab at Pennsylvania State University. We conclude that the FBI CODIS Core STR set is valid for admixture analysis, but not the most precise. We recommend using a combination of the most informative markers from the HGDP-CEPH and Shriver loci sets.

  16. CODIS STR loci data from 41 sample populations.

    Science.gov (United States)

    Budowle, B; Shea, B; Niezgoda, S; Chakraborty, R

    2001-05-01

    Allele distributions for 12 or 13 CODIS core tetrameric short tandem repeat (STR) loci CSFIPO, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11, FGA, TH01, TPOX, and vWA were determined in 41 population data sets. The major population groups comprise African Americans, U.S. Caucasians, Hispanics, Far East Asians, and Native Americans. There was little evidence for departures from Hardy-Weinberg expectations (HWE) in any of the populations. The FST estimates over all thirteen STR loci are 0.0006 for African Americans, -0.0005 for Caucasians, 0.0021 for Hispanics, 0.0039 for Asians, and 0.0282 for Native Americans.

  17. PROPERTY IDENTIFICATION OF SINGULARITY LOCI OF GOUGH-STEWART MANIPULATOR

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The problem of identifying the property of singularity loci of Gough-Stewart manipulators is addressed. After constructing the Jacobian matrix of the Gough-Stewart manipulator, a cubic polynomial expression in the mobile platform position parameters, which represents the constantorientation singularity locus of the manipulator, is derived. Graphical representations of the singularity locus of the manipulator for different orientations are illustrated with examples. Further,the singularity locus of the manipulator in the principal-section, where the mobile platform lies, is analyzed. It shows that singularity loci of the manipulator in parallel pfincipal-sections are all quadratic expressions including a parabola, four pairs of intersecting straight lines and infinite hyperbolas. Their geometric and kinematic properties are also researched as well.

  18. 52 Genetic Loci Influencing Myocardial Mass.

    Science.gov (United States)

    van der Harst, Pim; van Setten, Jessica; Verweij, Niek; Vogler, Georg; Franke, Lude; Maurano, Matthew T; Wang, Xinchen; Mateo Leach, Irene; Eijgelsheim, Mark; Sotoodehnia, Nona; Hayward, Caroline; Sorice, Rossella; Meirelles, Osorio; Lyytikäinen, Leo-Pekka; Polašek, Ozren; Tanaka, Toshiko; Arking, Dan E; Ulivi, Sheila; Trompet, Stella; Müller-Nurasyid, Martina; Smith, Albert V; Dörr, Marcus; Kerr, Kathleen F; Magnani, Jared W; Del Greco M, Fabiola; Zhang, Weihua; Nolte, Ilja M; Silva, Claudia T; Padmanabhan, Sandosh; Tragante, Vinicius; Esko, Tõnu; Abecasis, Gonçalo R; Adriaens, Michiel E; Andersen, Karl; Barnett, Phil; Bis, Joshua C; Bodmer, Rolf; Buckley, Brendan M; Campbell, Harry; Cannon, Megan V; Chakravarti, Aravinda; Chen, Lin Y; Delitala, Alessandro; Devereux, Richard B; Doevendans, Pieter A; Dominiczak, Anna F; Ferrucci, Luigi; Ford, Ian; Gieger, Christian; Harris, Tamara B; Haugen, Eric; Heinig, Matthias; Hernandez, Dena G; Hillege, Hans L; Hirschhorn, Joel N; Hofman, Albert; Hubner, Norbert; Hwang, Shih-Jen; Iorio, Annamaria; Kähönen, Mika; Kellis, Manolis; Kolcic, Ivana; Kooner, Ishminder K; Kooner, Jaspal S; Kors, Jan A; Lakatta, Edward G; Lage, Kasper; Launer, Lenore J; Levy, Daniel; Lundby, Alicia; Macfarlane, Peter W; May, Dalit; Meitinger, Thomas; Metspalu, Andres; Nappo, Stefania; Naitza, Silvia; Neph, Shane; Nord, Alex S; Nutile, Teresa; Okin, Peter M; Olsen, Jesper V; Oostra, Ben A; Penninger, Josef M; Pennacchio, Len A; Pers, Tune H; Perz, Siegfried; Peters, Annette; Pinto, Yigal M; Pfeufer, Arne; Pilia, Maria Grazia; Pramstaller, Peter P; Prins, Bram P; Raitakari, Olli T; Raychaudhuri, Soumya; Rice, Ken M; Rossin, Elizabeth J; Rotter, Jerome I; Schafer, Sebastian; Schlessinger, David; Schmidt, Carsten O; Sehmi, Jobanpreet; Silljé, Herman H W; Sinagra, Gianfranco; Sinner, Moritz F; Slowikowski, Kamil; Soliman, Elsayed Z; Spector, Timothy D; Spiering, Wilko; Stamatoyannopoulos, John A; Stolk, Ronald P; Strauch, Konstantin; Tan, Sian-Tsung; Tarasov, Kirill V; Trinh, Bosco; Uitterlinden, Andre G; van den Boogaard, Malou; van Duijn, Cornelia M; van Gilst, Wiek H; Viikari, Jorma S; Visscher, Peter M; Vitart, Veronique; Völker, Uwe; Waldenberger, Melanie; Weichenberger, Christian X; Westra, Harm-Jan; Wijmenga, Cisca; Wolffenbuttel, Bruce H; Yang, Jian; Bezzina, Connie R; Munroe, Patricia B; Snieder, Harold; Wright, Alan F; Rudan, Igor; Boyer, Laurie A; Asselbergs, Folkert W; van Veldhuisen, Dirk J; Stricker, Bruno H; Psaty, Bruce M; Ciullo, Marina; Sanna, Serena; Lehtimäki, Terho; Wilson, James F; Bandinelli, Stefania; Alonso, Alvaro; Gasparini, Paolo; Jukema, J Wouter; Kääb, Stefan; Gudnason, Vilmundur; Felix, Stephan B; Heckbert, Susan R; de Boer, Rudolf A; Newton-Cheh, Christopher; Hicks, Andrew A; Chambers, John C; Jamshidi, Yalda; Visel, Axel; Christoffels, Vincent M; Isaacs, Aaron; Samani, Nilesh J; de Bakker, Paul I W

    2016-09-27

    Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death. This meta-analysis sought to gain insights into the genetic determinants of myocardial mass. We carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 × 10(-8). These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus. We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo. Taken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  19. Genomic Loci Modulating the Retinal Transcriptome in Wound Healing

    OpenAIRE

    Vázquez-Chona, Félix R; Lu Lu; Robert W Williams; Geisert, Eldon E.

    2007-01-01

    Purpose: The present study predicts and tests genetic networks that modulate gene expression during the retinal wound-healing response.Methods: Upstream modulators and target genes were defined using meta-analysis and bioinfor matic approaches. Quantitative trait loci (QTLs) for retinal acute phase genes (Vazquez-Chona et al. 2005) were defi ned using QTL analysis of CNS gene expression (Chesler et al. 2005). Candidate modulators were defi ned using computational analysis of gene and motif se...

  20. Incomplete Lineage Sorting: Consistent Phylogeny Estimation From Multiple Loci

    CERN Document Server

    Mossel, Elchanan

    2008-01-01

    We introduce a simple algorithm for reconstructing phylogenies from multiple gene trees in the presence of incomplete lineage sorting, that is, when the topology of the gene trees may differ from that of the species tree. We show that our technique is statistically consistent under standard stochastic assumptions, that is, it returns the correct tree given sufficiently many unlinked loci. We also show that it can tolerate moderate estimation errors.

  1. Simultaneous mapping of multiple gene loci with pooled segregants.

    Directory of Open Access Journals (Sweden)

    Jürgen Claesen

    Full Text Available The analysis of polygenic, phenotypic characteristics such as quantitative traits or inheritable diseases remains an important challenge. It requires reliable scoring of many genetic markers covering the entire genome. The advent of high-throughput sequencing technologies provides a new way to evaluate large numbers of single nucleotide polymorphisms (SNPs as genetic markers. Combining the technologies with pooling of segregants, as performed in bulked segregant analysis (BSA, should, in principle, allow the simultaneous mapping of multiple genetic loci present throughout the genome. The gene mapping process, applied here, consists of three steps: First, a controlled crossing of parents with and without a trait. Second, selection based on phenotypic screening of the offspring, followed by the mapping of short offspring sequences against the parental reference. The final step aims at detecting genetic markers such as SNPs, insertions and deletions with next generation sequencing (NGS. Markers in close proximity of genomic loci that are associated to the trait have a higher probability to be inherited together. Hence, these markers are very useful for discovering the loci and the genetic mechanism underlying the characteristic of interest. Within this context, NGS produces binomial counts along the genome, i.e., the number of sequenced reads that matches with the SNP of the parental reference strain, which is a proxy for the number of individuals in the offspring that share the SNP with the parent. Genomic loci associated with the trait can thus be discovered by analyzing trends in the counts along the genome. We exploit the link between smoothing splines and generalized mixed models for estimating the underlying structure present in the SNP scatterplots.

  2. The Isoconditioning Loci of Planar Three-DOF Parallel Manipulators

    CERN Document Server

    Chablat, Damien; Caro, Stéphane; Angeles, Jorge

    2007-01-01

    The subject of this paper is a special class of three-degree-of-freedom parallel manipulators. The singular configurations of the two Jacobian matrices are first studied. The isotropic configurations are then found based on the characteristic length of this manipulator. The isoconditioning loci for the Jacobian matrices are plotted to define a global performance index allowing the comparison of the different working modes. The index thus resulting is compared with the Cartesian workspace surface and the average of the condition number.

  3. Adaptive Linkage Disequilibrium Between Two Esterase Loci of a Salamander

    Science.gov (United States)

    Webster, T. Preston

    1973-01-01

    In some populations of the salamander Plethodon cinereus, two polymorphic esterase loci are in linkage disequilibrium. Short-term stability of the linkage disequilibrium is demonstrated by an age class analysis. Long, perhaps very long, term stability is suggested by its distribution. This stability and concordant geographic variation in allelic frequencies imply selective origin and maintenance. Data on the frequencies of two color morphs suggest that formation of the linkage disequilibrium is dependent on the genetic background. Images PMID:4515614

  4. Investigating the viability of genetic screening/testing for RA susceptibility using combinations of five confirmed risk loci

    Science.gov (United States)

    McClure, Annie; Lunt, Mark; Eyre, Steve; Ke, Xiayi; Thomson, Wendy; Hinks, Anne; Bowes, John; Gibbons, Laura; Plant, Darren; Wilson, Anthony G.; Marinou, Ioanna; Morgan, Ann W.; Emery, Paul; Steer, Sophia; Hocking, Lynne J.; Reid, David M.; Wordsworth, Paul; Harrison, Pille; Worthington, Jane

    2009-01-01

    Objective. Five loci—the shared epitope (SE) of HLA-DRB1, the PTPN22 gene, a locus on 6q23, the STAT4 gene and a locus mapping to the TRAF1/C5 genetic region—have now been unequivocally confirmed as conferring susceptibility to RA. The largest single effect is conferred by SE. We hypothesized that combinations of susceptibility alleles may increase risk over and above that of any individual locus alone. Methods. We analysed data from 4238 RA cases and 1811 controls, for which genotypes were available at all five loci. Results. Statistical analysis identified eight high-risk combinations conferring an odds ratio >6 compared with carriage of no susceptibility variants and, interestingly, 10% population controls carried a combination conferring high risk. All high-risk combinations included SE, and all but one contained PTPN22. Statistical modelling showed that a model containing only these two loci could achieve comparable sensitivity and specificity to a model including all five. Furthermore, replacing SE (which requires full subtyping at the HLA-DRB1 gene) with DRB1*1/4/10 carriage resulted in little further loss of information (correlation coefficient between models = 0.93). Conclusions. This represents the first exploration of the viability of population screening for RA and identifies several high-risk genetic combinations. However, given the population incidence of RA, genetic screening based on these loci alone is neither sufficiently sensitive nor specific at the current time. PMID:19741008

  5. An investigation of genome-wide studies reported susceptibility loci for ulcerative colitis shows limited replication in north Indians.

    Directory of Open Access Journals (Sweden)

    Garima Juyal

    Full Text Available Genome-Wide Association studies (GWAS of both Crohn's Disease (CD and Ulcerative Colitis (UC have unearthed over 40 risk conferring variants. Recently, a meta-analysis on UC revealed several loci, most of which were either previously associated with UC or CD susceptibility in populations of European origin. In this study, we attempted to replicate these findings in an ethnically distinct north Indian UC cohort. 648 UC cases and 850 controls were genotyped using Infinium Human 660W-quad. Out of 59 meta-analysis index SNPs, six were not in the SNP array used in the study. Of the remaining 53 SNPs, four were found monomorphic. Association (p<0.05 at 25 SNPs was observed, of which 15 were CD specific. Only five SNPs namely rs2395185 (HLA-DRA, rs3024505 (IL10, rs6426833 (RNF186, rs3763313 (BTNL2 and rs2066843 (NOD2 retained significance after Bonferroni correction. These results (i reveal limited replication of Caucasian based meta-analysis results; (ii reiterate overlapping molecular mechanism(s in UC and CD; (iii indicate differences in genetic architecture between populations; and (iv suggest that resources such as HapMap need to be extended to cover diverse ethnic populations. They also suggest a systematic GWAS in this terrain may be insightful for identifying population specific IBD risk conferring loci and thus enable cross-ethnicity fine mapping of disease loci.

  6. Four loci explain 83% of size variation in the horse.

    Directory of Open Access Journals (Sweden)

    Shokouh Makvandi-Nejad

    Full Text Available Horse body size varies greatly due to intense selection within each breed. American Miniatures are less than one meter tall at the withers while Shires and Percherons can exceed two meters. The genetic basis for this variation is not known. We hypothesize that the breed population structure of the horse should simplify efforts to identify genes controlling size. In support of this, here we show with genome-wide association scans (GWAS that genetic variation at just four loci can explain the great majority of horse size variation. Unlike humans, which are naturally reproducing and possess many genetic variants with weak effects on size, we show that horses, like other domestic mammals, carry just a small number of size loci with alleles of large effect. Furthermore, three of our horse size loci contain the LCORL, HMGA2 and ZFAT genes that have previously been found to control human height. The LCORL/NCAPG locus is also implicated in cattle growth and HMGA2 is associated with dog size. Extreme size diversification is a hallmark of domestication. Our results in the horse, complemented by the prior work in cattle and dog, serve to pinpoint those very few genes that have played major roles in the rapid evolution of size during domestication.

  7. Genome-wide search for strabismus susceptibility loci.

    Directory of Open Access Journals (Sweden)

    Fujiwara H

    2003-06-01

    Full Text Available The purpose of this study was to search for chromosomal susceptibility loci for comitant strabismus. Genomic DNA was isolated from 10mL blood taken from each member of 30 nuclear families in which 2 or more siblings are affected by either esotropia or exotropia. A genome-wide search was performed with amplification by polymerase chain reaction of 400 markers in microsatellite regions with approximately 10 cM resolution. For each locus, non-parametric affected sib-pair analysis and non-parametric linkage analysis for multiple pedigrees (Genehunter software, http://linkage.rockefeller.edu/soft/ were used to calculate multipoint lod scores and non-parametric linkage (NPL scores, respectively. In sib-pair analysis, lod scores showed basically flat lines with several peaks of 0.25 on all chromosomes. In non-parametric linkage analysis for multiple pedigrees, NPL scores showed one peak as high as 1.34 on chromosomes 1, 2, 4, 7, 10, 15, and 16, while 2 such peaks were found on chromosomes 3, 9, 11, 12, 18, and 20. Non-parametric linkage analysis for multiple pedigrees of 30 families with comitant strabismus suggested a number of chromosomal susceptibility loci. Our ongoing study involving a larger number of families will refine the accuracy of statistical analysis to pinpoint susceptibility loci for comitant strabismus.

  8. Genome-wide association study identifies five new schizophrenia loci.

    LENUS (Irish Health Repository)

    Ripke, Stephan

    2011-10-01

    We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10(-9)), ANK3 (rs10994359, P = 2.5 × 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10(-9)).

  9. Evolution of V genes from the TRV loci of mammals.

    Science.gov (United States)

    Olivieri, David N; Gambón-Cerdá, Santiago; Gambón-Deza, Francisco

    2015-07-01

    Information concerning the evolution of T lymphocyte receptors (TCR) can be deciphered from that part of the molecule that recognizes antigen presented by major histocompatibility complex (MHC), namely the variable (V) regions. The genes that code for these variable regions are found within the TCR loci. Here, we describe a study of the evolutionary origin of V genes that code for the α and β chains of the TCR loci of mammals. In particular, we demonstrate that most of the 35 TRAV and 25 TRBV conserved genes found in Primates are also found in other Eutheria, while in Marsupials, Monotremes, and Reptiles, these genes diversified in a different manner. We also show that in mammals, all TRAV genes are derived from five ancestral genes, while all TRBV genes originate from four such genes. In Reptiles, the five TRAV and three out of the four TRBV ancestral genes exist, as well as other V genes not found in mammals. We also studied the TRGV and TRDV loci from all mammals, and we show a relationship of the TRDV to the TRAV locus throughout evolutionary time.

  10. Genome-wide Meta-analyses of Breast, Ovarian and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by At Least Two Cancer Types

    Science.gov (United States)

    Kar, Siddhartha P.; Beesley, Jonathan; Al Olama, Ali Amin; Michailidou, Kyriaki; Tyrer, Jonathan; Kote-Jarai, ZSofia; Lawrenson, Kate; Lindstrom, Sara; Ramus, Susan J.; Thompson, Deborah J.; Kibel, Adam S.; Dansonka-Mieszkowska, Agnieszka; Michael, Agnieszka; Dieffenbach, Aida K.; Gentry-Maharaj, Aleksandra; Whittemore, Alice S.; Wolk, Alicja; Monteiro, Alvaro; Peixoto, Ana; Kierzek, Andrzej; Cox, Angela; Rudolph, Anja; Gonzalez-Neira, Anna; Wu, Anna H.; Lindblom, Annika; Swerdlow, Anthony; Ziogas, Argyrios; Ekici, Arif B.; Burwinkel, Barbara; Karlan, Beth Y.; Nordestgaard, Børge G.; Blomqvist, Carl; Phelan, Catherine; McLean, Catriona; Pearce, Celeste Leigh; Vachon, Celine; Cybulski, Cezary; Slavov, Chavdar; Stegmaier, Christa; Maier, Christiane; Ambrosone, Christine B.; Høgdall, Claus K.; Teerlink, Craig C.; Kang, Daehee; Tessier, Daniel C.; Schaid, Daniel J.; Stram, Daniel O.; Cramer, Daniel W.; Neal, David E.; Eccles, Diana; Flesch-Janys, Dieter; Velez Edwards, Digna R.; Wokozorczyk, Dominika; Levine, Douglas A.; Yannoukakos, Drakoulis; Sawyer, Elinor J.; Bandera, Elisa V.; Poole, Elizabeth M.; Goode, Ellen L.; Khusnutdinova, Elza; Høgdall, Estrid; Song, Fengju; Bruinsma, Fiona; Heitz, Florian; Modugno, Francesmary; Hamdy, Freddie C.; Wiklund, Fredrik; Giles, Graham G.; Olsson, Håkan; Wildiers, Hans; Ulmer, Hans-Ulrich; Pandha, Hardev; Risch, Harvey A.; Darabi, Hatef; Salvesen, Helga B.; Nevanlinna, Heli; Gronberg, Henrik; Brenner, Hermann; Brauch, Hiltrud; Anton-Culver, Hoda; Song, Honglin; Lim, Hui-Yi; McNeish, Iain; Campbell, Ian; Vergote, Ignace; Gronwald, Jacek; Lubiński, Jan; Stanford, Janet L.; Benítez, Javier; Doherty, Jennifer A.; Permuth, Jennifer B.; Chang-Claude, Jenny; Donovan, Jenny L.; Dennis, Joe; Schildkraut, Joellen M.; Schleutker, Johanna; Hopper, John L.; Kupryjanczyk, Jolanta; Park, Jong Y.; Figueroa, Jonine; Clements, Judith A.; Knight, Julia A.; Peto, Julian; Cunningham, Julie M.; Pow-Sang, Julio; Batra, Jyotsna; Czene, Kamila; Lu, Karen H.; Herkommer, Kathleen; Khaw, Kay-Tee; Matsuo, Keitaro; Muir, Kenneth; Offitt, Kenneth; Chen, Kexin; Moysich, Kirsten B.; Aittomäki, Kristiina; Odunsi, Kunle; Kiemeney, Lambertus A.; Massuger, Leon F.A.G.; Fitzgerald, Liesel M.; Cook, Linda S.; Cannon-Albright, Lisa; Hooning, Maartje J.; Pike, Malcolm C.; Bolla, Manjeet K.; Luedeke, Manuel; Teixeira, Manuel R.; Goodman, Marc T.; Schmidt, Marjanka K.; Riggan, Marjorie; Aly, Markus; Rossing, Mary Anne; Beckmann, Matthias W.; Moisse, Matthieu; Sanderson, Maureen; Southey, Melissa C.; Jones, Michael; Lush, Michael; Hildebrandt, Michelle A. T.; Hou, Ming-Feng; Schoemaker, Minouk J.; Garcia-Closas, Montserrat; Bogdanova, Natalia; Rahman, Nazneen; Le, Nhu D.; Orr, Nick; Wentzensen, Nicolas; Pashayan, Nora; Peterlongo, Paolo; Guénel, Pascal; Brennan, Paul; Paulo, Paula; Webb, Penelope M.; Broberg, Per; Fasching, Peter A.; Devilee, Peter; Wang, Qin; Cai, Qiuyin; Li, Qiyuan; Kaneva, Radka; Butzow, Ralf; Kopperud, Reidun Kristin; Schmutzler, Rita K.; Stephenson, Robert A.; MacInnis, Robert J.; Hoover, Robert N.; Winqvist, Robert; Ness, Roberta; Milne, Roger L.; Travis, Ruth C.; Benlloch, Sara; Olson, Sara H.; McDonnell, Shannon K.; Tworoger, Shelley S.; Maia, Sofia; Berndt, Sonja; Lee, Soo Chin; Teo, Soo-Hwang; Thibodeau, Stephen N.; Bojesen, Stig E.; Gapstur, Susan M.; Kjær, Susanne Krüger; Pejovic, Tanja; Tammela, Teuvo L.J.; Dörk, Thilo; Brüning, Thomas; Wahlfors, Tiina; Key, Tim J.; Edwards, Todd L.; Menon, Usha; Hamann, Ute; Mitev, Vanio; Kosma, Veli-Matti; Setiawan, Veronica Wendy; Kristensen, Vessela; Arndt, Volker; Vogel, Walther; Zheng, Wei; Sieh, Weiva; Blot, William J.; Kluzniak, Wojciech; Shu, Xiao-Ou; Gao, Yu-Tang; Schumacher, Fredrick; Freedman, Matthew L.; Berchuck, Andrew; Dunning, Alison M.; Simard, Jacques; Haiman, Christopher A.; Spurdle, Amanda; Sellers, Thomas A.; Hunter, David J.; Henderson, Brian E.; Kraft, Peter; Chanock, Stephen J.; Couch, Fergus J.; Hall, Per; Gayther, Simon A.; Easton, Douglas F.; Chenevix-Trench, Georgia; Eeles, Rosalind; Pharoah, Paul D.P.; Lambrechts, Diether

    2016-01-01

    Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10−8 seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10−5 in the three-cancer meta-analysis. PMID:27432226

  11. Association between the Igk and Igh loci mediated by the 3’ Igk enhancer induces decontraction of the Igh locus in pre-B cells

    Science.gov (United States)

    Hewitt, Susannah L; Farmer, Deborah; Marszalek, Katarzyna; Cadera, Emily; Liang, Hong-Erh; Xu, Yang; Schlissel, Mark S; Skok, Jane A

    2008-01-01

    V(D)J recombination at Igh and Igk loci takes place sequentially during successive stages in B cell development. Using 3-dimensional DNA fluorescence in situ hybridization (FISH), we identified a lineage- and stage-specific interchromosomal association between these two loci which marks the transition between Igh and Igk recombination. Co-localization occured between pericentromerically located alleles in pre-B cells, and was mediated by the 3’ Igk enhancer. Deletion of this regulatory element prevented association of the Igh and Igk loci, inhibited pericentromeric recruitment and locus decontraction of an Igh allele, and resulted in increased distal VH gene rearrangement. Our data indicate a role for the Igk locus and its 3’ enhancer in directing the Igh locus to a repressive nuclear subcompartment, and in rendering the Igh locus unable to contract. PMID:18297074

  12. Distributions of allele combination in single and cross loci among patients with several kinds of chronic diseases and the normal population.

    Science.gov (United States)

    Gai, Li-ping; Liu, Hui; Cui, Jing-hui; Ji, Na; Ding, Xiao-dong; Sun, Cui; Yu, Lai-shui

    2015-03-01

    Genetic research has progressed along with scientific and technological developments. However, it is difficult to identify frequency differences in a particular allele distribution at a single locus. Such differences can be identified by examining the allele combination distribution. We explored different mathematical methods for statistical analyses to assess the association between the genotype and phenotype. We investigated the frequency distributions of alleles, combinations of single-locus genes, and combinations of cross-loci genes at 15 loci using 447 blood samples of 200 normal subjects, 72 patients with chronic obstructive pulmonary resistance, 50 liver cancers, 75 stomach cancers and 50 hematencephalon and identified each population as having a unique gene distribution and that the distribution followed certain rules. The probability of illness followed different rules and had apparent specificity. Differences obtained using statistics of combinations of cross-loci genes are superior to single-locus gene statistics, and combinations of single-locus gene statistics are better than allelic statistics.

  13. Microsatellites loci reveal heterozygosis and population structure in vampire bats (Desmodus rotundus) (Chiroptera: Phyllostomidae) of Mexico.

    Science.gov (United States)

    Romero-Nava, Claudia; León-Paniagua, Livia; Ortega, Jorge

    2014-06-01

    A limited number of studies have focused on the population genetic structure of vampire bats (Desmous rotundus) in America. This medium-sized bat is distributed in tropical areas of the continent with high prevalence in forested livestock areas. The aim of this work was to characterize the vampire population structure and their genetic differentiation. For this, we followed standard methods by which live vampires (caught by mist-netting) and preserved material from scientific collections, were obtained for a total of 15 different locations, ranging from Chihuahua (North) to Quintana Roo (Southeast). Tissue samples were obtained from both live and collected animals, and the genetic differentiation, within and among localities, was assessed by the use of seven microsatellite loci. Our results showed that all loci were polymorphic and no private alleles were detected. High levels of heterozygosis were detected when the proportion of alleles in each locus were compared. Pairwise (ST) and R(ST) detected significant genetic differentiation among individuals from different localities. Our population structure results indicate the presence of eleven clusters, with a high percentage of assigned individuals to some specific collecting site.

  14. AMBIGUITY OF LOCI DURING HLA-TYPING ON SSO TECHNOLOGY AND ATTEMPT TO RESOLVE THEM

    Directory of Open Access Journals (Sweden)

    M. A. Loginova

    2010-01-01

    Full Text Available Sequence specific oligonucleotides typing was used to identify human leukocyte antigen (HLA-A, B, DRB1 alleles from 705 recruited volunteers with Volga Federal District for unrelated hematopoietic stem cell registry and 155 of their number at locus HLA-C. 48 samples cannot be entered into the database because of ambiguities in the identification of allelic loci on HLA-class I – HLA-A, HLA-B. To resolution of ambiguity use reagents kits AlleleSEQR HLA Sequencing, which allowed to reveal the ambiguity of the locus HLA-A, 44% of cases, the loci HLA-B and HLA-C – 40% of cases. Application software HARPs Finder showed the possibility of resolution of all identified allelic ambiguities (with the exception of types of ambiguity – A*03/A*32 or A*74:13/A*32:04 and A*01/A*11 or A*36:04/A*11 with the addition of basic kits AlleleSEQR HLA Sequencing reagents kit Al- leleSEQR HARPs. 

  15. Identification of six new susceptibility loci for invasive epithelial ovarian cancer.

    Science.gov (United States)

    Kuchenbaecker, Karoline B; Ramus, Susan J; Tyrer, Jonathan; Lee, Andrew; Shen, Howard C; Beesley, Jonathan; Lawrenson, Kate; McGuffog, Lesley; Healey, Sue; Lee, Janet M; Spindler, Tassja J; Lin, Yvonne G; Pejovic, Tanja; Bean, Yukie; Li, Qiyuan; Coetzee, Simon; Hazelett, Dennis; Miron, Alexander; Southey, Melissa; Terry, Mary Beth; Goldgar, David E; Buys, Saundra S; Janavicius, Ramunas; Dorfling, Cecilia M; van Rensburg, Elizabeth J; Neuhausen, Susan L; Ding, Yuan Chun; Hansen, Thomas V O; Jønson, Lars; Gerdes, Anne-Marie; Ejlertsen, Bent; Barrowdale, Daniel; Dennis, Joe; Benitez, Javier; Osorio, Ana; Garcia, Maria Jose; Komenaka, Ian; Weitzel, Jeffrey N; Ganschow, Pamela; Peterlongo, Paolo; Bernard, Loris; Viel, Alessandra; Bonanni, Bernardo; Peissel, Bernard; Manoukian, Siranoush; Radice, Paolo; Papi, Laura; Ottini, Laura; Fostira, Florentia; Konstantopoulou, Irene; Garber, Judy; Frost, Debra; Perkins, Jo; Platte, Radka; Ellis, Steve; Godwin, Andrew K; Schmutzler, Rita Katharina; Meindl, Alfons; Engel, Christoph; Sutter, Christian; Sinilnikova, Olga M; Damiola, Francesca; Mazoyer, Sylvie; Stoppa-Lyonnet, Dominique; Claes, Kathleen; De Leeneer, Kim; Kirk, Judy; Rodriguez, Gustavo C; Piedmonte, Marion; O'Malley, David M; de la Hoya, Miguel; Caldes, Trinidad; Aittomäki, Kristiina; Nevanlinna, Heli; Collée, J Margriet; Rookus, Matti A; Oosterwijk, Jan C; Tihomirova, Laima; Tung, Nadine; Hamann, Ute; Isaccs, Claudine; Tischkowitz, Marc; Imyanitov, Evgeny N; Caligo, Maria A; Campbell, Ian G; Hogervorst, Frans B L; Olah, Edith; Diez, Orland; Blanco, Ignacio; Brunet, Joan; Lazaro, Conxi; Pujana, Miquel Angel; Jakubowska, Anna; Gronwald, Jacek; Lubinski, Jan; Sukiennicki, Grzegorz; Barkardottir, Rosa B; Plante, Marie; Simard, Jacques; Soucy, Penny; Montagna, Marco; Tognazzo, Silvia; Teixeira, Manuel R; Pankratz, Vernon S; Wang, Xianshu; Lindor, Noralane; Szabo, Csilla I; Kauff, Noah; Vijai, Joseph; Aghajanian, Carol A; Pfeiler, Georg; Berger, Andreas; Singer, Christian F; Tea, Muy-Kheng; Phelan, Catherine M; Greene, Mark H; Mai, Phuong L; Rennert, Gad; Mulligan, Anna Marie; Tchatchou, Sandrine; Andrulis, Irene L; Glendon, Gord; Toland, Amanda Ewart; Jensen, Uffe Birk; Kruse, Torben A; Thomassen, Mads; Bojesen, Anders; Zidan, Jamal; Friedman, Eitan; Laitman, Yael; Soller, Maria; Liljegren, Annelie; Arver, Brita; Einbeigi, Zakaria; Stenmark-Askmalm, Marie; Olopade, Olufunmilayo I; Nussbaum, Robert L; Rebbeck, Timothy R; Nathanson, Katherine L; Domchek, Susan M; Lu, Karen H; Karlan, Beth Y; Walsh, Christine; Lester, Jenny; Hein, Alexander; Ekici, Arif B; Beckmann, Matthias W; Fasching, Peter A; Lambrechts, Diether; Van Nieuwenhuysen, Els; Vergote, Ignace; Lambrechts, Sandrina; Dicks, Ed; Doherty, Jennifer A; Wicklund, Kristine G; Rossing, Mary Anne; Rudolph, Anja; Chang-Claude, Jenny; Wang-Gohrke, Shan; Eilber, Ursula; Moysich, Kirsten B; Odunsi, Kunle; Sucheston, Lara; Lele, Shashi; Wilkens, Lynne R; Goodman, Marc T; Thompson, Pamela J; Shvetsov, Yurii B; Runnebaum, Ingo B; Dürst, Matthias; Hillemanns, Peter; Dörk, Thilo; Antonenkova, Natalia; Bogdanova, Natalia; Leminen, Arto; Pelttari, Liisa M; Butzow, Ralf; Modugno, Francesmary; Kelley, Joseph L; Edwards, Robert P; Ness, Roberta B; du Bois, Andreas; Heitz, Florian; Schwaab, Ira; Harter, Philipp; Matsuo, Keitaro; Hosono, Satoyo; Orsulic, Sandra; Jensen, Allan; Kjaer, Susanne Kruger; Hogdall, Estrid; Hasmad, Hanis Nazihah; Azmi, Mat Adenan Noor; Teo, Soo-Hwang; Woo, Yin-Ling; Fridley, Brooke L; Goode, Ellen L; Cunningham, Julie M; Vierkant, Robert A; Bruinsma, Fiona; Giles, Graham G; Liang, Dong; Hildebrandt, Michelle A T; Wu, Xifeng; Levine, Douglas A; Bisogna, Maria; Berchuck, Andrew; Iversen, Edwin S; Schildkraut, Joellen M; Concannon, Patrick; Weber, Rachel Palmieri; Cramer, Daniel W; Terry, Kathryn L; Poole, Elizabeth M; Tworoger, Shelley S; Bandera, Elisa V; Orlow, Irene; Olson, Sara H; Krakstad, Camilla; Salvesen, Helga B; Tangen, Ingvild L; Bjorge, Line; van Altena, Anne M; Aben, Katja K H; Kiemeney, Lambertus A; Massuger, Leon F A G; Kellar, Melissa; Brooks-Wilson, Angela; Kelemen, Linda E; Cook, Linda S; Le, Nhu D; Cybulski, Cezary; Yang, Hannah; Lissowska, Jolanta; Brinton, Louise A; Wentzensen, Nicolas; Hogdall, Claus; Lundvall, Lene; Nedergaard, Lotte; Baker, Helen; Song, Honglin; Eccles, Diana; McNeish, Ian; Paul, James; Carty, Karen; Siddiqui, Nadeem; Glasspool, Rosalind; Whittemore, Alice S; Rothstein, Joseph H; McGuire, Valerie; Sieh, Weiva; Ji, Bu-Tian; Zheng, Wei; Shu, Xiao-Ou; Gao, Yu-Tang; Rosen, Barry; Risch, Harvey A; McLaughlin, John R; Narod, Steven A; Monteiro, Alvaro N; Chen, Ann; Lin, Hui-Yi; Permuth-Wey, Jenny; Sellers, Thomas A; Tsai, Ya-Yu; Chen, Zhihua; Ziogas, Argyrios; Anton-Culver, Hoda; Gentry-Maharaj, Aleksandra; Menon, Usha; Harrington, Patricia; Lee, Alice W; Wu, Anna H; Pearce, Celeste L; Coetzee, Gerry; Pike, Malcolm C; Dansonka-Mieszkowska, Agnieszka; Timorek, Agnieszka; Rzepecka, Iwona K; Kupryjanczyk, Jolanta; Freedman, Matt; Noushmehr, Houtan; Easton, Douglas F; Offit, Kenneth; Couch, Fergus J; Gayther, Simon; Pharoah, Paul P; Antoniou, Antonis C; Chenevix-Trench, Georgia

    2015-02-01

    Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.

  16. Genetic fine-mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci

    Science.gov (United States)

    Mahajan, Anubha; Locke, Adam; Rayner, N William; Robertson, Neil; Scott, Robert A; Prokopenko, Inga; Scott, Laura J; Green, Todd; Sparso, Thomas; Thuillier, Dorothee; Yengo, Loic; Grallert, Harald; Wahl, Simone; Frånberg, Mattias; Strawbridge, Rona J; Kestler, Hans; Chheda, Himanshu; Eisele, Lewin; Gustafsson, Stefan; Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Qi, Lu; Karssen, Lennart C; van Leeuwen, Elisabeth M; Willems, Sara M; Li, Man; Chen, Han; Fuchsberger, Christian; Kwan, Phoenix; Ma, Clement; Linderman, Michael; Lu, Yingchang; Thomsen, Soren K; Rundle, Jana K; Beer, Nicola L; van de Bunt, Martijn; Chalisey, Anil; Kang, Hyun Min; Voight, Benjamin F; Abecasis, Goncalo R; Almgren, Peter; Baldassarre, Damiano; Balkau, Beverley; Benediktsson, Rafn; Blüher, Matthias; Boeing, Heiner; Bonnycastle, Lori L; Borringer, Erwin P; Burtt, Noël P; Carey, Jason; Charpentier, Guillaume; Chines, Peter S; Cornelis, Marilyn C; Couper, David J; Crenshaw, Andrew T; van Dam, Rob M; Doney, Alex SF; Dorkhan, Mozhgan; Edkins, Sarah; Eriksson, Johan G; Esko, Tonu; Eury, Elodie; Fadista, João; Flannick, Jason; Fontanillas, Pierre; Fox, Caroline; Franks, Paul W; Gertow, Karl; Gieger, Christian; Gigante, Bruna; Gottesman, Omri; Grant, George B; Grarup, Niels; Groves, Christopher J; Hassinen, Maija; Have, Christian T; Herder, Christian; Holmen, Oddgeir L; Hreidarsson, Astradur B; Humphries, Steve E; Hunter, David J; Jackson, Anne U; Jonsson, Anna; Jørgensen, Marit E; Jørgensen, Torben; Kerrison, Nicola D; Kinnunen, Leena; Klopp, Norman; Kong, Augustine; Kovacs, Peter; Kraft, Peter; Kravic, Jasmina; Langford, Cordelia; Leander, Karin; Liang, Liming; Lichtner, Peter; Lindgren, Cecilia M; Lindholm, Eero; Linneberg, Allan; Liu, Ching-Ti; Lobbens, Stéphane; Luan, Jian’an; Lyssenko, Valeriya; Männistö, Satu; McLeod, Olga; Meyer, Julia; Mihailov, Evelin; Mirza, Ghazala; Mühleisen, Thomas W; Müller-Nurasyid, Martina; Navarro, Carmen; Nöthen, Markus M; Oskolkov, Nikolay N; Owen, Katharine R; Palli, Domenico; Pechlivanis, Sonali; Perry, John RB; Platou, Carl GP; Roden, Michael; Ruderfer, Douglas; Rybin, Denis; van der Schouw, Yvonne T; Sennblad, Bengt; Sigurðsson, Gunnar; Stančáková, Alena; Steinbach, Gerald; Storm, Petter; Strauch, Konstantin; Stringham, Heather M; Sun, Qi; Thorand, Barbara; Tikkanen, Emmi; Tonjes, Anke; Trakalo, Joseph; Tremoli, Elena; Tuomi, Tiinamaija; Wennauer, Roman; Wood, Andrew R; Zeggini, Eleftheria; Dunham, Ian; Birney, Ewan; Pasquali, Lorenzo; Ferrer, Jorge; Loos, Ruth JF; Dupuis, Josée; Florez, Jose C; Boerwinkle, Eric; Pankow, James S; van Duijn, Cornelia; Sijbrands, Eric; Meigs, James B; Hu, Frank B; Thorsteinsdottir, Unnur; Stefansson, Kari; Lakka, Timo A; Rauramaa, Rainer; Stumvoll, Michael; Pedersen, Nancy L; Lind, Lars; Keinanen-Kiukaanniemi, Sirkka M; Korpi-Hyövälti, Eeva; Saaristo, Timo E; Saltevo, Juha; Kuusisto, Johanna; Laakso, Markku; Metspalu, Andres; Erbel, Raimund; Jöckel, Karl-Heinz; Moebus, Susanne; Ripatti, Samuli; Salomaa, Veikko; Ingelsson, Erik; Boehm, Bernhard O; Bergman, Richard N; Collins, Francis S; Mohlke, Karen L; Koistinen, Heikki; Tuomilehto, Jaakko; Hveem, Kristian; Njølstad, Inger; Deloukas, Panagiotis; Donnelly, Peter J; Frayling, Timothy M; Hattersley, Andrew T; de Faire, Ulf; Hamsten, Anders; Illig, Thomas; Peters, Annette; Cauchi, Stephane; Sladek, Rob; Froguel, Philippe; Hansen, Torben; Pedersen, Oluf; Morris, Andrew D; Palmer, Collin NA; Kathiresan, Sekar; Melander, Olle; Nilsson, Peter M; Groop, Leif C; Barroso, Inês; Langenberg, Claudia; Wareham, Nicholas J; O’Callaghan, Christopher A; Gloyn, Anna L; Altshuler, David; Boehnke, Michael; Teslovich, Tanya M; McCarthy, Mark I; Morris, Andrew P

    2015-01-01

    We performed fine-mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in/near KCNQ1. “Credible sets” of variants most likely to drive each distinct signal mapped predominantly to non-coding sequence, implying that T2D association is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine-mapping implicated rs10830963 as driving T2D association. We confirmed that this T2D-risk allele increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D-risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease. PMID:26551672

  17. Microsatellites loci reveal heterozygosis and population structure in vampire bats (Desmodus rotundus (Chiroptera: Phyllostomidae of Mexico

    Directory of Open Access Journals (Sweden)

    Claudia Romero-Nava

    2014-08-01

    Full Text Available A limited number of studies have focused on the population genetic structure of vampire bats (Desmodus rotundus in America. This medium-sized bat is distributed in tropical areas of the continent with high prevalence in forested livestock areas. The aim of this work was to characterize the vampire population structure and their genetic differentiation. For this, we followed standard methods by which live vampires (caught by mist-netting and preserved material from scientific collections, were obtained for a total of 15 different locations, ranging from Chihuahua (North to Quintana Roo (Southeast. Tissue samples were obtained from both live and collected animals, and the genetic differentiation, within and among localities, was assessed by the use of seven microsatellite loci. Our results showed that all loci were polymorphic and no private alleles were detected. High levels of heterozygosis were detected when the proportion of alleles in each locus were compared. Pairwise F ST and R ST detected significant genetic differentiation among individuals from different localities. Our population structure results indicate the presence of eleven clusters, with a high percentage of assigned individuals to some specific collecting site. Rev. Biol. Trop. 62 (2: 659-669. Epub 2014 June 01.

  18. Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.

    Science.gov (United States)

    Gaulton, Kyle J; Ferreira, Teresa; Lee, Yeji; Raimondo, Anne; Mägi, Reedik; Reschen, Michael E; Mahajan, Anubha; Locke, Adam; Rayner, N William; Robertson, Neil; Scott, Robert A; Prokopenko, Inga; Scott, Laura J; Green, Todd; Sparso, Thomas; Thuillier, Dorothee; Yengo, Loic; Grallert, Harald; Wahl, Simone; Frånberg, Mattias; Strawbridge, Rona J; Kestler, Hans; Chheda, Himanshu; Eisele, Lewin; Gustafsson, Stefan; Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Qi, Lu; Karssen, Lennart C; van Leeuwen, Elisabeth M; Willems, Sara M; Li, Man; Chen, Han; Fuchsberger, Christian; Kwan, Phoenix; Ma, Clement; Linderman, Michael; Lu, Yingchang; Thomsen, Soren K; Rundle, Jana K; Beer, Nicola L; van de Bunt, Martijn; Chalisey, Anil; Kang, Hyun Min; Voight, Benjamin F; Abecasis, Gonçalo R; Almgren, Peter; Baldassarre, Damiano; Balkau, Beverley; Benediktsson, Rafn; Blüher, Matthias; Boeing, Heiner; Bonnycastle, Lori L; Bottinger, Erwin P; Burtt, Noël P; Carey, Jason; Charpentier, Guillaume; Chines, Peter S; Cornelis, Marilyn C; Couper, David J; Crenshaw, Andrew T; van Dam, Rob M; Doney, Alex S F; Dorkhan, Mozhgan; Edkins, Sarah; Eriksson, Johan G; Esko, Tonu; Eury, Elodie; Fadista, João; Flannick, Jason; Fontanillas, Pierre; Fox, Caroline; Franks, Paul W; Gertow, Karl; Gieger, Christian; Gigante, Bruna; Gottesman, Omri; Grant, George B; Grarup, Niels; Groves, Christopher J; Hassinen, Maija; Have, Christian T; Herder, Christian; Holmen, Oddgeir L; Hreidarsson, Astradur B; Humphries, Steve E; Hunter, David J; Jackson, Anne U; Jonsson, Anna; Jørgensen, Marit E; Jørgensen, Torben; Kao, Wen-Hong L; Kerrison, Nicola D; Kinnunen, Leena; Klopp, Norman; Kong, Augustine; Kovacs, Peter; Kraft, Peter; Kravic, Jasmina; Langford, Cordelia; Leander, Karin; Liang, Liming; Lichtner, Peter; Lindgren, Cecilia M; Lindholm, Eero; Linneberg, Allan; Liu, Ching-Ti; Lobbens, Stéphane; Luan, Jian'an; Lyssenko, Valeriya; Männistö, Satu; McLeod, Olga; Meyer, Julia; Mihailov, Evelin; Mirza, Ghazala; Mühleisen, Thomas W; Müller-Nurasyid, Martina; Navarro, Carmen; Nöthen, Markus M; Oskolkov, Nikolay N; Owen, Katharine R; Palli, Domenico; Pechlivanis, Sonali; Peltonen, Leena; Perry, John R B; Platou, Carl G P; Roden, Michael; Ruderfer, Douglas; Rybin, Denis; van der Schouw, Yvonne T; Sennblad, Bengt; Sigurðsson, Gunnar; Stančáková, Alena; Steinbach, Gerald; Storm, Petter; Strauch, Konstantin; Stringham, Heather M; Sun, Qi; Thorand, Barbara; Tikkanen, Emmi; Tonjes, Anke; Trakalo, Joseph; Tremoli, Elena; Tuomi, Tiinamaija; Wennauer, Roman; Wiltshire, Steven; Wood, Andrew R; Zeggini, Eleftheria; Dunham, Ian; Birney, Ewan; Pasquali, Lorenzo; Ferrer, Jorge; Loos, Ruth J F; Dupuis, Josée; Florez, Jose C; Boerwinkle, Eric; Pankow, James S; van Duijn, Cornelia; Sijbrands, Eric; Meigs, James B; Hu, Frank B; Thorsteinsdottir, Unnur; Stefansson, Kari; Lakka, Timo A; Rauramaa, Rainer; Stumvoll, Michael; Pedersen, Nancy L; Lind, Lars; Keinanen-Kiukaanniemi, Sirkka M; Korpi-Hyövälti, Eeva; Saaristo, Timo E; Saltevo, Juha; Kuusisto, Johanna; Laakso, Markku; Metspalu, Andres; Erbel, Raimund; Jöcke, Karl-Heinz; Moebus, Susanne; Ripatti, Samuli; Salomaa, Veikko; Ingelsson, Erik; Boehm, Bernhard O; Bergman, Richard N; Collins, Francis S; Mohlke, Karen L; Koistinen, Heikki; Tuomilehto, Jaakko; Hveem, Kristian; Njølstad, Inger; Deloukas, Panagiotis; Donnelly, Peter J; Frayling, Timothy M; Hattersley, Andrew T; de Faire, Ulf; Hamsten, Anders; Illig, Thomas; Peters, Annette; Cauchi, Stephane; Sladek, Rob; Froguel, Philippe; Hansen, Torben; Pedersen, Oluf; Morris, Andrew D; Palmer, Collin N A; Kathiresan, Sekar; Melander, Olle; Nilsson, Peter M; Groop, Leif C; Barroso, Inês; Langenberg, Claudia; Wareham, Nicholas J; O'Callaghan, Christopher A; Gloyn, Anna L; Altshuler, David; Boehnke, Michael; Teslovich, Tanya M; McCarthy, Mark I; Morris, Andrew P

    2015-12-01

    We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.

  19. Changing carbonate chemistry in ocean waters surrounding coral reefs in the CMIP5 ensemble

    Science.gov (United States)

    Ricke, K.; Schneider, K.; Cao, L.; Caldeira, K.

    2012-12-01

    Coral reefs comprise some of the most biodiverse ecosystems in the world. Today they are threatened by a number of stressors, including pollution, bleaching from global warming and ocean acidification. In this study, we focus on the implications of ocean acidification for the open ocean chemistry surrounding coral reefs. We use results from 13 Earth System Models included in the Coupled Model Intercomparison Project 5 (CMIP5) to examine the changing aragonite saturations (Ωa) of open ocean waters surrounding approximately 6,000 coral reefs. These 13 Earth System Models participating in CMIP5 each have interactive ocean biogeochemistry models that output state variables including DIC, alkalinity, SST, and salinity. Variation in these values were combined with values from the GLODAP database to calculate aragonite, the form of calcium carbonate that corals use to make their skeletons. We used reef locations from ReefBase that were within one degree (in latitude or longitude) of water masses represented both in the GLODAP database and in the climate models. Carbonate chemistry calculations were performed by Dr. James C. Orr (IPSL) as part of a separate study. We find that in preindustrial times, 99.9 % of coral reefs were located in regions of the ocean with aragonite saturations of 3.5 or more. The saturation threshold for viable reef ecosystems in uncertain, but the pre-industrial distribution of water chemistry surrounding coral reefs may nevertheless provide some indication of viability. We examine the fate of coral reefs in the context of several potential aragonite saturation thresholds, i.e., when Ωa_crit equals 3, 3.25, or 3.5. We show that under a business-as-usual scenario Representative Concentration Pathway (RCP) 8.5, the specific value of Ωa_crit does not affect the long-term fate of coral reefs -- by the end of the 21st century, no coral reef considered is surrounded by water with Ωa> 3. However, under scenarios with significant CO2 emissions

  20. Detection of quantitative trait loci and heterotic loci for plant height using an immortalized F2 population in maize

    Institute of Scientific and Technical Information of China (English)

    TANG JiHua; MA XiQing; TENG WenTao; YAN JianBing; WU WeiRen; DAI JingRui; LI JianSheng

    2007-01-01

    A set of recombinant inbred lines (RIL) derived from Yuyu22, an elite hybrid widespread in China, was used to construct an immortalized F2 (IF2) population comprising 441 different crosses. Genetic linkage maps were constructed containing 10 linkages groups with 263 simple sequence repeat (SSR) molecular markers. Twelve and ten quantitative trait loci (QTL) were detected for plant height in the IF2 and RIL populations respectively, using the composite interval mapping method, and six same QTL were identified in the two populations. In addition, ten unique heterotic loci (HL) located on seven different chromosomes were revealed for plant height using the mid-parent heterosis as the input data. These HL explained 1.26%-8.41% of the genotypic variance in plant height heterosis and most expressed overdominant effects. Only three QTL and HL were located in the same chromosomal region, it implied that plant height and its heterosis might be controlled by two types of genetic mechanisms.

  1. Characterization of new microsatellite loci for population genetic studies in the Smooth Cauliflower Coral (Stylophora sp.)

    KAUST Repository

    Banguera-Hinestroza, E.

    2013-01-09

    A total of one hundred microsatellites loci were selected from the draft genome of Stylophora pistillata and evaluated in previously characterized samples of Stylophora cf pistillata from the Red Sea. 17 loci were amplified successfully and tested in 24 individuals from samples belonging to a single population from the central region of the Red Sea. The number of alleles ranged from 3 to 15 alleles per locus, while observed heterozygosity ranged from 0. 292 to 0. 95. Six of these loci showed significant deviations from Hardy-Weinberg equilibrium (HWE) expectations, and 4/136 paired loci comparisons suggested linkage disequilibrium after Bonferroni corrections. After excluding loci with significant HWE deviation and evidence of null alleles, average genetic diversity over loci in the population studied (N = 24, Nloci = 11) was 0. 701 ± 0. 380. This indicates that these loci can be used effectively to evaluate genetic diversity and undertake population genetics studies in Stylophora sp. populations. 2013 The Author(s).

  2. Evolutionary history of chloridoid grasses estimated from 122 nuclear loci.

    Science.gov (United States)

    Fisher, Amanda E; Hasenstab, Kristen M; Bell, Hester L; Blaine, Ellen; Ingram, Amanda L; Columbus, J Travis

    2016-12-01

    Chloridoideae (chloridoid grasses) are a subfamily of ca. 1700 species with high diversity in arid habitats. Until now, their evolutionary relationships have primarily been studied with DNA sequences from the chloroplast, a maternally inherited organelle. Next-generation sequencing is able to efficiently recover large numbers of nuclear loci that can then be used to estimate the species phylogeny based upon bi-parentally inherited data. We sought to test our chloroplast-based hypotheses of relationships among chloridoid species with 122 nuclear loci generated through targeted-enrichment next-generation sequencing, sometimes referred to as hyb-seq. We targeted putative single-copy housekeeping genes, as well as genes that have been implicated in traits characteristic of, or particularly labile in, chloridoids: e.g., drought and salt tolerance. We recovered ca. 70% of the targeted loci (122 of 177 loci) in all 47 species sequenced using hyb-seq. We then analyzed the nuclear loci with Bayesian and coalescent methods and the resulting phylogeny resolves relationships between the four chloridoid tribes. Several novel findings with this data were: the sister lineage to Chloridoideae is unresolved; Centropodia+Ellisochloa are excluded from Chloridoideae in phylogenetic estimates using a coalescent model; Sporobolus subtilis is more closely related to Eragrostis than to other species of Sporobolus; and Tragus is more closely related to Chloris and relatives than to a lineage of mainly New World species. Relationships in Cynodonteae in the nuclear phylogeny are quite different from chloroplast estimates, but were not robust to changes in the method of phylogenetic analysis. We tested the data signal with several partition schemes, a concatenation analysis, and tests of alternative hypotheses to assess our confidence in this new, nuclear estimate of evolutionary relationships. Our work provides markers and a framework for additional phylogenetic studies that sample more

  3. STELLAR LOCI. I. METALLICITY DEPENDENCE AND INTRINSIC WIDTHS

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Haibo; Liu, Xiaowei [Kavli Institute for Astronomy and Astrophysics, Peking University, Beijing 100871 (China); Xiang, Maosheng; Huang, Yang; Chen, Bingqiu, E-mail: yuanhb4861@pku.edu.cn, E-mail: x.liu@pku.edu.cn [Department of Astronomy, Peking University, Beijing 100871 (China)

    2015-02-01

    Stellar loci are widely used for selection of interesting outliers, reddening determinations, and calibrations. However, until now, the dependence of stellar loci on metallicity has not been fully explored, and their intrinsic widths are unclear. In this paper, by combining the spectroscopic and recalibrated imaging data of the Sloan Digital Sky Survey (SDSS) Stripe 82, we have built a large, clean sample of dwarf stars with accurate colors and well-determined metallicities to investigate the metallicity dependence and intrinsic widths of the SDSS stellar loci. Typically, 1 dex decrease in metallicity causes 0.20 and 0.02 mag decrease in colors u – g and g – r and 0.02 and 0.02 mag increase in colors r – i and i – z, respectively. The variations are larger for metal-rich stars than for metal-poor ones, and larger for F/G/K stars than for A/M ones. Using the sample, we have performed two-dimensional polynomial fitting to the u – g, g – r, r – i, and i – z colors as a function of color g – i and metallicity [Fe/H]. The residuals, at the level of 0.029, 0.008, 0.008, and 0.011 mag for the u – g, g – r, r – i, and i – z colors, respectively, can be fully accounted for by the photometric errors and metallicity uncertainties, suggesting that the intrinsic widths of the loci are at maximum a few millimagnitudes. The residual distributions are asymmetric, revealing that a significant fraction of stars are binaries. In a companion paper, we will present an unbiased estimate of the binary fraction for field stars. Other potential applications of the metallicity-dependent stellar loci are briefly discussed.

  4. An analysis of amino acid sequences surrounding archaeal glycoprotein sequons.

    Science.gov (United States)

    Abu-Qarn, Mehtap; Eichler, Jerry

    2007-05-01

    Despite having provided the first example of a prokaryal glycoprotein, little is known of the rules governing the N-glycosylation process in Archaea. As in Eukarya and Bacteria, archaeal N-glycosylation takes place at the Asn residues of Asn-X-Ser/Thr sequons. Since not all sequons are utilized, it is clear that other factors, including the context in which a sequon exists, affect glycosylation efficiency. As yet, the contribution to N-glycosylation made by sequon-bordering residues and other related factors in Archaea remains unaddressed. In the following, the surroundings of Asn residues confirmed by experiment as modified were analyzed in an attempt to define sequence rules and requirements for archaeal N-glycosylation.

  5. An analysis of amino acid sequences surrounding archaeal glycoprotein sequons

    Directory of Open Access Journals (Sweden)

    Mehtap Abu-Qarn

    2006-01-01

    Full Text Available Despite having provided the first example of a prokaryal glycoprotein, little is known of the rules governing the N-glycosylation process in Archaea. As in Eukarya and Bacteria, archaeal N-glycosylation takes place at the Asn residues of Asn-X-Ser/Thr sequons. Since not all sequons are utilized, it is clear that other factors, including the context in which a sequon exists, affect glycosylation efficiency. As yet, the contribution to N-glycosylation made by sequon-bordering residues and other related factors in Archaea remains unaddressed. In the following, the surroundings of Asn residues confirmed by experiment as modified were analyzed in an attempt to define sequence rules and requirements for archaeal N-glycosylation.

  6. Wave rectification in plasma sheaths surrounding electric field antennas

    Science.gov (United States)

    Boehm, M. H.; Carlson, C. W.; Mcfadden, J. P.; Clemmons, J. H.; Ergun, R. E.; Mozer, F. S.

    1994-01-01

    Combined measurements of Langmuir or broadband whistler wave intensity and lower-frequency electric field waveforms, all at 10-microsecond time resolution, were made on several recent sounding rockets in the auroral ionosphere. It is found that Langmuir and whistler waves are partically rectified in the plasma sheaths surrounding the payload and the spheres used as antennas. This sheath rectification occurs whenever the high frequency (HF) potential across the sheath becomes of the same order as the electron temperature or higher, for wave frequencies near or above the ion plasma frequency. This rectification can introduce false low-frequency waves into measurements of electric field spectra when strong high-frequency waves are present. Second harmonic signals are also generated, although at much lower levels. The effect occurs in many different plasma conditions, primarily producing false waves at frequencies that are low enough for the antenna coupling to the plasma to be resistive.

  7. The nature of plerions surrounding soft gamma-ray repeaters

    CERN Document Server

    Harding, A K

    1995-01-01

    Compact steady sources of X-ray emission have been detected at the positions of at least two soft gamma-ray repeaters (SGRs). These sources have been interpreted as synchrotron nebulae powered by the neutron star that is causing the bursts. We explore a plerion model for the sources surrounding SGRs where the steady observed emission is powered by the SGR bursts rather than by the spin-down of a pulsar. In this case there is no limit on the neutron star magnetic field. We find that the synchrotron lifetime of the particles injected into the plerion around SGR1806-20 is long enough to smear out nebular emission from individual bursts. Transient nebular emission would therefore not be detected following an SGR burst. The combined radio emission from multiple burst injections is expected to have a steeper spectrum than that of a typical plerion.

  8. Casimir Effect in the Kerr Spacetime Surrounded by Quintessence

    CERN Document Server

    Bezerra, V B; Freitas, L F F; Muniz, C R

    2016-01-01

    We calculate the Casimir energy of a massless scalar field in a cavity formed by nearby parallel plates orbiting a rotating spherical body surrounded by quintessence, investigating the influence of the gravitational field on that energy, at zero temperature. This influence includes the effects due to the spacetime dragging caused by the source rotation as well as those ones due to the quintessence. We show that the energy depends on all the involved parameters, as source mass, angular momentum and quintessence state parameter, for any radial coordinate and polar angle. We show that at the north pole the Casimir energy is not influenced by the quintessential matter. At the equatorial plane, when the quintessence is canceled, the result obtained in the literature is recovered. Finally, constraints in the quintessence parameters are obtained from the uncertainty in the current measurements of Casimir effect.

  9. Ozone bioindication in Barcelona and surrounding area of Catalonia

    Energy Technology Data Exchange (ETDEWEB)

    Ribas, A.; Penuelas, J. [Univ. Autonoma de Barcelona, Barcelona (Spain). Ecophysiology Unit of CSIC

    2002-07-01

    A field study was conducted from July to September 2000 to assess ozone (O{sub 3}) phytotoxicity in Barcelona and surrounding areas of Catalonia (NE Spain) by using tobacco plants Bel-W3 and Populus nigra 'Brandaris' as bioindicators. The study was conducted simultaneously at eight sites where ozone concentrations and meteorological variables were continuously monitored. The ozone levels correlated well with ozone injury on the Bel-W3 cultivar, especially at stations established in the urban area of Barcelona, and in the first months of summer. In the second half of summer plants showed a decreasing efficiency in its biomonitoring capacity. The behaviour of Populus as bioindicator or biomonitor was less satisfactory. For both species it is necessary to improve cultivation conditions since water deficits seem to play an important role in bioindication in the Mediterranean region. (orig.)

  10. Physical Coupling of Kazarian Galaxies with Surrounding Galaxies

    Science.gov (United States)

    Kazarian, M. A.; Martirosian, J. R.

    2003-04-01

    Results from a statistical study of Kazarian galaxies and the objects surrounding them are presented. It is shown that: (1) the sample of Kazarian galaxies up to 16m.0 is complete. (2) Roughly 35.7% of the Kazarian galaxies are members of clusters, 14.0% of groups, and 13.6% of binary systems, while 36.7% are single galaxies. (3) Of the 580 Kazarian galaxies, roughly 61.2% are infrared, 8.8% radio, and 2.8% x-ray sources. (4) The relative numbers of Kazarian galaxies for complete samples of I, R, and X in the different groups are systematically higher than the corresponding numbers for samples of all Kazarian galaxies.

  11. On radial oscillations in viscous accretion discs surrounding neutron stars

    Science.gov (United States)

    Chen, Xingming; Taam, Ronald E.

    1992-01-01

    Radial oscillations resulting from axisymmetric perturbations in viscous accretion disks surrounding neutron stars in X-ray binary systems have been investigated. Within the framework of the alpha-viscosity model a series of hydrodynamic calculations demonstrates that the oscillations are global for alpha of about 1. On the other hand, for alpha of 0.4 or less, the oscillations are local and confined to the disk boundaries. If viscous stresses acting in the radial direction are included, however, it is found that the disk can be stabilized. The application of such instabilities in accretion disks, without reference to the boundary layer region between the neutron star (or magnetosphere) and the inner edge of the disk, to the phenomenology of quasi-periodic oscillations is brought into question.

  12. Natural convection between a vertical cylinder and a surrounding array

    Energy Technology Data Exchange (ETDEWEB)

    McEligot, D.M.; O`Brien, J.E.; Stoots, C.M.; Larson, T.K.; Christenson, W.A.; Mecham, D.C.; Lussie, W.G.

    1992-09-01

    The generic situation considered is natural convection between a single heated, vertical cylinder and a surrounding array of cooler vertical cylinders in a triangular pattern. The ratio of the test section temperature to the cooling tube temperature was varied up to 2.6 by adjusting the electrical power. The Rayleigh number, based on test section diameter and air properties evaluated at cooling tube temperature, ranged from 2.9 x 10{sup 4} to 4.6 x 10{sup 5}. Results indicate that the convective heat transfer data could be approximated as Nu{sub D} (T{sub ts}/T{sub ct}){sup 0.14} = 0.156 Ra{sub D}{sup 1/3} in the apparent turbulent region for Ra{sub L} > 1.2 x 10{sup 11.}

  13. Natural convection between a vertical cylinder and a surrounding array

    Energy Technology Data Exchange (ETDEWEB)

    McEligot, D.M.; O' Brien, J.E.; Stoots, C.M.; Larson, T.K.; Christenson, W.A.; Mecham, D.C.; Lussie, W.G.

    1992-01-01

    The generic situation considered is natural convection between a single heated, vertical cylinder and a surrounding array of cooler vertical cylinders in a triangular pattern. The ratio of the test section temperature to the cooling tube temperature was varied up to 2.6 by adjusting the electrical power. The Rayleigh number, based on test section diameter and air properties evaluated at cooling tube temperature, ranged from 2.9 x 10{sup 4} to 4.6 x 10{sup 5}. Results indicate that the convective heat transfer data could be approximated as Nu{sub D} (T{sub ts}/T{sub ct}){sup 0.14} = 0.156 Ra{sub D}{sup 1/3} in the apparent turbulent region for Ra{sub L} > 1.2 x 10{sup 11.}

  14. Rotation of the Warm Molecular Gas Surrounding Ultracompact HII Regions

    CERN Document Server

    Klaassen, P D; Keto, E R; Zhang, Q

    2009-01-01

    We present molecular line and 1.4 mm continuum observations towards five massive star forming regions at arcsecond resolution using the Submillimeter Array (SMA). We find that the warm molecular gas surrounding each HII region (as traced by SO_2 and OCS) appears to be undergoing bulk rotation. From the molecular line emission and thermal component of the continuum emission, we independently derived gas masses for each region which are consistent with each other. From the free-free component of the continuum emission we estimate the minimum stellar mass required to power the HII region and find that this mass, when added to the derived gas mass, is a significant fraction of the dynamical mass for that region.

  15. A 500 Parsec Halo Surrounding the Galactic Globular NGC 1851

    CERN Document Server

    Olszewski, Edward W; Knezek, Patricia; Subramaniam, Annapurni; de Boer, Thomas; Seitzer, Patrick

    2009-01-01

    Using imaging that shows four magnitudes of main sequence stars, we have discovered that the Galactic globular cluster NGC 1851 is surrounded by a halo that is visible from the tidal radius of 700 arcsec (41 pc) to more than 4500 arcsec (>250 pc). This halo is symmetric and falls in density as a power law of $r^{-1.24}$. It contains approximately 0.1% of the dynamical mass of NGC 1851. There is no evidence for tidal tails. Current models of globular cluster evolution do not explain this feature, although simulations of tidal influences on dwarf spheroidal galaxies qualitatively mimic these results. Given the state of published models it is not possible to decide between creation of this halo from isolated cluster evaporation, or from tidal or disk shocking, or from destruction of a dwarf galaxy in which this object may have once been embedded.

  16. Thermodynamic stability of black holes surrounded by quintessence

    CERN Document Server

    Ma, Meng-Sen; Ma, Ya-Qin

    2016-01-01

    We study the thermodynamic stabilities of uncharged and charged black holes surrounded by quintessence (BHQ) by means of effective thermodynamic quantities. When the state parameter of quintessence $\\omega_q$ is appropriately chosen, the structures of BHQ are something like that of black holes in de Sitter space. Constructing the effective first law of thermodynamics in two different ways, we can derive the effective thermodynamic quantities of BHQ. Especially, these effective thermodynamic quantities also satisfy Smarr-like formulae. It is found that the uncharged BHQ is always thermodynamically unstable due to negative heat capacity, while for the charged BHQ there are phase transitions of the second order. We also show that there is a great deal of difference on the thermodynamic properties and critical behaviors of BHQ between the two ways we employed.

  17. Thermodynamic stability of black holes surrounded by quintessence

    Science.gov (United States)

    Ma, Meng-Sen; Zhao, Ren; Ma, Ya-Qin

    2017-06-01

    We study the thermodynamic stabilities of uncharged and charged black holes surrounded by quintessence (BHQ) by means of effective thermodynamic quantities. When the state parameter of quintessence ω _q is appropriately chosen, the structures of BHQ are something like that of black holes in de Sitter space. Constructing the effective first law of thermodynamics in two different ways, we can derive the effective thermodynamic quantities of BHQ. Especially, these effective thermodynamic quantities also satisfy Smarr-like formulae. It is found that the uncharged BHQ is always thermodynamically unstable due to negative heat capacity, while for the charged BHQ there are phase transitions of the second order. We also show that there are several differences on the thermodynamic properties and critical behaviors of BHQ between the two ways we employed.

  18. Impact-Generated Dust Clouds Surrounding the Galilean Moons

    CERN Document Server

    Krüger, H; Grün, E; Kr\\"uger, Harald~; Krivov, Alexander V.; Gr\\"un, Eberhard

    2003-01-01

    Tenuous dust clouds of Jupiter's Galilean moons Io, Europa, Ganymede and Callisto have been detected with the in-situ dust detector on board the Galileo spacecraft. The majority of the dust particles have been sensed at altitudes below five radii of these lunar-sized satellites. We identify the particles in the dust clouds surrounding the moons by their impact direction, impact velocity, and mass distribution. Average particle sizes are 0.5 to $\\rm 1 \\mu m$, just above the detector threshold, indicating a size distribution with decreasing numbers towards bigger particles. Our results imply that the particles have been kicked up by hypervelocity impacts of micrometeoroids onto the satellites' surfaces. The measured radial dust density profiles are consistent with predictions by dynamical modeling for satellite ejecta produced by interplanetary impactors (Krivov et al., PSS, 2003, 51, 251--269), assuming yield, mass and velocity distributions of the ejecta from laboratory measurements. The dust clouds of the th...

  19. Thousands of microsatellite loci from the venomous coralsnake (Micrurus fulvius) and variability of select loci across populations and related species

    OpenAIRE

    Castoe, Todd A.; Streicher, Jeffrey W.; Jesse M Meik; Ingrasci, Matthew J.; Poole, Alexander W.; de Koning, A. P. Jason; Campbell, Jonathan A.; Parkinson, Christopher L; Eric N. Smith; Pollock, David D.

    2012-01-01

    Studies of population genetics increasingly use next-generation DNA sequencing to identify microsatellite loci in non-model organisms. There are, however, relatively few studies that validate the feasibility of transitioning from marker development to experimental application across populations and species. North American coralsnakes of the Micrurus fulvius species complex occur in the United States and Mexico, and little is known about their population structure and phylogenetic relationship...

  20. Nine Loci for Ocular Axial Length Identified through Genome-wide Association Studies, Including Shared Loci with Refractive Error

    Science.gov (United States)

    Cheng, Ching-Yu; Schache, Maria; Ikram, M. Kamran; Young, Terri L.; Guggenheim, Jeremy A.; Vitart, Veronique; MacGregor, Stuart; Verhoeven, Virginie J.M.; Barathi, Veluchamy A.; Liao, Jiemin; Hysi, Pirro G.; Bailey-Wilson, Joan E.; St. Pourcain, Beate; Kemp, John P.; McMahon, George; Timpson, Nicholas J.; Evans, David M.; Montgomery, Grant W.; Mishra, Aniket; Wang, Ya Xing; Wang, Jie Jin; Rochtchina, Elena; Polasek, Ozren; Wright, Alan F.; Amin, Najaf; van Leeuwen, Elisabeth M.; Wilson, James F.; Pennell, Craig E.; van Duijn, Cornelia M.; de Jong, Paulus T.V.M.; Vingerling, Johannes R.; Zhou, Xin; Chen, Peng; Li, Ruoying; Tay, Wan-Ting; Zheng, Yingfeng; Chew, Merwyn; Rahi, Jugnoo S.; Hysi, Pirro G.; Yoshimura, Nagahisa; Yamashiro, Kenji; Miyake, Masahiro; Delcourt, Cécile; Maubaret, Cecilia; Williams, Cathy; Guggenheim, Jeremy A.; Northstone, Kate; Ring, Susan M.; Davey-Smith, George; Craig, Jamie E.; Burdon, Kathryn P.; Fogarty, Rhys D.; Iyengar, Sudha K.; Igo, Robert P.; Chew, Emily; Janmahasathian, Sarayut; Iyengar, Sudha K.; Igo, Robert P.; Chew, Emily; Janmahasathian, Sarayut; Stambolian, Dwight; Wilson, Joan E. Bailey; MacGregor, Stuart; Lu, Yi; Jonas, Jost B.; Xu, Liang; Saw, Seang-Mei; Baird, Paul N.; Rochtchina, Elena; Mitchell, Paul; Wang, Jie Jin; Jonas, Jost B.; Nangia, Vinay; Hayward, Caroline; Wright, Alan F.; Vitart, Veronique; Polasek, Ozren; Campbell, Harry; Vitart, Veronique; Rudan, Igor; Vatavuk, Zoran; Vitart, Veronique; Paterson, Andrew D.; Hosseini, S. Mohsen; Iyengar, Sudha K.; Igo, Robert P.; Fondran, Jeremy R.; Young, Terri L.; Feng, Sheng; Verhoeven, Virginie J.M.; Klaver, Caroline C.; van Duijn, Cornelia M.; Metspalu, Andres; Haller, Toomas; Mihailov, Evelin; Pärssinen, Olavi; Wedenoja, Juho; Wilson, Joan E. Bailey; Wojciechowski, Robert; Baird, Paul N.; Schache, Maria; Pfeiffer, Norbert; Höhn, René; Pang, Chi Pui; Chen, Peng; Meitinger, Thomas; Oexle, Konrad; Wegner, Aharon; Yoshimura, Nagahisa; Yamashiro, Kenji; Miyake, Masahiro; Pärssinen, Olavi; Yip, Shea Ping; Ho, Daniel W.H.; Pirastu, Mario; Murgia, Federico; Portas, Laura; Biino, Genevra; Wilson, James F.; Fleck, Brian; Vitart, Veronique; Stambolian, Dwight; Wilson, Joan E. Bailey; Hewitt, Alex W.; Ang, Wei; Verhoeven, Virginie J.M.; Klaver, Caroline C.; van Duijn, Cornelia M.; Saw, Seang-Mei; Wong, Tien-Yin; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Wong, Tien-Yin; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Wong, Tien-Yin; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Tai, E-Shyong; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Mackey, David A.; MacGregor, Stuart; Hammond, Christopher J.; Hysi, Pirro G.; Deangelis, Margaret M.; Morrison, Margaux; Zhou, Xiangtian; Chen, Wei; Paterson, Andrew D.; Hosseini, S. Mohsen; Mizuki, Nobuhisa; Meguro, Akira; Lehtimäki, Terho; Mäkelä, Kari-Matti; Raitakari, Olli; Kähönen, Mika; Burdon, Kathryn P.; Craig, Jamie E.; Iyengar, Sudha K.; Igo, Robert P.; Lass, Jonathan H.; Reinhart, William; Belin, Michael W.; Schultze, Robert L.; Morason, Todd; Sugar, Alan; Mian, Shahzad; Soong, Hunson Kaz; Colby, Kathryn; Jurkunas, Ula; Yee, Richard; Vital, Mark; Alfonso, Eduardo; Karp, Carol; Lee, Yunhee; Yoo, Sonia; Hammersmith, Kristin; Cohen, Elisabeth; Laibson, Peter; Rapuano, Christopher; Ayres, Brandon; Croasdale, Christopher; Caudill, James; Patel, Sanjay; Baratz, Keith; Bourne, William; Maguire, Leo; Sugar, Joel; Tu, Elmer; Djalilian, Ali; Mootha, Vinod; McCulley, James; Bowman, Wayne; Cavanaugh, H. Dwight; Verity, Steven; Verdier, David; Renucci, Ann; Oliva, Matt; Rotkis, Walter; Hardten, David R.; Fahmy, Ahmad; Brown, Marlene; Reeves, Sherman; Davis, Elizabeth A.; Lindstrom, Richard; Hauswirth, Scott; Hamilton, Stephen; Lee, W. Barry; Price, Francis; Price, Marianne; Kelly, Kathleen; Peters, Faye; Shaughnessy, Michael; Steinemann, Thomas; Dupps, B.J.; Meisler, David M.; Mifflin, Mark; Olson, Randal; Aldave, Anthony; Holland, Gary; Mondino, Bartly J.; Rosenwasser, George; Gorovoy, Mark; Dunn, Steven P.; Heidemann, David G.; Terry, Mark; Shamie, Neda; Rosenfeld, Steven I.; Suedekum, Brandon; Hwang, David; Stone, Donald; Chodosh, James; Galentine, Paul G.; Bardenstein, David; Goddard, Katrina; Chin, Hemin; Mannis, Mark; Varma, Rohit; Borecki, Ingrid; Chew, Emily Y.; Haller, Toomas; Mihailov, Evelin; Metspalu, Andres; Wedenoja, Juho; Simpson, Claire L.; Wojciechowski, Robert; Höhn, René; Mirshahi, Alireza; Zeller, Tanja; Pfeiffer, Norbert; Lackner, Karl J.; Donnelly, Peter; Barroso, Ines; Blackwell, Jenefer M.; Bramon, Elvira; Brown, Matthew A.; Casas, Juan P.; Corvin, Aiden; Deloukas, Panos; Duncanson, Audrey; Jankowski, Janusz; Markus, Hugh S.; Mathew, Christopher G.; Palmer, Colin N.A.; Plomin, Robert; Rautanen, Anna; Sawcer, Stephen J.; Trembath, Richard C.; Viswanathan, Ananth C.; Wood, Nicholas W.; Spencer, Chris C.A.; Band, Gavin; Bellenguez, Céline; Freeman, Colin; Hellenthal, Garrett; Giannoulatou, Eleni; Pirinen, Matti; Pearson, Richard; Strange, Amy; Su, Zhan; Vukcevic, Damjan; Donnelly, Peter; Langford, Cordelia; Hunt, Sarah E.; Edkins, Sarah; Gwilliam, Rhian; Blackburn, Hannah; Bumpstead, Suzannah J.; Dronov, Serge; Gillman, Matthew; Gray, Emma; Hammond, Naomi; Jayakumar, Alagurevathi; McCann, Owen T.; Liddle, Jennifer; Potter, Simon C.; Ravindrarajah, Radhi; Ricketts, Michelle; Waller, Matthew; Weston, Paul; Widaa, Sara; Whittaker, Pamela; Barroso, Ines; Deloukas, Panos; Mathew, Christopher G.; Blackwell, Jenefer M.; Brown, Matthew A.; Corvin, Aiden; Spencer, Chris C.A.; Bettecken, Thomas; Meitinger, Thomas; Oexle, Konrad; Pirastu, Mario; Portas, Laura; Nag, Abhishek; Williams, Katie M.; Yonova-Doing, Ekaterina; Klein, Ronald; Klein, Barbara E.; Hosseini, S. Mohsen; Paterson, Andrew D.; Genuth, S.; Nathan, D.M.; Zinman, B.; Crofford, O.; Crandall, J.; Reid, M.; Brown-Friday, J.; Engel, S.; Sheindlin, J.; Martinez, H.; Shamoon, H.; Engel, H.; Phillips, M.; Gubitosi-Klug, R.; Mayer, L.; Pendegast, S.; Zegarra, H.; Miller, D.; Singerman, L.; Smith-Brewer, S.; Novak, M.; Quin, J.; Dahms, W.; Genuth, Saul; Palmert, M.; Brillon, D.; Lackaye, M.E.; Kiss, S.; Chan, R.; Reppucci, V.; Lee, T.; Heinemann, M.; Whitehouse, F.; Kruger, D.; Jones, J.K.; McLellan, M.; Carey, J.D.; Angus, E.; Thomas, A.; Galprin, A.; Bergenstal, R.; Johnson, M.; Spencer, M.; Morgan, K.; Etzwiler, D.; Kendall, D.; Aiello, Lloyd Paul; Golden, E.; Jacobson, A.; Beaser, R.; Ganda, O.; Hamdy, O.; Wolpert, H.; Sharuk, G.; Arrigg, P.; Schlossman, D.; Rosenzwieg, J.; Rand, L.; Nathan, D.M.; Larkin, M.; Ong, M.; Godine, J.; Cagliero, E.; Lou, P.; Folino, K.; Fritz, S.; Crowell, S.; Hansen, K.; Gauthier-Kelly, C.; Service, J.; Ziegler, G.; Luttrell, L.; Caulder, S.; Lopes-Virella, M.; Colwell, J.; Soule, J.; Fernandes, J.; Hermayer, K.; Kwon, S.; Brabham, M.; Blevins, A.; Parker, J.; Lee, D.; Patel, N.; Pittman, C.; Lindsey, P.; Bracey, M.; Lee, K.; Nutaitis, M.; Farr, A.; Elsing, S.; Thompson, T.; Selby, J.; Lyons, T.; Yacoub-Wasef, S.; Szpiech, M.; Wood, D.; Mayfield, R.; Molitch, M.; Schaefer, B.; Jampol, L.; Lyon, A.; Gill, M.; Strugula, Z.; Kaminski, L.; Mirza, R.; Simjanoski, E.; Ryan, D.; Kolterman, O.; Lorenzi, G.; Goldbaum, M.; Sivitz, W.; Bayless, M.; Counts, D.; Johnsonbaugh, S.; Hebdon, M.; Salemi, P.; Liss, R.; Donner, T.; Gordon, J.; Hemady, R.; Kowarski, A.; Ostrowski, D.; Steidl, S.; Jones, B.; Herman, W.H.; Martin, C.L.; Pop-Busui, R.; Sarma, A.; Albers, J.; Feldman, E.; Kim, K.; Elner, S.; Comer, G.; Gardner, T.; Hackel, R.; Prusak, R.; Goings, L.; Smith, A.; Gothrup, J.; Titus, P.; Lee, J.; Brandle, M.; Prosser, L.; Greene, D.A.; Stevens, M.J.; Vine, A.K.; Bantle, J.; Wimmergren, N.; Cochrane, A.; Olsen, T.; Steuer, E.; Rath, P.; Rogness, B.; Hainsworth, D.; Goldstein, D.; Hitt, S.; Giangiacomo, J.; Schade, D.S.; Canady, J.L.; Chapin, J.E.; Ketai, L.H.; Braunstein, C.S.; Bourne, P.A.; Schwartz, S.; Brucker, A.; Maschak-Carey, B.J.; Baker, L.; Orchard, T.; Silvers, N.; Ryan, C.; Songer, T.; Doft, B.; Olson, S.; Bergren, R.L.; Lobes, L.; Rath, P. Paczan; Becker, D.; Rubinstein, D.; Conrad, P.W.; Yalamanchi, S.; Drash, A.; Morrison, A.; Bernal, M.L.; Vaccaro-Kish, J.; Malone, J.; Pavan, P.R.; Grove, N.; Iyer, M.N.; Burrows, A.F.; Tanaka, E.A.; Gstalder, R.; Dagogo-Jack, S.; Wigley, C.; Ricks, H.; Kitabchi, A.; Murphy, M.B.; Moser, S.; Meyer, D.; Iannacone, A.; Chaum, E.; Yoser, S.; Bryer-Ash, M.; Schussler, S.; Lambeth, H.; Raskin, P.; Strowig, S.; Zinman, B.; Barnie, A.; Devenyi, R.; Mandelcorn, M.; Brent, M.; Rogers, S.; Gordon, A.; Palmer, J.; Catton, S.; Brunzell, J.; Wessells, H.; de Boer, I.H.; Hokanson, J.; Purnell, J.; Ginsberg, J.; Kinyoun, J.; Deeb, S.; Weiss, M.; Meekins, G.; Distad, J.; Van Ottingham, L.; Dupre, J.; Harth, J.; Nicolle, D.; Driscoll, M.; Mahon, J.; Canny, C.; May, M.; Lipps, J.; Agarwal, A.; Adkins, T.; Survant, L.; Pate, R.L.; Munn, G.E.; Lorenz, R.; Feman, S.; White, N.; Levandoski, L.; Boniuk, I.; Grand, G.; Thomas, M.; Joseph, D.D.; Blinder, K.; Shah, G.; Boniuk; Burgess; Santiago, J.; Tamborlane, W.; Gatcomb, P.; Stoessel, K.; Taylor, K.; Goldstein, J.; Novella, S.; Mojibian, H.; Cornfeld, D.; Lima, J.; Bluemke, D.; Turkbey, E.; van der Geest, R.J.; Liu, C.; Malayeri, A.; Jain, A.; Miao, C.; Chahal, H.; Jarboe, R.; Maynard, J.; Gubitosi-Klug, R.; Quin, J.; Gaston, P.; Palmert, M.; Trail, R.; Dahms, W.; Lachin, J.; Cleary, P.; Backlund, J.; Sun, W.; Braffett, B.; Klumpp, K.; Chan, K.; Diminick, L.; Rosenberg, D.; Petty, B.; Determan, A.; Kenny, D.; Rutledge, B.; Younes, Naji; Dews, L.; Hawkins, M.; Cowie, C.; Fradkin, J.; Siebert, C.; Eastman, R.; Danis, R.; Gangaputra, S.; Neill, S.; Davis, M.; Hubbard, L.; Wabers, H.; Burger, M.; Dingledine, J.; Gama, V.; Sussman, R.; Steffes, M.; Bucksa, J.; Nowicki, M.; Chavers, B.; O’Leary, D.; Polak, J.; Harrington, A.; Funk, L.; Crow, R.; Gloeb, B.; Thomas, S.; O’Donnell, C.; Soliman, E.; Zhang, Z.M.; Prineas, R.; Campbell, C.; Ryan, C.; Sandstrom, D.; Williams, T.; Geckle, M.; Cupelli, E.; Thoma, F.; Burzuk, B.; Woodfill, T.; Low, P.; Sommer, C.; Nickander, K.; Budoff, M.; Detrano, R.; Wong, N.; Fox, M.; Kim, L.; Oudiz, R.; Weir, G.; Espeland, M.; Manolio, T.; Rand, L.; Singer, D.; Stern, M.; Boulton, A.E.; Clark, C.; D’Agostino, R.; Lopes-Virella, M.; Garvey, W.T.; Lyons, T.J.; Jenkins, A.; Virella, G.; Jaffa, A.; Carter, Rickey; Lackland, D.; Brabham, M.; McGee, D.; Zheng, D.; Mayfield, R.K.; Boright, A.; Bull, S.; Sun, L.; Scherer, S.; Zinman, B.; Natarajan, R.; Miao, F.; Zhang, L.; Chen;, Z.; Nathan, D.M.; Makela, Kari-Matti; Lehtimaki, Terho; Kahonen, Mika; Raitakari, Olli; Yoshimura, Nagahisa; Matsuda, Fumihiko; Chen, Li Jia; Pang, Chi Pui; Yip, Shea Ping; Yap, Maurice K.H.; Meguro, Akira; Mizuki, Nobuhisa; Inoko, Hidetoshi; Foster, Paul J.; Zhao, Jing Hua; Vithana, Eranga; Tai, E-Shyong; Fan, Qiao; Xu, Liang; Campbell, Harry; Fleck, Brian; Rudan, Igor; Aung, Tin; Hofman, Albert; Uitterlinden, André G.; Bencic, Goran; Khor, Chiea-Chuen; Forward, Hannah; Pärssinen, Olavi; Mitchell, Paul; Rivadeneira, Fernando; Hewitt, Alex W.; Williams, Cathy; Oostra, Ben A.; Teo, Yik-Ying; Hammond, Christopher J.; Stambolian, Dwight; Mackey, David A.; Klaver, Caroline C.W.; Wong, Tien-Yin; Saw, Seang-Mei; Baird, Paul N.

    2013-01-01

    Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LAMA2, GJD2, CD55, ALPPL2, and ZC3H11B) were associated with refraction in 18 independent cohorts (n = 23,591). Differential gene expression was observed for these loci in minus-lens-induced myopia mouse experiments and human ocular tissues. Two of the AL genes, RSPO1 and ZNRF3, are involved in Wnt signaling, a pathway playing a major role in the regulation of eyeball size. This study provides evidence of shared genes between AL and refraction, but importantly also suggests that these traits may have unique pathways. PMID:24144296

  1. Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error.

    Science.gov (United States)

    Cheng, Ching-Yu; Schache, Maria; Ikram, M Kamran; Young, Terri L; Guggenheim, Jeremy A; Vitart, Veronique; MacGregor, Stuart; Verhoeven, Virginie J M; Barathi, Veluchamy A; Liao, Jiemin; Hysi, Pirro G; Bailey-Wilson, Joan E; St Pourcain, Beate; Kemp, John P; McMahon, George; Timpson, Nicholas J; Evans, David M; Montgomery, Grant W; Mishra, Aniket; Wang, Ya Xing; Wang, Jie Jin; Rochtchina, Elena; Polasek, Ozren; Wright, Alan F; Amin, Najaf; van Leeuwen, Elisabeth M; Wilson, James F; Pennell, Craig E; van Duijn, Cornelia M; de Jong, Paulus T V M; Vingerling, Johannes R; Zhou, Xin; Chen, Peng; Li, Ruoying; Tay, Wan-Ting; Zheng, Yingfeng; Chew, Merwyn; Burdon, Kathryn P; Craig, Jamie E; Iyengar, Sudha K; Igo, Robert P; Lass, Jonathan H; Chew, Emily Y; Haller, Toomas; Mihailov, Evelin; Metspalu, Andres; Wedenoja, Juho; Simpson, Claire L; Wojciechowski, Robert; Höhn, René; Mirshahi, Alireza; Zeller, Tanja; Pfeiffer, Norbert; Lackner, Karl J; Bettecken, Thomas; Meitinger, Thomas; Oexle, Konrad; Pirastu, Mario; Portas, Laura; Nag, Abhishek; Williams, Katie M; Yonova-Doing, Ekaterina; Klein, Ronald; Klein, Barbara E; Hosseini, S Mohsen; Paterson, Andrew D; Makela, Kari-Matti; Lehtimaki, Terho; Kahonen, Mika; Raitakari, Olli; Yoshimura, Nagahisa; Matsuda, Fumihiko; Chen, Li Jia; Pang, Chi Pui; Yip, Shea Ping; Yap, Maurice K H; Meguro, Akira; Mizuki, Nobuhisa; Inoko, Hidetoshi; Foster, Paul J; Zhao, Jing Hua; Vithana, Eranga; Tai, E-Shyong; Fan, Qiao; Xu, Liang; Campbell, Harry; Fleck, Brian; Rudan, Igor; Aung, Tin; Hofman, Albert; Uitterlinden, André G; Bencic, Goran; Khor, Chiea-Chuen; Forward, Hannah; Pärssinen, Olavi; Mitchell, Paul; Rivadeneira, Fernando; Hewitt, Alex W; Williams, Cathy; Oostra, Ben A; Teo, Yik-Ying; Hammond, Christopher J; Stambolian, Dwight; Mackey, David A; Klaver, Caroline C W; Wong, Tien-Yin; Saw, Seang-Mei; Baird, Paul N

    2013-08-08

    Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LAMA2, GJD2, CD55, ALPPL2, and ZC3H11B) were associated with refraction in 18 independent cohorts (n = 23,591). Differential gene expression was observed for these loci in minus-lens-induced myopia mouse experiments and human ocular tissues. Two of the AL genes, RSPO1 and ZNRF3, are involved in Wnt signaling, a pathway playing a major role in the regulation of eyeball size. This study provides evidence of shared genes between AL and refraction, but importantly also suggests that these traits may have unique pathways. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  2. Genome-wide association studies identify four ER negative-specific breast cancer risk loci

    NARCIS (Netherlands)

    Garcia-Closas, Montserrat; Couch, Fergus J.; Lindstrom, Sara; Michailidouo, Kyriaki; Schmidt, Marjanka K.; Brook, Mark N.; Orr, Nick; Rhie, Suhn Kyong; Riboli, Elio; Feigelson, Heather S.; Le Marchand, Loic; Buring, Julie E.; Eccles, Diana; Miron, Penelope; Fasching, Peter A.; Brauch, Hiltrud; Chang-Claude, Jenny; Carpenter, Jane; Godwin, Andrew K.; Nevanlinna, Heli; Giles, Graham G.; Cox, Angela; Hopper, John L.; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Dicks, Ed; Howat, Will J.; Schoof, Nils; Bojesen, Stig E.; Lambrechts, Diether; Broeks, Annegien; Andrulis, Irene L.; Guenel, Pascal; Burwinkel, Barbara; Sawyer, Elinor J.; Hollestelle, Antoinette; Fletcher, Olivia; Winqvist, Robert; Brenner, Hermann; Mannermaa, Arto; Hamann, Ute; Meindl, Alfons; Lindblom, Annika; Zheng, Wei; Devillee, Peter; Goldberg, Mark S.; Lubinski, Jan; Kristensen, Vessela; Swerdlow, Anthony; Anton-Culver, Hoda; Doerk, Thilo; Muir, Kenneth; Matsuo, Keitaro; Wu, Anna H.; Radice, Paolo; Teo, Soo Hwang; Shu, Xiao-Ou; Blot, William; Kang, Daehee; Hartman, Mikael; Sangrajrang, Suleeporn; Shen, Chen-Yang; Southey, Melissa C.; Park, Daniel J.; Hammet, Fleur; Stone, Jennifer; Van't Veer, Laura J.; Rutgers, Emiel J.; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Peto, Julian; Schrauder, Michael G.; Ekici, Arif B.; Beckmann, Matthias W.; Silva, Isabel dos Santos; Johnson, Nichola; Warren, Helen; Tomlins, Ian; Kerin, Michael J.; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Nordestgaard, Borge G.; Nielsen, Sune F.; Flyger, Henrik; Milne, Roger L.; Arias Perez, Jose Ignacio; Menendez, Primitiva; Mueller, Heiko; Arndt, Volker; Stegmaier, Christa; Lichtner, Peter; Lochmann, Magdalena; Justenhoven, Christina; Ko, Yon-Dschun; Muranen, Taru A.; Aittomaki, Kristiina; Blomqvist, Carl; Greco, Dario; Heikkinen, Tuomas; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Antonenkova, Natalia N.; Margolin, Sara; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Balleine, Rosemary; Tseng, Chiu-Chen; Van den Berg, David; Stram, Daniel O.; Neven, Patrick; Dieudonne, Anne-Sophie; Leunen, Karin; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Peterlongo, Paolo; Peissel, Bernard; Bernard, Loris; Olson, Janet E.; Wang, Xianshu; Stevens, Kristen; Severi, Gianluca; Baglietto, Laura; McLean, Catriona; Coetzee, Gerhard A.; Feng, Ye; Henderson, Brian E.; Schumacher, Fredrick; Bogdanova, Natalia V.; Labreche, France; Dumont, Martine; Yip, Cheng Har; Taib, Nur Aishah Mohd; Cheng, Ching-Yu; Shrubsole, Martha; Long, Jirong; Pylkas, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Tollenaar, Robertus A. E. M.; Seynaeve, Caroline M.; Kriege, Mieke; Hooning, Maartje J.; van den Ouweland, Ans M. W.; van Deurzen, Carolien H. M.; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Balasubramanian, Sabapathy P.; Cross, Simon S.; Reed, Malcolm W. R.; Signorello, Lisa; Cai, Qiuyin; Shah, Mitul; Miao, Hui; Chan, Ching Wan; Chia, Kee Seng; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Hsiung, Chia-Ni; Wu, Peiei; Yu, Jyh-Cherng; Ashworth, Alan; Jones, Michael; Tessier, Daniel C.; Gonzalez-Neira, Anna; Pita, Guillermo; Alonso, M. Rosario; Vincent, Daniel; Bacot, Francois; Ambrosone, Christine B.; Bandera, Elisa V.; John, Esther M.; Chen, Gary K.; Hu, Jennifer J.; Rodriguez-Gil, Jorge L.; Bernstein, Leslie; Press, Michael F.; Ziegler, Regina G.; Millikan, Robert M.; Deming-Halverson, Sandra L.; Nyante, Sarah; Ingles, Sue A.; Waisfisz, Quinten; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel; Bui, Minh; Gibson, Lorna; Mueller-Myhsok, Bertram; Schmutzler, Rita K.; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Turnbull, Clare; Rahman, Nazneen; Meijers-Heijboer, Hanne; Uitterlinden, Andre G.; Rivadeneira, Fernando; Olswold, Curtis; Slager, Susan; Pilarski, Robert; Ademuyiwa, Foluso; Konstantopoulou, Irene; Martin, Nicholas G.; Montgomery, Grant W.; Slamon, Dennis J.; Rauh, Claudia; Lux, Michael P.; Jud, Sebastian M.; Bruning, Thomas; Weaver, JoEllen; Harma, Priyanka; Pathak, Harsh; Tapper, Will; Gerty, Sue; Durcan, Lorraine; Trichopoulos, Dimitrios; Tumino, Rosario; Peeters, Petra H.; Kaaks, Rudolf; Campa, Daniele; Canzian, Federico; Weiderpass, Elisabete; Johansson, Mattias; Khaw, Kay-Tee; Travis, Ruth; Clavel-Chapelon, Francoise; Kolonel, Laurence N.; Chen, Constance; Beck, Andy; Hankinson, Susan E.; Berg, Christine D.; Hoover, Robert N.; Lissowska, Jolanta; Figueroa, Jonine D.; Chasman, Daniel I.; Gaudet, Mia M.; Diver, W. Ryan; Willett, Walter C.; Hunter, David J.; Simard, Jacques; Benitez, Javier; Dunning, Alison M.; Sherman, Mark E.; Chenevix-Trench, Georgia; Chanock, Stephen J.; Hall, Per; Pharoah, Paul D. P.; Vachon, Celine; Easton, Douglas F.; Haiman, Christopher A.; Kraft, Peter

    2013-01-01

    Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differe

  3. Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche

    NARCIS (Netherlands)

    Perry, J.R.; Day, F.; Elks, C.E.; Sulem, P.; Thompson, D.J.; Ferreira, T.; He, C.; Chasman, D.I.; Esko, T.; Thorleifsson, G.; Albrecht, E.; Ang, W.Q.; Corre, T.; Cousminer, D.L.; Feenstra, B.; Franceschini, N.; Ganna, A.; Johnson, A.D.; Kjellqvist, S.; Lunetta, K.L.; McMahon, G.; Nolte, I.M.; Paternoster, L.; Porcu, E.; Smith, A.V.; Stolk, L.; Teumer, A.; Tsernikova, N.; Tikkanen, E.; Ulivi, S.; Wagner, E.K.; Amin, N.; Bierut, L.J.; Byrne, E.M.; Hottenga, J.J.; Koller, D.L.; Mangino, M.; Pers, T.H.; Yerges-Armstrong, L.M.; Zhao, J.; Andrulis, I.L.; Anton-Culver, H.; Atsma, F.; Bandinelli, S.; Beckmann, M.W.; Benitez, J.; Blomqvist, C.; Bojesen, S.E.; Bolla, M.K.; Bonanni, B.; Brauch, H.; Brenner, H.; Buring, J.E.; Chang-Claude, J.; Chanock, S.; Chen, J.; Chenevix-Trench, G.; Collee, J.M.; Couch, F.J.; Couper, D.; Coviello, A.D.; Cox, A; Czene, K.; D'Adamo, P.; Smith, G.; Vivo, I. De; Demerath, E.W.; Dennis, J.; Devilee, P.; Dieffenbach, A.K.; Dunning, A.M.; Eiriksdottir, G.; Eriksson, J.G.; Fasching, P.A.; Ferrucci, L.; Flesch-Janys, D.; Flyger, H.; Foroud, T.; Franke, L.; Garcia, M.E.; Garcia-Closas, M.; Geller, F.; Geus, E.E. de; Giles, G.G.; Gudbjartsson, D.F.; Gudnason, V.; Guenel, P.; Guo, S.; Hall, P.; Hamann, U.; Haring, R.; Hartman, C.A.; Heath, A.C.; Hofman, A.; Hooning, M.J.; Hopper, J.L.; Hu, F.B.; Hunter, D.J.; Karasik, D.; Kiel, D.P.

    2014-01-01

    Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal

  4. Genome-wide association studies identify four ER negative-specific breast cancer risk loci

    NARCIS (Netherlands)

    Garcia-Closas, Montserrat; Couch, Fergus J.; Lindstrom, Sara; Michailidouo, Kyriaki; Schmidt, Marjanka K.; Brook, Mark N.; Orr, Nick; Rhie, Suhn Kyong; Riboli, Elio; Feigelson, Heather S.; Le Marchand, Loic; Buring, Julie E.; Eccles, Diana; Miron, Penelope; Fasching, Peter A.; Brauch, Hiltrud; Chang-Claude, Jenny; Carpenter, Jane; Godwin, Andrew K.; Nevanlinna, Heli; Giles, Graham G.; Cox, Angela; Hopper, John L.; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Dicks, Ed; Howat, Will J.; Schoof, Nils; Bojesen, Stig E.; Lambrechts, Diether; Broeks, Annegien; Andrulis, Irene L.; Guenel, Pascal; Burwinkel, Barbara; Sawyer, Elinor J.; Hollestelle, Antoinette; Fletcher, Olivia; Winqvist, Robert; Brenner, Hermann; Mannermaa, Arto; Hamann, Ute; Meindl, Alfons; Lindblom, Annika; Zheng, Wei; Devillee, Peter; Goldberg, Mark S.; Lubinski, Jan; Kristensen, Vessela; Swerdlow, Anthony; Anton-Culver, Hoda; Doerk, Thilo; Muir, Kenneth; Matsuo, Keitaro; Wu, Anna H.; Radice, Paolo; Teo, Soo Hwang; Shu, Xiao-Ou; Blot, William; Kang, Daehee; Hartman, Mikael; Sangrajrang, Suleeporn; Shen, Chen-Yang; Southey, Melissa C.; Park, Daniel J.; Hammet, Fleur; Stone, Jennifer; Van't Veer, Laura J.; Rutgers, Emiel J.; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Peto, Julian; Schrauder, Michael G.; Ekici, Arif B.; Beckmann, Matthias W.; Silva, Isabel dos Santos; Johnson, Nichola; Warren, Helen; Tomlins, Ian; Kerin, Michael J.; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Nordestgaard, Borge G.; Nielsen, Sune F.; Flyger, Henrik; Milne, Roger L.; Arias Perez, Jose Ignacio; Menendez, Primitiva; Mueller, Heiko; Arndt, Volker; Stegmaier, Christa; Lichtner, Peter; Lochmann, Magdalena; Justenhoven, Christina; Ko, Yon-Dschun; Muranen, Taru A.; Aittomaki, Kristiina; Blomqvist, Carl; Greco, Dario; Heikkinen, Tuomas; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Antonenkova, Natalia N.; Margolin, Sara; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Balleine, Rosemary; Tseng, Chiu-Chen; Van den Berg, David; Stram, Daniel O.; Neven, Patrick; Dieudonne, Anne-Sophie; Leunen, Karin; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Peterlongo, Paolo; Peissel, Bernard; Bernard, Loris; Olson, Janet E.; Wang, Xianshu; Stevens, Kristen; Severi, Gianluca; Baglietto, Laura; McLean, Catriona; Coetzee, Gerhard A.; Feng, Ye; Henderson, Brian E.; Schumacher, Fredrick; Bogdanova, Natalia V.; Labreche, France; Dumont, Martine; Yip, Cheng Har; Taib, Nur Aishah Mohd; Cheng, Ching-Yu; Shrubsole, Martha; Long, Jirong; Pylkas, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Tollenaar, Robertus A. E. M.; Seynaeve, Caroline M.; Kriege, Mieke; Hooning, Maartje J.; van den Ouweland, Ans M. W.; van Deurzen, Carolien H. M.; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Balasubramanian, Sabapathy P.; Cross, Simon S.; Reed, Malcolm W. R.; Signorello, Lisa; Cai, Qiuyin; Shah, Mitul; Miao, Hui; Chan, Ching Wan; Chia, Kee Seng; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Hsiung, Chia-Ni; Wu, Peiei; Yu, Jyh-Cherng; Ashworth, Alan; Jones, Michael; Tessier, Daniel C.; Gonzalez-Neira, Anna; Pita, Guillermo; Alonso, M. Rosario; Vincent, Daniel; Bacot, Francois; Ambrosone, Christine B.; Bandera, Elisa V.; John, Esther M.; Chen, Gary K.; Hu, Jennifer J.; Rodriguez-Gil, Jorge L.; Bernstein, Leslie; Press, Michael F.; Ziegler, Regina G.; Millikan, Robert M.; Deming-Halverson, Sandra L.; Nyante, Sarah; Ingles, Sue A.; Waisfisz, Quinten; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel; Bui, Minh; Gibson, Lorna; Mueller-Myhsok, Bertram; Schmutzler, Rita K.; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Turnbull, Clare; Rahman, Nazneen; Meijers-Heijboer, Hanne; Uitterlinden, Andre G.; Rivadeneira, Fernando; Olswold, Curtis; Slager, Susan; Pilarski, Robert; Ademuyiwa, Foluso; Konstantopoulou, Irene; Martin, Nicholas G.; Montgomery, Grant W.; Slamon, Dennis J.; Rauh, Claudia; Lux, Michael P.; Jud, Sebastian M.; Bruning, Thomas; Weaver, JoEllen; Harma, Priyanka; Pathak, Harsh; Tapper, Will; Gerty, Sue; Durcan, Lorraine; Trichopoulos, Dimitrios; Tumino, Rosario; Peeters, Petra H.; Kaaks, Rudolf; Campa, Daniele; Canzian, Federico; Weiderpass, Elisabete; Johansson, Mattias; Khaw, Kay-Tee; Travis, Ruth; Clavel-Chapelon, Francoise; Kolonel, Laurence N.; Chen, Constance; Beck, Andy; Hankinson, Susan E.; Berg, Christine D.; Hoover, Robert N.; Lissowska, Jolanta; Figueroa, Jonine D.; Chasman, Daniel I.; Gaudet, Mia M.; Diver, W. Ryan; Willett, Walter C.; Hunter, David J.; Simard, Jacques; Benitez, Javier; Dunning, Alison M.; Sherman, Mark E.; Chenevix-Trench, Georgia; Chanock, Stephen J.; Hall, Per; Pharoah, Paul D. P.; Vachon, Celine; Easton, Douglas F.; Haiman, Christopher A.; Kraft, Peter

    2013-01-01

    Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differe

  5. Genome-wide association studies identify four ER negative-specific breast cancer risk loci

    DEFF Research Database (Denmark)

    Garcia-Closas, Montserrat; Couch, Fergus J; Lindstrom, Sara

    2013-01-01

    Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including diff...

  6. Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche

    NARCIS (Netherlands)

    J.R.B. Perry (John); F.R. Day (Felix); C.E. Elks (Cathy); P. Sulem (Patrick); D. Thompson (Deborah); T. Ferreira (Teresa); C. He (Chunyan); D.I. Chasman (Daniel); T. Esko (Tõnu); G. Thorleifsson (Gudmar); E. Albrecht (Eva); W.Q. Ang (Wei); T. Corre (Tanguy); D.L. Cousminer (Diana); B. Feenstra (Bjarke); N. Franceschini (Nora); A. Ganna (Andrea); A.D. Johnson (Andrew); S. Kjellqvist (Sanela); K.L. Lunetta (Kathryn); G. Mcmahon (George); I.M. Nolte (Ilja); L. Paternoster (Lavinia); E. Porcu (Eleonora); G.D. Smith; L. Stolk (Lisette); A. Teumer (Alexander); N. Tsernikova (Natalia); E. Tikkanen (Emmi); S. Ulivi (Shelia); E.K. Wagner (Erin K.); N. Amin (Najaf); L.J. Bierut (Laura); E.M. Byrne (Enda); J.J. Hottenga (Jouke Jan); D.L. Koller (Daniel); M. Mangino (Massimo); T.H. Pers (Tune); L.M. Yerges-Armstrong (Laura); J.H. Zhao; I.L. Andrulis (Irene); H. Anton-Culver (Hoda); F. Atsma (Femke); S. Bandinelli (Stefania); M.W. Beckmann (Matthias W.); J. Benítez (Javier); C. Blomqvist (Carl); S.E. Bojesen (Stig); M.K. Bolla (Manjeet); B. Bonnani (Bernardo); H. Brauch (Hiltrud); H. Brenner (Hermann); J.E. Buring (Julie); J. Chang-Claude (Jenny); S.J. Chanock (Stephen); J. Chen (Jinhui); G. Chenevix-Trench (Georgia); J.M. Collee (Margriet); F.J. Couch (Fergus); D.J. Couper (David); A.D. Coviello (Andrea); A. Cox (Angela); K. Czene (Kamila); P. d' Adamo (Pio); G.D. Smith; I. de Vivo (Immaculata); E.W. Demerath (Ellen); J. Dennis (Joe); P. Devilee (Peter); A.K. Dieffenbach (Aida Karina); A.M. Dunning (Alison); G. Eiriksdottir (Gudny); K. Hagen (Knut); P.A. Fasching (Peter); L. Ferrucci (Luigi); D. Flesch-Janys (Dieter); H. Flyger (Henrik); T. Foroud (Tatiana); L. Franke (Lude); M. Garcia (Melissa); M. García-Closas (Montserrat); F. Geller (Frank); E.E.J. De Geus (Eco E. J.); G.G. Giles (Graham); D.F. Gudbjartsson (Daniel); V. Gudnason (Vilmundur); P. Guénel (Pascal); S. Guo (Suiqun); P. Hall (Per); U. Hamann (Ute); R. Haring (Robin); C.A. Hartman (Catharina); A.C. Heath (Andrew); A. Hofman (Albert); M.J. Hooning (Maartje); J.L. Hopper (John); F.B. Hu (Frank); D. Hunter (David); D. Karasik (David); D.P. Kiel (Douglas P.); J.A. Knight (Julia); V-M. Kosma (Veli-Matti); Z. Kutalik (Zoltán); S. Lai (Sandra); D. Lambrechts (Diether); A. Lindblom (Annika); R. Mägi (Reedik); P.K. Magnusson (Patrik); A. Mannermaa (Arto); N.G. Martin (Nicholas); G. Masson (Gisli); P.F. McArdle (Patrick); W.L. McArdle (Wendy); M. Melbye (Mads); K. Michailidou (Kyriaki); E. Mihailov (Evelin); L. Milani (Lili); R.L. Milne (Roger L); H. Nevanlinna (Heli); P. Neven (Patrick); C. Nohr (Christian); A.J. Oldehinkel (Albertine); B.A. Oostra (Ben); A. Palotie (Aarno); M. Peacock (Munro); N.L. Pedersen (Nancy L.); P. Peterlongo (Paolo); J. Peto (Julian); P.D.P. Pharoah (Paul); D.S. Postma (Dirkje); A. Pouta (Anneli); K. Pykäs (Katri); P. Radice (Paolo); S.M. Ring (Susan); F. Rivadeneira Ramirez (Fernando); A. Robino (Antonietta); L.M. Rose (Lynda); A. Rudolph (Anja); V. Salomaa (Veikko); S. Sanna (Serena); D. Schlessinger (David); M.K. Schmidt (Marjanka); M.C. Southey (Mellissa C.); U. Sovio (Ulla); M.J. Stampfer (Meir J.); D. Stöckl (Doris); A.M. Storniolo (Anna M.); N. Timpson (Nicholas); J.P. Tyrer (Jonathan); J.A. Visser (Jenny); P. Vollenweider (Peter); H. Völzke (Henry); G. Waeber (Gérard); M. Waldenberger (Melanie); H. Wallaschofski (Henri); Q. Wang (Qing); G.A.H.M. Willemsen (Gonneke); R. Winqvist (Robert); B.H.R. Wolffenbuttel (Bruce H. R.); M.J. Wright (Margaret); D.I. Boomsma (Dorret); M.J. Econs (Michael); K.T. Khaw; R.J.F. Loos (Ruth); M.I. McCarthy (Mark); G.W. Montgomery (Grant); J.P. Rice (John); E.A. Streeten (Elizabeth); U. Thorsteinsdottir (Unnur); C.M. van Duijn (Cock); B.Z. Alizadeh (Behrooz); S.M. Bergmann (Sven); E.A. Boerwinkle (Eric); H.A. Boyd (Heather); L. Crisponi (Laura); P. Gasparini (Paolo); C. Gieger (Christian); T.B. Harris (Tamara); E. Ingelsson (Erik); M.-R. Jarvelin (Marjo-Riitta); P. Kraft (Peter); D.A. Lawlor (Debbie); A. Metspalu (Andres); C.E. Pennell (Craig); P.M. Ridker (Paul); H. Snieder (Harold); T.I.A. Sørensen; T.D. Spector (Timothy); D.P. Strachan (David P.); A.G. Uitterlinden (André); N.J. Wareham (Nick); E. Widen (Elisabeth); M. Zygmunt (Marek); A. Murray (Anna); D.F. Easton (Douglas); J-A. Zwart (John-Anker); J. Murabito (Joanne); K.K. Ong (Ken K.)

    2014-01-01

    textabstractAge at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and

  7. Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche

    NARCIS (Netherlands)

    Perry, John R. B.; Day, Felix; Elks, Cathy E.; Sulem, Patrick; Thompson, Deborah J.; Ferreira, Teresa; He, Chunyan; Chasman, Daniel I.; Esko, Toenu; Thorleifsson, Gudmar; Albrecht, Eva; Ang, Wei Q.; Corre, Tanguy; Cousminer, Diana L.; Feenstra, Bjarke; Franceschini, Nora; Ganna, Andrea; Johnson, Andrew D.; Kjellqvist, Sanela; Lunetta, Kathryn L.; McMahon, George; Nolte, Ilja M.; Paternoster, Lavinia; Porcu, Eleonora; Smith, Albert V.; Stolk, Lisette; Teumer, Alexander; Tsernikova, Natalia; Tikkanen, Emmi; Ulivi, Sheila; Wagner, Erin K.; Amin, Najaf; Bierut, Laura J.; Byrne, Enda M.; Hottenga, Jouke-Jan; Koller, Daniel L.; Mangino, Massimo; Pers, Tune H.; Yerges-Armstrong, Laura M.; Zhao, Jing Hua; Andrulis, Irene L.; Anton-Culver, Hoda; Atsma, Femke; Bandinelli, Stefania; Beckmann, Matthias W.; Benitez, Javier; Blomqvist, Carl; Bojesen, Stig E.; Bolla, Manjeet K.; Bonanni, Bernardo; Brauch, Hiltrud; Brenner, Hermann; Buring, Julie E.; Chang-Claude, Jenny; Chanock, Stephen; Chen, Jinhui; Chenevix-Trench, Georgia; Collee, J. Margriet; Couch, Fergus J.; Couper, David; Coviello, Andrea D.; Cox, Angela; Czene, Kamila; D'adamo, Adamo Pio; Smith, George Davey; De Vivo, Immaculata; Demerath, Ellen W.; Dennis, Joe; Devilee, Peter; Dieffenbach, Aida K.; Dunning, Alison M.; Eiriksdottir, Gudny; Eriksson, Johan G.; Fasching, Peter A.; Ferrucci, Luigi; Flesch-Janys, Dieter; Flyger, Henrik; Foroud, Tatiana; Franke, Lude; Garcia, Melissa E.; Garcia-Closas, Montserrat; Geller, Frank; de Geus, Eco E. J.; Giles, Graham G.; Gudbjartsson, Daniel F.; Gudnason, Vilmundur; Guenel, Pascal; Guo, Suiqun; Hall, Per; Hamann, Ute; Haring, Robin; Hartman, Catharina A.; Heath, AndrewC.; Hofman, Albert; Hooning, Maartje J.; Hopper, John L.; Hu, Frank B.; Hunter, David J.; Karasik, David; Kiel, Douglas P.; Knight, Julia A.; Kosma, Veli-Matti; Kutalik, Zoltan; Lai, Sandra; Lambrechts, Diether; Lindblom, Annika; Maegi, Reedik; Magnusson, Patrik K.; Mannermaa, Arto; Martin, Nicholas G.; Masson, Gisli; McArdle, Patrick F.; McArdle, Wendy L.; Melbye, Mads; Michailidou, Kyriaki; Mihailov, Evelin; Milani, Lili; Milne, Roger L.; Nevanlinna, Heli; Neven, Patrick; Nohr, Ellen A.; Oldehinkel, Albertine J.; Oostra, Ben A.; Palotie, Aarno; Peacock, Munro; Pedersen, Nancy L.; Peterlongo, Paolo; Peto, Julian; Pharoah, Paul D. P.; Postma, Dirkje S.; Pouta, Anneli; Pylkaes, Katri; Radice, Paolo; Ring, Susan; Rivadeneira, Fernando; Robino, Antonietta; Rose, Lynda M.; Rudolph, Anja; Salomaa, Veikko; Sanna, Serena; Schlessinger, David; Schmidt, Marjanka K.; Southey, Mellissa C.; Sovio, Ulla; Stampfer, Meir J.; Stoeckl, Doris; Storniolo, Anna M.; Timpson, Nicholas J.; Tyrer, Jonathan; Visser, Jenny A.; Vollenweider, Peter; Voelzke, Henry; Waeber, Gerard; Waldenberger, Melanie; Wallaschofski, Henri; Wang, Qin; Willemsen, Gonneke; Winqvist, Robert; Wolffenbuttel, Bruce H. R.; Wright, Margaret J.; Boomsma, Dorret I.; Econs, Michael J.; Khaw, Kay-Tee; Loos, Ruth J. F.; McCarthy, Mark I.; Montgomery, Grant W.; Rice, John P.; Streeten, Elizabeth A.; Thorsteinsdottir, Unnur; van Duijn, Cornelia M.; Alizadeh, Behrooz Z.; Bergmann, Sven; Boerwinkle, Eric; Boyd, Heather A.; Crisponi, Laura; Gasparini, Paolo; Gieger, Christian; Harris, Tamara B.; Ingelsson, Erik; Jaervelin, Marjo-Riitta; Kraft, Peter; Lawlor, Debbie; Metspalu, Andres; Pennell, Craig E.; Ridker, Paul M.; Snieder, Harold; Sorensen, Thorkild I. A.; Spector, Tim D.; Strachan, David P.; Uitterlinden, Andre G.; Wareham, Nicholas J.; Widen, Elisabeth; Zygmunt, Marek; Murray, Anna; Easton, Douglas F.; Stefansson, Kari; Murabito, Joanne M.; Ong, Ken K.

    2014-01-01

    Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-causemortality(1). Studies of rare human disorders of puberty and animal mo

  8. Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche

    NARCIS (Netherlands)

    Perry, John R. B.; Day, Felix; Elks, Cathy E.; Sulem, Patrick; Thompson, Deborah J.; Ferreira, Teresa; He, Chunyan; Chasman, Daniel I.; Esko, Toenu; Thorleifsson, Gudmar; Albrecht, Eva; Ang, Wei Q.; Corre, Tanguy; Cousminer, Diana L.; Feenstra, Bjarke; Franceschini, Nora; Ganna, Andrea; Johnson, Andrew D.; Kjellqvist, Sanela; Lunetta, Kathryn L.; McMahon, George; Nolte, Ilja M.; Paternoster, Lavinia; Porcu, Eleonora; Smith, Albert V.; Stolk, Lisette; Teumer, Alexander; Tsernikova, Natalia; Tikkanen, Emmi; Ulivi, Sheila; Wagner, Erin K.; Amin, Najaf; Bierut, Laura J.; Byrne, Enda M.; Hottenga, Jouke-Jan; Koller, Daniel L.; Mangino, Massimo; Pers, Tune H.; Yerges-Armstrong, Laura M.; Zhao, Jing Hua; Andrulis, Irene L.; Anton-Culver, Hoda; Atsma, Femke; Bandinelli, Stefania; Beckmann, Matthias W.; Benitez, Javier; Blomqvist, Carl; Bojesen, Stig E.; Bolla, Manjeet K.; Bonanni, Bernardo; Brauch, Hiltrud; Brenner, Hermann; Buring, Julie E.; Chang-Claude, Jenny; Chanock, Stephen; Chen, Jinhui; Chenevix-Trench, Georgia; Collee, J. Margriet; Couch, Fergus J.; Couper, David; Coviello, Andrea D.; Cox, Angela; Czene, Kamila; D'adamo, Adamo Pio; Smith, George Davey; De Vivo, Immaculata; Demerath, Ellen W.; Dennis, Joe; Devilee, Peter; Dieffenbach, Aida K.; Dunning, Alison M.; Eiriksdottir, Gudny; Eriksson, Johan G.; Fasching, Peter A.; Ferrucci, Luigi; Flesch-Janys, Dieter; Flyger, Henrik; Foroud, Tatiana; Franke, Lude; Garcia, Melissa E.; Garcia-Closas, Montserrat; Geller, Frank; de Geus, Eco E. J.; Giles, Graham G.; Gudbjartsson, Daniel F.; Gudnason, Vilmundur; Guenel, Pascal; Guo, Suiqun; Hall, Per; Hamann, Ute; Haring, Robin; Hartman, Catharina A.; Heath, AndrewC.; Hofman, Albert; Hooning, Maartje J.; Hopper, John L.; Hu, Frank B.; Hunter, David J.; Karasik, David; Kiel, Douglas P.; Knight, Julia A.; Kosma, Veli-Matti; Kutalik, Zoltan; Lai, Sandra; Lambrechts, Diether; Lindblom, Annika; Maegi, Reedik; Magnusson, Patrik K.; Mannermaa, Arto; Martin, Nicholas G.; Masson, Gisli; McArdle, Patrick F.; McArdle, Wendy L.; Melbye, Mads; Michailidou, Kyriaki; Mihailov, Evelin; Milani, Lili; Milne, Roger L.; Nevanlinna, Heli; Neven, Patrick; Nohr, Ellen A.; Oldehinkel, Albertine J.; Oostra, Ben A.; Palotie, Aarno; Peacock, Munro; Pedersen, Nancy L.; Peterlongo, Paolo; Peto, Julian; Pharoah, Paul D. P.; Postma, Dirkje S.; Pouta, Anneli; Pylkaes, Katri; Radice, Paolo; Ring, Susan; Rivadeneira, Fernando; Robino, Antonietta; Rose, Lynda M.; Rudolph, Anja; Salomaa, Veikko; Sanna, Serena; Schlessinger, David; Schmidt, Marjanka K.; Southey, Mellissa C.; Sovio, Ulla; Stampfer, Meir J.; Stoeckl, Doris; Storniolo, Anna M.; Timpson, Nicholas J.; Tyrer, Jonathan; Visser, Jenny A.; Vollenweider, Peter; Voelzke, Henry; Waeber, Gerard; Waldenberger, Melanie; Wallaschofski, Henri; Wang, Qin; Willemsen, Gonneke; Winqvist, Robert; Wolffenbuttel, Bruce H. R.; Wright, Margaret J.; Boomsma, Dorret I.; Econs, Michael J.; Khaw, Kay-Tee; Loos, Ruth J. F.; McCarthy, Mark I.; Montgomery, Grant W.; Rice, John P.; Streeten, Elizabeth A.; Thorsteinsdottir, Unnur; van Duijn, Cornelia M.; Alizadeh, Behrooz Z.; Bergmann, Sven; Boerwinkle, Eric; Boyd, Heather A.; Crisponi, Laura; Gasparini, Paolo; Gieger, Christian; Harris, Tamara B.; Ingelsson, Erik; Jaervelin, Marjo-Riitta; Kraft, Peter; Lawlor, Debbie; Metspalu, Andres; Pennell, Craig E.; Ridker, Paul M.; Snieder, Harold; Sorensen, Thorkild I. A.; Spector, Tim D.; Strachan, David P.; Uitterlinden, Andre G.; Wareham, Nicholas J.; Widen, Elisabeth; Zygmunt, Marek; Murray, Anna; Easton, Douglas F.; Stefansson, Kari; Murabito, Joanne M.; Ong, Ken K.

    2014-01-01

    Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-causemortality(1). Studies of rare human disorders of puberty and animal

  9. Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche

    NARCIS (Netherlands)

    J.R.B. Perry (John); F.R. Day (Felix); C.E. Elks (Cathy); P. Sulem (Patrick); D. Thompson (Deborah); T. Ferreira (Teresa); C. He (Chunyan); D.I. Chasman (Daniel); T. Esko (Tõnu); G. Thorleifsson (Gudmar); E. Albrecht (Eva); W.Q. Ang (Wei); T. Corre (Tanguy); D.L. Cousminer (Diana); B. Feenstra (Bjarke); N. Franceschini (Nora); A. Ganna (Andrea); A.D. Johnson (Andrew); S. Kjellqvist (Sanela); K.L. Lunetta (Kathryn); G. Mcmahon (George); I.M. Nolte (Ilja); L. Paternoster (Lavinia); E. Porcu (Eleonora); G.D. Smith; L. Stolk (Lisette); A. Teumer (Alexander); N. Tsernikova (Natalia); E. Tikkanen (Emmi); S. Ulivi (Shelia); E.K. Wagner (Erin K.); N. Amin (Najaf); L.J. Bierut (Laura); E.M. Byrne (Enda); J.J. Hottenga (Jouke Jan); D.L. Koller (Daniel); M. Mangino (Massimo); T.H. Pers (Tune); L.M. Yerges-Armstrong (Laura); J.H. Zhao; I.L. Andrulis (Irene); H. Anton-Culver (Hoda); F. Atsma (Femke); S. Bandinelli (Stefania); M.W. Beckmann (Matthias W.); J. Benítez (Javier); C. Blomqvist (Carl); S.E. Bojesen (Stig); M.K. Bolla (Manjeet); B. Bonnani (Bernardo); H. Brauch (Hiltrud); H. Brenner (Hermann); J.E. Buring (Julie); J. Chang-Claude (Jenny); S.J. Chanock (Stephen); J. Chen (Jinhui); G. Chenevix-Trench (Georgia); J.M. Collee (Margriet); F.J. Couch (Fergus); D.J. Couper (David); A.D. Coviello (Andrea); A. Cox (Angela); K. Czene (Kamila); P. d' Adamo (Pio); G.D. Smith; I. de Vivo (Immaculata); E.W. Demerath (Ellen); J. Dennis (Joe); P. Devilee (Peter); A.K. Dieffenbach (Aida Karina); A.M. Dunning (Alison); G. Eiriksdottir (Gudny); K. Hagen (Knut); P.A. Fasching (Peter); L. Ferrucci (Luigi); D. Flesch-Janys (Dieter); H. Flyger (Henrik); T. Foroud (Tatiana); L. Franke (Lude); M. Garcia (Melissa); M. García-Closas (Montserrat); F. Geller (Frank); E.E.J. De Geus (Eco E. J.); G.G. Giles (Graham); D.F. Gudbjartsson (Daniel); V. Gudnason (Vilmundur); P. Guénel (Pascal); S. Guo (Suiqun); P. Hall (Per); U. Hamann (Ute); R. Haring (Robin); C.A. Hartman (Catharina); A.C. Heath (Andrew); A. Hofman (Albert); M.J. Hooning (Maartje); J.L. Hopper (John); F.B. Hu (Frank); D. Hunter (David); D. Karasik (David); D.P. Kiel (Douglas P.); J.A. Knight (Julia); V-M. Kosma (Veli-Matti); Z. Kutalik (Zoltán); S. Lai (Sandra); D. Lambrechts (Diether); A. Lindblom (Annika); R. Mägi (Reedik); P.K. Magnusson (Patrik); A. Mannermaa (Arto); N.G. Martin (Nicholas); G. Masson (Gisli); P.F. McArdle (Patrick); W.L. McArdle (Wendy); M. Melbye (Mads); K. Michailidou (Kyriaki); E. Mihailov (Evelin); L. Milani (Lili); R.L. Milne (Roger L); H. Nevanlinna (Heli); P. Neven (Patrick); C. Nohr (Christian); A.J. Oldehinkel (Albertine); B.A. Oostra (Ben); A. Palotie (Aarno); M. Peacock (Munro); N.L. Pedersen (Nancy L.); P. Peterlongo (Paolo); J. Peto (Julian); P.D.P. Pharoah (Paul); D.S. Postma (Dirkje); A. Pouta (Anneli); K. Pykäs (Katri); P. Radice (Paolo); S.M. Ring (Susan); F. Rivadeneira Ramirez (Fernando); A. Robino (Antonietta); L.M. Rose (Lynda); A. Rudolph (Anja); V. Salomaa (Veikko); S. Sanna (Serena); D. Schlessinger (David); M.K. Schmidt (Marjanka); M.C. Southey (Mellissa C.); U. Sovio (Ulla); M.J. Stampfer (Meir J.); D. Stöckl (Doris); A.M. Storniolo (Anna M.); N. Timpson (Nicholas); J.P. Tyrer (Jonathan); J.A. Visser (Jenny); P. Vollenweider (Peter); H. Völzke (Henry); G. Waeber (Gérard); M. Waldenberger (Melanie); H. Wallaschofski (Henri); Q. Wang (Qing); G.A.H.M. Willemsen (Gonneke); R. Winqvist (Robert); B.H.R. Wolffenbuttel (Bruce H. R.); M.J. Wright (Margaret); D.I. Boomsma (Dorret); M.J. Econs (Michael); K.T. Khaw; R.J.F. Loos (Ruth); M.I. McCarthy (Mark); G.W. Montgomery (Grant); J.P. Rice (John); E.A. Streeten (Elizabeth); U. Thorsteinsdottir (Unnur); C.M. van Duijn (Cock); B.Z. Alizadeh (Behrooz); S.M. Bergmann (Sven); E.A. Boerwinkle (Eric); H.A. Boyd (Heather); L. Crisponi (Laura); P. Gasparini (Paolo); C. Gieger (Christian); T.B. Harris (Tamara); E. Ingelsson (Erik); M.-R. Jarvelin (Marjo-Riitta); P. Kraft (Peter); D.A. Lawlor (Debbie); A. Metspalu (Andres); C.E. Pennell (Craig); P.M. Ridker (Paul); H. Snieder (Harold); T.I.A. Sørensen; T.D. Spector (Timothy); D.P. Strachan (David P.); A.G. Uitterlinden (André); N.J. Wareham (Nick); E. Widen (Elisabeth); M. Zygmunt (Marek); A. Murray (Anna); D.F. Easton (Douglas); J-A. Zwart (John-Anker); J. Murabito (Joanne); K.K. Ong (Ken K.)

    2014-01-01

    textabstractAge at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and

  10. Multiple loci with different cancer specificities within the 8q24 gene desert

    DEFF Research Database (Denmark)

    Ghoussaini, M.; Song, H.; Koessler, T.

    2008-01-01

    Recent studies based on genome-wide association, linkage, and admixture scan analysis have reported associations of various genetic variants in 8q24 with susceptibility to breast, prostate, and colorectal cancer. This locus lies within a 1.18-Mb region that contains no known genes but is bounded ...

  11. Genomic conservation of cattle microsatellite loci in wild gaur (Bos gaurus and current genetic status of this species in Vietnam

    Directory of Open Access Journals (Sweden)

    Renard Jean-Paul

    2007-11-01

    Full Text Available Abstract Background The wild gaur (Bos gaurus is an endangered wild cattle species. In Vietnam, the total number of wild gaurs is estimated at a maximum of 500 individuals. Inbreeding and genetic drift are current relevant threats to this small population size. Therefore, information about the genetic status of the Vietnamese wild gaur population is essential to develop strategies for conservation and effective long-term management for this species. In the present study, we performed cross-species amplification of 130 bovine microsatellite markers, in order to evaluate the applicability and conservation of cattle microsatellite loci in the wild gaur genome. The genetic diversity of Vietnamese wild gaur was also investigated, based on data collected from the 117 successfully amplified loci. Results One hundred-thirty cattle microsatellite markers were tested on a panel of 11 animals. Efficient amplifications were observed for 117 markers (90% with a total of 264 alleles, and of these, 68 (58.1% gave polymorphic band patterns. The number of alleles per locus among the polymorphic markers ranged from two to six. Thirteen loci (BM1314, BM2304, BM6017, BMC2228, BMS332, BMS911, CSSM023, ETH123, HAUT14, HEL11, HEL5, ILSTS005 and INRA189 distributed on nine different cattle chromosomes failed to amplify wild gaur genomic DNA. Three cattle Y-chromosome specific microsatellite markers (INRA124, INRA126 and BM861 were also highly specific in wild gaur, only displaying an amplification product in the males. Genotype data collected from the 117 successfully amplified microsatellites were used to assess the genetic diversity of this species in Vietnam. Polymorphic Information Content (PIC values varied between 0.083 and 0.767 with a mean of 0.252 while observed heterozygosities (Ho ranged from 0.091 to 0.909 (mean of 0.269. Nei's unbiased mean heterozygosity and the mean allele number across loci were 0.298 and 2.2, respectively. Conclusion Extensive

  12. Tetraploid and hexaploid wheat varieties reveal large differences in expression of alpha-gliadins from homoeologous Gli-2 loci

    Directory of Open Access Journals (Sweden)

    Bastien Thomas

    2009-01-01

    Full Text Available Abstract Background Α-gliadins form a multigene protein family encoded by multiple α-gliadin (Gli-2 genes at three genomic loci, Gli-A2, Gli-B2 and Gli-D2, respectively located on the homoeologous wheat chromosomes 6AS, 6BS, and 6DS. These proteins contain a number of important celiac disease (CD-immunogenic domains. The α-gliadins expressed from the Gli-B2 locus harbour fewer conserved CD-epitopes than those from Gli-A2, whereas the Gli-D2 gliadins have the highest CD-immunogenic potential. In order to detect differences in the highly CD-immunogenic α-gliadin fraction we determined the relative expression level from the homoeologous Gli-2 loci in various tetraploid and hexaploid wheat genotypes by using a quantitative pyrosequencing method and by analyzing expressed sequence tag (EST sequences. Results We detected large differences in relative expression levels of α-gliadin genes from the three homoeologous loci among wheat genotypes, both as relative numbers of expressed sequence tag (EST sequences from specific varieties and when using a quantitative pyrosequencing assay specific for Gli-A2 genes. The relative Gli-A2 expression level in a tetraploid durum wheat cultivar ('Probstdorfer Pandur' was 41%. In genotypes derived from landraces, the Gli-A2 frequency varied between 12% and 58%. In some advanced hexaploid bread wheat cultivars the genes from locus Gli-B2 were hardly expressed (e.g., less than 5% in 'Lavett' but in others they made up more than 40% (e.g., in 'Baldus'. Conclusion Here, we have shown that large differences exist in relative expression levels of α-gliadins from the homoeologous Gli-2 loci among wheat genotypes. Since the homoelogous genes differ in the amount of conserved CD-epitopes, screening for differential expression from the homoeologous Gli-2 loci can be employed for the pre-selection of wheat varieties in the search for varieties with very low CD-immunogenic potential. Pyrosequencing is a method that can be

  13. Tomography images of the Alpine roots and surrounding upper mantle

    Science.gov (United States)

    Plomerova, Jaroslava; Babuska, Vladislav

    2017-04-01

    Teleseismic body-wave tomography represents powerful tool to study regional velocity structure of the upper mantle and to image velocity anomalies, such as subducted lithosphere plates in collisional zones. In this contribution, we recapitulate 3D models of the upper mantle beneath the Alps, which developed at a collision zone of the Eurasian and African plates. Seismic tomography studies indicate a leading role of the rigid mantle lithosphere that functioned as a major stress guide during the plate collisions. Interactions of the European lithosphere with several micro-plates in the south resulted in an arcuate shape of this mountain range on the surface and in a complicated geometry of the Alpine subductions in the mantle. Early models with one bended lithosphere root have been replaced with more advanced models showing two separate lithosphere roots beneath the Western and Eastern Alps (Babuska et al., Tectonophysics 1990; Lippitsch et al., JGR 2003). The standard isotropic velocity tomography, based on pre-AlpArray data (the currently performed passive seismic experiment in the Alps and surroundings) images the south-eastward dipping curved slab of the Eurasian lithosphere in the Western Alps. On the contrary, beneath the Eastern Alps the results indicate a very steep northward dipping root that resulted from the collision of the European plate with the Adriatic microplate. Dando et al. (2011) interpret high-velocity heterogeneities at the bottom of their regional tomographic model as a graveyard of old subducted lithospheres. High density of stations, large amount of rays and dense ray-coverage of the volume studied are not the only essential pre-requisites for reliable tomography results. A compromise between the amount of pre-processed data and the high-quality of the tomography input (travel-time residuals) is of the high importance as well. For the first time, the existence of two separate roots beneath the Alps has been revealed from carefully pre

  14. The water exchange between Chinchorro Bank and its surroundings

    Science.gov (United States)

    Candela, Julio; Ochoa, Jose Luis; Sheinbaum, Julio; Lopez, Manuel; Cornado, Cesar

    2015-04-01

    Chinchorro Bank is a relatively large (~500 km^ 2) atoll situated 33 km in front of the Yucatan Peninsula in the Caribbean coast of Mexico. Two years of continuous measurements of the subsurface pressure field inside and around Chinchorro Bank, along with currents and waves observed outside, suggest four major processes governing the water exchange of the Bank with its surroundings: 1) surface wave pumping of water into the Bank through its eastern edge, 2) the large scale circulation in the region that drives the sea level changes through geostrophy, 3) the tidal pumping with imposed cyclic flows into and out of the Bank and 4) the imposed drift by the wind. Waves impinging all along the eastern barrier reef induce water inflows (from overtopping the reef) and generate a pressure gradient that drives a drift from east to west throughout the Bank. This western drift can normally replenish the water over the Bank with a time scale of ~10 days. However, extreme wave events, lasting around 24 hours, can replenish the whole Bank's water in the order of day. The region's large scale circulation is dominated by the zonal Cayman Current impinging on the Yucatan Peninsula becoming the Yucatan Current as it turns northward. Variability in the strength and impacting latitude of this current causes sea level gradients within the Bank, i.e., a Yucatan Current increase of 1 m/s, over a period of a couple of weeks, sets up a zonal sea level gradient within that can replenish the whole Bank's water in a time scale of ~14 days. At such times, the large scale current around the Bank is at a maximum thus ensuring an effective removal and dispersal of the exported waters. The Bank has a micro-tidal regime with a semidiurnal amplitude of ~12 cm during spring tides and a diurnal of ~2 cm, these imply that the Bank is exchanging ~10% of its waters with its surroundings daily. However small, this tidal pumping is effective for the ventilation of the Banks' waters in ~10 days due to the

  15. Natural radionuclides in soil profiles surrounding the largest coal-fired power plant in Serbia

    Directory of Open Access Journals (Sweden)

    Tanić Milan N.

    2016-01-01

    Full Text Available This study evaluates the influence of the largest Serbian coal-fired power plant on radionuclide concentrations in soil profiles up to 50 cm in depth. Thirty soil profiles were sampled from the plant surroundings (up to 10 km distance and analyzed using standard methods for soil physicochemical properties and gamma ray spectrometry for specific activities of natural radionuclides (40K, 226Ra and 232Th. Spatial and vertical distribution of radionuclides was determined and analyzed to show the relations between the specific activities in the soil and soil properties and the most influential factors of natural radionuclide variability were identified. The radiological indices for surface soil were calculated and radiological risk assessment was performed. The measured specific activities were similar to values of background levels for Serbia. The sampling depth did not show any significant influence on specific activities of natural radionuclides. The strongest predictor of specific activities of the investigated radionuclides was soil granulometry. All parameters of radiological risk assessment were below the recommended values and adopted limits. It appears that the coal-fired power plant does not have a significant impact on the spatial and vertical distribution of natural radionuclides in the area of interest, but technologically enhanced natural radioactivity as a consequence of the plant operations was identified within the first 1.5 km from the power plant. [Projekat Ministarstva nauke Republike Srbije br. III43009 i br. III41005

  16. Genetic Diversity and Population Structure for the Conservation of Giant Spiny Frog (Quasipaa spinosa) Using Microsatellite Loci and Mitochondrial DNA

    Institute of Scientific and Technical Information of China (English)

    Danna YU; Rongquan ZHENG; Qinfang LU; Guang YANG; Yao FU; Yun ZHANG

    2016-01-01

    The giant spiny frog (Quasipaa spinosa) is an endangered species with a relatively small distribution limited to southern China and Northern Vietnam. This species is becoming increasingly threatened because of over-exploitation and habitat degradation. This study provides data on the genetic diversity and population genetic structure of the giant spiny frog to facilitate the further development of effective conservation recommendations for this economically important but threatened species. We examined 10 species-specific microsatellite loci and Cyt b genes (562 bp) collected from 13 wild populations across the entire range of this species. Results of 10 microsatellite loci analysis showed a generally high level of genetic diversity. Moreover, the genetic differentiation among all 12 populations was moderate to large (overall FST= 0.1057). A total of 51 haplotypes were identified for Cyt b, which suggests high haplotype nucleotide diversities. Phylogeographic and population structure analyses using both DNA markers suggested that the wild giant spiny frog can be divided into four distinct major clades, i.e., Northern Vietnam, Western China, Central China, and Eastern China. The clades with significant genetic divergence are reproductively isolated, as evidenced by a high number of private alleles and strong incidence of failed amplification in microsatellite loci. Our research, coupled with other studies, suggests that Q. spinosa might be a species complex within which no detectable morphological variation has been revealed. The four phylogenetic clades and some subclades with distinct geographical distribution should be regarded as independent management units for conservation purposes.

  17. Molecular Characterization of Sec2 Loci in Wheat—Secale africanum Derivatives Demonstrates Genomic Divergence of Secale Species

    Directory of Open Access Journals (Sweden)

    Guangrong Li

    2015-04-01

    Full Text Available The unique 75 K γ-secalins encoded by Sec2 loci in Secale species is composed of almost half rye storage proteins. The chromosomal location of Sec2 loci in wild Secale species, Secale africanum, was carried out by the wheat—S. africanum derivatives, which were identified by genomic in situ hybridization and multi-color fluorescence in situ hybridization. The Sec2 gene-specific PCR analysis indicated that the S. cereale Sec2 was located on chromosome 2R, while the S. africanum Sec2 was localized on chromosome 6Rafr of S. africanum. A total of 38 Sec2 gene sequences were isolated from S. africanum, S. cereale and S. sylvestre by PCR-based cloning. Phylogenetic analysis showed that S. africanum Sec2 diverged from S. cereale Sec2 approximately 2–3 million years ago. The illegitimate recombination of chromosome 2R–6R involving the Sec2 loci region may accelerate sequence variation during evolutionary process from wild to cultivated Secale species.

  18. Inheritance Pattern of Microsatellite Loci and Their Use for Kinship Analysis m the Japanese Scallop Patinopecten yessoensis

    Institute of Scientific and Technical Information of China (English)

    XU Kefeng; LI Qi

    2009-01-01

    The inheritance mode of seven microsatellite markers was investigated in Patinopecten yessoensis larvae from four con-trolled crosses, and the feasibility of using these markers for kinship estimation was also examined. All the seven microsatellite loci were compatible with Mendelian inheritance. Neither sex-linked barriers to transmission nor major barriers to fertilization between gametes from the parents were evident. Two of the seven loci showed the presence of null alleles in two families, suggesting the need to conduct comprehensive species-specific inheritance studies for microsatellite loci used in population genetic studies. However, even if the null allele heterozygotes were considered as homozygotes in the calculation of genetic distance, offspring from four fami-lies were all unambiguously discriminated in the neighbor-joining dendrogram. This result indicates that the microsatellite markers used may be capable of discriminating between related and unrelated scallop larvae in the absence of pedigree information, and of investigating the effective number of parents contributing to the hatchery population of the Japanese scallop.

  19. Genetic diversity at neutral and adaptive loci determines individual fitness in a long-lived territorial bird.

    Science.gov (United States)

    Agudo, Rosa; Carrete, Martina; Alcaide, Miguel; Rico, Ciro; Hiraldo, Fernando; Donázar, José Antonio

    2012-08-22

    There is compelling evidence about the manifest effects of inbreeding depression on individual fitness and populations' risk of extinction. The majority of studies addressing inbreeding depression on wild populations are generally based on indirect measures of inbreeding using neutral markers. However, the study of functional loci, such as genes of the major histocompatibility complex (MHC), is highly recommended. MHC genes constitute an essential component of the immune system of individuals, which is directly related to individual fitness and survival. In this study, we analyse heterozygosity fitness correlations of neutral and adaptive genetic variation (22 microsatellite loci and two loci of the MHC class II, respectively) with the age of recruitment and breeding success of a decimated and geographically isolated population of a long-lived territorial vulture. Our results indicate a negative correlation between neutral genetic diversity and age of recruitment, suggesting that inbreeding may be delaying reproduction. We also found a positive correlation between functional (MHC) genetic diversity and breeding success, together with a specific positive effect of the most frequent pair of cosegregating MHC alleles in the population. Globally, our findings demonstrate that genetic depauperation in small populations has a negative impact on the individual fitness, thus increasing the populations' extinction risk.

  20. Positive Selection on Loci Associated with Drug and Alcohol Dependence.

    Directory of Open Access Journals (Sweden)

    Brooke Sadler

    Full Text Available Much of the evolution of human behavior remains a mystery, including how certain disadvantageous behaviors are so prevalent. Nicotine addiction is one such phenotype. Several loci have been implicated in nicotine related phenotypes including the nicotinic receptor gene clusters (CHRNs on chromosomes 8 and 15. Here we use 1000 Genomes sequence data from 3 populations (Africans, Asians and Europeans to examine whether natural selection has occurred at these loci. We used Tajima's D and the integrated haplotype score (iHS to test for evidence of natural selection. Our results provide evidence for strong selection in the nicotinic receptor gene cluster on chromosome 8, previously found to be significantly associated with both nicotine and cocaine dependence, as well as evidence selection acting on the region containing the CHRNA5 nicotinic receptor gene on chromosome 15, that is genome wide significant for risk for nicotine dependence. To examine the possibility that this selection is related to memory and learning, we utilized genetic data from the Collaborative Studies on the Genetics of Alcoholism (COGA to test variants within these regions with three tests of memory and learning, the Wechsler Adult Intelligence Scale (WAIS Block Design, WAIS Digit Symbol and WAIS Information tests. Of the 17 SNPs genotyped in COGA in this region, we find one significantly associated with WAIS digit symbol test results. This test captures aspects of reaction time and memory, suggesting that a phenotype relating to memory and learning may have been the driving force behind selection at these loci. This study could begin to explain why these seemingly deleterious SNPs are present at their current frequencies.

  1. Development of polymorphic microsatellite loci for conservation genetic studies of the coral reef fish Centropyge bicolor

    KAUST Repository

    Herrera, M.

    2015-08-14

    A total of 23 novel polymorphic microsatellite marker loci were developed for the angelfish Centropyge bicolor through 454 sequencing, and further tested on two spatially separated populations (90 individuals each) from Kimbe Bay in Papua New Guinea. The mean ± s.e. number of alleles per locus was 14·65 ± 1·05, and mean ± s.e. observed (HO) and expected (HE) heterozygosity frequencies were 0·676 ± 0·021 and 0·749 ± 0·018, respectively. The markers reported here constitute the first specific set for this genus and will be useful for future conservation genetic studies in the Indo-Pacific region. © 2015 The Fisheries Society of the British Isles.

  2. Novel Association Between Immune-Mediated Susceptibility Loci and Persistent Autoantibody Positivity in Type 1 Diabetes

    DEFF Research Database (Denmark)

    Brorsson, Caroline A; Onengut, Suna; Chen, Wei-Min

    2015-01-01

    ), tissue transglutaminase, and 21-hydroxylase was tested using a linear mixed-model regression approach to simultaneously control for population structure and family relatedness. Four loci were associated with autoantibody positivity at genome-wide significance. Positivity for GADA was associated with 3q28......Islet autoantibodies detected at disease onset in patients with type 1 diabetes are signs of an autoimmune destruction of the insulin-producing β-cells. To further investigate the genetic determinants of autoantibody positivity, we performed dense immune-focused genotyping on the Immunochip array...... and tested for association with seven disease-specific autoantibodies in a large cross-sectional cohort of 6,160 type 1 diabetes-affected siblings. The genetic association with positivity for GAD autoantibodies (GADAs), IA2 antigen (IA-2A), zinc transporter 8, thyroid peroxidase, gastric parietal cells (PCAs...

  3. Genome-wide methylation analysis identifies differentially methylated CpG loci associated with severe obesity in childhood.

    Science.gov (United States)

    Huang, R C; Garratt, E S; Pan, H; Wu, Y; Davis, E A; Barton, S J; Burdge, G C; Godfrey, K M; Holbrook, J D; Lillycrop, K A

    2015-01-01

    Childhood obesity is a major public health issue. Here we investigated whether differential DNA methylation was associated with childhood obesity. We studied DNA methylation profiles in whole blood from 78 obese children (mean BMI Z-score: 2.6) and 71 age- and sex-matched controls (mean BMI Z-score: 0.1). DNA samples from obese and control groups were pooled and analyzed using the Infinium HumanMethylation450 BeadChip array. Comparison of the methylation profiles between obese and control subjects revealed 129 differentially methylated CpG (DMCpG) loci associated with 80 unique genes that had a greater than 10% difference in methylation (P-value obesity were validated using sodium bisulfite pyrosequencing across loci within the FYN, PIWIL4, and TAOK3 genes in individual subjects. Three CpG loci within FYN were hypermethylated in obese individuals (all P obesity was associated with lower methylation of CpG loci within PIWIL4 (P = 0.003) and TAOK3 (P = 0.001). After building logistic regression models, we determined that a 1% increase in methylation in TAOK3, multiplicatively decreased the odds of being obese by 0.91 (95% CI: 0.86 - 0.97), and an increase of 1% methylation in FYN CpG3, multiplicatively increased the odds of being obese by 1.03 (95% CI: 0.99 - 1.07). In conclusion, these findings provide evidence that childhood obesity is associated with specific DNA methylation changes in whole blood, which may have utility as biomarkers of obesity risk.

  4. Plant-symbiotic fungi as chemical engineers: multi-genome analysis of the clavicipitaceae reveals dynamics of alkaloid loci.

    Directory of Open Access Journals (Sweden)

    Christopher L Schardl

    Full Text Available The fungal family Clavicipitaceae includes plant symbionts and parasites that produce several psychoactive and bioprotective alkaloids. The family includes grass symbionts in the epichloae clade (Epichloë and Neotyphodium species, which are extraordinarily diverse both in their host interactions and in their alkaloid profiles. Epichloae produce alkaloids of four distinct classes, all of which deter insects, and some-including the infamous ergot alkaloids-have potent effects on mammals. The exceptional chemotypic diversity of the epichloae may relate to their broad range of host interactions, whereby some are pathogenic and contagious, others are mutualistic and vertically transmitted (seed-borne, and still others vary in pathogenic or mutualistic behavior. We profiled the alkaloids and sequenced the genomes of 10 epichloae, three ergot fungi (Claviceps species, a morning-glory symbiont (Periglandula ipomoeae, and a bamboo pathogen (Aciculosporium take, and compared the gene clusters for four classes of alkaloids. Results indicated a strong tendency for alkaloid loci to have conserved cores that specify the skeleton structures and peripheral genes that determine chemical variations that are known to affect their pharmacological specificities. Generally, gene locations in cluster peripheries positioned them near to transposon-derived, AT-rich repeat blocks, which were probably involved in gene losses, duplications, and neofunctionalizations. The alkaloid loci in the epichloae had unusual structures riddled with large, complex, and dynamic repeat blocks. This feature was not reflective of overall differences in repeat contents in the genomes, nor was it characteristic of most other specialized metabolism loci. The organization and dynamics of alkaloid loci and abundant repeat blocks in the epichloae suggested that these fungi are under selection for alkaloid diversification. We suggest that such selection is related to the variable life histories

  5. Plant-symbiotic fungi as chemical engineers: multi-genome analysis of the clavicipitaceae reveals dynamics of alkaloid loci.

    Science.gov (United States)

    Schardl, Christopher L; Young, Carolyn A; Hesse, Uljana; Amyotte, Stefan G; Andreeva, Kalina; Calie, Patrick J; Fleetwood, Damien J; Haws, David C; Moore, Neil; Oeser, Birgitt; Panaccione, Daniel G; Schweri, Kathryn K; Voisey, Christine R; Farman, Mark L; Jaromczyk, Jerzy W; Roe, Bruce A; O'Sullivan, Donal M; Scott, Barry; Tudzynski, Paul; An, Zhiqiang; Arnaoudova, Elissaveta G; Bullock, Charles T; Charlton, Nikki D; Chen, Li; Cox, Murray; Dinkins, Randy D; Florea, Simona; Glenn, Anthony E; Gordon, Anna; Güldener, Ulrich; Harris, Daniel R; Hollin, Walter; Jaromczyk, Jolanta; Johnson, Richard D; Khan, Anar K; Leistner, Eckhard; Leuchtmann, Adrian; Li, Chunjie; Liu, JinGe; Liu, Jinze; Liu, Miao; Mace, Wade; Machado, Caroline; Nagabhyru, Padmaja; Pan, Juan; Schmid, Jan; Sugawara, Koya; Steiner, Ulrike; Takach, Johanna E; Tanaka, Eiji; Webb, Jennifer S; Wilson, Ella V; Wiseman, Jennifer L; Yoshida, Ruriko; Zeng, Zheng

    2013-01-01

    The fungal family Clavicipitaceae includes plant symbionts and parasites that produce several psychoactive and bioprotective alkaloids. The family includes grass symbionts in the epichloae clade (Epichloë and Neotyphodium species), which are extraordinarily diverse both in their host interactions and in their alkaloid profiles. Epichloae produce alkaloids of four distinct classes, all of which deter insects, and some-including the infamous ergot alkaloids-have potent effects on mammals. The exceptional chemotypic diversity of the epichloae may relate to their broad range of host interactions, whereby some are pathogenic and contagious, others are mutualistic and vertically transmitted (seed-borne), and still others vary in pathogenic or mutualistic behavior. We profiled the alkaloids and sequenced the genomes of 10 epichloae, three ergot fungi (Claviceps species), a morning-glory symbiont (Periglandula ipomoeae), and a bamboo pathogen (Aciculosporium take), and compared the gene clusters for four classes of alkaloids. Results indicated a strong tendency for alkaloid loci to have conserved cores that specify the skeleton structures and peripheral genes that determine chemical variations that are known to affect their pharmacological specificities. Generally, gene locations in cluster peripheries positioned them near to transposon-derived, AT-rich repeat blocks, which were probably involved in gene losses, duplications, and neofunctionalizations. The alkaloid loci in the epichloae had unusual structures riddled with large, complex, and dynamic repeat blocks. This feature was not reflective of overall differences in repeat contents in the genomes, nor was it characteristic of most other specialized metabolism loci. The organization and dynamics of alkaloid loci and abundant repeat blocks in the epichloae suggested that these fungi are under selection for alkaloid diversification. We suggest that such selection is related to the variable life histories of the

  6. Evolutionary site-number changes of ribosomal DNA loci during speciation: complex scenarios of ancestral and more recent polyploid events.

    Science.gov (United States)

    Rosato, Marcela; Moreno-Saiz, Juan C; Galián, José A; Rosselló, Josep A

    2015-11-16

    Several genome duplications have been identified in the evolution of seed plants, providing unique systems for studying karyological processes promoting diversification and speciation. Knowledge about the number of ribosomal DNA (rDNA) loci, together with their chromosomal distribution and structure, provides clues about organismal and molecular evolution at various phylogenetic levels. In this work, we aim to elucidate the evolutionary dynamics of karyological and rDNA site-number variation in all known taxa of subtribe Vellinae, showing a complex scenario of ancestral and more recent polyploid events. Specifically, we aim to infer the ancestral chromosome numbers and patterns of chromosome number variation, assess patterns of variation of both 45S and 5S rDNA families, trends in site-number change of rDNA loci within homoploid and polyploid series, and reconstruct the evolutionary history of rDNA site number using a phylogenetic hypothesis as a framework. The best-fitting model of chromosome number evolution with a high likelihood score suggests that the Vellinae core showing x = 17 chromosomes arose by duplication events from a recent x = 8 ancestor. Our survey suggests more complex patterns of polyploid evolution than previously noted for Vellinae. High polyploidization events (6x, 8x) arose independently in the basal clade Vella castrilensis-V. lucentina, where extant diploid species are unknown. Reconstruction of ancestral rDNA states in Vellinae supports the inference that the ancestral number of loci in the subtribe was two for each multigene family, suggesting that an overall tendency towards a net loss of 5S rDNA loci occurred during the splitting of Vellinae ancestors from the remaining Brassiceae lineages. A contrasting pattern for rDNA site change in both paleopolyploid and neopolyploid species was linked to diversification of Vellinae lineages. This suggests dynamic and independent changes in rDNA site number during speciation processes and a

  7. Systems Genetics Reveals the Functional Context of PCOS Loci and Identifies Genetic and Molecular Mechanisms of Disease Heterogeneity.

    Directory of Open Access Journals (Sweden)

    Michelle R Jones

    2015-08-01

    Full Text Available Genome wide association studies (GWAS have revealed 11 independent risk loci for polycystic ovary syndrome (PCOS, a common disorder in young women characterized by androgen excess and oligomenorrhea. To put these risk loci and the single nucleotide polymorphisms (SNPs therein into functional context, we measured DNA methylation and gene expression in subcutaneous adipose tissue biopsies to identify PCOS-specific alterations. Two genes from the LHCGR region, STON1-GTF2A1L and LHCGR, were overexpressed in PCOS. In analysis stratified by obesity, LHCGR was overexpressed only in non-obese PCOS women. Although not differentially expressed in the entire PCOS group, INSR was underexpressed in obese PCOS subjects only. Alterations in gene expression in the LHCGR, RAB5B and INSR regions suggest that SNPs in these loci may be functional and could affect gene expression directly or indirectly via epigenetic alterations. We identified reduced methylation in the LHCGR locus and increased methylation in the INSR locus, changes that are concordant with the altered gene expression profiles. Complex patterns of meQTL and eQTL were identified in these loci, suggesting that local genetic variation plays an important role in gene regulation. We propose that non-obese PCOS women possess significant alterations in LH receptor expression, which drives excess androgen secretion from the ovary. Alternatively, obese women with PCOS possess alterations in insulin receptor expression, with underexpression in metabolic tissues and overexpression in the ovary, resulting in peripheral insulin resistance and excess ovarian androgen production. These studies provide a genetic and molecular basis for the reported clinical heterogeneity of PCOS.

  8. Systems Genetics Reveals the Functional Context of PCOS Loci and Identifies Genetic and Molecular Mechanisms of Disease Heterogeneity.

    Science.gov (United States)

    Jones, Michelle R; Brower, Meredith A; Xu, Ning; Cui, Jinrui; Mengesha, Emebet; Chen, Yii-Der I; Taylor, Kent D; Azziz, Ricardo; Goodarzi, Mark O

    2015-08-01

    Genome wide association studies (GWAS) have revealed 11 independent risk loci for polycystic ovary syndrome (PCOS), a common disorder in young women characterized by androgen excess and oligomenorrhea. To put these risk loci and the single nucleotide polymorphisms (SNPs) therein into functional context, we measured DNA methylation and gene expression in subcutaneous adipose tissue biopsies to identify PCOS-specific alterations. Two genes from the LHCGR region, STON1-GTF2A1L and LHCGR, were overexpressed in PCOS. In analysis stratified by obesity, LHCGR was overexpressed only in non-obese PCOS women. Although not differentially expressed in the entire PCOS group, INSR was underexpressed in obese PCOS subjects only. Alterations in gene expression in the LHCGR, RAB5B and INSR regions suggest that SNPs in these loci may be functional and could affect gene expression directly or indirectly via epigenetic alterations. We identified reduced methylation in the LHCGR locus and increased methylation in the INSR locus, changes that are concordant with the altered gene expression profiles. Complex patterns of meQTL and eQTL were identified in these loci, suggesting that local genetic variation plays an important role in gene regulation. We propose that non-obese PCOS women possess significant alterations in LH receptor expression, which drives excess androgen secretion from the ovary. Alternatively, obese women with PCOS possess alterations in insulin receptor expression, with underexpression in metabolic tissues and overexpression in the ovary, resulting in peripheral insulin resistance and excess ovarian androgen production. These studies provide a genetic and molecular basis for the reported clinical heterogeneity of PCOS.

  9. Dilemmas surrounding passive euthanasia--a Malaysian perspective.

    Science.gov (United States)

    Talib, Norchaya

    2005-09-01

    In western societies where the principle of autonomy is jealously guarded, perhaps active euthanasia is more often the focus of public concern and debates rather than any other forms of euthanasia. However due to the advance in technology and its corresponding ability in prolonging life, in Malaysia passive euthanasia presents more of a dilemma. For those concerned and involved with end of life decision-making, it is generally agreed that this is an area fraught with not only medical but legal and ethical issues. In Malaysia where the society is not homogenous but is multi-cultural and multi-religious, in addition to medical, legal and ethical issues, religious principles and cultural norms further impact and play significant roles in end of life decision-making. This paper seeks to identify the issues surrounding the practice of passive euthanasia in Malaysia. It will be shown that despite applicable legal provisions, current practice of the medical profession combined with religious and cultural values together affect decision-making which involves the withholding and/or withdrawing of life-saving treatment.

  10. Mercury's interior, surface, and surrounding environment latest discoveries

    CERN Document Server

    Clark, Pamela Elizabeth

    2015-01-01

    This SpringerBrief details the MESSENGER Mission, the findings of which present challenges to widely held conventional views and remaining mysteries surrounding the planet. The work answers the question of why Mercury is so dense, and the implications from geochemical data on its planetary formation. It summarizes imaging and compositional data from the terrestrial planet surface processes and explains the geologic history of Mercury.  It also discusses the lack of southern hemisphere coverage. Our understanding of the planet Mercury has been in a transitional phase over the decades since Mariner 10. The influx of new data from the NASA MESSENGER Mission since it was inserted into the orbit of Mercury in March of 2011 has greatly accelerated that shift. The combined compositional data of relatively high volatiles (S, K), relatively low refractories (Al, Ca), and low crustal iron, combined with an active, partially molten iron rich core, has major implications for Mercury and Solar System formation. From a s...

  11. Zonal disintegration phenomenon in rock mass surrounding deep tunnels

    Institute of Scientific and Technical Information of China (English)

    WU Hao; FANG Qin; GUO Zhi-kun

    2008-01-01

    Zonal disintegration is a typical static phenomenon of deep rock masses. It has been defined as alternating regions of fractured and relatively intact rock mass that appear around or in front of the working stope during excavation of a deep tunnel. Zonal disintegration phenomenon was successfully demonstrated in the laboratory with 3D tests on analogous gypsum models, two circular cracked zones were observed in the test. The linear Mohr-Coulomb yield criterion was used with a constitutive model that showed linear softening and ideal residual plastic to analyze the elasto-plastic field of the enclosing rock mass around a deep tunnel. The results show that tunneling causes a maximum stress zone to appear between an elastic and plastic zone in the surrounding rock. The zonal disintegration phenomenon is analyzed by considering the stress-strain state of the rock mass in the vicinity of the maximum stress zone. Creep instability failure of the rock due to the development of the plastic zone, and transfer of the maximum stress zone into the rock mass, are the cause of zonal disintegration. An analytical criterion for the critical depth at which zonal disintegration can occur is derived. This depth depends mainly on the character and stress concentration coefficient of the rock mass.

  12. Beliefs and practices surrounding postpartum period among Myanmar women.

    Science.gov (United States)

    Sein, Kyi Kyi

    2013-11-01

    to examine the postpartum beliefs and practices among young women (15-24 years) both quantitative and qualitative approaches were used: a cross-sectional comparative study using a semi-structured questionnaire and focus group discussions (FGDs). Kyimyindaing Township in the western district of Yangon, Myanmar. young women (15-24 years) who had experience of at least one live birth were included. A total of 196 women for a quantitative survey and 31 women for FGDs were recruited. postpartum beliefs and practices at the last childbirth were explored by a pretested semi-structured questionnaire and four FGDs (two in urban and two in rural areas). The survey questionnaire covered socio-demographic data, food and behavioural restrictions and observances during the last postpartum period and underlying reasons for those practices. Majority of participants followed the traditional postpartum practices regardless of the area of residence and education level. Notion of 'dirty lochia' was identified. traditional beliefs and practices surrounding post partum were highly prevalent among young women. Variation in degree and duration of adherence to postpartum taboos was noted. These beliefs and practices were imparted and perpetuated by women's close social network. the findings point out the importance of awareness of postpartum beliefs and practices among health staff for providing culturally sensitive health care and gaining better co-operation and mutual understanding in giving health care. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Unilateral lung agenesis--detrimental roles of surrounding vessels.

    Science.gov (United States)

    Chou, An-Kou; Huang, Shu-Chien; Chen, Shyh-Jye; Huang, Pei-Ming; Wang, Jou-Kou; Wu, Mei-Hwan; Chen, Yih-Sharng; Chang, Chung-I; Chiu, Ing-Sh; Wu, En-Ting

    2007-03-01

    Unilateral lung agenesis is a rare congenital defect and could be associated with multiple abnormalities. The patients usually have poor long-term outcomes especially in those with right lung agenesis. We reviewed the 10-year experience in our hospital to describe special clinical features and try to delineate the causes of poor outcomes. From 1995 to 2005, 14 patients less than 18 years of age with unilateral lung agenesis (4 with left agenesis, 10 with right agenesis) were enrolled. Medical records reviewed included diagnosis, presentation, chromosome anomalies, cardiovascular anomalies and interventions, outcomes. We found that the mechanisms of severe airway disease in right lung agenesis included (1) trachea compression by the aortic arch, (2) the presence of "pseudo-ring-sling complex," (3) distended pulmonary artery due to left to right shunt which impinged the only bronchus, and finally (4) the persistent LSVC that restricts the growth of trachea. The etiologies of airway complication in left lung agenesis included anomalous aortic arch compression on trachea and the coexisting heart disease with significant left to right shunt, which impinged on the bronchus. In conclusion, unilateral lung agenesis has frequently associated airway problems due to its surrounding vessels. Satisfactory airway intervention remains challenging. This disease still requires great effort to improve patient outcomes.

  14. The interstellar cloud surrounding the Sun -- a new perspective

    CERN Document Server

    Gry, Cecile

    2014-01-01

    Aims: We offer a new, simpler picture of the local interstellar medium around the Sun (LISM) made of a single continuous cloud enveloping the Sun. This new outlook enables the description of a diffuse cloud from within and brings to light some unexpected properties. Methods: We re-examine the kinematics and abundances of the local interstellar medium, as revealed by the published results for the ultraviolet absorption lines of MgII, FeII and HI. Results: In contrast to previous representations, our new picture of the LISM consists of a single, monolithic cloud that surrounds the Sun in all directions and accounts for most of the matter present in the first 50 parsecs around the Sun. The cloud fills the space around us out to about 9 pc in most directions, although its boundary is very irregular with possibly a few extensions up to 20 pc. The cloud does not behave like a rigid body: gas within the cloud is being differentially decelerated in the direction of motion, and the cloud is expanding in directions per...

  15. Dense Ionized and Neutral Gas Surrounding Sgr A*

    CERN Document Server

    Shukla, Hemant; Scoville, N Z

    2004-01-01

    We present high resolution H41a hydrogen recombination line observations of the 1.2' (3 pc) region surrounding Sgr A* at 92 GHz using the OVRO Millimeter Array with an angular resolution of 7" x 3" and velocity resolution of 13 km/s. New observations of H31a, H35a, H41a, and H44a lines were obtained using the NRAO 12-m telescope, and their relative line strengths are interpreted in terms of various emission mechanisms. These are the most extensive and most sensitive observations of recombination line to date. Observations of HCO+ (1 - 0) transition at 89 GHz are also obtained simultaneously with a 40% improved angular resolution and 4-15 times improved sensitivity over previous observations, and the distribution and kinematics of the dense molecular gas in the circumnuclear disk (CND) are mapped and compared with those of the ionized gas. The line brightness ratios of the hydrogen recombination lines are consistent with purely spontaneous emission from 7000 K gas with n_e = 20,000 cm$^{-3}$ near LTE condition...

  16. Instability of Magnetized Ionization Fronts Surrounding H II Regions

    CERN Document Server

    Kim, Jeong-Gyu

    2014-01-01

    An ionization front (IF) surrounding an H II region is a sharp interface where a cold neutral gas makes transition to a warm ionized phase by absorbing UV photons from central stars. We investigate the instability of a plane-parallel D-type IF threaded by parallel magnetic fields, by neglecting the effects of recombination within the ionized gas. We find that weak D-type IFs always have the post-IF magnetosonic Mach number $\\mathcal{M}_{\\rm M2} \\leq 1$. For such fronts, magnetic fields increase the maximum propagation speed of the IFs, while reducing the expansion factor $\\alpha$ by a factor of $1+1/(2\\beta_1)$ compared to the unmagnetized case, with $\\beta_1$ denoting the plasma beta in the pre-IF region. IFs become unstable to distortional perturbations due to gas expansion across the fronts, exactly analogous to the Darrieus-Landau instability of ablation fronts in terrestrial flames. The growth rate of the IF instability is proportional linearly to the perturbation wavenumber as well as the upstream flow ...

  17. An insight in the surroundings of HR4796

    CERN Document Server

    Lagrange, A -M; Boccaletti, A; Lacour, S; Thebault, P; Chauvin, G; Mouillet, D; Augereau, J C; Bonnefoy, M; Ehrenreich, D; Kral, Q

    2012-01-01

    HR4796 is a young, early A-type star harbouring a well structured debris disk, shaped as a ring with sharp inner edges. It forms with the M-type star HR4796B a binary system, with a proj. sep. ~560 AU. Our aim is to explore the surroundings of HR4796A and B, both in terms of extended or point-like structures. Adaptive optics images at L'-band were obtained with NaCo in Angular Differential Mode and with Sparse Aperture Masking (SAM). We analyse the data as well as the artefacts that can be produced by ADI reduction on an extended structure with a shape similar to that of HR4796A dust ring. We determine constraints on the presence of companions using SAM and ADI on HR4796A, and ADI on HR4796B. We also performed dynamical simulations of a disk of planetesimals and dust produced by collisions, perturbed by a planet located close to the disk outer edge. The disk ring around HR4796A is well resolved. We highlight the potential effects of ADI reduction of the observed disk shape and surface brightness distribution,...

  18. Dead discs, unstable discs and the stars they surround

    Directory of Open Access Journals (Sweden)

    D’Angelo Caroline

    2014-01-01

    Full Text Available Strong stellar magnetic fields significantly alter the behaviour of surrounding accretion discs. Recent work has demonstrated that at low accretion rates a large amount of mass can remain confined in the disc, contrary to the standard assumption that the magnetic field will expel the disc in an outflow (the “propeller regime”. These “dead discs” often become unstable, causing cycles of accretion onto the central star. Here I present the main predictions of this model, and argue that it provides a good explanation for the peculiar behaviour seen in several accreting sources with strong magnetic fields. I will focus in particular on three accreting millisecond X-ray pulsars: SAX J1808.4-3658, NGC 6440 X-2 and IGR J00291+5934. These sources all show low-frequency quasi-periodic oscillations consistent with a variable accretion rate, as well as unusual outburst patterns that suggest gas is confined in the inner disc regions during quiescence.

  19. Preliminary Analysis of Slope Stability in Kuok and Surrounding Areas

    Directory of Open Access Journals (Sweden)

    Dewandra Bagus Eka Putra

    2016-12-01

    Full Text Available The level of slope influenced by the condition of the rocks beneath the surface. On high level of slopes, amount of surface runoff and water transport energy is also enlarged. This caused by greater gravity, in line with the surface tilt from the horizontal plane. In other words, topsoil eroded more and more. When the slope becomes twice as steep, then the amount of erosion per unit area be 2.0 - 2.5 times more. Kuok and surrounding area is the road access between the West Sumatra and Riau which plays an important role economies of both provinces. The purpose of this study is to map the locations that have fairly steep slopes and potential mode of landslides. Based on SRTM data obtained,  the roads in Kuok area has a minimum elevation of + 33 m and a maximum  + 217.329 m. Rugged road conditions with slope ranging from 24.08 ° to 44.68 ° causing this area having frequent landslides. The result of slope stability analysis in a slope near the Water Power Plant Koto Panjang, indicated that mode of active failure is toppling failure or rock fall and the potential zone of failure is in the center part of the slope.

  20. Expression of zebrafish nos2b surrounds oral cavity.

    Science.gov (United States)

    Poon, Kar-Lai; Richardson, Michael; Korzh, Vladimir

    2008-06-01

    Inducible nitric oxide synthase (NOS2) catalyzes the production of nitric oxide (NO), and is one of the factors establishing innate immunity. In zebrafish, Nos2 is represented by nos2a and nos2b. Here, we report the cloning and expression pattern of the zebrafish nos2b gene, which does not seem to participate in induced immune response. nos2b was mapped to zebrafish linkage group 15. The spatial and temporal expression pattern of nos2b in embryonic zebrafish was analyzed by whole-mount in situ hybridization. nos2b is expressed constitutively in two primordia located along the ventral midline. The first group of cells contributes to the neurohypophysis. Initially at the level of the ventral hindbrain, the second group of cells migrates closely with the thyroid primordium to its final position at the basihyal by 3 dpf. Thus, the analysis of expression pattern of nos2b reveals complex morphogenetic movements resulting in its expression surrounding the oral cavity.

  1. Thermoelectric Performance Enhancement by Surrounding Crystalline Semiconductors with Metallic Nanoparticles

    Science.gov (United States)

    Kim, Hyun-Jung; King, Glen C.; Park, Yeonjoon; Lee, Kunik; Choi, Sang H.

    2011-01-01

    Direct conversion of thermal energy to electricity by thermoelectric (TE) devices may play a key role in future energy production and utilization. However, relatively poor performance of current TE materials has slowed development of new energy conversion applications. Recent reports have shown that the dimensionless Figure of Merit, ZT, for TE devices can be increased beyond the state-of-the-art level by nanoscale structuring of materials to reduce their thermal conductivity. New morphologically designed TE materials have been fabricated at the NASA Langley Research Center, and their characterization is underway. These newly designed materials are based on semiconductor crystal grains whose surfaces are surrounded by metallic nanoparticles. The nanoscale particles are used to tailor the thermal and electrical conduction properties for TE applications by altering the phonon and electron transport pathways. A sample of bismuth telluride decorated with metallic nanoparticles showed less thermal conductivity and twice the electrical conductivity at room temperature as compared to pure Bi2Te3. Apparently, electrons cross easily between semiconductor crystal grains via the intervening metallic nanoparticle bridges, but phonons are scattered at the interfacing gaps. Hence, if the interfacing gap is larger than the mean free path of the phonon, thermal energy transmission from one grain to others is reduced. Here we describe the design and analysis of these new materials that offer substantial improvements in thermoelectric performance.

  2. Democratizing rendering for multiple viewers in surround VR systems

    KAUST Repository

    Schulze, Jürgen P.

    2012-03-01

    We present a new approach for how multiple users\\' views can be rendered in a surround virtual environment without using special multi-view hardware. It is based on the idea that different parts of the screen are often viewed by different users, so that they can be rendered from their own view point, or at least from a point closer to their view point than traditionally expected. The vast majority of 3D virtual reality systems are designed for one head-tracked user, and a number of passive viewers. Only the head tracked user gets to see the correct view of the scene, everybody else sees a distorted image. We reduce this problem by algorithmically democratizing the rendering view point among all tracked users. Researchers have proposed solutions for multiple tracked users, but most of them require major changes to the display hardware of the VR system, such as additional projectors or custom VR glasses. Our approach does not require additional hardware, except the ability to track each participating user. We propose three versions of our multi-viewer algorithm. Each of them balances image distortion and frame rate in different ways, making them more or less suitable for certain application scenarios. Our most sophisticated algorithm renders each pixel from its own, optimized camera perspective, which depends on all tracked users\\' head positions and orientations. © 2012 IEEE.

  3. Representing the egocentric auditory space: relationships of surrounding region concepts.

    Science.gov (United States)

    Campos, Marcella C; Hermann, Thomas; Schack, Thomas; Bläsing, Bettina

    2013-03-01

    We investigated the representation of azimuthal directions of sound sources under two different conditions. In the first experiment, we examined the participants' mental representation of sound source directions via similarity judgments. Auditory stimuli originating from sixteen loudspeakers positioned equidistantly around the participant were presented in pairs, with the first stimulus serving as the anchor, and thereby providing the context for the second stimulus. For each pair of stimuli, participants had to rate the sound source directions as either similar or dissimilar. In the second experiment, the same participants categorized single sound source directions using verbal direction labels (front, back, left, right, and combinations of any two of these). In both experiments, the directions within the front and back regions were more distinctively categorized than those on the sides, and the sides' categories included more directions than those of the front or back. Furthermore, we found evidence that the left-right decision comprises the basic differentiation of the surrounding regions. These findings illustrate what seem to be central features of the representation of directions in auditory space.

  4. Mapping autism risk loci using genetic linkage and chromosomal rearrangements

    Science.gov (United States)

    Szatmari, Peter; Paterson, Andrew; Zwaigenbaum, Lonnie; Roberts, Wendy; Brian, Jessica; Liu, Xiao-Qing; Vincent, John; Skaug, Jennifer; Thompson, Ann; Senman, Lili; Feuk, Lars; Qian, Cheng; Bryson, Susan; Jones, Marshall; Marshall, Christian; Scherer, Stephen; Vieland, Veronica; Bartlett, Christopher; Mangin, La Vonne; Goedken, Rhinda; Segre, Alberto; Pericak-Vance, Margaret; Cuccaro, Michael; Gilbert, John; Wright, Harry; Abramson, Ruth; Betancur, Catalina; Bourgeron, Thomas; Gillberg, Christopher; Leboyer, Marion; Buxbaum, Joseph; Davis, Kenneth; Hollander, Eric; Silverman, Jeremy; Hallmayer, Joachim; Lotspeich, Linda; Sutcliffe, James; Haines, Jonathan; Folstein, Susan; Piven, Joseph; Wassink, Thomas; Sheffield, Val; Geschwind, Daniel; Bucan, Maja; Brown, Ted; Cantor, Rita; Constantino, John; Gilliam, Conrad; Herbert, Martha; Lajonchere, Clara; Ledbetter, David; Lese-Martin, Christa; Miller, Janet; Nelson, Stan; Samango-Sprouse, Carol; Spence, Sarah; State, Matthew; Tanzi, Rudolph; Coon, Hilary; Dawson, Geraldine; Devlin, Bernie; Estes, Annette; Flodman, Pamela; Klei, Lambertus; Mcmahon, William; Minshew, Nancy; Munson, Jeff; Korvatska, Elena; Rodier, Patricia; Schellenberg, Gerard; Smith, Moyra; Spence, Anne; Stodgell, Chris; Tepper, Ping Guo; Wijsman, Ellen; Yu, Chang-En; Rogé, Bernadette; Mantoulan, Carine; Wittemeyer, Kerstin; Poustka, Annemarie; Felder, Bärbel; Klauck, Sabine; Schuster, Claudia; Poustka, Fritz; Bölte, Sven; Feineis-Matthews, Sabine; Herbrecht, Evelyn; Schmötzer, Gabi; Tsiantis, John; Papanikolaou, Katerina; Maestrini, Elena; Bacchelli, Elena; Blasi, Francesca; Carone, Simona; Toma, Claudio; Van Engeland, Herman; De Jonge, Maretha; Kemner, Chantal; Koop, Frederieke; Langemeijer, Marjolein; Hijmans, Channa; Staal, Wouter; Baird, Gillian; Bolton, Patrick; Rutter, Michael; Weisblatt, Emma; Green, Jonathan; Aldred, Catherine; Wilkinson, Julie-Anne; Pickles, Andrew; Le Couteur, Ann; Berney, Tom; Mcconachie, Helen; Bailey, Anthony; Francis, Kostas; Honeyman, Gemma; Hutchinson, Aislinn; Parr, Jeremy; Wallace, Simon; Monaco, Anthony; Barnby, Gabrielle; Kobayashi, Kazuhiro; Lamb, Janine; Sousa, Ines; Sykes, Nuala; Cook, Edwin; Guter, Stephen; Leventhal, Bennett; Salt, Jeff; Lord, Catherine; Corsello, Christina; Hus, Vanessa; Weeks, Daniel; Volkmar, Fred; Tauber, Maïté; Fombonne, Eric; Shih, Andy; Meyer, Kacie

    2007-01-01

    Autism spectrum disorders (ASD) are common, heritable neurodevelopmental conditions. The genetic architecture of ASD is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASD by using Affymetrix 10K single nucleotide polymorphism (SNP) arrays and 1168 families with ≥ 2 affected individuals to perform the largest linkage scan to date, while also analyzing copy number variation (CNV) in these families. Linkage and CNV analyses implicate chromosome 11p12-p13 and neurexins, respectively, amongst other candidate loci. Neurexins team with previously-implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for ASD. PMID:17322880

  5. Quantitative Trait Loci for Fertility Traits in Finnish Ayrshire Cattle

    DEFF Research Database (Denmark)

    Schulman, Nina F; Sahana, Goutam; Lund, Mogens S

    2008-01-01

    A whole genome scan was carried out to detect quantitative trait loci (QTL) for fertility traits in Finnish Ayrshire cattle. The mapping population consisted of 12 bulls and 493 sons. Estimated breeding values for days open, fertility treatments, maternal calf mortality and paternal non-return rate...... if these effects were due to a pleiotropic QTL affecting fertility and milk yield traits or to linked QTL causing the effects. This distinction could only be made with confidence on BTA1 where a QTL affecting milk yield is linked to a pleiotropic QTL affecting days open and fertility treatments...

  6. Nine microsatellite loci developed from the octocoral, Paragorgia arborea

    Science.gov (United States)

    Coykendall, Dolly K.; Morrison, Cheryl L.

    2015-01-01

    Paragorgia arborea, or bubblegum coral, occurs in continental slope habitats worldwide, which are increasingly threatened by human activities such as energy development and fisheries practices. From 101 putative loci screened, nine microsatellite markers were developed from samples taken from Baltimore canyon in the western North Atlantic Ocean. The number of alleles ranged from two to thirteen per locus and each displayed equilibrium. These nuclear resources will help further research on population connectivity in threatened coral species where mitochondrial markers are known to lack fine-scale genetic diversity.

  7. Structures of the Mating-Type Loci of Cordyceps takaomontana

    Science.gov (United States)

    Yokoyama, Eiji; Yamagishi, Kenzo; Hara, Akira

    2003-01-01

    Nucleotide sequences of the mating-type loci MAT1-1 and MAT1-2 of Cordyceps takaomontana were determined, which is the first such report for the clavicipitaceous fungi. MAT1-1 contains two mating-type genes, MAT1-1-1 and MAT1-1-2, but MAT1-1-3 could not be found. On the other hand, MAT1-2 has MAT1-2-1. A pseudogene of MAT1-1-1 is located next to MAT1-2. PMID:12902305

  8. The Isoconditioning Loci of Planar Three-DOF Parallel Manipulators

    CERN Document Server

    Chablat, Damien; Wenger, Philippe; Angeles, Jorge

    2002-01-01

    The subject of this paper is a special class of parallel manipulators. First, we analyze a family of three-degree-of-freedom manipulators. Two Jacobian matrices appear in the kinematic relations between the joint-rate and the Cartesian-velocity vectors, which are called the "inverse kinematics" and the "direct kinematics" matrices. The singular configurations of these matrices are studied. The isotropic configurations are then studied based on the characteristic length of this manipulator. The isoconditioning loci of all Jacobian matrices are computed to define a global performance index to compare the different working modes.

  9. Brugada syndrome risk loci seem protective against atrial fibrillation

    DEFF Research Database (Denmark)

    Andreasen, Laura; Nielsen, Jonas B; Darkner, Stine;

    2014-01-01

    Several studies have shown an overlap between genes involved in the pathophysiological mechanisms of atrial fibrillation (AF) and Brugada Syndrome (BrS). We investigated whether three single-nucleotide polymorphisms (SNPs) (rs11708996; G>C located intronic to SCN5A, rs10428132; T>G located in SCN10...... associated with BrS was lower in AF patients than in patients free of AF, suggesting a protective role of these loci in developing AF.European Journal of Human Genetics advance online publication, 26 March 2014; doi:10.1038/ejhg.2014.46....

  10. Investigation of type 1 diabetes and coeliac disease susceptibility loci for association with juvenile idiopathic arthritis

    Science.gov (United States)

    Hinks, Anne; Martin, Paul; Flynn, Edward; Eyre, Steve; Packham, Jon; Barton, Anne; Worthington, Jane; Thomson, Wendy

    2010-01-01

    Background There is strong evidence suggesting that juvenile idiopathic arthritis (JIA) shares many susceptibility loci with other autoimmune diseases. Objective To investigate variants robustly associated with type 1 diabetes (T1D) or coeliac disease (CD) for association with JIA. Methods Sixteen single-nucleotide polymorphisms (SNPs) already identified as susceptibility loci for T1D/CD were selected for genotyping in patients with JIA (n=1054) and healthy controls (n=3129). Genotype and allele frequencies were compared using the Cochrane–Armitage trend test implemented in PLINK. Results One SNP in the LPP gene, rs1464510, showed significant association with JIA (ptrend=0.002, OR=1.18, 95% CI 1.06 to 1.30). A second SNP, rs653178 in ATXN2, also showed nominal evidence for association with JIA (ptrend=0.02, OR=1.13, 95% CI 1.02 to 1.25). The SNP, rs17810546, in IL12A showed subtype-specific association with enthesitis-related arthritis (ERA) subtype (ptrend=0.005, OR=1.88, 95% CI 1.2 to 2.94). Conclusions Evidence for a novel JIA susceptibility locus, LPP, is presented. Association at the SH2B3/ATXN2 locus, previously reported to be associated with JIA in a US series, also supports this region as contributing to JIA susceptibility. In addition, a subtype-specific association of IL12A with ERA is identified. All findings will require validation in independent JIA cohorts. PMID:20647273

  11. Anodal transcranial direct current stimulation reduces psychophysically measured surround suppression in the human visual cortex.

    Directory of Open Access Journals (Sweden)

    Daniel P Spiegel

    Full Text Available Transcranial direct current stimulation (tDCS is a safe, non-invasive technique for transiently modulating the balance of excitation and inhibition within the human brain. It has been reported that anodal tDCS can reduce both GABA mediated inhibition and GABA concentration within the human motor cortex. As GABA mediated inhibition is thought to be a key modulator of plasticity within the adult brain, these findings have broad implications for the future use of tDCS. It is important, therefore, to establish whether tDCS can exert similar effects within non-motor brain areas. The aim of this study was to assess whether anodal tDCS could reduce inhibitory interactions within the human visual cortex. Psychophysical measures of surround suppression were used as an index of inhibition within V1. Overlay suppression, which is thought to originate within the lateral geniculate nucleus (LGN, was also measured as a control. Anodal stimulation of the occipital poles significantly reduced psychophysical surround suppression, but had no effect on overlay suppression. This effect was specific to anodal stimulation as cathodal stimulation had no effect on either measure. These psychophysical results provide the first evidence for tDCS-induced reductions of intracortical inhibition within the human visual cortex.

  12. Optical detection of carotenoid antioxidants in human bone and surrounding tissue.

    Science.gov (United States)

    Ermakov, Igor V; Ermakova, Maia R; Rosenberg, Thomas D; Gellermann, Werner

    2013-11-01

    Carotenoids are known to play an important role in health and disease state of living human tissue based on their antioxidant and optical filtering functions. In this study, we show that carotenoids exist in human bone and surrounding fatty tissue both in significant and individually variable concentrations. Measurements of biopsied tissue samples with molecule-specific Raman spectroscopy and high-performance liquid chromatography reveal that all carotenoids that are known to exist in human skin are also present in human bone. This includes all carotenes, lycopene, β-cryptoxanthin, lutein, and zeaxanthin. We propose quantitative reflection imaging as a noncontact optical method suitable for the measurement of composite carotenoid levels in bone and surrounding tissue exposed during open surgeries such as total knee arthroplasty, and as a proof of concept, demonstrate carotenoid measurements in biopsied bone samples. This will allow one to establish potential correlations between internal tissue carotenoid levels and levels in skin and to potentially use already existing optical skin carotenoid tests as surrogate marker for bone carotenoid status.

  13. Micromorphology and chemistry of airborne particles in Brussels during agriculture working periods in surrounding region.

    Science.gov (United States)

    Vanderstraeten, P; Lénelle, Y; Meurrens, A; Carati, D; Brenig, L; Offer, Z Y; Zaady, E

    2008-11-01

    The main objective of our research was to compare the airborne particle micromorphology and chemistry in the Brussels environment during agriculture working periods in the surrounding farming region. We used specific methods and instrumentation that are adapted to the climate peculiarities of the Brussels region, the period of investigations (12 months) and the proposed objectives. For the agricultural works we defined the following six periods: before sowing, sowing, after sowing, before harvest, harvest and after harvest. The results indicate a possible temporal correlation between agricultural work periods and airborne particle concentration, micromorphology and chemistry in the Brabant-Brussels region. For wheat and corn plant-growth periods, the average particle size, defined as the area obtained by a planar projection of the particulate, showed important variations in time. For sugar beet and endive, the average area size variations are less important. The roughness and sphericity parameters for the growth periods of the four different plants also showed significant differences. Many of the larger particulates (> 10 microm) are aggregates of even finer particles coated with many still finer ones. The airborne particle chemistry averages (atomic percentage At%), showed that three constituents (Si, S and Fe) dominate all the samples (except for particles 3-10 microm in size, which contain a relatively large percentage of Al). Applying similar investigation methods to study the correlations between airborne particle dynamics in urban zones and the agriculture working periods in their surrounding regions could be of interest to better understand the complexity of the PM problematic.

  14. Theoretical Investigation of the Optical Spectra of Organic Compounds in Natural Surrounding

    Science.gov (United States)

    Pomogaev, V. A.; Artyukhov, V. Ya.

    2016-08-01

    The hybrid multiscale approximation based on molecular dynamics, quantum mechanics, and statistical theory is used to generate profiles of electronic vibrational absorption and fluorescence bands of some organic compounds and biological objects whose photophysical properties specifically depend on external conditions. A temperature dependence of the spectrum width and intensity of transition to the long-wavelength band of benzene surrounded by cyclohexane molecules is demonstrated. Statistical broadband absorption spectra for estradiol in ethanol, hexane, and dimethyl sulfoxide have been obtained and analyzed at room temperature together with a wide spectrum of transitions to numerous excited states of Trp-cage miniprotein. The absorption and emission spectra of 9-cyan anthracene have been generated under various thermodynamic conditions. This allows changes in the spectral profile with increasing temperatures and pressure to be detected. A dependence of the tryptophan spectra on the protein microsurrounding is investigated. The possibility of charge transfer from tryptophan residue to the eupatorin molecule trapped by human serum albumin is analyzed. Spectral properties and charge transfer from the excited donor to acceptor states are calculated using the polarizable embedding approach for modeling of surrounding protein structure.

  15. Developing criteria and data to determine best options for expanding the core CODIS loci

    Directory of Open Access Journals (Sweden)

    Ge Jianye

    2012-01-01

    Full Text Available Abstract Background Recently, the Combined DNA Index System (CODIS Core Loci Working Group established by the US Federal Bureau of Investigation (FBI reviewed and recommended changes to the CODIS core loci. The Working Group identified 20 short tandem repeat (STR loci (composed of the original CODIS core set loci (minus TPOX, four European recommended loci, PentaE, and DYS391 plus the Amelogenin marker as the new core set. Before selecting and finalizing the core loci, some evaluations are needed to provide guidance for the best options of core selection. Method The performance of current and newly proposed CODIS core loci sets were evaluated with simplified analyses for adventitious hit rates in reasonably large datasets under single-source profile comparisons, mixture comparisons and kinship searches, and for international data sharing. Informativeness (for example, match probability, average kinship index (AKI and mutation rates of each locus were some of the criteria to consider for loci selection. However, the primary factor was performance with challenged forensic samples. Results The current battery of loci provided in already validated commercial kits meet the needs for single-source profile comparisons and international data sharing, even with relatively large databases. However, the 13 CODIS core loci are not sufficiently powerful for kinship analyses and searching potential contributors of mixtures in larger databases; 19 or more autosomal STR loci perform better. Y-chromosome STR (Y-STR loci are very useful to trace paternal lineage, deconvolve female and male mixtures, and resolve inconsistencies with Amelogenin typing. The DYS391 locus is of little theoretical or practical use. Combining five or six Y-chromosome STR loci with existing autosomal STR loci can produce better performance than the same number of autosomal loci for kinship analysis and still yield a sufficiently low match probability for single-source profile comparisons

  16. Development of microsatellite loci in Artocarpus altilis (Moraceae) and cross-amplification in congeneric species.

    Science.gov (United States)

    Witherup, Colby; Ragone, Diane; Wiesner-Hanks, Tyr; Irish, Brian; Scheffler, Brian; Simpson, Sheron; Zee, Francis; Zuberi, M Iqbal; Zerega, Nyree J C

    2013-07-01

    Microsatellite loci were isolated and characterized from enriched genomic libraries of Artocarpus altilis (breadfruit) and tested in four Artocarpus species and one hybrid. The microsatellite markers provide new tools for further studies in Artocarpus. • A total of 25 microsatellite loci were evaluated across four Artocarpus species and one hybrid. Twenty-one microsatellite loci were evaluated on A. altilis (241), A. camansi (34), A. mariannensis (15), and A. altilis × mariannensis (64) samples. Nine of those loci plus four additional loci were evaluated on A. heterophyllus (jackfruit, 426) samples. All loci are polymorphic for at least one species. The average number of alleles ranges from two to nine within taxa. • These microsatellite primers will facilitate further studies on the genetic structure and evolutionary and domestication history of Artocarpus species. They will aid in cultivar identification and establishing germplasm conservation strategies for breadfruit and jackfruit.

  17. Development of microsatellite loci in Artocarpus altilis (Moraceae) and cross-amplification in congeneric species1

    Science.gov (United States)

    Witherup, Colby; Ragone, Diane; Wiesner-Hanks, Tyr; Irish, Brian; Scheffler, Brian; Simpson, Sheron; Zee, Francis; Zuberi, M. Iqbal; Zerega, Nyree J. C.

    2013-01-01

    • Premise of the study: Microsatellite loci were isolated and characterized from enriched genomic libraries of Artocarpus altilis (breadfruit) and tested in four Artocarpus species and one hybrid. The microsatellite markers provide new tools for further studies in Artocarpus. • Methods and Results: A total of 25 microsatellite loci were evaluated across four Artocarpus species and one hybrid. Twenty-one microsatellite loci were evaluated on A. altilis (241), A. camansi (34), A. mariannensis (15), and A. altilis × mariannensis (64) samples. Nine of those loci plus four additional loci were evaluated on A. heterophyllus (jackfruit, 426) samples. All loci are polymorphic for at least one species. The average number of alleles ranges from two to nine within taxa. • Conclusions: These microsatellite primers will facilitate further studies on the genetic structure and evolutionary and domestication history of Artocarpus species. They will aid in cultivar identification and establishing germplasm conservation strategies for breadfruit and jackfruit. PMID:25202565

  18. Development of Microsatellite Loci in Artocarpus altilis (Moraceae and Cross-Amplification in Congeneric Species

    Directory of Open Access Journals (Sweden)

    Colby Witherup

    2013-07-01

    Full Text Available Premise of the study: Microsatellite loci were isolated and characterized from enriched genomic libraries of Artocarpus altilis (breadfruit and tested in four Artocarpus species and one hybrid. The microsatellite markers provide new tools for further studies in Artocarpus. Methods and Results: A total of 25 microsatellite loci were evaluated across four Artocarpus species and one hybrid. Twenty-one microsatellite loci were evaluated on A. altilis (241, A. camansi (34, A. mariannensis (15, and A. altilis × mariannensis (64 samples. Nine of those loci plus four additional loci were evaluated on A. heterophyllus (jackfruit, 426 samples. All loci are polymorphic for at least one species. The average number of alleles ranges from two to nine within taxa. Conclusions: These microsatellite primers will facilitate further studies on the genetic structure and evolutionary and domestication history of Artocarpus species. They will aid in cultivar identification and establishing germplasm conservation strategies for breadfruit and jackfruit.

  19. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index.

    Science.gov (United States)

    Speliotes, Elizabeth K; Willer, Cristen J; Berndt, Sonja I; Monda, Keri L; Thorleifsson, Gudmar; Jackson, Anne U; Lango Allen, Hana; Lindgren, Cecilia M; Luan, Jian'an; Mägi, Reedik; Randall, Joshua C; Vedantam, Sailaja; Winkler, Thomas W; Qi, Lu; Workalemahu, Tsegaselassie; Heid, Iris M; Steinthorsdottir, Valgerdur; Stringham, Heather M; Weedon, Michael N; Wheeler, Eleanor; Wood, Andrew R; Ferreira, Teresa; Weyant, Robert J; Segrè, Ayellet V; Estrada, Karol; Liang, Liming; Nemesh, James; Park, Ju-Hyun; Gustafsson, Stefan; Kilpeläinen, Tuomas O; Yang, Jian; Bouatia-Naji, Nabila; Esko, Tõnu; Feitosa, Mary F; Kutalik, Zoltán; Mangino, Massimo; Raychaudhuri, Soumya; Scherag, Andre; Smith, Albert Vernon; Welch, Ryan; Zhao, Jing Hua; Aben, Katja K; Absher, Devin M; Amin, Najaf; Dixon, Anna L; Fisher, Eva; Glazer, Nicole L; Goddard, Michael E; Heard-Costa, Nancy L; Hoesel, Volker; Hottenga, Jouke-Jan; Johansson, Asa; Johnson, Toby; Ketkar, Shamika; Lamina, Claudia; Li, Shengxu; Moffatt, Miriam F; Myers, Richard H; Narisu, Narisu; Perry, John R B; Peters, Marjolein J; Preuss, Michael; Ripatti, Samuli; Rivadeneira, Fernando; Sandholt, Camilla; Scott, Laura J; Timpson, Nicholas J; Tyrer, Jonathan P; van Wingerden, Sophie; Watanabe, Richard M; White, Charles C; Wiklund, Fredrik; Barlassina, Christina; Chasman, Daniel I; Cooper, Matthew N; Jansson, John-Olov; Lawrence, Robert W; Pellikka, Niina; Prokopenko, Inga; Shi, Jianxin; Thiering, Elisabeth; Alavere, Helene; Alibrandi, Maria T S; Almgren, Peter; Arnold, Alice M; Aspelund, Thor; Atwood, Larry D; Balkau, Beverley; Balmforth, Anthony J; Bennett, Amanda J; Ben-Shlomo, Yoav; Bergman, Richard N; Bergmann, Sven; Biebermann, Heike; Blakemore, Alexandra I F; Boes, Tanja; Bonnycastle, Lori L; Bornstein, Stefan R; Brown, Morris J; Buchanan, Thomas A; Busonero, Fabio; Campbell, Harry; Cappuccio, Francesco P; Cavalcanti-Proença, Christine; Chen, Yii-Der Ida; Chen, Chih-Mei; Chines, Peter S; Clarke, Robert; Coin, Lachlan; Connell, John; Day, Ian N M; den Heijer, Martin; Duan, Jubao; Ebrahim, Shah; Elliott, Paul; Elosua, Roberto; Eiriksdottir, Gudny; Erdos, Michael R; Eriksson, Johan G; Facheris, Maurizio F; Felix, Stephan B; Fischer-Posovszky, Pamela; Folsom, Aaron R; Friedrich, Nele; Freimer, Nelson B; Fu, Mao; Gaget, Stefan; Gejman, Pablo V; Geus, Eco J C; Gieger, Christian; Gjesing, Anette P; Goel, Anuj; Goyette, Philippe; Grallert, Harald; Grässler, Jürgen; Greenawalt, Danielle M; Groves, Christopher J; Gudnason, Vilmundur; Guiducci, Candace; Hartikainen, Anna-Liisa; Hassanali, Neelam; Hall, Alistair S; Havulinna, Aki S; Hayward, Caroline; Heath, Andrew C; Hengstenberg, Christian; Hicks, Andrew A; Hinney, Anke; Hofman, Albert; Homuth, Georg; Hui, Jennie; Igl, Wilmar; Iribarren, Carlos; Isomaa, Bo; Jacobs, Kevin B; Jarick, Ivonne; Jewell, Elizabeth; John, Ulrich; Jørgensen, Torben; Jousilahti, Pekka; Jula, Antti; Kaakinen, Marika; Kajantie, Eero; Kaplan, Lee M; Kathiresan, Sekar; Kettunen, Johannes; Kinnunen, Leena; Knowles, Joshua W; Kolcic, Ivana; König, Inke R; Koskinen, Seppo; Kovacs, Peter; Kuusisto, Johanna; Kraft, Peter; Kvaløy, Kirsti; Laitinen, Jaana; Lantieri, Olivier; Lanzani, Chiara; Launer, Lenore J; Lecoeur, Cecile; Lehtimäki, Terho; Lettre, Guillaume; Liu, Jianjun; Lokki, Marja-Liisa; Lorentzon, Mattias; Luben, Robert N; Ludwig, Barbara; Manunta, Paolo; Marek, Diana; Marre, Michel; Martin, Nicholas G; McArdle, Wendy L; McCarthy, Anne; McKnight, Barbara; Meitinger, Thomas; Melander, Olle; Meyre, David; Midthjell, Kristian; Montgomery, Grant W; Morken, Mario A; Morris, Andrew P; Mulic, Rosanda; Ngwa, Julius S; Nelis, Mari; Neville, Matt J; Nyholt, Dale R; O'Donnell, Christopher J; O'Rahilly, Stephen; Ong, Ken K; Oostra, Ben; Paré, Guillaume; Parker, Alex N; Perola, Markus; Pichler, Irene; Pietiläinen, Kirsi H; Platou, Carl G P; Polasek, Ozren; Pouta, Anneli; Rafelt, Suzanne; Raitakari, Olli; Rayner, Nigel W; Ridderstråle, Martin; Rief, Winfried; Ruokonen, Aimo; Robertson, Neil R; Rzehak, Peter; Salomaa, Veikko; Sanders, Alan R; Sandhu, Manjinder S; Sanna, Serena; Saramies, Jouko; Savolainen, Markku J; Scherag, Susann; Schipf, Sabine; Schreiber, Stefan; Schunkert, Heribert; Silander, Kaisa; Sinisalo, Juha; Siscovick, David S; Smit, Jan H; Soranzo, Nicole; Sovio, Ulla; Stephens, Jonathan; Surakka, Ida; Swift, Amy J; Tammesoo, Mari-Liis; Tardif, Jean-Claude; Teder-Laving, Maris; Teslovich, Tanya M; Thompson, John R; Thomson, Brian; Tönjes, Anke; Tuomi, Tiinamaija; van Meurs, Joyce B J; van Ommen, Gert-Jan; Vatin, Vincent; Viikari, Jorma; Visvikis-Siest, Sophie

    2010-11-01

    Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10⁻⁸), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

  20. Comprehensive Annotation of Physcomitrella patens Small RNA Loci Reveals That the Heterochromatic Short Interfering RNA Pathway Is Largely Conserved in Land Plants.

    Science.gov (United States)

    Coruh, Ceyda; Cho, Sung Hyun; Shahid, Saima; Liu, Qikun; Wierzbicki, Andrzej; Axtell, Michael J

    2015-08-01

    Many plant small RNAs are sequence-specific negative regulators of target mRNAs and/or chromatin. In angiosperms, the two most abundant endogenous small RNA populations are usually 21-nucleotide microRNAs (miRNAs) and 24-nucleotide heterochromatic short interfering RNAs (siRNAs). Heterochromatic siRNAs are derived from repetitive regions and reinforce DNA methylation at targeted loci. The existence and extent of heterochromatic siRNAs in other land plant lineages has been unclear. Using small RNA-sequencing (RNA-seq) of the moss Physcomitrella patens, we identified 1090 loci that produce mostly 23- to 24-nucleotide siRNAs. These loci are mostly in intergenic regions with dense DNA methylation. Accumulation of siRNAs from these loci depends upon P. patens homologs of DICER-LIKE3 (DCL3), RNA-DEPENDENT RNA POLYMERASE2, and the largest subunit of DNA-DEPENDENT RNA POLYMERASE IV, with the largest subunit of a Pol V homolog contributing to expression at a smaller subset of the loci. A MINIMAL DICER-LIKE (mDCL) gene, which lacks the N-terminal helicase domain typical of DCL proteins, is specifically required for 23-nucleotide siRNA accumulation. We conclude that heterochromatic siRNAs, and their biogenesis pathways, are largely identical between angiosperms and P. patens, with the notable exception of the P. patens-specific use of mDCL to produce 23-nucleotide siRNAs. © 2015 American Society of Plant Biologists. All rights reserved.

  1. GIANT Hα NEBULA SURROUNDING THE STARBURST MERGER NGC 6240

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Michitoshi [Hiroshima Astrophysical Science Center, Hiroshima University, Higashi-Hiroshima, Hiroshima 739-8526 (Japan); Yagi, Masafumi; Komiyama, Yutaka; Kashikawa, Nobunari [Optical and Infrared Astronomy Division, National Astronomical Observatory, Mitaka, Tokyo 181-8588 (Japan); Ohyama, Youichi [Institute of Astronomy and Astrophysics, Academia Sinica, 11F of Astronomy-Mathematics Building, AS/NTU No.1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan, R.O.C. (China); Tanaka, Hisashi [Department of Physical Science, Hiroshima University, Higashi-Hiroshima, Hiroshima 739-8526 (Japan); Okamura, Sadanori, E-mail: yoshidam@hiroshima-u.ac.jp [Department of Advanced Sciences, Faculty of Science and Engineering, Hosei University, Koganei, Tokyo 184-8584 (Japan)

    2016-03-20

    We revealed the detailed structure of a vastly extended Hα-emitting nebula (“Hα nebula”) surrounding the starburst/merging galaxy NGC 6240 by deep narrow-band imaging observations with the Subaru Suprime-Cam. The extent of the nebula is ∼90 kpc in diameter and the total Hα luminosity amounts to L{sub Hα} ≈ 1.6 × 10{sup 42} erg s{sup −1}. The volume filling factor and the mass of the warm ionized gas are ∼10{sup −4}–10{sup −5} and ∼5 × 10{sup 8} M{sub ⊙}, respectively. The nebula has a complicated structure, which includes numerous filaments, loops, bubbles, and knots. We found that there is a tight spatial correlation between the Hα nebula and the extended soft-X-ray-emitting gas, both in large and small scales. The overall morphology of the nebula is dominated by filamentary structures radially extending from the center of the galaxy. A large-scale bipolar bubble extends along the minor axis of the main stellar disk. The morphology strongly suggests that the nebula was formed by intense outflows—superwinds—driven by starbursts. We also found three bright knots embedded in a looped filament of ionized gas that show head-tail morphologies in both emission-line and continuum, suggesting close interactions between the outflows and star-forming regions. Based on the morphology and surface brightness distribution of the Hα nebula, we propose the scenario that three major episodes of starburst/superwind activities, which were initiated ∼10{sup 2} Myr ago, formed the extended ionized gas nebula of NGC 6240.

  2. IRIS Observation of a Sunspot and the Surrounding Plage Region

    Science.gov (United States)

    TIAN, H.; DeLuca, E. E.; Mcintosh, S. W.; Reeves, K. K.; McKillop, S.; Weber, M.; Saar, S.; Golub, L.; Testa, P.

    2013-12-01

    NASA's IRIS mission is providing high-cadence and high-resolution observations of the solar transition region and chromosphere. We present preliminary results from IRIS observation of a sunspot and the surrounding plage region. The major findings in this observation can be summarized as following: (1) The slit jaw images in the filters of 1400Å and 1330Å reveal the presence of many rapidly evolving fibril-like structures in the transition region for the first time. These thin and long structures mainly reside in the plage region. They could be strands of low-lying cool transition region loops or the transition region counterpart of chromospheric spicules. (2) The C II and Mg II line profiles are almost Gaussian in the sunspot umbra and clearly exhibit a deep reversal at the line center in the plage region, suggesting a greatly reduced opacity in the sunspot atmosphere. (3) Bidirectional jets are frequently occurring mainly in the plage region immediately outside the sunspot throughout the observation. Triple or double Gaussian fit to the line profiles of Si IV suggests a velocity as high as 100 km/s. These velocity values are of the same order of the Alfven speed in the transition region. (4)Three-minute oscillation is clearly present in the sunspot umbra. The oscillation is identified in not only the slit jaw images of 2796Å, 1400Å and 1330Å, but also in spectra of the bright Mg II, C II and Si IV lines. Strong non-linearity is clearly seen in the intensity and Doppler shift oscillations. Interestingly, the obvious increase of the line width only occurs at the times of largest blue shift. The correlated change of the intensity and Doppler shift suggests an upward propagating magneto-acoustic shock wave.

  3. Isoperimetric inequalities in surround system and space science

    Directory of Open Access Journals (Sweden)

    JiaJin Wen

    2016-02-01

    Full Text Available Abstract By means of the algebraic, analysis, convex geometry, computer, and inequality theories we establish the following isoperimetric inequality in the centered 2-surround system S ( 2 { P , Γ , l } $S^{(2} \\{P,\\varGamma ,l \\}$ : ( 1 | Γ | ∮ Γ r ¯ P p 1 / p ⩽ | Γ | 4 π sin l π | Γ | [ csc l π | Γ | + cot 2 l π | Γ | ln ( tan l π | Γ | + sec l π | Γ | ] , ∀ p ⩽ − 2 . $$\\begin{aligned}& \\biggl(\\frac{1}{|\\varGamma |} \\oint_{\\varGamma }\\bar{r}_{P}^{p} \\biggr^{1/p}\\leqslant\\frac{|\\varGamma |}{4\\pi}\\sin\\frac{l\\pi}{|\\varGamma |} \\biggl[ \\csc \\frac{l\\pi}{|\\varGamma |}+\\cot^{2} \\frac{l\\pi}{|\\varGamma |} \\ln \\biggl(\\tan \\frac{l\\pi}{|\\varGamma |}+\\sec\\frac{l\\pi}{|\\varGamma |} \\biggr \\biggr], \\\\& \\quad \\forall p\\leqslant -2. \\end{aligned}$$ As an application of the inequality in space science, we obtain the best lower bounds of the mean λ-gravity norm ∥ F λ ( Γ , P ∥ ‾ $\\overline{\\Vert {\\mathbf{F}}_{\\lambda} ( \\varGamma ,P \\Vert }$ as follows: ∥ F λ ( Γ , P ∥ ‾ ≜ 1 | Γ | ∮ Γ 1 ∥ A − P ∥ λ ⩾ ( 2 π | Γ | λ , ∀ λ ⩾ 2 . $$\\overline{\\bigl\\Vert {\\mathbf{F}}_{\\lambda} ( \\varGamma ,P \\bigr\\Vert } \\triangleq\\frac{1}{|\\varGamma |} \\oint_{\\varGamma }\\frac{1}{\\|A-P\\|^{\\lambda }}\\geqslant \\biggl(\\frac{2\\pi}{|\\varGamma |} \\biggr^{\\lambda},\\quad \\forall \\lambda\\geqslant2. $$

  4. The interstellar cloud surrounding the Sun: a new perspective

    Science.gov (United States)

    Gry, Cécile; Jenkins, Edward B.

    2014-07-01

    Aims: We offer a new, simpler picture of the local interstellar medium, made of a single continuous cloud enveloping the Sun. This new outlook enables the description of a diffuse cloud from within and brings to light some unexpected properties. Methods: We re-examine the kinematics and abundances of the local interstellar gas, as revealed by the published results for the ultraviolet absorption lines of Mg II, Fe II, and H I. Results: In contrast to previous representations, our new picture of the local interstellar medium consists of a single, monolithic cloud that surrounds the Sun in all directions and accounts for most of the matter present in the first 50 parsecs around the Sun. The cloud fills the space around us out to about 9 pc in most directions, although its boundary is very irregular with possibly a few extensions up to 20 pc. The cloud does not behave like a rigid body: gas within the cloud is being differentially decelerated in the direction of motion, and the cloud is expanding in directions perpendicular to this flow, much like a squashed balloon. Average H I volume densities inside the cloud vary between 0.03 and 0.1 cm-3 over different directions. Metals appear to be significantly depleted onto grains, and there is a steady increase in depletion from the rear of the cloud to the apex of motion. There is no evidence that changes in the ionizing radiation influence the apparent abundances. Secondary absorption components are detected in 60% of the sight lines. Almost all of them appear to be interior to the volume occupied by the main cloud. Half of the sight lines exhibit a secondary component moving at about -7.2 km s-1 with respect to the main component, which may be the signature of a shock propagating toward the cloud's interior.

  5. DEFORMATION OF MOISTURE FLUX CIRCULATION SURROUNDING THE LANDFALL TYPHOON "BILIS"

    Institute of Scientific and Technical Information of China (English)

    RAN Ling-kun; YANG Wen-xia; HONG Yan-chao

    2009-01-01

    The deformation parameter (DP), which is defined as the product of shear deformation and stretching deformation of moisture flux circulation, is introduced. The tendency equation of DP is derived in pressure coordinates. Furthermore, DP is used to diagnose the deformation character of moisture flux circulation in the periphery of Bilis. The analysis showed that before Bilis landed, DP presented eight abnormal areas, which distributed alternately and closely encircled the low-pressure center. This indicated that the moisture flux circulation in the periphery of Bilis rotated counterclockwise and stretched longitudinally and latitudinally to deform. After Bilis landed, DP weakened gradually and its regular pattern of horizontal distribution loosened. The shear and stretching deformations of moisture flux circulation surrounding Bilis weakened after the typhoon landed. The deformation of moisture flux circulation in the periphery of Bilis mainly appeared in the middle-lower troposphere. There existed 1/2 phase difference between the shear and stretching deformations in the vertical-latitudinal cross section and a π/4 phase difference between them on the horizontal plane. As Bilis landed and further moved inland of China, the intensities of DP, shear and stretching deformations decreased, meanwhile their vertical and horizontal structures became irregular. The chief dynamic factors responsible for the deformation of moisture flux circulation in the periphery of Bilis were the three terms associated with the three-dimensional advection transportation of DP, square difference between shear and stretching deformations coupling with Coriolis parameter, and horizontal gradient of geopotential height before Bilis landed. The last two dynamic factors impacted jointly on the deformation of moisture flux circulation after Bilis landed.

  6. Rain Simulation for the Test of Automotive Surround Sensors

    Science.gov (United States)

    Hasirlioglu, Sinan; Riener, Andreas; Doric, Igor

    2017-04-01

    The WHO Global Health Observatory data indicates that over 1.25 million people die in traffic accidents annually. To save lives, car manufacturers spend lot of efforts on the development of novel safety systems aiming to avoid or mitigate accidents and provide maximum protection for vehicle occupants as well as vulnerable road users. All the safety features mainly rely on data from surround sensors such as radar, lidar and camera and intelligent vehicles today use these environmental data for instant decision making and vehicle control. As already small errors in sensor data measurements could lead to catastrophes like major injuries or road traffic fatalities, it is of utmost importance to ensure high reliability and accuracy of sensors and safety systems. This work focuses on the influence of environmental factors such as rain conditions, as it is known that rain drops scatter the electromagnetic waves. The result is incorrect measurements with a direct negative impact on environment detection. To identify potential problems of sensors under varying environmental conditions, systems are today tested in real-world settings with two main problems: First, tests are time-consuming and second, environmental conditions are not reproducible. Our approach to test the influence of weather on automotive sensors is to use an indoor rain simulator. Our artificial rain maker, installed at CARISSMA (Center of Automotive Research on Integrated Safety Systems and Measurement Area), is parametrized with rain characteristics measured in the field using a standard disdrometer. System behavior on artificial rain is compared and validated with natural rainfall. With this simulator it is finally possible to test environmental influence at various levels and under reproducible conditions. This saves lot of efforts required for the test process itself and furthermore has a positive impact on the reliability of sensor systems due to the fact that test driven development is enabled.

  7. Genetic susceptibility loci, pesticide exposure and prostate cancer risk.

    Directory of Open Access Journals (Sweden)

    Stella Koutros

    Full Text Available Uncovering SNP (single nucleotide polymorphisms-environment interactions can generate new hypotheses about the function of poorly characterized genetic variants and environmental factors, like pesticides. We evaluated SNP-environment interactions between 30 confirmed prostate cancer susceptibility loci and 45 pesticides and prostate cancer risk in 776 cases and 1,444 controls in the Agricultural Health Study. We used unconditional logistic regression to estimate odds ratios (ORs and 95% confidence intervals (CIs. Multiplicative SNP-pesticide interactions were calculated using a likelihood ratio test. After correction for multiple tests using the False Discovery Rate method, two interactions remained noteworthy. Among men carrying two T alleles at rs2710647 in EH domain binding protein 1 (EHBP1 SNP, the risk of prostate cancer in those with high malathion use was 3.43 times those with no use (95% CI: 1.44-8.15 (P-interaction= 0.003. Among men carrying two A alleles at rs7679673 in TET2, the risk of prostate cancer associated with high aldrin use was 3.67 times those with no use (95% CI: 1.43, 9.41 (P-interaction= 0.006. In contrast, associations were null for other genotypes. Although additional studies are needed and the exact mechanisms are unknown, this study suggests known genetic susceptibility loci may modify the risk between pesticide use and prostate cancer.

  8. High polymorphism at microsatellite loci in the Chinese donkey.

    Science.gov (United States)

    Zhang, R F; Xie, W M; Zhang, T; Lei, C Z

    2016-06-24

    To reveal the genetic diversity and phylogenetic relationships between Chinese donkey breeds, 415 individuals representing ten breeds were investigated using ten microsatellite markers. The observed number of alleles, mean effective number of alleles (NE), mean expected heterozygosity (HE), and polymorphic information content (PIC) of each breed and polymorphic locus were analyzed. The results showed that seven (HTG7, HTG10, AHT4, HTG6, HMS6, HMS3, and HMS7) of ten microsatellite loci were polymorphic. The mean PIC, HE, and NE of seven polymorphic loci for the ten donkey breeds were 0.7679, 0.8072, and 6.0275, respectively. These results suggest that domestic Chinese donkey breeds possess higher levels of genetic diversity and heterozygosity than foreign donkeys. A neighbor-joining tree based on Nei's standard genetic distance showed that there was close genetic distance among Xinjiang, Qingyang, Xiji, and Guanzhong donkey breeds. In addition, Mongolia and Dezhou donkey breeds were placed in the same category. The phylogenetic tree revealed that the genetic relationships between Chinese donkey breeds are consistent with their geographic distribution and breeding history.

  9. Evolution of Microsatellite Loci of Tropical and Temperate Anguilla Eels

    Directory of Open Access Journals (Sweden)

    Mei-Chen Tseng

    2012-04-01

    Full Text Available Anguilla eels are divided into temperate and tropical eels, based on their major distributions. The present study collected two temperate eels, Anguilla japonica and Anguilla anguilla, and two tropical eels, Anguilla marmorata and Anguilla bicolor pacifica, to examine two questions: do temperate and tropical Anguilla eels have different genetic polymorphic patterns?; and do temperate Anguilla japonica and Anguilla anguilla have a closer relationship to each other than to tropical eels? In total, 274 sequences were cloned and sequenced from six conserved microsatellite loci to examine polymorphic patterns of these four catadromous eels. Different mutational events, including substitutions, and repeat-unit deletions and insertions, appeared in major regions, while different point mutations were observed in flanking regions. The results implied that parallel patterns of microsatellite sequences occurred within both tropical and temperate freshwater eels. Consensus flanking sequences of six homologous loci from each of the four species were constructed. Genetic distances ranged from 0.044 (Anguilla bicolor pacifica vs. Anguilla marmorata to 0.061 (Anguilla marmorata vs. Anguilla anguilla. The tree topology suggests the hypothesis of Anguilla japonica and Anguilla anguilla being a sister group must be rejected.

  10. Quantitative disease resistance and quantitative resistance Loci in breeding.

    Science.gov (United States)

    St Clair, Dina A

    2010-01-01

    Quantitative disease resistance (QDR) has been observed within many crop plants but is not as well understood as qualitative (monogenic) disease resistance and has not been used as extensively in breeding. Mapping quantitative trait loci (QTLs) is a powerful tool for genetic dissection of QDR. DNA markers tightly linked to quantitative resistance loci (QRLs) controlling QDR can be used for marker-assisted selection (MAS) to incorporate these valuable traits. QDR confers a reduction, rather than lack, of disease and has diverse biological and molecular bases as revealed by cloning of QRLs and identification of the candidate gene(s) underlying QRLs. Increasing our biological knowledge of QDR and QRLs will enhance understanding of how QDR differs from qualitative resistance and provide the necessary information to better deploy these resources in breeding. Application of MAS for QRLs in breeding for QDR to diverse pathogens is illustrated by examples from wheat, barley, common bean, tomato, and pepper. Strategies for optimum deployment of QRLs require research to understand effects of QDR on pathogen populations over time.

  11. Development of microsatellite loci in Artocarpus altilis (Moraceae) and cross-amplification in congeneric species 1

    OpenAIRE

    Colby Witherup; Diane Ragone; Tyr Wiesner-Hanks; Brian Irish; Brian Scheffler; Sheron Simpson; Francis Zee; M. Iqbal Zuberi; Zerega, Nyree J. C.

    2013-01-01

    Premise of the study: Microsatellite loci were isolated and characterized from enriched genomic libraries of Artocarpus altilis (breadfruit) and tested in four Artocarpus species and one hybrid. The microsatellite markers provide new tools for further studies in Artocarpus. Methods and Results: A total of 25 microsatellite loci were evaluated across four Artocarpus species and one hybrid. Twenty-one microsatellite loci were evaluated on A. altilis (241), A. camansi (34), A. mariannensis (1...

  12. Association analyses of 249,796 individuals reveal eighteen new loci associated with body mass index

    Science.gov (United States)

    Speliotes, Elizabeth K.; Willer, Cristen J.; Berndt, Sonja I.; Monda, Keri L.; Thorleifsson, Gudmar; Jackson, Anne U.; Allen, Hana Lango; Lindgren, Cecilia M.; Luan, Jian’an; Mägi, Reedik; Randall, Joshua C.; Vedantam, Sailaja; Winkler, Thomas W.; Qi, Lu; Workalemahu, Tsegaselassie; Heid, Iris M.; Steinthorsdottir, Valgerdur; Stringham, Heather M.; Weedon, Michael N.; Wheeler, Eleanor; Wood, Andrew R.; Ferreira, Teresa; Weyant, Robert J.; Segré, Ayellet V.; Estrada, Karol; Liang, Liming; Nemesh, James; Park, Ju-Hyun; Gustafsson, Stefan; Kilpeläinen, Tuomas O.; Yang, Jian; Bouatia-Naji, Nabila; Esko, Tõnu; Feitosa, Mary F.; Kutalik, Zoltán; Mangino, Massimo; Raychaudhuri, Soumya; Scherag, Andre; Smith, Albert Vernon; Welch, Ryan; Zhao, Jing Hua; Aben, Katja K.; Absher, Devin M.; Amin, Najaf; Dixon, Anna L.; Fisher, Eva; Glazer, Nicole L.; Goddard, Michael E.; Heard-Costa, Nancy L.; Hoesel, Volker; Hottenga, Jouke-Jan; Johansson, Åsa; Johnson, Toby; Ketkar, Shamika; Lamina, Claudia; Li, Shengxu; Moffatt, Miriam F.; Myers, Richard H.; Narisu, Narisu; Perry, John R.B.; Peters, Marjolein J.; Preuss, Michael; Ripatti, Samuli; Rivadeneira, Fernando; Sandholt, Camilla; Scott, Laura J.; Timpson, Nicholas J.; Tyrer, Jonathan P.; van Wingerden, Sophie; Watanabe, Richard M.; White, Charles C.; Wiklund, Fredrik; Barlassina, Christina; Chasman, Daniel I.; Cooper, Matthew N.; Jansson, John-Olov; Lawrence, Robert W.; Pellikka, Niina; Prokopenko, Inga; Shi, Jianxin; Thiering, Elisabeth; Alavere, Helene; Alibrandi, Maria T. S.; Almgren, Peter; Arnold, Alice M.; Aspelund, Thor; Atwood, Larry D.; Balkau, Beverley; Balmforth, Anthony J.; Bennett, Amanda J.; Ben-Shlomo, Yoav; Bergman, Richard N.; Bergmann, Sven; Biebermann, Heike; Blakemore, Alexandra I.F.; Boes, Tanja; Bonnycastle, Lori L.; Bornstein, Stefan R.; Brown, Morris J.; Buchanan, Thomas A.; Busonero, Fabio; Campbell, Harry; Cappuccio, Francesco P.; Cavalcanti-Proença, Christine; Chen, Yii-Der Ida; Chen, Chih-Mei; Chines, Peter S.; Clarke, Robert; Coin, Lachlan; Connell, John; Day, Ian N.M.; den Heijer, Martin; Duan, Jubao; Ebrahim, Shah; Elliott, Paul; Elosua, Roberto; Eiriksdottir, Gudny; Erdos, Michael R.; Eriksson, Johan G.; Facheris, Maurizio F.; Felix, Stephan B.; Fischer-Posovszky, Pamela; Folsom, Aaron R.; Friedrich, Nele; Freimer, Nelson B.; Fu, Mao; Gaget, Stefan; Gejman, Pablo V.; Geus, Eco J.C.; Gieger, Christian; Gjesing, Anette P.; Goel, Anuj; Goyette, Philippe; Grallert, Harald; Gräßler, Jürgen; Greenawalt, Danielle M.; Groves, Christopher J.; Gudnason, Vilmundur; Guiducci, Candace; Hartikainen, Anna-Liisa; Hassanali, Neelam; Hall, Alistair S.; Havulinna, Aki S.; Hayward, Caroline; Heath, Andrew C.; Hengstenberg, Christian; Hicks, Andrew A.; Hinney, Anke; Hofman, Albert; Homuth, Georg; Hui, Jennie; Igl, Wilmar; Iribarren, Carlos; Isomaa, Bo; Jacobs, Kevin B.; Jarick, Ivonne; Jewell, Elizabeth; John, Ulrich; Jørgensen, Torben; Jousilahti, Pekka; Jula, Antti; Kaakinen, Marika; Kajantie, Eero; Kaplan, Lee M.; Kathiresan, Sekar; Kettunen, Johannes; Kinnunen, Leena; Knowles, Joshua W.; Kolcic, Ivana; König, Inke R.; Koskinen, Seppo; Kovacs, Peter; Kuusisto, Johanna; Kraft, Peter; Kvaløy, Kirsti; Laitinen, Jaana; Lantieri, Olivier; Lanz