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Sample records for age-at-onset linkage analysis

  1. Age at onset mixture analysis and systematic comparison in schizophrenia spectrum disorders: Is the onset heterogeneity dependent on heterogeneous diagnosis?

    Science.gov (United States)

    Nowrouzi, Behdin; Kamhi, Roy; Hu, Jayi; Kennedy, James L; Matmari, Michelle; De Luca, Vincenzo

    2015-05-01

    A major obstacle to the identification of the neurobiological correlates of schizophrenia is the substantial diagnostic heterogeneity of this disorder. Dividing schizophrenia into "early" and "late" subtypes may reduce heterogeneity and facilitate identification of biomarkers related to this disease. Our objective was to assess the presence of different sub-groups in schizophrenia by age at onset analysis. The participants in this study were 612 unrelated patients with schizophrenia. Admixture analysis was applied in order to identify a model of separate normal distributions of age at onset characterized by different means, variances and population proportions to evaluate the effect of winter birth and ethnicity on early onset schizophrenia. The best-fitting model suggested three subgroups with means and standard deviations of 17.11 ± 2.09, 21.96 ± 3.43 and 30.02 ± 7.1 years, comprising 34.6%, 42.6% and 22.8% of the sample respectively. We considered as predictors of early onset schizophrenia: male gender, winter birth, white ethnicity and positive family history for psychiatric disorders. Earlier onset was significantly associated with male gender. We also compared our age at onset distribution with those published in other studies and we found significant differences with several studies suggesting heterogeneity in age at onset that is likely influenced by diagnostic heterogeneity in applying the DSM-IV criteria. Overall, our study showed that a typical early onset schizophrenia patient is more likely to be a white male with cannabis abuse and positive family history of psychiatric disorders. The heterogeneity in reporting age at onset across different studies suggests the application of more stringent criteria in diagnosing schizophrenia. PMID:25818628

  2. Eating disorders: What age at onset?

    Science.gov (United States)

    Volpe, Umberto; Tortorella, Alfonso; Manchia, Mirko; Monteleone, Alessio M; Albert, Umberto; Monteleone, Palmiero

    2016-04-30

    Age at onset (AAO) of eating disorders has classically been described in adolescence. We analyzed data from 806 subjects with anorexia nervosa (AN) or bulimia nervosa (BN) and performed a normal distribution admixture analysis to determine their AAO. No significant differences were found concerning the AAO functions of AN and BN subjects. Both groups had a mean AAO of about 18 years. Most of the subjects with AN (75.3%) and BN (83.3%) belonged to the early onset group. The definition of AAO for ED may be crucial for planning treatment modalities, with specific consideration of their clinical history and course. PMID:27086237

  3. ADEM: Age at Onset and Neuropsychological Outcome

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2004-09-01

    Full Text Available The influence of age at onset of acute disseminated encephalomyelitis (ADEM on cognitive, educational, and social functioning was evaluated in 19 children (10 < 5 years of age admitted to the Royal Children’s Hospital, Melbourne, Australia.

  4. Evidence for three loci modifying age-at-onset of Alzheimer's disease in early-onset PSEN2 families.

    Science.gov (United States)

    Marchani, Elizabeth E; Bird, Thomas D; Steinbart, Ellen J; Rosenthal, Elisabeth; Yu, Chang-En; Schellenberg, Gerard D; Wijsman, Ellen M

    2010-07-01

    Families with early-onset Alzheimer's disease (AD) sharing a single PSEN2 mutation exhibit a wide range of age-at-onset, suggesting that modifier loci segregate within these families. While APOE is known to be an age-at-onset modifier, it does not explain all of this variation. We performed a genome scan within nine such families for loci influencing age-at-onset, while simultaneously controlling for variation in the primary PSEN2 mutation (N141I) and APOE. We found significant evidence of linkage between age-at-onset and chromosome 1q23.3 (P 17p13.2 (P = 0.0002), 7q33 (P = 0.017), and 11p14.2 (P = 0.017) in a single large pedigree. Simultaneous analysis of these four chromosomes maintained strong evidence of linkage to chromosomes 1q23.3 and 17p13.2 when all families were analyzed, and to chromosomes 1q23.3, 7q33, and 17p13.2 within the same single pedigree. Inclusion of major gene covariates proved essential to detect these linkage signals, as all linkage signals dissipated when PSEN2 and APOE were excluded from the model. The four chromosomal regions with evidence of linkage all coincide with previous linkage signals, associated SNPs, and/or candidate genes identified in independent AD study populations. This study establishes several candidate regions for further analysis and is consistent with an oligogenic model of AD risk and age-at-onset. More generally, this study also demonstrates the value of searching for modifier loci in existing datasets previously used to identify primary causal variants for complex disease traits. PMID:20333730

  5. PARK3 Influences Age at Onset in Parkinson Disease: A Genome Scan in the GenePD Study

    Science.gov (United States)

    DeStefano, Anita L.; Lew, Mark F.; Golbe, Lawrence I.; Mark, Margery H.; Lazzarini, Alice M.; Guttman, Mark; Montgomery, Erwin; Waters, Cheryl H.; Singer, Carlos; Watts, Ray L.; Currie, Lillian J.; Wooten, G. Frederick; Maher, Nancy E.; Wilk, Jemma B.; Sullivan, Kristin M.; Slater, Karen M.; Saint-Hilaire, Marie H.; Feldman, Robert G.; Suchowersky, Oksana; Lafontaine, Anne-Louise; Labelle, Nancy; Growdon, John H.; Vieregge, Peter; Pramstaller, Peter P.; Klein, Christine; Hubble, Jean P.; Reider, Carson R.; Stacy, Mark; MacDonald, Marcy E.; Gusella, James F.; Myers, Richard H.

    2002-01-01

    Parkinson disease (PD) is a late-onset neurodegenerative disorder. The mean age at onset is 61 years, but the disease can range from juvenile cases to cases in the 8th or 9th decade of life. The parkin gene on chromosome 6q and loci on chromosome 1p35-36 and 1p36 are responsible for some cases of autosomal recessive early-onset parkinsonism, but they do not appear to influence susceptibility or variability of age at onset for idiopathic PD. We have performed a genomewide linkage analysis using variance-component methodology to identify genes influencing age at onset of PD in a population of affected relatives (mainly affected sibling pairs) participating in the GenePD study. Four chromosomal loci showed suggestive evidence of linkage: chromosome 2p (maximum multipoint LOD [MaxLOD] = 2.08), chromosome 9q (MaxLOD = 2.00), chromosome 20 (MaxLOD = 1.82), and chromosome 21 (MaxLOD = 2.21). The 2p and 9q locations that we report here have previously been reported as loci influencing PD affection status. Association between PD age at onset and allele 174 of marker D2S1394, located on 2p13, was observed in the GenePD sample (P=.02). This 174 allele is common to the PD haplotype observed in two families that show linkage to PARK3 and have autosomal dominant PD, which suggests that this allele may be in linkage disequilibrium with a mutation influencing PD susceptibility or age at onset of PD. PMID:11920285

  6. Evidence for Three Loci Modifying Age-at-Onset of Alzheimer’s Disease in Early-Onset PSEN2 Families

    Science.gov (United States)

    Marchani, Elizabeth E.; Bird, Thomas D.; Steinbart, Ellen J.; Rosenthal, Elisabeth; Yu, Chang-En; Schellenberg, Gerard D.; Wijsman, Ellen M.

    2011-01-01

    Families with early-onset Alzheimer’s disease (AD) sharing a single PSEN2 mutation exhibit a wide range of age-at-onset, suggesting that modifier loci segregate within these families. While APOE is known to be an age-at-onset modifier, it does not explain all of this variation. We performed a genome scan within nine such families for loci influencing age-at-onset, while simultaneously controlling for variation in the primary PSEN2 mutation (N141I) and APOE. We found significant evidence of linkage between age-at-onset and chromosome 1q23.3 (P 17p13.2 (P = 0.0002), 7q33 (P = 0.017), and 11p14.2 (P = 0.017) in a single large pedigree. Simultaneous analysis of these four chromosomes maintained strong evidence of linkage to chromosomes 1q23.3 and 17p13.2 when all families were analyzed, and to chromosomes 1q23.3, 7q33, and 17p13.2 within the same single pedigree. Inclusion of major gene covariates proved essential to detect these linkage signals, as all linkage signals dissipated when PSEN2 and APOE were excluded from the model. The four chromosomal regions with evidence of linkage all coincide with previous linkage signals, associated SNPs, and/or candidate genes identified in independent AD study populations. This study establishes several candidate regions for further analysis and is consistent with an oligogenic model of AD risk and age-at-onset. More generally, this study also demonstrates the value of searching for modifier loci in existing datasets previously used to identify primary causal variants for complex disease traits. PMID:20333730

  7. Genetic influence on the age at onset of asthma

    DEFF Research Database (Denmark)

    Thomsen, Simon Francis; Duffy, David Lorenzo; Kyvik, Kirsten Ohm;

    2010-01-01

    Although the genetics of asthma susceptibility have been frequently explored, little is known about genetic factors that influence the age at onset of asthma.......Although the genetics of asthma susceptibility have been frequently explored, little is known about genetic factors that influence the age at onset of asthma....

  8. Speech disorders did not correlate with age at onset of Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Alice Estevo Dias

    2016-02-01

    Full Text Available ABSTRACT Speech disorders are common manifestations of Parkinson´s disease. Objective To compare speech articulation in patients according to age at onset of the disease. Methods Fifty patients was divided into two groups: Group I consisted of 30 patients with age at onset between 40 and 55 years; Group II consisted of 20 patients with age at onset after 65 years. All patients were evaluated based on the Unified Parkinson’s Disease Rating Scale scores, Hoehn and Yahr scale and speech evaluation by perceptual and acoustical analysis. Results There was no statistically significant difference between the two groups regarding neurological involvement and speech characteristics. Correlation analysis indicated differences in speech articulation in relation to staging and axial scores of rigidity and bradykinesia for middle and late-onset. Conclusions Impairment of speech articulation did not correlate with age at onset of disease, but was positively related with disease duration and higher scores in both groups.

  9. Influence of age at onset on social functioning in outpatients with schizophrenia

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    S. Ochoa

    2006-09-01

    Full Text Available Background and Objectives: There are different factors that have been found to predict disability in schizophrenia. The aim of our study is to evaluate the influence of age at onset on social functioning in schizophrenia in a large sample of schizophrenic outpatients controlling for gender. Methods: Two hundred and thirty-one subjects with schizophrenia (DSM-IV criteria were randomly selected from a register that included all patients under treatment in five mental health care centers (MHCC in Spain. Patients were evaluated with a sociodemographic and clinical questionnaire, and the Spanish version of the Living Skills Profile (LSP. Pearson's analyses were performed between age at onset and LSP, and an ANOVA analysis to compare three groups of age at onset (early, middle and late. Gender was introduced as a covariable. Results: Mean age at onset of the total sample was 23 (sd 7.35, with women having a later age at onset than men (women 24.6 (sd 9.1 ; men 22.2 (sd 5.9 (p<0.05. The relation between age at onset and social functioning was only significant in the not interpersonal social behavior subscale (p<0.01. Early age at onset was positively related to social contact-communication (p<0.05, not interpersonal social behavior (p<0.05 and total LSP score (p<0.05. When including gender as a covariable, a significant relationship between age at onset and social functioning was found in most of the LSP subscales. Conclusions: Early onset of illness negatively influences psychosocial functioning, especially in the areas of communication, not interpersonal social behaviour and self-care. Female gender positively influences most aspects of social functioning.

  10. Analysis of relationship between age at onset and clinical features of migraine%发病年龄与偏头痛临床特点的关系分析

    Institute of Scientific and Technical Information of China (English)

    冯智英; 李颖; 邹静; 李焰生

    2011-01-01

    目的 分析发病年龄与偏头痛临床特点的关系,为临床判断偏头痛的预后提供参考.方法 收集门诊诊断为偏头痛的连续患者447例,其中先兆性偏头痛(MA组)62例,无先兆性偏头痛(MO组)385例.记录两组患者的年龄、性别、头痛发病年龄(AAO)、首次就诊年龄、病程、家族史以及头痛强度、频率和持续时间等相关资料.两组患者按AAO进行再分组(≤18岁为未成年组,>18岁为成年组),分别对AAO与家族史和头痛强度、频率、持续时间的关系进行统计学分析.结果 MA组和MO组患者中女性分别占81.3%和66.1% (P <0.05),两组患者的首次就诊年龄、病程和头痛持续时间比较,差异均有统计学意义(P<0.05).在MO患者中,未成年组与成年组的首次就诊年龄、病程、家族史及头痛频率和持续时间比较,差异均有统计学意义(P<0.05).多变量Logistic回归分析发现,就诊年龄、病程、家族史、头痛频率是独立危险因素.结论 起病早、家族史明显、头痛严重的偏头痛患者,预后较差;在中国人群中,AAO可作为反映偏头痛预后的指标之一.%Objective To investigate the relationship between age at onset (AAO) and clinical features of migraine so as to provide references for prognosis estimation of migraine. Methods Four hundred and forty-seven consecutive patients with migraine were enrolled, among whom 62 were migraine with aura ( MA group), and 385 were migraine without aura ( MO group). The related data about age, gender, AAO, age of first diagnosis, course of disease, family history, intensity of migraine, frequency of migraine and duration of migraine of patients in two groups were recorded. Patients in both groups were subdivided into immaturity group ( ^ 18 years old) and adult group( > 18 years old) respectively. The relationship between AAO and family history, intensity of migraine, frequency of migraine and duration of migraine was statistically

  11. Genetic Factors Explain Variation in the Age at Onset of Psoriasis

    DEFF Research Database (Denmark)

    Lønnberg, Ann Sophie; Skov, Lone; Duffy, David Lorenzo;

    2016-01-01

    The aim of this study was to determine the age at onset of psoriasis in a population-based twin sample. Questionnaire-data in 10,725 twin pairs, 20-71 years of age, from the Danish Twin Registry, was collected, and analysed using survival regression analysis. Median age at onset was 25 and 28 years...... among women and men, respectively. The correlation between the ages was 0.84 (bootstrap standard error?=?0.044) in monozygotic twin pairs and 0.60 (0.051) in dizygotic twin pairs, permutation p?=?0.001. Age at onset of psoriasis in the index twin did not predict risk of psoriasis in the co-twin, hazard...... ratio (per year of later onset =?1.01 (0.99-1.03), p?=?0.434. In conclusion, these data support that the age at onset of psoriasis is, in part, an inherited property. Our results do not support that early-onset psoriasis is more genetically determined....

  12. Clinical Differences between Men and Women with Psoriatic Arthritis: Relevance of the Analysis of Genes and Polymorphisms in the Major Histocompatibility Complex Region and of the Age at Onset of Psoriasis

    Directory of Open Access Journals (Sweden)

    Rubén Queiro

    2013-01-01

    Full Text Available It has been shown that males with spondyloarthritis tend to suffer from more severe spinal disease while females are more likely to have peripheral joint involvement. Nevertheless, gender-related differences have not been thoroughly explored in psoriatic arthritis (PsA. In PsA, males accumulate more peripheral and axial joint damage compared to women. However, it is not clear whether these findings are secondary to differences in occupational physical activity, hormonal changes, or other factors. The present study analyzed the differences in clinical expression of PsA between men and women. We have also evaluated the possible existence of gender-linked differences in the distribution of genes and polymorphisms within the major histocompatibility complex and whether patients’ age at the onset of psoriasis established any differences in these aspects. Women suffered more polyarthritis, greater functional impairment, and a larger number of swollen joints during followup. We appreciated a differential expression of certain MHC genes according to gender and age at onset of psoriasis. Our results point to the need to include patient’s age at the onset of psoriasis and gender as key stratification elements in future studies of genetic associations in PsA.

  13. CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion

    Science.gov (United States)

    Lee, J.-M.; Ramos, E.M.; Lee, J.-H.; Gillis, T.; Mysore, J.S.; Hayden, M.R.; Warby, S.C.; Morrison, P.; Nance, M.; Ross, C.A.; Margolis, R.L.; Squitieri, F.; Orobello, S.; Di Donato, S.; Gomez-Tortosa, E.; Ayuso, C.; Suchowersky, O.; Trent, R.J.A.; McCusker, E.; Novelletto, A.; Frontali, M.; Jones, R.; Ashizawa, T.; Frank, S.; Saint-Hilaire, M.H.; Hersch, S.M.; Rosas, H.D.; Lucente, D.; Harrison, M.B.; Zanko, A.; Abramson, R.K.; Marder, K.; Sequeiros, J.; Paulsen, J.S.; Landwehrmeyer, G.B.; Myers, R.H.; MacDonald, M.E.; Durr, Alexandra; Rosenblatt, Adam; Frati, Luigi; Perlman, Susan; Conneally, Patrick M.; Klimek, Mary Lou; Diggin, Melissa; Hadzi, Tiffany; Duckett, Ayana; Ahmed, Anwar; Allen, Paul; Ames, David; Anderson, Christine; Anderson, Karla; Anderson, Karen; Andrews, Thomasin; Ashburner, John; Axelson, Eric; Aylward, Elizabeth; Barker, Roger A.; Barth, Katrin; Barton, Stacey; Baynes, Kathleen; Bea, Alexandra; Beall, Erik; Beg, Mirza Faisal; Beglinger, Leigh J.; Biglan, Kevin; Bjork, Kristine; Blanchard, Steve; Bockholt, Jeremy; Bommu, Sudharshan Reddy; Brossman, Bradley; Burrows, Maggie; Calhoun, Vince; Carlozzi, Noelle; Chesire, Amy; Chiu, Edmond; Chua, Phyllis; Connell, R.J.; Connor, Carmela; Corey-Bloom, Jody; Craufurd, David; Cross, Stephen; Cysique, Lucette; Santos, Rachelle Dar; Davis, Jennifer; Decolongon, Joji; DiPietro, Anna; Doucette, Nicholas; Downing, Nancy; Dudler, Ann; Dunn, Steve; Ecker, Daniel; Epping, Eric A.; Erickson, Diane; Erwin, Cheryl; Evans, Ken; Factor, Stewart A.; Farias, Sarah; Fatas, Marta; Fiedorowicz, Jess; Fullam, Ruth; Furtado, Sarah; Garde, Monica Bascunana; Gehl, Carissa; Geschwind, Michael D.; Goh, Anita; Gooblar, Jon; Goodman, Anna; Griffith, Jane; Groves, Mark; Guttman, Mark; Hamilton, Joanne; Harrington, Deborah; Harris, Greg; Heaton, Robert K.; Helmer, Karl; Henneberry, Machelle; Hershey, Tamara; Herwig, Kelly; Howard, Elizabeth; Hunter, Christine; Jankovic, Joseph; Johnson, Hans; Johnson, Arik; Jones, Kathy; Juhl, Andrew; Kim, Eun Young; Kimble, Mycah; King, Pamela; Klimek, Mary Lou; Klöppel, Stefan; Koenig, Katherine; Komiti, Angela; Kumar, Rajeev; Langbehn, Douglas; Leavitt, Blair; Leserman, Anne; Lim, Kelvin; Lipe, Hillary; Lowe, Mark; Magnotta, Vincent A.; Mallonee, William M.; Mans, Nicole; Marietta, Jacquie; Marshall, Frederick; Martin, Wayne; Mason, Sarah; Matheson, Kirsty; Matson, Wayne; Mazzoni, Pietro; McDowell, William; Miedzybrodzka, Zosia; Miller, Michael; Mills, James; Miracle, Dawn; Montross, Kelsey; Moore, David; Mori, Sasumu; Moser, David J.; Moskowitz, Carol; Newman, Emily; Nopoulos, Peg; Novak, Marianne; O'Rourke, Justin; Oakes, David; Ondo, William; Orth, Michael; Panegyres, Peter; Pease, Karen; Perlman, Susan; Perlmutter, Joel; Peterson, Asa; Phillips, Michael; Pierson, Ron; Potkin, Steve; Preston, Joy; Quaid, Kimberly; Radtke, Dawn; Rae, Daniela; Rao, Stephen; Raymond, Lynn; Reading, Sarah; Ready, Rebecca; Reece, Christine; Reilmann, Ralf; Reynolds, Norm; Richardson, Kylie; Rickards, Hugh; Ro, Eunyoe; Robinson, Robert; Rodnitzky, Robert; Rogers, Ben; Rosenblatt, Adam; Rosser, Elisabeth; Rosser, Anne; Price, Kathy; Price, Kathy; Ryan, Pat; Salmon, David; Samii, Ali; Schumacher, Jamy; Schumacher, Jessica; Sendon, Jose Luis Lópenz; Shear, Paula; Sheinberg, Alanna; Shpritz, Barnett; Siedlecki, Karen; Simpson, Sheila A.; Singer, Adam; Smith, Jim; Smith, Megan; Smith, Glenn; Snyder, Pete; Song, Allen; Sran, Satwinder; Stephan, Klaas; Stober, Janice; Sü?muth, Sigurd; Suter, Greg; Tabrizi, Sarah; Tempkin, Terry; Testa, Claudia; Thompson, Sean; Thomsen, Teri; Thumma, Kelli; Toga, Arthur; Trautmann, Sonja; Tremont, Geoff; Turner, Jessica; Uc, Ergun; Vaccarino, Anthony; van Duijn, Eric; Van Walsem, Marleen; Vik, Stacie; Vonsattel, Jean Paul; Vuletich, Elizabeth; Warner, Tom; Wasserman, Paula; Wassink, Thomas; Waterman, Elijah; Weaver, Kurt; Weir, David; Welsh, Claire; Werling-Witkoske, Chris; Wesson, Melissa; Westervelt, Holly; Weydt, Patrick; Wheelock, Vicki; Williams, Kent; Williams, Janet; Wodarski, Mary; Wojcieszek, Joanne; Wood, Jessica; Wood-Siverio, Cathy; Wu, Shuhua; Yastrubetskaya, Olga; de Yebenes, Justo Garcia; Zhao, Yong Qiang; Zimbelman, Janice; Zschiegner, Roland; Aaserud, Olaf; Abbruzzese, Giovanni; Andrews, Thomasin; Andrich, Jurgin; Antczak, Jakub; Arran, Natalie; Artiga, Maria J. Saiz; Bachoud-Lévi, Anne-Catherine; Banaszkiewicz, Krysztof; di Poggio, Monica Bandettini; Bandmann, Oliver; Barbera, Miguel A.; Barker, Roger A.; Barrero, Francisco; Barth, Katrin; Bas, Jordi; Beister, Antoine; Bentivoglio, Anna Rita; Bertini, Elisabetta; Biunno, Ida; Bjørgo, Kathrine; Bjørnevoll, Inga; Bohlen, Stefan; Bonelli, Raphael M.; Bos, Reineke; Bourne, Colin; Bradbury, Alyson; Brockie, Peter; Brown, Felicity; Bruno, Stefania; Bryl, Anna; Buck, Andrea; Burg, Sabrina; Burgunder, Jean-Marc; Burns, Peter; Burrows, Liz; Busquets, Nuria; Busse, Monica; Calopa, Matilde; Carruesco, Gemma T.; Casado, Ana Gonzalez; Catena, Judit López; Chu, Carol; Ciesielska, Anna; Clapton, Jackie; Clayton, Carole; Clenaghan, Catherine; Coelho, Miguel; Connemann, Julia; Craufurd, David; Crooks, Jenny; Cubillo, Patricia Trigo; Cubo, Esther; Curtis, Adrienne; De Michele, Giuseppe; De Nicola, A.; de Souza, Jenny; de Weert, A. Marit; de Yébenes, Justo Garcia; Dekker, M.; Descals, A. Martínez; Di Maio, Luigi; Di Pietro, Anna; Dipple, Heather; Dose, Matthias; Dumas, Eve M.; Dunnett, Stephen; Ecker, Daniel; Elifani, F.; Ellison-Rose, Lynda; Elorza, Marina D.; Eschenbach, Carolin; Evans, Carole; Fairtlough, Helen; Fannemel, Madelein; Fasano, Alfonso; Fenollar, Maria; Ferrandes, Giovanna; Ferreira, Jaoquim J.; Fillingham, Kay; Finisterra, Ana Maria; Fisher, K.; Fletcher, Amy; Foster, Jillian; Foustanos, Isabella; Frech, Fernando A.; Fullam, Robert; Fullham, Ruth; Gago, Miguel; García, RocioGarcía-Ramos; García, Socorro S.; Garrett, Carolina; Gellera, Cinzia; Gill, Paul; Ginestroni, Andrea; Golding, Charlotte; Goodman, Anna; Gørvell, Per; Grant, Janet; Griguoli, A.; Gross, Diana; Guedes, Leonor; BascuñanaGuerra, Monica; Guerra, Maria Rosalia; Guerrero, Rosa; Guia, Dolores B.; Guidubaldi, Arianna; Hallam, Caroline; Hamer, Stephanie; Hammer, Kathrin; Handley, Olivia J.; Harding, Alison; Hasholt, Lis; Hedge, Reikha; Heiberg, Arvid; Heinicke, Walburgis; Held, Christine; Hernanz, Laura Casas; Herranhof, Briggitte; Herrera, Carmen Durán; Hidding, Ute; Hiivola, Heli; Hill, Susan; Hjermind, Lena. E.; Hobson, Emma; Hoffmann, Rainer; Holl, Anna Hödl; Howard, Liz; Hunt, Sarah; Huson, Susan; Ialongo, Tamara; Idiago, Jesus Miguel R.; Illmann, Torsten; Jachinska, Katarzyna; Jacopini, Gioia; Jakobsen, Oda; Jamieson, Stuart; Jamrozik, Zygmunt; Janik, Piotr; Johns, Nicola; Jones, Lesley; Jones, Una; Jurgens, Caroline K.; Kaelin, Alain; Kalbarczyk, Anna; Kershaw, Ann; Khalil, Hanan; Kieni, Janina; Klimberg, Aneta; Koivisto, Susana P.; Koppers, Kerstin; Kosinski, Christoph Michael; Krawczyk, Malgorzata; Kremer, Berry; Krysa, Wioletta; Kwiecinski, Hubert; Lahiri, Nayana; Lambeck, Johann; Lange, Herwig; Laver, Fiona; Leenders, K.L.; Levey, Jamie; Leythaeuser, Gabriele; Lezius, Franziska; Llesoy, Joan Roig; Löhle, Matthias; López, Cristobal Diez-Aja; Lorenza, Fortuna; Loria, Giovanna; Magnet, Markus; Mandich, Paola; Marchese, Roberta; Marcinkowski, Jerzy; Mariotti, Caterina; Mariscal, Natividad; Markova, Ivana; Marquard, Ralf; Martikainen, Kirsti; Martínez, Isabel Haro; Martínez-Descals, Asuncion; Martino, T.; Mason, Sarah; McKenzie, Sue; Mechi, Claudia; Mendes, Tiago; Mestre, Tiago; Middleton, Julia; Milkereit, Eva; Miller, Joanne; Miller, Julie; Minster, Sara; Möller, Jens Carsten; Monza, Daniela; Morales, Blas; Moreau, Laura V.; Moreno, Jose L. López-Sendón; Münchau, Alexander; Murch, Ann; Nielsen, Jørgen E.; Niess, Anke; Nørremølle, Anne; Novak, Marianne; O'Donovan, Kristy; Orth, Michael; Otti, Daniela; Owen, Michael; Padieu, Helene; Paganini, Marco; Painold, Annamaria; Päivärinta, Markku; Partington-Jones, Lucy; Paterski, Laurent; Paterson, Nicole; Patino, Dawn; Patton, Michael; Peinemann, Alexander; Peppa, Nadia; Perea, Maria Fuensanta Noguera; Peterson, Maria; Piacentini, Silvia; Piano, Carla; Càrdenas, Regina Pons i; Prehn, Christian; Price, Kathleen; Probst, Daniela; Quarrell, Oliver; Quiroga, Purificacion Pin; Raab, Tina; Rakowicz, Maryla; Raman, Ashok; Raymond, Lucy; Reilmann, Ralf; Reinante, Gema; Reisinger, Karin; Retterstol, Lars; Ribaï, Pascale; Riballo, Antonio V.; Ribas, Guillermo G.; Richter, Sven; Rickards, Hugh; Rinaldi, Carlo; Rissling, Ida; Ritchie, Stuart; Rivera, Susana Vázquez; Robert, Misericordia Floriach; Roca, Elvira; Romano, Silvia; Romoli, Anna Maria; Roos, Raymond A.C.; Røren, Niini; Rose, Sarah; Rosser, Elisabeth; Rosser, Anne; Rossi, Fabiana; Rothery, Jean; Rudzinska, Monika; Ruíz, Pedro J. García; Ruíz, Belan Garzon; Russo, Cinzia Valeria; Ryglewicz, Danuta; Saft, Carston; Salvatore, Elena; Sánchez, Vicenta; Sando, Sigrid Botne; Šašinková, Pavla; Sass, Christian; Scheibl, Monika; Schiefer, Johannes; Schlangen, Christiane; Schmidt, Simone; Schöggl, Helmut; Schrenk, Caroline; Schüpbach, Michael; Schuierer, Michele; Sebastián, Ana Rojo; Selimbegovic-Turkovic, Amina; Sempolowicz, Justyna; Silva, Mark; Sitek, Emilia; Slawek, Jaroslaw; Snowden, Julie; Soleti, Francesco; Soliveri, Paola; Sollom, Andrea; Soltan, Witold; Sorbi, Sandro; Sorensen, Sven Asger; Spadaro, Maria; Städtler, Michael; Stamm, Christiane; Steiner, Tanja; Stokholm, Jette; Stokke, Bodil; Stopford, Cheryl; Storch, Alexander; Straßburger, Katrin; Stubbe, Lars; Sulek, Anna; Szczudlik, Andrzej; Tabrizi, Sarah; Taylor, Rachel; Terol, Santiago Duran-Sindreu; Thomas, Gareth; Thompson, Jennifer; Thomson, Aileen; Tidswell, Katherine; Torres, Maria M. Antequera; Toscano, Jean; Townhill, Jenny; Trautmann, Sonja; Tucci, Tecla; Tuuha, Katri; Uhrova, Tereza; Valadas, Anabela; van Hout, Monique S.E.; van Oostrom, J.C.H.; van Vugt, Jeroen P.P.; vanm, Walsem Marleen R.; Vandenberghe, Wim; Verellen-Dumoulin, Christine; Vergara, Mar Ruiz; Verstappen, C.C.P.; Verstraelen, Nichola; Viladrich, Celia Mareca; Villanueva, Clara; Wahlström, Jan; Warner, Thomas; Wehus, Raghild; Weindl, Adolf; Werner, Cornelius J.; Westmoreland, Leann; Weydt, Patrick; Wiedemann, Alexandra; Wild, Edward; Wild, Sue; Witjes-Ané, Marie-Noelle; Witkowski, Grzegorz; Wójcik, Magdalena; Wolz, Martin; Wolz, Annett; Wright, Jan; Yardumian, Pam; Yates, Shona; Yudina, Elizaveta; Zaremba, Jacek; Zaugg, Sabine W.; Zdzienicka, Elzbieta; Zielonka, Daniel; Zielonka, Euginiusz; Zinzi, Paola; Zittel, Simone; Zucker, Birgrit; Adams, John; Agarwal, Pinky; Antonijevic, Irina; Beck, Christopher; Chiu, Edmond; Churchyard, Andrew; Colcher, Amy; Corey-Bloom, Jody; Dorsey, Ray; Drazinic, Carolyn; Dubinsky, Richard; Duff, Kevin; Factor, Stewart; Foroud, Tatiana; Furtado, Sarah; Giuliano, Joe; Greenamyre, Timothy; Higgins, Don; Jankovic, Joseph; Jennings, Dana; Kang, Un Jung; Kostyk, Sandra; Kumar, Rajeev; Leavitt, Blair; LeDoux, Mark; Mallonee, William; Marshall, Frederick; Mohlo, Eric; Morgan, John; Oakes, David; Panegyres, Peter; Panisset, Michel; Perlman, Susan; Perlmutter, Joel; Quaid, Kimberly; Raymond, Lynn; Revilla, Fredy; Robertson, Suzanne; Robottom, Bradley; Sanchez-Ramos, Juan; Scott, Burton; Shannon, Kathleen; Shoulson, Ira; Singer, Carlos; Tabbal, Samer; Testa, Claudia; van, Kammen Dan; Vetter, Louise; Walker, Francis; Warner, John; Weiner, illiam; Wheelock, Vicki; Yastrubetskaya, Olga; Barton, Stacey; Broyles, Janice; Clouse, Ronda; Coleman, Allison; Davis, Robert; Decolongon, Joji; DeLaRosa, Jeanene; Deuel, Lisa; Dietrich, Susan; Dubinsky, Hilary; Eaton, Ken; Erickson, Diane; Fitzpatrick, Mary Jane; Frucht, Steven; Gartner, Maureen; Goldstein, Jody; Griffith, Jane; Hickey, Charlyne; Hunt, Victoria; Jaglin, Jeana; Klimek, Mary Lou; Lindsay, Pat; Louis, Elan; Loy, Clemet; Lucarelli, Nancy; Malarick, Keith; Martin, Amanda; McInnis, Robert; Moskowitz, Carol; Muratori, Lisa; Nucifora, Frederick; O'Neill, Christine; Palao, Alicia; Peavy, Guerry; Quesada, Monica; Schmidt, Amy; Segro, Vicki; Sperin, Elaine; Suter, Greg; Tanev, Kalo; Tempkin, Teresa; Thiede, Curtis; Wasserman, Paula; Welsh, Claire; Wesson, Melissa; Zauber, Elizabeth

    2012-01-01

    Objective: Age at onset of diagnostic motor manifestations in Huntington disease (HD) is strongly correlated with an expanded CAG trinucleotide repeat. The length of the normal CAG repeat allele has been reported also to influence age at onset, in interaction with the expanded allele. Due to profound implications for disease mechanism and modification, we tested whether the normal allele, interaction between the expanded and normal alleles, or presence of a second expanded allele affects age at onset of HD motor signs. Methods: We modeled natural log-transformed age at onset as a function of CAG repeat lengths of expanded and normal alleles and their interaction by linear regression. Results: An apparently significant effect of interaction on age at motor onset among 4,068 subjects was dependent on a single outlier data point. A rigorous statistical analysis with a well-behaved dataset that conformed to the fundamental assumptions of linear regression (e.g., constant variance and normally distributed error) revealed significance only for the expanded CAG repeat, with no effect of the normal CAG repeat. Ten subjects with 2 expanded alleles showed an age at motor onset consistent with the length of the larger expanded allele. Conclusions: Normal allele CAG length, interaction between expanded and normal alleles, and presence of a second expanded allele do not influence age at onset of motor manifestations, indicating that the rate of HD pathogenesis leading to motor diagnosis is determined by a completely dominant action of the longest expanded allele and as yet unidentified genetic or environmental factors. Neurology® 2012;78:690–695 PMID:22323755

  14. Polygenic risk of Parkinson disease is correlated with disease age at onset

    OpenAIRE

    Escott-Price, V; International, Parkinson s. Disease Genomics Consortium; Nalls, M.A.; Morris, H R; Lubbe, S; Brice, A.; Gasser, T.; Heutink, P; Wood, N W; Hardy, J.; Singleton, A.B.; Williams, N.M.; IPDGC, consortium members

    2015-01-01

    Objective We have investigated the polygenic architecture of Parkinson disease (PD) and have also explored the potential relationship between an individual's polygenic risk score and their disease age at onset. Methods This study used genotypic data from 4,294 cases and 10,340 controls obtained from the meta‐analysis of PD genome‐wide association studies. Polygenic score analysis was performed as previously described by the International Schizophrenia Consortium, testing whether the polygenic...

  15. The gene coding for PGC-1α modifies age at onset in Huntington's Disease

    Directory of Open Access Journals (Sweden)

    Oberkofler Hannes

    2009-01-01

    Full Text Available Abstract Huntington's disease (HD is one of the most common autosomal dominant inherited, neurodegenerative disorders. It is characterized by progressive motor, emotional and cognitive dysfunction. In addition metabolic abnormalities such as wasting and altered energy expenditure are increasingly recognized as clinical hallmarks of the disease. HD is caused by an unstable CAG repeat expansion in the HD gene (HTT, localized on chromosome 4p16.3. The number of CAG repeats in the HD gene is the main predictor of disease-onset, but the remaining variation is strongly heritable. Transcriptional dysregulation, mitochondrial dysfunction and enhanced oxidative stress have been implicated in the pathogenesis. Recent studies suggest that PGC-1α, a transcriptional master regulator of mitochondrial biogenesis and metabolism, is defective in HD. A genome wide search for modifier genes of HD age-of-onset had suggested linkage at chromosomal region 4p16-4p15, near the locus of PPARGC1A, the gene coding for PGC-1α. We now present data of 2-loci PPARGC1A block 2 haplotypes, showing an effect upon age-at-onset in 447 unrelated HD patients after statistical consideration of CAG repeat lengths in both HTT alleles. Block 1 haplotypes were not associated with the age-at-onset. Homozygosity for the 'protective' block 2 haplotype was associated with a significant delay in disease onset. To our knowledge this is the first study to show clinically relevant effects of the PGC-1α system on the course of Huntington's disease in humans.

  16. CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion

    DEFF Research Database (Denmark)

    Lee, J-M; Ramos, E M; Lee, J-H;

    2012-01-01

    Age at onset of diagnostic motor manifestations in Huntington disease (HD) is strongly correlated with an expanded CAG trinucleotide repeat. The length of the normal CAG repeat allele has been reported also to influence age at onset, in interaction with the expanded allele. Due to profound...

  17. Combined effect of TLR2 gene polymorphism and early life stress on the age at onset of bipolar disorders.

    Directory of Open Access Journals (Sweden)

    José Oliveira

    Full Text Available Gene-environment interactions may play an important role in modulating the impact of early-life stressful events on the clinical course of bipolar disorder (BD, particularly associated to early age at onset. Immune dysfunction is thought to be an important mechanism linking childhood trauma with early-onset BD, thus the genetic diversity of immune-related loci may account for an important part of the interindividual susceptibility to this severe subform. Here we investigated the potential interaction between genetic variants of Toll-like receptors 2 (TLR2 and 4 (TLR4, major innate immune response molecules to pathogens, and the childhood trauma questionnaire (CTQ in age at onset of BD. We recruited 531 BD patients (type I and II or not otherwise specified, genotyped for the TLR2 rs4696480 and rs3804099 and TLR4 rs1927914 and rs11536891 single-nucleotide polymorphisms and recorded for history of childhood trauma using the CTQ. TLR2 and TLR4 risk genotype carrier state and history of childhood emotional, physical and sexual abuses were evaluated in relation to age at onset as defined by the age at first manic or depressive episode. We observed a combined effect of TLR2 rs3804099 TT genotype and reported sexual abuse on determining an earlier age at onset of BD by means of a Kaplan-Meier survival curve (p = 0.002; corrected p = 0.02. Regression analysis, however, was non-significant for the TLR2-CTQ sexual abuse interaction term. The negative effects of childhood sexual abuse on age at onset of BD may be amplified in TLR2 rs3804099 risk genotype carriers through immune-mediated pathways. Clinical characteristics of illness severity, immune phenotypes and history of early life infectious insults should be included in future studies involving large patient cohorts.

  18. Combined effect of TLR2 gene polymorphism and early life stress on the age at onset of bipolar disorders.

    Science.gov (United States)

    Oliveira, José; Etain, Bruno; Lajnef, Mohamed; Hamdani, Nora; Bennabi, Meriem; Bengoufa, Djaouida; Sundaresh, Aparna; Chaabane, Arij Ben; Bellivier, Frank; Henry, Chantal; Kahn, Jean-Pierre; Charron, Dominique; Krishnamoorthy, Rajagopal; Leboyer, Marion; Tamouza, Ryad

    2015-01-01

    Gene-environment interactions may play an important role in modulating the impact of early-life stressful events on the clinical course of bipolar disorder (BD), particularly associated to early age at onset. Immune dysfunction is thought to be an important mechanism linking childhood trauma with early-onset BD, thus the genetic diversity of immune-related loci may account for an important part of the interindividual susceptibility to this severe subform. Here we investigated the potential interaction between genetic variants of Toll-like receptors 2 (TLR2) and 4 (TLR4), major innate immune response molecules to pathogens, and the childhood trauma questionnaire (CTQ) in age at onset of BD. We recruited 531 BD patients (type I and II or not otherwise specified), genotyped for the TLR2 rs4696480 and rs3804099 and TLR4 rs1927914 and rs11536891 single-nucleotide polymorphisms and recorded for history of childhood trauma using the CTQ. TLR2 and TLR4 risk genotype carrier state and history of childhood emotional, physical and sexual abuses were evaluated in relation to age at onset as defined by the age at first manic or depressive episode. We observed a combined effect of TLR2 rs3804099 TT genotype and reported sexual abuse on determining an earlier age at onset of BD by means of a Kaplan-Meier survival curve (p = 0.002; corrected p = 0.02). Regression analysis, however, was non-significant for the TLR2-CTQ sexual abuse interaction term. The negative effects of childhood sexual abuse on age at onset of BD may be amplified in TLR2 rs3804099 risk genotype carriers through immune-mediated pathways. Clinical characteristics of illness severity, immune phenotypes and history of early life infectious insults should be included in future studies involving large patient cohorts. PMID:25790282

  19. A Genome Scan for Modifiers of Age at Onset in Huntington Disease: The HD MAPS Study

    OpenAIRE

    Li, Jian-Liang; Hayden, Michael R.; Almqvist, Elisabeth W.; Brinkman, Ryan R; Durr, Alexandra; Dodé, Catherine; Morrison, Patrick J.; Suchowersky, Oksana; Ross, Christopher A.; Margolis, Russell L.; Rosenblatt, Adam; Gómez-Tortosa, Estrella; Cabrero, David Mayo; Novelletto, Andrea; Frontali, Marina

    2003-01-01

    Huntington disease (HD) is caused by the expansion of a CAG repeat within the coding region of a novel gene on 4p16.3. Although the variation in age at onset is partly explained by the size of the expanded repeat, the unexplained variation in age at onset is strongly heritable (h2=0.56), which suggests that other genes modify the age at onset of HD. To identify these modifier loci, we performed a 10-cM density genomewide scan in 629 affected sibling pairs (295 pedigrees and 695 individuals), ...

  20. Order of age at onset for substance use, substance use disorder, conduct disorder and psychiatric illness

    DEFF Research Database (Denmark)

    Guldager, Steen; Linneberg, Inger Holm; Hesse, Morten

    2012-01-01

    of Personality – Abbreviated Scale (SAPAS), completed the MCMI-III, the Beck Anxiety Inventory (BAI), and were rated with the Montgomery Åsberg Depression Rating Scale. Age at onset was lowest for conduct disorder/antisocial behaviour, followed by tasting alcohol, trying drugs, post-traumatic stress disorder......This study aimed to assess the number of patients who reported earlier age at onset for psychiatric illness versus those with an earlier age at onset for substance use. Subjects were 194 patients from substance use disorder (SUD) treatment services in the Municipality of Fredericia who accepted...... an offer of psychological assessment. Patients were administered the Mini International Neuropsychiatric Interview (MINI), and when diagnoses were indicated, queried about the age at onset for each disorder. Additionally, subjects were administered the WAIS-III vocabulary scale, the Structured Assessment...

  1. Semiparametric Quantitative-Trait-Locus Mapping: II. on Censored Age-at-Onset

    OpenAIRE

    Ying Chen; Chengcheng Hu; Rongling Wu

    2004-01-01

    In genetic studies, the variation in genotypes may not only affect different inheritance patterns in qualitative traits, but may also affect the age-at-onset as quantitative trait. In this article, we use standard cross designs, such as backcross or F2, to propose some hazard regression models, namely, the additive hazards model in quantitative trait loci mapping for age-at-onset, although the developed method can be extended to more complex designs. With additive invariance of the additive h...

  2. Younger age at onset of sporadic Parkinson's disease among subjects occupationally exposed to metals and pesticides

    OpenAIRE

    Ratner Marcia H.; Farb David H.; Ozer Josef; Feldman Robert G.; Durso Raymon

    2014-01-01

    An earlier age at onset of Parkinson’s disease (PD) has been reported to be associated with occupational exposures to manganese and hydrocarbon solvents suggesting that exposure to neurotoxic chemicals may hasten the progression of idiopathic PD. In this study the role of occupational exposure to metals and pesticides in the progression of idiopathic PD was assessed by looking at age at disease onset. The effects of heritable genetic risk factors, which may also influence age at onset, was mi...

  3. Variants located upstream of CHRNB4 on chromosome 15q25.1 are associated with age at onset of daily smoking and habitual smoking.

    Directory of Open Access Journals (Sweden)

    Manav Kapoor

    Full Text Available Several genome-wide association and candidate gene studies have linked chromosome 15q24-q25.1 (a region including the CHRNA5-CHRNA3-CHRNB4 gene cluster with alcohol dependence, nicotine dependence and smoking-related illnesses such as lung cancer and chronic obstructive pulmonary disease. To further examine the impact of these genes on the development of substance use disorders, we tested whether variants within and flanking the CHRNA5-CHRNA3-CHRNB4 gene cluster affect the transition to daily smoking (individuals who smoked cigarettes 4 or more days per week in a cross sectional sample of adolescents and young adults from the COGA (Collaborative Study of the Genetics of Alcoholism families. Subjects were recruited from families affected with alcoholism (either as a first or second degree relative and the comparison families. Participants completed the SSAGA interview, a comprehensive assessment of alcohol and other substance use and related behaviors. Using the Quantitative trait disequilibrium test (QTDT significant association was detected between age at onset of daily smoking and variants located upstream of CHRNB4. Multivariate analysis using a Cox proportional hazards model further revealed that these variants significantly predict the age at onset of habitual smoking among daily smokers. These variants were not in high linkage disequilibrium (0.28

  4. How Does Age at Onset Influence the Outcome of Autoimmune Diseases?

    Directory of Open Access Journals (Sweden)

    Manuel J. Amador-Patarroyo

    2012-01-01

    Full Text Available The age at onset refers to the time period at which an individual experiences the first symptoms of a disease. In autoimmune diseases (ADs, these symptoms can be subtle but are very relevant for diagnosis. They can appear during childhood, adulthood or late in life and may vary depending on the age at onset. Variables like mortality and morbidity and the role of genes will be reviewed with a focus on the major autoimmune disorders, namely, systemic lupus erythematosus (SLE, rheumatoid arthritis (RA, multiple sclerosis (MS, type 1 diabetes mellitus (T1D, Sjögren's syndrome, and autoimmune thyroiditis (AITD. Early age at onset is a worst prognostic factor for some ADs (i.e., SLE and T1D, while for others it does not have a significant influence on the course of disease (i.e., SS or no unanimous consensus exists (i.e., RA and MS.

  5. Age at Onset of Epilepsy and Effect of Uncontrolled Seizures on Cognitive Outcome

    OpenAIRE

    J Gordon Millichap

    2012-01-01

    Researchers at the Epilepsy Center and Department of Psychiatry at Lurie Children’s Hospital of Chicago examined the association of cognitive scores and age at onset of epilepsy, pharmacoresistance, and interaction between the two in a prospective community-based study of 198 children, aged

  6. Polymorphisms associated with age at onset in patients with moderate-to-severe plaque psoriasis

    OpenAIRE

    Prieto-Pérez, Rocío; Solano-López, Guillermo; Cabaleiro, Teresa; Román, Manuel (fl. 1682-1725), Hereus de, imp.; Ochoa, Dolores; Talegón, María; Baniandrés, Ofelia; López-Estebaranz, José Luis; de la Cueva, Pablo; Daudén, Esteban; Abad-Santos, Francisco

    2015-01-01

    Psoriasis is a chronic skin disease in which genetics play a major role. Although many genome-wide association studies have been performed in psoriasis, knowledge of the age at onset remains limited. Therefore, we analyzed 173 single-nucleotide polymorphisms in genes associatedwith psoriasis and other autoimmune diseases in patients with moderate-to-severe plaque psoriasis type I (earlyonset,

  7. Polymorphisms Associated with Age at Onset in Patients with Moderate-to-Severe Plaque Psoriasis

    OpenAIRE

    Rocío Prieto-Pérez; Guillermo Solano-López; Teresa Cabaleiro; Manuel Román; Dolores Ochoa; María Talegón; Ofelia Baniandrés; José Luis López-Estebaranz; Pablo de la Cueva; Esteban Daudén; Francisco Abad-Santos

    2015-01-01

    Psoriasis is a chronic skin disease in which genetics play a major role. Although many genome-wide association studies have been performed in psoriasis, knowledge of the age at onset remains limited. Therefore, we analyzed 173 single-nucleotide polymorphisms in genes associated with psoriasis and other autoimmune diseases in patients with moderate-to-severe plaque psoriasis type I (early-onset,

  8. 4p16.3 haplotype modifying age at onset of Huntington disease

    DEFF Research Database (Denmark)

    Nørremølle, A; Budtz-Jørgensen, E; Fenger, K;

    2009-01-01

    Huntington disease (HD) is caused by an expanded CAG repeat sequence in the HD gene. Although the age at onset is correlated to the CAG repeat length, this correlation only explains approximately half of the variation in onset age. Less variation between siblings indicates that the variation is...

  9. Excessive cannabis use is associated with earlier age at onset in bipolar disorder

    OpenAIRE

    Lagerberg, Trine V; Sundet, Kjetil; Aminoff, Sofie R.; Berg, Akiah O.; Ringen, Petter A.; Ole A. Andreassen; Melle, Ingrid

    2011-01-01

    The aim of the study was to investigate which factors are associated with age at onset in bipolar disorder with a specific focus on excessive alcohol and cannabis use, and the sequence of the onsets of excessive substance use and bipolar disorder. We investigated a naturalistic sample of 151 patients with bipolar I and II disorder receiving psychiatric treatment. Whether the presence of excessive substance use prior to bipolar disorder onset or the type of substance used (alcohol or cannabis)...

  10. Influence of age at onset on social functioning in outpatients with schizophrenia

    OpenAIRE

    Ochoa, S; J. Usall; V. Villalta-Gil; M. Vilaplana; M. Márquez; M. Valdelomar; Haro, J. M.

    2006-01-01

    Background and Objectives: There are different factors that have been found to predict disability in schizophrenia. The aim of our study is to evaluate the influence of age at onset on social functioning in schizophrenia in a large sample of schizophrenic outpatients controlling for gender. Methods: Two hundred and thirty-one subjects with schizophrenia (DSM-IV criteria) were randomly selected from a register that included all patients under treatment in five mental health care centers (MHCC)...

  11. Age at Onset of Type 1 Diabetes in Parents and Recurrence Risk in Offspring

    OpenAIRE

    Harjutsalo, Valma; Lammi, Niina; Karvonen, Marjatta; Groop, Per-Henrik

    2009-01-01

    OBJECTIVE Our aim was to study the recurrence risk of type 1 diabetes in the offspring of parents with adult-onset (15–39 years) type 1 diabetes and to evaluate the transmission of diabetes within a continuum of parental age at onset of diabetes from childhood to adulthood. RESEARCH DESIGN AND METHODS Diabetes status of all offspring (n = 9,636) in two Finnish cohorts of parents with type 1 diabetes was defined until the end of year 2007. Cumulative incidences of type 1 diabetes among the off...

  12. Polymorphisms Associated with Age at Onset in Patients with Moderate-to-Severe Plaque Psoriasis.

    Science.gov (United States)

    Prieto-Pérez, Rocío; Solano-López, Guillermo; Cabaleiro, Teresa; Román, Manuel; Ochoa, Dolores; Talegón, María; Baniandrés, Ofelia; López-Estebaranz, José Luis; de la Cueva, Pablo; Daudén, Esteban; Abad-Santos, Francisco

    2015-01-01

    Psoriasis is a chronic skin disease in which genetics play a major role. Although many genome-wide association studies have been performed in psoriasis, knowledge of the age at onset remains limited. Therefore, we analyzed 173 single-nucleotide polymorphisms in genes associated with psoriasis and other autoimmune diseases in patients with moderate-to-severe plaque psoriasis type I (early-onset, psoriasis and patients with type II psoriasis. Our comparison of a stratified population with type I psoriasis (n = 155) and healthy controls (N = 197) is the first to reveal a relationship between the CLMN, FBXL19, CCL4L, C17orf51, TYK2, IL13, SLC22A4, CDKAL1, and HLA-B/MICA genes. When we compared type I psoriasis with type II psoriasis (N = 36), we found a significant association between age at onset and the genes PSORS6, TNF-α, FCGR2A, TNFR1, CD226, HLA-C, TNFAIP3, and CCHCR1. Moreover, we replicated the association between rs12191877 (HLA-C) and type I psoriasis and between type I and type II psoriasis. Our findings highlight the role of genetics in age of onset of psoriasis. PMID:26613086

  13. A Formalization of Linkage Analysis

    DEFF Research Database (Denmark)

    Ingolfsdottir, Anna; Christensen, A.I.; Hansen, Jens A.;

    In this report a formalization of genetic linkage analysis is introduced. Linkage analysis is a computationally hard biomathematical method, which purpose is to locate genes on the human genome. It is rooted in the new area of bioinformatics and no formalization of the method has previously been ...

  14. Glutathione S-Transferase Ω 1 variation does not influence age at onset of Huntington's disease

    Directory of Open Access Journals (Sweden)

    Saft Carsten

    2004-03-01

    Full Text Available Abstract Background Huntington's disease (HD is a fully penetrant, autosomal dominantly inherited disorder associated with abnormal expansions of a stretch of perfect CAG repeats in the 5' part of the IT15 gene. The number of repeat units is highly predictive for the age at onset (AO of the disorder. But AO is only modestly correlated with repeat length when intermediate HD expansions are considered. Circumstantial evidence suggests that additional features of the HD course are based on genetic traits. Therefore, it may be possible to investigate the genetic background of HD, i.e. to map the loci underlying the development and progression of the disease. Recently an association of Glutathione S-Transferase Ω 1 (GSTO1 and possibly of GSTO2 with AO was demonstrated for, both, Alzheimer's (AD and Parkinson's disease (PD. Methods We have genotyped the polymorphisms rs4925 GSTO1 and rs2297235 GSTO2 in 232 patients with HD and 228 controls. Results After genotyping GSTO1 and GSTO2 polymorphisms, firstly there was no statistically significant difference in AO for HD patients, as well as secondly for HD patients vs. controls concerning, both, genotype and allele frequencies, respectively. Conclusion The GSTO1 and GSTO2 genes flanked by the investigated polymorphisms are not comprised in a primary candidate region influencing AO in HD.

  15. Body mass index is associated with age-at-onset of HCVinfected hepatocellular carcinoma patients

    Institute of Scientific and Technical Information of China (English)

    Takumi Akiyama; Toshihiko Mizuta; Seiji Kawazoe; Yuichiro Eguchi; Yasunori Kawaguchi; Hirokazu Takahashi; Iwata Ozaki; Kazuma Fujimoto

    2011-01-01

    AIM:To identify factors associated with the age at onset of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC).METHODS:Five hundred and fifty-six consecutive patients positive for HCV antibody and treatmentna(i)ve HCC diagnosed between 1995 and 2004 were analyzed.Patients were classified into three groups according to age at HCC onset: 60 years old were lower and mean BMI values of female patients 25 kg/m2 [hazard ratio (HR),1.8,P = 0.045],excessive alcohol consumption (HR,2.5,P = 0.024),male sex (HR,3.6,P = 0.002),and GGT levels > 50 IU/L (HR,2.4,P = 0.014) were independently associated with HCC onset in patients < 60 years.Low ALT level was the only factor associated with HCC onset in patients aged ≥ 80 years.CONCLUSION:Increased BMI is associated with increased risk for early HCC development in HCV-infected patients.Achieving recommended BMI and reducing alcohol intake could help prevent hepatic carcinogenesis.

  16. Effect of age at onset on cortical thickness and cognition in posterior cortical atrophy.

    Science.gov (United States)

    Suárez-González, Aida; Lehmann, Manja; Shakespeare, Timothy J; Yong, Keir X X; Paterson, Ross W; Slattery, Catherine F; Foulkes, Alexander J M; Rabinovici, Gil D; Gil-Néciga, Eulogio; Roldán-Lora, Florinda; Schott, Jonathan M; Fox, Nick C; Crutch, Sebastian J

    2016-08-01

    Age at onset (AAO) has been shown to influence the phenotype of Alzheimer's disease (AD), but how it affects atypical presentations of AD remains unknown. Posterior cortical atrophy (PCA) is the most common form of atypical AD. In this study, we aimed to investigate the effect of AAO on cortical thickness and cognitive function in 98 PCA patients. We used Freesurfer (v5.3.0) to compare cortical thickness with AAO both as a continuous variable, and by dichotomizing the groups based on median age (58 years). In both the continuous and dichotomized analyses, we found a pattern suggestive of thinner cortex in precuneus and parietal areas in earlier-onset PCA, and lower cortical thickness in anterior cingulate and prefrontal cortex in later-onset PCA. These cortical thickness differences between PCA subgroups were consistent with earlier-onset PCA patients performing worse on cognitive tests involving parietal functions. Our results provide a suggestion that AAO may not only affect the clinico-anatomical characteristics in AD but may also affect atrophy patterns and cognition within atypical AD phenotypes. PMID:27318138

  17. Failure to confirm influence of Methyltetrahydrofolate reductase (MTHFR polymorphisms on age at onset of Huntington disease

    Directory of Open Access Journals (Sweden)

    Wieczorek Stefan

    2005-12-01

    Full Text Available Abstract Background Huntington disease (HD is a fully penetrant, autosomal dominantly inherited disorder associated with abnormal expansions of a stretch of perfect CAG repeats in the 5' part of the IT15 gene. The number of repeat units is highly predictive for the age at onset (AO of the disorder. But AO is only modestly correlated with repeat length when intermediate HD expansions are considered. Recently, suggestive association has been reported between a single nucleotide polymorphism (SNP; rs1801131, also known as A1298C in the methyltetrahydrofolate reductase (MTHFR gene and AO of HD. 5,10-MTHFR is a key enzyme in the folate metabolism, diverting metabolites toward methylation reactions or nucleotide synthesis. Using part of a previously established study cohort plus additional patients and appropriate statistical methods, we reinvestigated two polymorphisms in the MTHFR gene, C677T and A1298C, as well as their association with AO in 167 HD patients. Results There was no statistically significant impact on AO for HD patients, neither of MTHFR SNPs nor of the combinations thereof. Conclusion Contrary to previously described evidence the A1298C polymorphism in the MTHFR gene does not appear to modulate AO of HD patients.

  18. Study of factors influencing susceptibility and age at onset of type 1 diabetes: A review of data from Continental Italy and Sardinia

    Institute of Scientific and Technical Information of China (English)

    Fulvia; Gloria-Bottini; Patrizia; Saccucci; Gian; Franco; Meloni; Maria; Luisa; Manca-Bitti; Luca; Coppeta; Anna; Neri; Andrea; Magrini; Bottini; Egidio

    2014-01-01

    AIM:To investigate the role of protein tyrosin phosphatase 22(PTPN22),maternal age at conception and sex on susceptibility and age at onset of type 1 diabetes(T1D)in Continental Italy and Sardinian populations.METHODS:Three hundred seventy six subjects admitted consecutively to the hospital for T1D and 1032healthy subjects as controls were studied in Continental Italy and 284 subjects admitted consecutively to the hospital for T1D and 5460 healthy newborns were studied in Sardinia.PTPN22 genotype was determined by DNA analysis.Maternal age at conception and age at onset of disease were obtained from clinical records.χ2 test of independence,student t test for differences between means and odds ratio analysis were carried out by SPSS programs.Three way contingency table analysis was carried out according to Sokal and Rohlf.RESULTS:The pattern of association between PTPN22and T1D is similar in Continental Italy and Sardinia:the proportion of*T allele carriers is 13.6%in T1D vs6.7%in controls in Continental Italy while in Sardinia is 7.3%in T1D vs 4.4%in controls.The association between T1D and maternal age at conception is much stronger in Sardinia than in Italy:the proportion of newborn from mother aging more than 32 years is89.3%in T1D vs 32.7%in consecutive newborn in Sardinia(P<10-6)while in Continental Italy is 32.2%in T1D vs 19.1%in consecutive newborns(P=0.005).This points to an important role of ethnicity.A slight prevalence of T1D males on T1D females is observed both in Continental Italy and Sardinia.PTPN22 genotype does not exert significant effect on the age at onset neither in Continental Italy nor and Sardinia.Maternal age does not influence significantly age at onset in Italy(8.2 years in T1D infants from mothers aging32 years or less vs 7.89 years in T1D infants from mothers aging more than 32 years:P=0.824)while in Sardinia a border line effect is observed(5.75 years in T1D infants from mothers aging 32 years or less vs7.54 years in T1D infants from

  19. Whole-genome sequencing suggests a chemokine gene cluster that modifies age at onset in familial Alzheimer's disease.

    Science.gov (United States)

    Lalli, M A; Bettcher, B M; Arcila, M L; Garcia, G; Guzman, C; Madrigal, L; Ramirez, L; Acosta-Uribe, J; Baena, A; Wojta, K J; Coppola, G; Fitch, R; de Both, M D; Huentelman, M J; Reiman, E M; Brunkow, M E; Glusman, G; Roach, J C; Kao, A W; Lopera, F; Kosik, K S

    2015-11-01

    We have sequenced the complete genomes of 72 individuals affected with early-onset familial Alzheimer's disease caused by an autosomal dominant, highly penetrant mutation in the presenilin-1 (PSEN1) gene, and performed genome-wide association testing to identify variants that modify age at onset (AAO) of Alzheimer's disease. Our analysis identified a haplotype of single-nucleotide polymorphisms (SNPs) on chromosome 17 within a chemokine gene cluster associated with delayed onset of mild-cognitive impairment and dementia. Individuals carrying this haplotype had a mean AAO of mild-cognitive impairment at 51.0 ± 5.2 years compared with 41.1 ± 7.4 years for those without these SNPs. This haplotype thus appears to modify Alzheimer's AAO, conferring a large (~10 years) protective effect. The associated locus harbors several chemokines including eotaxin-1 encoded by CCL11, and the haplotype includes a missense polymorphism in this gene. Validating this association, we found plasma eotaxin-1 levels were correlated with disease AAO in an independent cohort from the University of California San Francisco Memory and Aging Center. In this second cohort, the associated haplotype disrupted the typical age-associated increase of eotaxin-1 levels, suggesting a complex regulatory role for this haplotype in the general population. Altogether, these results suggest eotaxin-1 as a novel modifier of Alzheimer's disease AAO and open potential avenues for therapy.

  20. The effect of cannabis use and cognitive reserve on age at onset and psychosis outcomes in first-episode schizophrenia

    OpenAIRE

    Leeson, V. C.; I. Harrison; Ron, M A; Barnes, T. R.; Joyce, E M

    2012-01-01

    Objective: Cannabis use is associated with a younger age at onset of psychosis, an indicator of poor prognosis, but better cognitive function, a positive prognostic indicator. We aimed to clarify the role of age at onset and cognition on outcomes in cannabis users with first-episode schizophrenia as well as the effect of cannabis dose and cessation of use. Methods: Ninety-nine patients without alcohol or substance abuse other than cannabis were divided into lifetime users and never-users of c...

  1. Younger age at onset of sporadic Parkinson’s disease among subjects occupationally exposed to metals and pesticides

    Directory of Open Access Journals (Sweden)

    Ratner Marcia H.

    2014-09-01

    Full Text Available An earlier age at onset of Parkinson’s disease (PD has been reported to be associated with occupational exposures to manganese and hydrocarbon solvents suggesting that exposure to neurotoxic chemicals may hasten the progression of idiopathic PD. In this study the role of occupational exposure to metals and pesticides in the progression of idiopathic PD was assessed by looking at age at disease onset. The effects of heritable genetic risk factors, which may also influence age at onset, was minimized by including only sporadic cases of PD with no family history of the disease (n=58. Independent samples Student t-test revealed that subjects with occupational exposure to metals and/or pesticides (n=36 were significantly (p=0.013 younger than unexposed controls (n=22. These subjects were then divided into three groups [high (n=18, low (n=18, and unexposed (n=22] to ascertain if duration of exposure further influenced age at onset of PD. One-way ANOVA revealed that subjects in the high exposure group were significantly (p=0.0121 younger (mean age: 50.33 years than unexposed subjects (mean age: 60.45 years. Subjects were also stratified by exposure type (metals vs. pesticides. These results suggest that chronic exposure to metals and pesticides is associated with a younger age at onset of PD among patients with no family history of the disease and that duration of exposure is a factor in the magnitude of this effect.

  2. Participation and Life Satisfaction in Aged People with Spinal Cord Injury : Does Age at Onset Make a Difference?

    NARCIS (Netherlands)

    Post, Marcel W M; Reinhardt, Jan D

    2015-01-01

    BACKGROUND: Few studies have reported on outcomes in samples of elderly people with SCI and the impact of the age at onset of SCI is unclear. OBJECTIVE: To study levels of participation and life satisfaction in individuals with SCI aged 65 years or older and to analyze differences in participation a

  3. A length polymorphism in the circadian clock gene Per3 influences age at onset of bipolar disorder.

    Science.gov (United States)

    Benedetti, Francesco; Dallaspezia, Sara; Colombo, Cristina; Pirovano, Adele; Marino, Elena; Smeraldi, Enrico

    2008-11-14

    Age at onset of bipolar disorder might represent the penetrance of the system for specific genetic liability involved in the genesis of the illness. Genetic factors influencing age at onset have been shown to play a role in shaping core characteristics of the illness, such as severity and pattern of recurrence. Genetic variants of genes regulating the circadian clock could contribute to define endophenotypes of bipolar disorder, and have been associated with clinical features of the disease. The coding region of Per3 gene contains a variable-number tandem-repeat (VNTR) polymorphism which has been associated with diurnal preference, sleep structure and sleep homeostasis in healthy subjects. In a homogeneous sample of 99 patients affected by bipolar disorder type I we observed that Per3 VNTR influenced age at onset of illness: earlier age at onset in homozygote carriers of Per35 variant, later in homozygotes for Per34, and intermediate in heterozygotes. Allele frequencies were not significantly different from those reported in healthy subjects. Results need to be confirmed in larger samples, but warrant interest for the variants of molecular clock genes as possible endophenotypes of bipolar disorder.

  4. Single nucleotide polymorphisms in the mitochondrial displacement loop and age-at-onset of familial breast cancer.

    Science.gov (United States)

    Lee, Haiping; Geng, Cuizhi; Cheng, Meng; Lee, Zheng; Guo, Zhanjun

    2016-09-01

    Single nucleotide polymorphisms (SNPs) are accumulated frequently in the mitochondrial displacement loop (D-loop) in various types of cancer, and their association with cancer risk and disease outcome has been extensively identified. We have identified specific risk-associated SNP for familial breast cancer patients previously. In this study, we investigated the association between age-at-onset and the SNPs in familial breast cancer patients. The SNP sites of nucleotides 16 311 T/C were identified for their association with age-at-onset using the log-rank test. The age-at-onset of the patients with the minor allele C genotype was significantly earlier than that of patients carrying the T genotype at the site 16 311 (p = 0.032). Accordingly, the genetic polymorphisms in the mitochondrial D-loop are predictive markers for age-at-onset in familial breast cancer patients, which may help to identify familial breast cancer patient subgroups at high risk of early onset. PMID:27158866

  5. Rectal cancer profiling identifies distinct subtypes in India based on age at onset, genetic, epigenetic and clinicopathological characteristics.

    Science.gov (United States)

    Laskar, Ruhina Shirin; Ghosh, Sankar Kumar; Talukdar, Fazlur Rahman

    2015-12-01

    Rectal cancer is a heterogeneous disease that develops through multiple pathways characterized by genetic and epigenetic alterations. India has a comparatively higher proportion of rectal cancers and early-onset cases. We analyzed genetic (KRAS, TP53 and BRAF mutations, and MSI), epigenetic alterations (CpG island methylation detection of 10 tumor-related genes/loci), the associated clinicopathological features and survival trend in 80 primary rectal cancer patients from India. MSI was detected using BAT 25 and BAT 26 mononucleotide markers and mutation of KRAS, TP53, and BRAF V600E was detected by direct sequencing. Methyl specific polymerase chain reaction was used to determine promoter methylation status of the classic CIMP panel markers (P16, hMLH1, MINT1, MINT2, and MINT31) as well as other tumor specific genes (DAPK, RASSF1, BRCA1, and GSTP1). MSI and BRAF mutations were uncommon but high frequencies of overall KRAS mutations (67.5%); low KRAS codon 12 and a novel KRAS G15S mutation with concomitant RASSF1 methylation in early onset cases were remarkable. Hierarchical clustering as well as principal component analysis identified three distinct subgroups of patients having discrete age at onset, clinicopathological, molecular and survival characteristics: (i) a KRAS associated CIMP-high subgroup; (ii) a significantly younger MSS, CIMP low, TP53 mutant group having differential KRAS mutation patterns, and (iii) a CIMP-negative, TP53 mutated group. The early onset subgroup exhibited the most unfavorable disease characteristics with advanced stage, poorly differentiated tumors and had the poorest survival compared to the other subgroups. Genetic and epigenetic profiling of rectal cancer patients identified distinct subtypes in Indian population.

  6. Clinical characteristics and long-term response to mood stabilizers in patients with bipolar disorder and different age at onset

    OpenAIRE

    Dell’Osso, Bernardo; Buoli, Massimiliano; Riundi, Riccardo; D’Urso, Nazario; Pozzoli, Sara; Bassetti, Roberta; Mundo, Emanuela; Altamura, A Carlo

    2009-01-01

    Introduction Bipolar disorder (BD) is a prevalent, comorbid, and impairing condition. Potential predictors of response to pharmacological treatment are object of continuous investigation in patients with BD. The present naturalistic study was aimed to assess clinical features and long-term response to mood stabilizers in a sample of bipolar subjects with different ages at onset. Methods The study sample included 108 euthymic patients, diagnosed as affected by BD, either type I or II, accordin...

  7. Combined Effect of TLR2 Gene Polymorphism and Early Life Stress on the Age at Onset of Bipolar Disorders

    OpenAIRE

    José Oliveira; Bruno Etain; Mohamed Lajnef; Nora Hamdani; Meriem Bennabi; Djaouida Bengoufa; Aparna Sundaresh; Arij Ben Chaabane; Frank Bellivier; Chantal Henry; Jean-Pierre Kahn; Dominique Charron; Rajagopal Krishnamoorthy; Marion Leboyer; Ryad Tamouza

    2015-01-01

    Gene-environment interactions may play an important role in modulating the impact of early-life stressful events on the clinical course of bipolar disorder (BD), particularly associated to early age at onset. Immune dysfunction is thought to be an important mechanism linking childhood trauma with early-onset BD, thus the genetic diversity of immune-related loci may account for an important part of the interindividual susceptibility to this severe subform. Here we investigated the potential in...

  8. Improving risk assessment and familial aggregation of age at onset in schizophrenia using minor physical anomalies and craniofacial measures.

    Science.gov (United States)

    Tsai, I-Ning; Lin, Jin-Jia; Lu, Ming-Kun; Tan, Hung-Pin; Jang, Fong-Lin; Gan, Shu-Ting; Lin, Sheng-Hsiang

    2016-07-01

    Age at onset is the most important feature of schizophrenia that could indicate its origin. Minor physical anomalies (MPAs) characterize potential marker indices of disturbances in early neurodevelopment. However, the association between MPAs and age at onset of schizophrenia is still unclear. We aimed to compare risk assessment and familial aggregation in patients with early-onset schizophrenia (EOS) and adult-onset schizophrenia (AOS) with MPAs and craniofacial measures.We estimated the risk assessment of MPAs among patients with EOS (n = 68), patients with AOS (n = 183), nonpsychotic relatives (n = 147), and healthy controls (n = 241) using 3 data-mining algorithms. In addition, we assessed the magnitude of familial aggregation of MPAs with respect to the age at onset of schizophrenia.The performance of EOS was superior to that of AOS, with discrimination accuracies of 89% and 76%, respectively. Combined MPA scores as the risk assessment were significantly higher in all schizophrenia subgroups and the nonpsychotic relatives of EOS patients than in the healthy controls. The recurrence risk ratio for familial aggregation of the MPA scores of EOS families (odds ratio 9.27) was substantially higher than that of AOS families (odds ratio 2.47).The results highlight that EOS improves risk assessment and has a severe magnitude of familial aggregation of MPAs. These findings indicate that EOS might result from a stronger genetic susceptibility to neurodevelopmental deficits. PMID:27472737

  9. TATA box-binding protein gene is associated with risk for schizophrenia, age at onset and prefrontal function.

    Science.gov (United States)

    Ohi, K; Hashimoto, R; Yasuda, Y; Kiribayashi, M; Iike, N; Yoshida, T; Azechi, M; Ikezawa, K; Takahashi, H; Morihara, T; Ishii, R; Tagami, S; Iwase, M; Okochi, M; Kamino, K; Kazui, H; Tanaka, T; Kudo, T; Takeda, M

    2009-06-01

    Schizophrenia is a common polygenic disease in distinct populations, while spinocerebellar ataxia type 17 (SCA17) is a rare autosomal dominant neurodegenerative disorder. Both diseases involve psychotic symptoms. SCA17 is caused by an expanded polyglutamine tract in the TATA box-binding protein (TBP) gene. In the present study, we investigated the association between schizophrenia and CAG repeat length in common TBP alleles with fewer than 42 CAG repeats in a Japanese population (326 patients with schizophrenia and 116 healthy controls). We found that higher frequency of alleles with greater than 35 CAG repeats in patients with schizophrenia compared with that in controls (p = 0.042). We also examined the correlation between CAG repeats length and age at onset of schizophrenia. We observed a negative correlation between the number of CAG repeats in the chromosome with longer CAG repeats out of two chromosomes and age at onset of schizophrenia (p = 0.020). We further provided evidence that TBP genotypes with greater than 35 CAG repeats, which were enriched in patients with schizophrenia, were significantly associated with hypoactivation of the prefrontal cortex measured by near-infrared spectroscopy during the tower of Hanoi, a task of executive function (right PFC; p = 0.015, left PFC; p = 0.010). These findings suggest possible associations of the genetic variations of the TBP gene with risk for schizophrenia, age at onset and prefrontal function. PMID:19566714

  10. Clinical characteristics and long-term response to mood stabilizers in patients with bipolar disorder and different age at onset

    Directory of Open Access Journals (Sweden)

    Bernardo Dell’Osso

    2009-07-01

    Full Text Available Bernardo Dell’Osso1, Massimiliano Buoli1, Riccardo Riundi2, Nazario D’Urso1, Sara Pozzoli1, Roberta Bassetti2, Emanuela Mundo1,  A Carlo Altamura11Department of Psychiatry, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milano, Italy; 2Department of Clinical Sciences, Luigi Sacco, Milano, ItalyIntroduction: Bipolar disorder (BD is a prevalent, comorbid, and impairing condition. Potential predictors of response to pharmacological treatment are object of continuous investigation in patients with BD. The present naturalistic study was aimed to assess clinical features and longterm response to mood stabilizers in a sample of bipolar subjects with different ages at onset. Methods: The study sample included 108 euthymic patients, diagnosed as affected by BD, either type I or II, according to the DSM-IV-TR, who were started on mood stabilizer treatment. Patients were followed-up for 24 months and the occurrence of any mood episode collected. At the end of the follow-up, patients were divided in three subgroups according to the age at onset (early-onset ≤30 years, middle-onset >30–≤45 years, and late-onset >45 years, respectively and the long-term response to mood stabilizers was compared between them along with other clinical features.Results: The three subgroups showed significant differences in terms of clinical and demographic features and, with respect to long-term response to mood stabilizers, the early-onset subgroup showed a better outcome in terms of reduction of major depressive episodes during the 24-month follow-up compared to the other subgroups (one way ANOVA, F = 3.57, p = 0.032. Conclusions: Even though further controlled studies are needed to clarify the relationship between age at onset and outcome in BD, the present follow-up study suggests clinical peculiarities and different patterns of response to mood stabilizers across distinct subgroups of patients with BD and

  11. Interaction between SLC6A4 promoter variants and childhood trauma on the age at onset of bipolar disorders

    OpenAIRE

    Etain, B.; Lajnef, M.; Henrion, A; A.A. Dargél; Stertz, L.; Kapczinski, F. ??; Mathieu, F.; Henry, C.; Gard, S.; Kahn, J. P.; Leboyer, M.; Jamain, S; Bellivier, F

    2015-01-01

    Age at onset (AAO) of bipolar disorders (BD) could be influenced both by a repeat length polymorphism (5HTTLPR) in the promoter region of the serotonin transporter gene (SLC6A4) and exposure to childhood trauma. We assessed 308 euthymic patients with BD for the AAO of their first mood episode and childhood trauma. Patients were genotyped for the 5HTTLPR (long/short variant) and the rs25531. Genotypes were classified on functional significance (LL, LS, SS). A sample of 126 Brazilian euthymic p...

  12. Evidence for Three Loci Modifying Age-at-Onset of Alzheimer’s Disease in Early-Onset PSEN2 Families

    OpenAIRE

    Marchani, Elizabeth E; Bird, Thomas D.; Steinbart, Ellen J; Rosenthal, Elisabeth; Yu, Chang-En; Schellenberg, Gerard D; Wijsman, Ellen M.

    2010-01-01

    Families with early-onset Alzheimer’s disease (AD) sharing a single PSEN2 mutation exhibit a wide range of age-at-onset, suggesting that modifier loci segregate within these families. While APOE is known to be an age-at-onset modifier, it does not explain all of this variation. We performed a genome scan within nine such families for loci influencing age-at-onset, while simultaneously controlling for variation in the primary PSEN2 mutation (N141I) and APOE. We found significant evidence of li...

  13. Effect of age at onset on frequency of depression in Parkinson's disease.

    OpenAIRE

    Kostíc, V S; Filipović, S R; Lecić, D; Momcilović, D; Sokić, D; Sternić, N

    1994-01-01

    In a consecutive series of 169 outpatients with Parkinson's disease the frequency of depression was compared in two groups: those who developed Parkinson's disease before the age of 50, and those who developed the disease after 50. Major depression was found in 36% of patients with early onset and in 16% of patients with late onset Parkinson's disease. This significant difference disappeared when both groups were matched for duration of Parkinson's disease. A stepwise regression analysis in b...

  14. Impact of age at onset and newborn screening on outcome in organic acidurias

    DEFF Research Database (Denmark)

    Heringer, Jana; Valayannopoulos, Vassili; Lund, Allan M;

    2016-01-01

    analyses, symptomatic patients were divided into those presenting with first symptoms during (i.e. early onset, EO) or after the newborn period (i.e. late onset, LO). RESULTS: Patients identified by newborn screening (NBS) had a significantly lower median age of diagnosis (8 days) compared to the LO group......BACKGROUND AND AIM: To describe current diagnostic and therapeutic strategies in organic acidurias (OADs) and to evaluate their impact on the disease course allowing harmonisation. METHODS: Datasets of 567 OAD patients from the E-IMD registry were analysed. The sample includes patients...... with methylmalonic (MMA, n = 164), propionic (PA, n = 144) and isovaleric aciduria (IVA, n = 83), and glutaric aciduria type 1 (GA1, n = 176). Statistical analysis included description and recursive partitioning of diagnostic and therapeutic strategies, and odds ratios (OR) for health outcome parameters. For some...

  15. Normal ATXN3 allele but not CHIP polymorphisms modulates age at onset in Machado-Joseph Disease

    Directory of Open Access Journals (Sweden)

    Marcondes C. França Jr

    2012-11-01

    Full Text Available Background: Age at onset (AO in Machado-Joseph disease (MJD is closely associated with the length of the CAG repeat at the mutant ATXN3 allele, but there are other intervening factors. Experimental evidence indicates that the normal ATXN3 allele and the C-terminal heat shock protein 70 (Hsp70-interacting protein (CHIP may be genetic modifiers of AO in MJD. Methods: To investigate this hypothesis, we determined the length of normal and expanded CAG repeats at the ATXN3 gene in 210 unrelated patients with MJD. In addition, we genotyped five single nucleotide polymorphisms (SNPs within the CHIP gene. We first compared the frequencies of the different genotypes in two subgroups of patients who were highly discordant for AO after correction for the length of the expanded CAG allele. The possible modifier effect of each gene was then evaluated in a stepwise multiple linear regression model. Results: AO was associated with the length of the expanded CAG allele (r2 = 0.596, p<0.001. Frequencies of the normal CAG repeats at the ATXN3 gene and of CHIP polymorphisms did not differ significantly between groups with highly discordant ages at onset. However, addition of the normal allele improved the model fit for prediction of AO (r2 = 0.604, p=0.014. Indeed, we found that the normal CAG allele at ATXN3 had a positive independent effect on AO. Conclusion: The normal CAG repeat at the ATXN3 gene has a small but significant influence on AO of MJD.

  16. Linkage analysis in Marfan syndrome.

    OpenAIRE

    Schwartz, R C; Blanton, S H; Hyde, C A; Sottile, T R; Hudgins, L.; Sarfarazi, M; Tsipouras, P

    1990-01-01

    We have analysed 40 marker loci on 13 chromosomes for linkage with Marfan syndrome. None of the loci was linked to the Marfan syndrome locus at theta = 0.00. This study provides a basis for an exclusion map and for further collaboration in mapping of the locus.

  17. INTERLEUKIN 28 RECEPTOR GENE ALPHA IL28RA AND PSORIASIS: ASSOCIATION WITH DISEASE SEVERITY AND AGE AT ONSET

    Directory of Open Access Journals (Sweden)

    E. S. Galimova

    2015-01-01

    Full Text Available Molecular basis still remains unclear for psoriasis, a chronic inflammatory skin disease. It biological features are presented by abnormal differentiation of epidermal keratinocytes, overgrowth and dilation of blood vessels, and leukocyte infiltration of dermal and epidermal skin layers. These events appear to be driven, mainly, by various cytokines and chemokines released by activated T cell populations. The aim of this replication study was to determine, whether the rs4649203 SNP of IL28RA gene is associated with susceptibility to psoriasis. A total of 341 patients with psoriasis and 407 matched healthy controls were enrolled to carry out a case control study. Genotyping was performed using a Real-Time PCR assay. Our preliminary data suggest that the polymorphism located in IL28RA gene, known to be related to inflammatory and immunity processes, showed an association with patients’ age at onset and the disease severity. The results of this study are promising, with respect to development of a personalized approach to psoriasis treatment.

  18. Association of age at onset in Huntington disease with functional promoter variations in NPY and NPY2R.

    Science.gov (United States)

    Kloster, Eugen; Saft, Carsten; Akkad, Denis A; Epplen, Jörg T; Arning, Larissa

    2014-02-01

    Huntington disease (HD) is caused by the expansion of a CAG repeat within exon 1 of the HTT gene. Although the variation in age at onset (AO) is partly explained by the lengths of the expanded repeats, the unexplained variation is highly heritable, emphasizing the role of the so-called genetic background on disease expression. Neuropeptide Y (NPY) has been implicated in the modulation of neuroprotection, neurogenesis, and neuroinflammation. Therefore, the aim of the present study was to analyze different single nucleotide polymorphisms (SNPs) in order to test the possibility that genetic variation in NPY or three of its receptor genes (NPY1R, NPY2R, and NPY5R) may explain some of the variation in AO of HD motor manifestations, in a comprehensive cohort of 487 German HD patients. We found modest association of the AO with two NPY promoter variations and a highly significant association with a NPY2R promoter SNP (rs2234759; p = 0.0004). Investigating the functional impact of rs2234759 by luciferase assays revealed that the high-expression NPY2R genotypes were associated with later AO in HD. Additionally, treatment of PC12 cells expressing mutant huntingtin (htt) exon 1 with NPY and the NPY2R agonist NPY(3-36) has a protective effect against mutant htt-induced cell death. Thus, NPY might act through Y2 receptors to slow down the course of HD, and hence, this peptide could be of interest as a possible therapeutic agent.

  19. The Relative Importance of Family History, Gender, Mode of Onset, and Age at Onset in Predicting Clinical Features of First-Episode Psychotic Disorders.

    Science.gov (United States)

    Compton, Michael T; Berez, Chantal; Walker, Elaine F

    2014-11-01

    Objective: Family history of psychosis, gender, mode of onset, and age at onset are considered prognostic factors important to clinicians evaluating first-episode psychosis; yet, clinicians have little guidance as to how these four factors differentially predict early-course substance abuse, symptomatology, and functioning. We conducted a "head-to-head comparison" of these four factors regarding their associations with key clinical features at initial hospitalization. We also assessed potential interactions between gender and family history with regard to age at onset of psychosis and symptom severity.Methods: Consecutively admitted first-episode patients (n=334) were evaluated in two studies that rigorously assessed a number of early-course variables. Associations among variables of interest were examined using Pearson correlations, ÷2 tests, Student's t-tests, and 2x2 factorial analyses of variance.Results: Substance (nicotine, alcohol, and cannabis) abuse and positive symptom severity were predicted only by male gender. Negative symptom severity and global functioning impairments were predicted by earlier age at onset of psychosis. General psychopathology symptom severity was predicted by both mode of onset and age at onset. Interaction effects were not observed with regard to gender and family history in predicting age at onset or symptom severity.Conclusions: The four prognostic features have differential associations with substance abuse, domains of symptom severity, and global functioning. Gender and age at onset of psychosis appear to be more predictive of clinical features at the time of initial evaluation (and thus presumably longer-term outcomes) than the presence of a family history of psychosis and a more gradual mode of onset. PMID:25367167

  20. The GBA, DYRK1A and MS4A6A polymorphisms influence the age at onset of Chinese Parkinson patients.

    Science.gov (United States)

    Fan, Kuan; Tang, Bei-Sha; Wang, Ya-Qin; Kang, Ji-Feng; Li, Kai; Liu, Zhen-Hua; Sun, Qi-Ying; Xu, Qian; Yan, Xin-Xiang; Guo, Ji-Feng

    2016-05-16

    Parkinson's disease (PD) is known as the most common neurodegenerative disease after Alzheimer's disease (AD). The precise pathogenic mechanism of PD remains unclear, but genetic and environmental factors are widely recognized to be associated with it. Although many associated genes have been discovered, they account for only a few PD patients. Recently, there are growing evidences indicating that patients with PD and AD share similarities in clinical features, pathology and genetic risks. However, no study has been conducted on the relations between AD associated genes and age at onset (AAO) of PD. In this study, we have detected 14 single nucleotide polymorphisms (SNPs) in 9 AD genome wide association studies top hit genes and 4 SNPs in 4 PD-cognitive impairment related genes among 297 Chinese PD patients. Through the linear regression analysis, we identified the significant associations of the GBA L444P mutation and DYRK1A rs8126696 T allele with the earlier AAO in PD patients, and the A allele at MS4A6A rs610932 with the delayed AAO of PD. This is the first report of significant associations of DYRK1A and MS4A6A SNPs and the AAO of PD. On account of their effects both in AD and PD, it is indicated that AD and PD possibly share some common pathways. PMID:27085534

  1. The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients

    DEFF Research Database (Denmark)

    Metzger, Silke; Walter, Carolin; Riess, Olaf;

    2013-01-01

    , we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second...

  2. Age at onset and seizure frequency affect white matter diffusion coefficient in patients with mesial temporal lobe epilepsy.

    Science.gov (United States)

    Nagy, Szilvia A; Horváth, Réka; Perlaki, Gábor; Orsi, Gergely; Barsi, Péter; John, Flóra; Horváth, Andrea; Kovács, Norbert; Bogner, Péter; Ábrahám, Hajnalka; Bóné, Beáta; Gyimesi, Csilla; Dóczi, Tamás; Janszky, József

    2016-08-01

    In mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), structural abnormalities are present not only in the hippocampus but also in the white matter with ipsilateral predominance. Although the timing of epilepsy onset is commonly associated with clinical and semiological dissimilarities, limited data exist regarding white matter diffusion changes with respect to age at epilepsy onset. The aim of this study was to investigate diffusion changes in the white matter of patients with unilateral MTLE-HS with respect to clinical parameters and to compare them with an age- and sex-matched healthy control group. Apparent diffusion coefficients (ADCs) were derived using monoexponential approaches from 22 (11 early and 11 late age at onset) patients with unilateral MTLE-HS and 22 age- and sex-matched control subjects after acquiring diffusion-weighted images on a 3T MRI system. Data were analyzed using two-tailed t-tests and multiple linear regression models. In the group with early onset MTLE-HS, ADC was significantly elevated in the ipsilateral hemispheric (p=0.04) and temporal lobe white matter (p=0.01) compared with that in controls. These differences were not detectable in late onset MTLE-HS patients. Apparent diffusion coefficient of the group with early onset MTLE-HS was negatively related to age at epilepsy onset in the ipsilateral hemispheric white matter (p=0.03) and the uncinate fasciculus (p=0.03), while in patients with late onset MTLE-HS, ADC was no longer dependent on age at epilepsy onset itself but rather on the seizure frequency in the ipsilateral uncinate fasciculus (p=0.03). Such diffusivity pattern has been associated with chronic white matter degeneration, reflecting myelin loss and higher extracellular volume which are more pronounced in the frontotemporal regions and also depend on clinical features. In the group with early onset MTLE-HS, the timing of epilepsy seems to be the major cause of white matter abnormalities while in late

  3. PNPLA3 I148M (rs738409) genetic variant and age at onset of at-risk alcohol consumption are independent risk factors for alcoholic cirrhosis

    Science.gov (United States)

    Burza, Maria Antonella; Molinaro, Antonio; Attilia, Maria Luisa; Rotondo, Claudia; Attilia, Fabio; Ceccanti, Mauro; Ferri, Flaminia; Maldarelli, Federica; Maffongelli, Angela; De Santis, Adriano; Attili, Adolfo Francesco; Romeo, Stefano; Ginanni Corradini, Stefano

    2014-01-01

    Background & Aims Environmental and genetic factors contribute to alcoholic cirrhosis onset. In particular, age at exposure to liver stressors has been shown to be important in progression to fibrosis in hepatitis C individuals. However, no definite data on the role of age at onset of at-risk alcohol consumption are available. Moreover, patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M (rs738409) variant has been associated with alcoholic cirrhosis, but only in cross-sectional studies. The aim of this study was to investigate the role of age at onset of at-risk alcohol consumption and PNPLA3 I148M variant on alcoholic cirrhosis incidence. Methods A total of 384 at-risk alcohol drinkers were retrospectively examined. The association among age at onset of at-risk alcohol consumption, PNPLA3 I148M variant and cirrhosis incidence was tested. Results A higher incidence of alcoholic cirrhosis was observed in individuals with an older (≥24 years) compared with a younger (<24) age at onset of at-risk alcohol consumption (P-value < 0.001). Moreover, PNPLA3 148M allele carriers showed an increased incidence of cirrhosis (P-value < 0.001). Both age at onset of at-risk alcohol consumption and PNPLA3 148M allele were independent risk factors for developing cirrhosis (H.R. (95% C.I.): 2.76 (2.18–3.50), P-value < 0.001; 1.53(1.07–2.19), P-value = 0.021 respectively). The 148M allele was associated with a two-fold increased risk of cirrhosis in individuals with a younger compared with an older age at onset of at-risk alcohol consumption (H.R. (95% C.I.): 3.03(1.53–6.00) vs. 1.61(1.09–2.38). Conclusions Age at onset of at-risk alcohol consumption and PNPLA3 I148M genetic variant are independently associated with alcoholic cirrhosis incidence. PMID:24102786

  4. A COMPARISON BETWEEN SINGLE LINKAGE AND COMPLETE LINKAGE IN AGGLOMERATIVE HIERARCHICAL CLUSTER ANALYSIS FOR IDENTIFYING TOURISTS SEGMENTS

    OpenAIRE

    Noor Rashidah Rashid

    2012-01-01

    Cluster Analysis is a multivariate method in statistics. Agglomerative Hierarchical Cluster Analysis is one of approaches in Cluster Analysis. There are two linkage methods in Agglomerative Hierarchical Cluster Analysis which are Single Linkage and Complete Linkage. The purpose of this study is to compare between Single Linkage and Complete Linkage in Agglomerative Hierarchical Cluster Analysis. The comparison of performances between these linkage methods was shown by using Kruskal-Wallis tes...

  5. Manycore Algorithms for Genetic Linkage Analysis

    OpenAIRE

    Medlar, A. J.

    2012-01-01

    Exact algorithms to perform linkage analysis scale exponentially with the size of the input. Beyond a critical point, the amount of work that needs to be done exceeds both available time and memory. In these circumstances, we are forced to either abbreviate the input in some manner or else use an approximation. Approximate methods, like Markov chain Monte Carlo (MCMC), though they make the problem tractable, can take an immense amount of time to converge. The problem of high convergence time ...

  6. Model-based methods for linkage analysis.

    Science.gov (United States)

    Rice, John P; Saccone, Nancy L; Corbett, Jonathan

    2008-01-01

    The logarithm of an odds ratio (LOD) score method originated in a seminal article by Newton Morton in 1955. The method is broadly concerned with issues of power and the posterior probability of linkage, ensuring that a reported linkage has a high probability of being a true linkage. In addition, the method is sequential so that pedigrees or LOD curves may be combined from published reports to pool data for analysis. This approach has been remarkably successful for 50 years in identifying disease genes for Mendelian disorders. After discussing these issues, we consider the situation for complex disorders where the maximum LOD score statistic shares some of the advantages of the traditional LOD score approach, but is limited by unknown power and the lack of sharing of the primary data needed to optimally combine analytic results. We may still learn from the LOD score method as we explore new methods in molecular biology and genetic analysis to utilize the complete human DNA sequence and the cataloging of all human genes.

  7. APOE ε4 lowers age at onset and is a high risk factor for Alzheimer's disease; A case control study from central Norway

    Directory of Open Access Journals (Sweden)

    Saltvedt Ingvild

    2008-04-01

    Full Text Available Abstract Background The objective of this study was to analyze factors influencing the risk and timing of Alzheimer's disease (AD in central Norway. The APOE ε4 allele is the only consistently identified risk factor for late onset Alzheimer's disease (LOAD. We have described the allele frequencies of the apolipoprotein E gene (APOE in a large population of patients with AD compared to the frequencies in a cognitively-normal control group, and estimated the effect of the APOE ε4 allele on the risk and the age at onset of AD in this population. Methods 376 patients diagnosed with AD and 561 cognitively-normal control individuals with no known first degree relatives with dementia were genotyped for the APOE alleles. Allele frequencies and genotypes in patients and control individuals were compared. Odds Ratio for developing AD in different genotypes was calculated. Results Odds Ratio (OR for developing AD was significantly increased in carriers of the APOE ε4 allele compared to individuals with the APOE ε3/ε3 genotype. Individuals carrying APOE ε4/ε4 had OR of 12.9 for developing AD, while carriers of APOE ε2/ε4 and APOE ε3/ε4 had OR of 3.2 and 4.2 respectively. The effect of the APOE ε4 allele was weaker with increasing age. Carrying the APOE ε2 allele showed no significant protective effect against AD and did not influence age at onset of the disease. Onset in LOAD patients was significantly reduced in a dose dependent manner from 78.4 years in patients without the APOE ε4 allele, to 75.3 in carriers of one APOE ε4 allele and 72.9 in carriers of two APOE ε4 alleles. Age at onset in early onset AD (EOAD was not influenced by APOE ε4 alleles. Conclusion APOE ε4 is a very strong risk factor for AD in the population of central Norway, and lowers age at onset of LOAD significantly.

  8. A COMPARISON BETWEEN SINGLE LINKAGE AND COMPLETE LINKAGE IN AGGLOMERATIVE HIERARCHICAL CLUSTER ANALYSIS FOR IDENTIFYING TOURISTS SEGMENTS

    Directory of Open Access Journals (Sweden)

    Noor Rashidah Rashid

    2012-02-01

    Full Text Available Cluster Analysis is a multivariate method in statistics. Agglomerative Hierarchical Cluster Analysis is one of approaches in Cluster Analysis. There are two linkage methods in Agglomerative Hierarchical Cluster Analysis which are Single Linkage and Complete Linkage. The purpose of this study is to compare between Single Linkage and Complete Linkage in Agglomerative Hierarchical Cluster Analysis. The comparison of performances between these linkage methods was shown by using Kruskal-Wallis test. The result of the comparison used for segmenting tourists of Kapas Island. The statistical software SPSS has been applied to analyze data of this research. The result from Kruskal-Wallis test shows Complete Linkage is more useful in identifying tourists segments. Keywords : Agglomerative Hierarchical Cluster Analysis, Single Linkage, Complete Linkage, Kruskal-Wallis test, tourists

  9. Model-free linkage analysis of a binary trait.

    Science.gov (United States)

    Xu, Wei; Bull, Shelley B; Mirea, Lucia; Greenwood, Celia M T

    2012-01-01

    Genetic linkage analysis aims to detect chromosomal regions containing genes that influence risk of specific inherited diseases. The presence of linkage is indicated when a disease or trait cosegregates through the families with genetic markers at a particular region of the genome. Two main types of genetic linkage analysis are in common use, namely model-based linkage analysis and model-free linkage analysis. In this chapter, we focus solely on the latter type and specifically on binary traits or phenotypes, such as the presence or absence of a specific disease. Model-free linkage analysis is based on allele-sharing, where patterns of genetic similarity among affected relatives are compared to chance expectations. Because the model-free methods do not require the specification of the inheritance parameters of a genetic model, they are preferred by many researchers at early stages in the study of a complex disease. We introduce the history of model-free linkage analysis in Subheading 1. Table 1 describes a standard model-free linkage analysis workflow. We describe three popular model-free linkage analysis methods, the nonparametric linkage (NPL) statistic, the affected sib-pair (ASP) likelihood ratio test, and a likelihood approach for pedigrees. The theory behind each linkage test is described in this section, together with a simple example of the relevant calculations. Table 4 provides a summary of popular genetic analysis software packages that implement model-free linkage models. In Subheading 2, we work through the methods on a rich example providing sample software code and output. Subheading 3 contains notes with additional details on various topics that may need further consideration during analysis.

  10. Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG families

    Directory of Open Access Journals (Sweden)

    Bailey-Wilson Joan E

    2012-06-01

    Full Text Available Abstract Background Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive. Methods Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG. Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed. Results Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD of 1.28, and an allele-sharing lod score (LOD of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2–3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM. For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM when families used in the original published report of linkage to Xq27-28 were excluded. Conclusions Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2–3 affected individuals and with some evidence of male to male disease transmission

  11. A review and reanalysis of Bruno Schulz's "Erkrankungsalter schizophrener Eltern und Kinder [Age at onset of illness in schizophrenic parents and offspring]:" Zeitschrift für die gesamte Neurologie und Psychiatrie, 168, 709-721, 1940.

    Science.gov (United States)

    Sham, P C; Zerbin-Rüdin, E; Kendler, K S

    1995-01-01

    Nearly all previous evidence of the familial transmission of age at onset of schizophrenia has been in siblings and twins. In his paper, Bruno Schulz examined the age at onset distribution of schizophrenia in affected parent and offspring pairs, using a systematic series of ascertained cases (n = 106), as well as a second series of chronic in-patients (n = 36). The parent-offspring correlation in age at onset, for cases with a definite diagnosis in the systematically ascertained series, was estimated at 0.346 (95% confidence interval 0.134, 0.528). Schulz did not test for differences between the two series and between males and females, but our reanalysis, using correlational methods and a mixed linear model, did not detect any significant differences. These results are consistent with previous findings that age at onset of schizophrenia is influenced by familial factors which may be genetic.

  12. Linkage analysis in familial Angelman syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Wagstaff, J. (Harvard Medical School, Boston, MA (United States)); Shugart, Y.Y. (Columbia Univ., New York (United States)); Lalande, M. (Harvard Medical School, Boston, MA (United States) Howard Hughes Medical Institute, Boston, MA (United States))

    1993-07-01

    Familial Angelman syndrome (AS) can result from mutations in chromosome 15q11q13 that, when transmitted from father to child, result in no phenotypic abnormality but, when transmitted from mother to child, cause AS. These mutations therefore behave neither as dominant nor as recessive mutations but, rather, show an imprinted mode of inheritance. The authors have analyzed two sibling pairs with AS and a larger family with four AS offspring of three sisters with several recently described microsatellite polymorphisms in the AS region. AS siblings inherited the same maternal alleles at the GABRB3 and GABRA5 loci, and the unaffected siblings of AS individuals inherited the other maternal alleles at these loci. In one of the AS sibling pairs, analysis of a recombination event indicates that the mutation responsible for AS is distal to locus D15S63. This result is consistent with a previously described imprinted submicroscopic deletion causing AS, a deletion that includes loci D15S10, D15S113, and GABRB3, all distal to D15S63. The analysis of the larger AS family provides the first clear demonstration of a new mutation in nondeletion AS. Analysis of linkage of AS to GABRB3 in these three families, on the assumption of imprinted inheritance (i.e., penetrance of an AS mutation is 1 if transmitted maternally and is 0 if transmitted paternally), indicates a maximum lod score of 3.52 at 6 = 0. 34 refs., 4 figs., 1 tab.

  13. ANALYSIS OF INTER SECTORAL LINKAGES IN SEMARANG REGENCY

    Directory of Open Access Journals (Sweden)

    Fafurida

    2014-03-01

    Full Text Available This research aims to analyze inter economic sectoral linkages and to arrange the Klassen typology of economic sectors in Semarang Regency. The Klassen typology is composed from the result of the linkage analysis. To construct the analysis, this paper also utulizes the input-output analysis. It finds that service sector has the highest backward linkage while farming sector has the highest forward linkage. Based on the Klassen typology analysis, sectors with the highest backward and forward linkages and potential to be the leading sector are farming sector, dan trade, hotel and restaurant sector.Keywords: Backward linkage,forward linkage, Klassen typologyJEL classification number: R15, O21AbstrakPenelitian ini bertujuan untuk mengkaji seberapa besar keterkaitan antar sektor ekonomi di Kabupaten Semarang dan memetakan tipologi Klassennya. Tipologi Klasen disusun berdasarkan hasil perhitungan analisis keterkaitannya. Untuk menyusun analisis tersebut, paper ini juga menggunakan analisis input-output. Hasil penelitian menunjukkan bahwa sektor jasa memiliki keterkaitan ke belakang tertinggi dibandingkan dengan sektor lainnya. Sementara itu, sektor pertanian merupakan sektor yang memiliki keterkaitan ke depan tertinggi. Berdasarkan hasil analisis tipologi Klassen, sektor yang memiliki keterkaitan ke depan dan ke belakang yang tinggi dan dapat menjadi sektor unggulan adalah sektor perdagangan, hotel dan sektor restoran.Kata kunci: Keterkaitan ke belakang, keterkaitan ke depan, tipologi KlassenJEL classification numbers: R15, O21

  14. A glycogen synthase kinase 3-beta promoter gene single nucleotide polymorphism is associated with age at onset and response to total sleep deprivation in bipolar depression.

    Science.gov (United States)

    Benedetti, Francesco; Serretti, Alessandro; Colombo, Cristina; Lorenzi, Cristina; Tubazio, Viviana; Smeraldi, Enrico

    2004-09-23

    The molecular mechanisms driving the biological clock in the suprachiasmatic nucleus of the hypothalamus may play a role in mood disorders. A single nucleotide polymorphism (SNP) (-50T/C) falling into the effective promoter region (nt -171 to +29) of the gene coding for glycogen synthase kinase 3-beta (GSK3-beta) has been linked with different age at onset of bipolar illness. GSK3-beta codes for an enzyme which is a target for the action of lithium and valproic acid, and the inhibition of which causes antidepressant-like behaviors in a preclinical model. We studied the effect of this polymorphism on the acute response to total sleep deprivation of 60 depressed bipolar type I inpatients. Homozygotes for the mutant allele of GSK3-beta promoter (-50T/C) SNP showed a later onset of bipolar illness, and better acute effects of TSD treatment on perceived mood (as rated on VAS). Overall, these observations suggest a protective role for this genotype in respect to bipolar illness. Results warrant interest for the variants of genes pertaining to the molecular clock as possible endophenotypes of bipolar disorder, and for GSK3-beta as a target of a new class of antidepressant drugs, but caution ought to be taken in interpreting these preliminary results and future replication studies must be awaited because of the low frequency of the GSK3-beta*C/C genotype in the studied populations.

  15. Impaired facial emotion recognition in patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS): Side and age at onset matters.

    Science.gov (United States)

    Hlobil, Ulf; Rathore, Chaturbhuj; Alexander, Aley; Sarma, Sankara; Radhakrishnan, Kurupath

    2008-08-01

    To define the determinants of impaired facial emotion recognition (FER) in patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS), we examined 76 patients with unilateral MTLE-HS, 36 prior to antero-mesial temporal lobectomy (AMTL) and 40 after AMTL, and 28 healthy control subjects with a FER test consisting of 60 items (20 each for anger, fear, and happiness). Mean percentages of the accurate responses were calculated for different subgroups: right vs. left MTLE-HS, early (age at onset Happiness recognition was significantly better in post-AMTL MTLE-HS patients compared to pre-AMTL patients while anger and fear recognition did not differ. We conclude that patients with right MTLE-HS with age at seizure onset <6 years are maximally predisposed to impaired fear recognition. In them, right AMTL does not further worsen FER abilities. Longitudinal studies comparing FER in the same patients before and after AMTL will be required to refine and confirm our cross-sectional observations.

  16. Genetic heterogeneity in psoriasis vulgaris based on linkage analyses of a large family material

    Energy Technology Data Exchange (ETDEWEB)

    Wahlstroem, J.; Swanbeck, G.; Inerot, A. [ Univ. of Goeteborg (Sweden)] [and others

    1994-09-01

    Information on psoriasis among parents and siblings in 14,008 families has been collected. On the basis of this material, evidence for monogenetic autosomal recessive inheritance of psoriasis has recently been presented. Indications from more than one type of non-pustular psoriasis has been obtained from the population genetic data. Molecular genetic linkage analysis of psoriasis to a number of polymorphic genetic markers for a large number of families has been made. It is apparent that there is genetic heterogeneity in a psoriasis population with regard to psoriasis genes. Using the computer program Linkage 5.0 and a formula for heterogeneity, a lodscore over 3.0 for one locus has been obtained. This locus has further been confirmed by several other markers in the vicinity. The locus found is linked to slightly over half of the families, indicating that there are more genetically independent types of psoriasis. The age at onset of those families that are apparently linked to this locus have a slightly higher age at onset than those not linked to that locus but with a considerable overlap. In spite of close coverage of the whole chromosomes number 6 and 17, no linkage has been found in this regions. This indicates that neither the HLA region nor the region earlier found to be involved in one family with psoriasis are primarily involved in our families.

  17. Kinematical analysis on the several linkage drives for mechanical presses

    Energy Technology Data Exchange (ETDEWEB)

    Ham, Kyung Chun; Jang, Dong Hwan [Inha Technical College, Incheon (Korea, Republic of)

    2009-02-15

    In this paper, a kinematical analysis is preformed to see mechanical characteristics of various linkage drives for a mechanical press. Mechanical characteristics of conventional and newly designed drives are investigated and compared in terms of slide velocity, productivity, load capacity and possible work-piece size. A crank-slider mechanism with arc crank-pin guide is introduced and analyzed particularly for kinematical performance using kinematical analysis software. The new linkage drive turns out to be effective in terms of load and velocity characteristics and productivity. Kinematical performance also provides a basis for the proper selection of mechanical presses

  18. Broad scan linkage analysis in a large Tourette family pedigree

    Energy Technology Data Exchange (ETDEWEB)

    Peiffer, A.; Leppert, M. [Univ. of Utah Health Sciences Center, Salt Lake City, UT (United States); Wetering, B.J.M. van der [Univ. Hospital Rotterdam (Netherlands)

    1994-09-01

    Attempts to find a gene causing Tourette syndrome (TS) using linkage analysis have been unsuccessful even though as much as 65% of the autosomal genetic map has been excluded by the pooled results from several laboratories collaborating worldwide. One reason for this failure may be the misclassification of affection status of marry-in spouses. Specifically, we have found that six unrelated spouses in our Utah TS pedigree suffer from TS, obsessive-compulsive disorder or chronic motor tics. In light of these findings we decided to conduct a complete genomic scan from this Utah kindred with polymorphic markers in three related sibships in which there was no assortative mating. A linkage study assuming autosomal dominant inheritance was done using tetranucleotide repeat markers developed at the University of Utah. We selected markers that were less than 300 bp in size and that gave a heterozygosity of over 70% upon analysis in 4 CEPH families. Results to date with 95 markers run at an interval of 30 cM (covering 61% of the genome) show no evidence of linkage. We intend to extend the coverage to 100% of the genome. Pending completion of this scan, failure to provide evidence of linkage in our TS pedigree might then be attributed to phenotypic misclassification or erroneous assumptions regarding the genetic model of transmission.

  19. Identification of quantitative trait loci underlying milk traits in Spanish dairy sheep using linkage plus combined linkage disequilibrium and linkage analysis approaches.

    Science.gov (United States)

    Garcia-Gámez, E; Gutiérrez-Gil, B; Suarez-Vega, A; de la Fuente, L F; Arranz, J J

    2013-09-01

    In this study, 2 procedures were used to analyze a data set from a whole-genome scan, one based on linkage analysis information and the other combing linkage disequilibrium and linkage analysis (LDLA), to determine the quantitative trait loci (QTL) influencing milk production traits in sheep. A total of 1,696 animals from 16 half-sib families were genotyped using the OvineSNP50 BeadChip (Illumina Inc., San Diego, CA) and analysis was performed using a daughter design. Moreover, the same data set has been previously investigated through a genome-wide association (GWA) analysis and a comparison of results from the 3 methods has been possible. The linkage analysis and LDLA methodologies yielded different results, although some significantly associated regions were common to both procedures. The linkage analysis detected 3 overlapping genome-wise significant QTL on sheep chromosome (OAR) 2 influencing milk yield, protein yield, and fat yield, whereas 34 genome-wise significant QTL regions were detected using the LDLA approach. The most significant QTL for protein and fat percentages was detected on OAR3, which was reported in a previous GWA analysis. Both the linkage analysis and LDLA identified many other chromosome-wise significant associations across different sheep autosomes. Additional analyses were performed on OAR2 and OAR3 to determine the possible causality of the most significant polymorphisms identified for these genetic effects by the previously reported GWA analysis. For OAR3, the analyses demonstrated additional genetic proof of the causality previously suggested by our group for a single nucleotide polymorphism located in the α-lactalbumin gene (LALBA). In summary, although the results shown here suggest that in commercial dairy populations, the LDLA method exhibits a higher efficiency to map QTL than the simple linkage analysis or linkage disequilibrium methods, we believe that comparing the 3 analysis methods is the best approach to obtain a global

  20. Linkage analysis on chromosome 2 in essential hypotension pedigrees

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    It is a new approach to study the important genes related to the control of blood pressure by probing into hypotension and hypertension at the same time. Genome scanning on whole chromosome 2 in 8 hypotension pedigrees has been done and parameter (LOD score) and non-pa- rameter (NPL score) were used in the linkage analysis by GENEHUNTER software. The results show the evidence of linkage between D2S112 and D2S117, indicating a number of critical genes may lie in thisregion and contribute to the mechanism of blood pressure regulation. Also this region has been found in the previous study in hypertension pedigrees. These genes may play an important role in the regulation of blood pressure and can also be the important candidate genes in hypertension studies.

  1. Candidate gene linkage analysis indicates genetic heterogeneity in Marfan syndrome

    Directory of Open Access Journals (Sweden)

    L.V.S. Teixeira

    2011-08-01

    Full Text Available Marfan syndrome (MFS is an autosomal dominant disease of the connective tissue that affects the ocular, skeletal and cardiovascular systems, with a wide clinical variability. Although mutations in the FBN1 gene have been recognized as the cause of the disease, more recently other loci have been associated with MFS, indicating the genetic heterogeneity of this disease. We addressed the issue of genetic heterogeneity in MFS by performing linkage analysis of the FBN1 and TGFBR2 genes in 34 families (345 subjects who met the clinical diagnostic criteria for the disease according to Ghent. Using a total of six microsatellite markers, we found that linkage with the FBN1 gene was observed or not excluded in 70.6% (24/34 of the families, and in 1 family the MFS phenotype segregated with the TGFBR2 gene. Moreover, in 4 families linkage with the FBN1 and TGFBR2 genes was excluded, and no mutations were identified in the coding region of TGFBR1, indicating the existence of other genes involved in MFS. Our results suggest that the genetic heterogeneity of MFS may be greater that previously reported.

  2. Detection of tandam duplications and implications for linkage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Matise, T.C.; Weeks, D.E. (Univ. of Pittsburgh, PA (United States)); Chakravarti, A. (Case Western Reserve Univ., Cleveland, OH (United States)); Patel, P.I.; Lupski, J.R. (Baylor College of Medicine, Houston, TX (United States)); Nelis, E.; Timmerman, V.; Van Broeckhoven, C. (Univ. of Antwerp (Belgium))

    1994-06-01

    The first demonstration of an autosomal dominant human disease caused by segmental trisomy came in 1991 for Charcot-Marie-Tooth disease type 1A (CMT1A). For this disorder, the segmental trisomy is due to a large tandem duplication of 1.5 Mb of DNA located on chromosome 17p11.2-p12. The search for the CMT1A disease gene was misdirected and impeded because some chromosome 17 genetic markers that are linked to CMT1A lie within this duplication. To better understand how such a duplication might affect genetic analyses in the context of disease gene mapping, the authors studied the effects of marker duplication on transmission probabilities of marker alleles, on linkage analysis of an autosomal dominant disease, and on tests of linkage homogeneity. They demonstrate that the undetected presence of a duplication distorts transmission ratios, hampers fine localization of the disease gene, and increases false evidence of linkage heterogeneity. In addition, they devised a likelihood-based method for detecting the presence of a tandemly duplicated marker when one is suspected. They tested their methods through computer simulations and on CMT1A pedigrees genotyped at several chromosome 17 markers. On the simulated data, the method detected 96% of duplicated markers (with a false-positive rate of 5%). On the CMT1A data the method successfully identified two of three loci that are duplicated (with no false positives). This method could be used to identify duplicated markers in other regions of the genome and could be used to delineate the extent of duplications similar to that involved in CMT1A. 18 refs., 5 figs., 6 tabs.

  3. Association and linkage analysis of aluminum tolerance genes in maize.

    Directory of Open Access Journals (Sweden)

    Allison M Krill

    Full Text Available BACKGROUND: Aluminum (Al toxicity is a major worldwide constraint to crop productivity on acidic soils. Al becomes soluble at low pH, inhibiting root growth and severely reducing yields. Maize is an important staple food and commodity crop in acidic soil regions, especially in South America and Africa where these soils are very common. Al exclusion and intracellular tolerance have been suggested as two important mechanisms for Al tolerance in maize, but little is known about the underlying genetics. METHODOLOGY: An association panel of 282 diverse maize inbred lines and three F2 linkage populations with approximately 200 individuals each were used to study genetic variation in this complex trait. Al tolerance was measured as net root growth in nutrient solution under Al stress, which exhibited a wide range of variation between lines. Comparative and physiological genomics-based approaches were used to select 21 candidate genes for evaluation by association analysis. CONCLUSIONS: Six candidate genes had significant results from association analysis, but only four were confirmed by linkage analysis as putatively contributing to Al tolerance: Zea mays AltSB like (ZmASL, Zea mays aluminum-activated malate transporter2 (ALMT2, S-adenosyl-L-homocysteinase (SAHH, and Malic Enzyme (ME. These four candidate genes are high priority subjects for follow-up biochemical and physiological studies on the mechanisms of Al tolerance in maize. Immediately, elite haplotype-specific molecular markers can be developed for these four genes and used for efficient marker-assisted selection of superior alleles in Al tolerance maize breeding programs.

  4. Mapping multiple QTL using linkage disequilibrium and linkage analysis information and multitrait data

    Directory of Open Access Journals (Sweden)

    Goddard Mike E

    2004-05-01

    Full Text Available Abstract A multi-locus QTL mapping method is presented, which combines linkage and linkage disequilibrium (LD information and uses multitrait data. The method assumed a putative QTL at the midpoint of each marker bracket. Whether the putative QTL had an effect or not was sampled using Markov chain Monte Carlo (MCMC methods. The method was tested in dairy cattle data on chromosome 14 where the DGAT1 gene was known to be segregating. The DGAT1 gene was mapped to a region of 0.04 cM, and the effects of the gene were accurately estimated. The fitting of multiple QTL gave a much sharper indication of the QTL position than a single QTL model using multitrait data, probably because the multi-locus QTL mapping reduced the carry over effect of the large DGAT1 gene to adjacent putative QTL positions. This suggests that the method could detect secondary QTL that would, in single point analyses, remain hidden under the broad peak of the dominant QTL. However, no indications for a second QTL affecting dairy traits were found on chromosome 14.

  5. A statistical design for testing apomictic diversification through linkage analysis.

    Science.gov (United States)

    Zeng, Yanru; Hou, Wei; Song, Shuang; Feng, Sisi; Shen, Lin; Xia, Guohua; Wu, Rongling

    2014-03-01

    The capacity of apomixis to generate maternal clones through seed reproduction has made it a useful characteristic for the fixation of heterosis in plant breeding. It has been observed that apomixis displays pronounced intra- and interspecific diversification, but the genetic mechanisms underlying this diversification remains elusive, obstructing the exploitation of this phenomenon in practical breeding programs. By capitalizing on molecular information in mapping populations, we describe and assess a statistical design that deploys linkage analysis to estimate and test the pattern and extent of apomictic differences at various levels from genotypes to species. The design is based on two reciprocal crosses between two individuals each chosen from a hermaphrodite or monoecious species. A multinomial distribution likelihood is constructed by combining marker information from two crosses. The EM algorithm is implemented to estimate the rate of apomixis and test its difference between two plant populations or species as the parents. The design is validated by computer simulation. A real data analysis of two reciprocal crosses between hickory (Carya cathayensis) and pecan (C. illinoensis) demonstrates the utilization and usefulness of the design in practice. The design provides a tool to address fundamental and applied questions related to the evolution and breeding of apomixis.

  6. Further analysis of previously implicated linkage regions for Alzheimer's disease in affected relative pairs

    Directory of Open Access Journals (Sweden)

    Lannfelt Lars

    2009-12-01

    Full Text Available Abstract Background Genome-wide linkage studies for Alzheimer's disease have implicated several chromosomal regions as potential loci for susceptibility genes. Methods In the present study, we have combined a selection of affected relative pairs (ARPs from the UK and the USA included in a previous linkage study by Myers et al. (Am J Med Genet, 2002, with ARPs from Sweden and Washington University. In this total sample collection of 397 ARPs, we have analyzed linkage to chromosomes 1, 9, 10, 12, 19 and 21, implicated in the previous scan. Results The analysis revealed that linkage to chromosome 19q13 close to the APOE locus increased considerably as compared to the earlier scan. However, linkage to chromosome 10q21, which provided the strongest linkage in the previous scan could not be detected. Conclusion The present investigation provides yet further evidence that 19q13 is the only chromosomal region consistently linked to Alzheimer's disease.

  7. Genome-wide linkage analysis for human longevity

    DEFF Research Database (Denmark)

    Beekman, Marian; Blanché, Hélène; Perola, Markus;

    2013-01-01

    Clear evidence exists for heritability of human longevity, and much interest is focused on identifying genes associated with longer lives. To identify such longevity alleles, we performed the largest genome-wide linkage scan thus far reported. Linkage analyses included 2118 nonagenarian Caucasian...... sibling pairs that have been enrolled in 15 study centers of 11 European countries as part of the Genetics of Healthy Aging (GEHA) project. In the joint linkage analyses, we observed four regions that show linkage with longevity; chromosome 14q11.2 (LOD = 3.47), chromosome 17q12-q22 (LOD = 2.......02 and P-value = 1.0 × 10(-5) , respectively. In the largest linkage scan thus far performed for human familial longevity, we confirm that the APOE locus is a longevity gene and that additional longevity loci may be identified at 14q11.2, 17q12-q22, and 19p13.3-p13.11. As the latter linkage results...

  8. The optimal design for hypothesis test and its application in genetic linkage analysis

    Institute of Scientific and Technical Information of China (English)

    XIE; Minyu(谢民育); LI; Zhaohai(李照海)

    2003-01-01

    This paper proposes a class of linear models with inequable variance, based on background in genetic linkage analysis, and considers the optimal design problem for the hypothesis test of the parameters in such models. To assess a design for the test, a frame of decision theory is established. Under this frame, an admissible minimax design is obtained. It is shown to be not only admissible and minimax in genetic linkage analysis, but best among a reasonable subclass of designs. The power of the test in genetic linkage analysis is substantially improved by using this optimal design.

  9. Software for analysis and manipulation of genetic linkage data.

    Science.gov (United States)

    Weaver, R; Helms, C; Mishra, S K; Donis-Keller, H

    1992-06-01

    We present eight computer programs written in the C programming language that are designed to analyze genotypic data and to support existing software used to construct genetic linkage maps. Although each program has a unique purpose, they all share the common goals of affording a greater understanding of genetic linkage data and of automating tasks to make computers more effective tools for map building. The PIC/HET and FAMINFO programs automate calculation of relevant quantities such as heterozygosity, PIC, allele frequencies, and informativeness of markers and pedigrees. PREINPUT simplifies data submissions to the Centre d'Etude du Polymorphisme Humain (CEPH) data base by creating a file with genotype assignments that CEPH's INPUT program would otherwise require to be input manually. INHERIT is a program written specifically for mapping the X chromosome: by assigning a dummy allele to males, in the nonpseudoautosomal region, it eliminates falsely perceived noninheritances in the data set. The remaining four programs complement the previously published genetic linkage mapping software CRI-MAP and LINKAGE. TWOTABLE produces a more readable format for the output of CRI-MAP two-point calculations; UNMERGE is the converse to CRI-MAP's merge option; and GENLINK and LINKGEN automatically convert between the genotypic data file formats required by these packages. All eight applications read input from the same types of data files that are used by CRI-MAP and LINKAGE. Their use has simplified the management of data, has increased knowledge of the content of information in pedigrees, and has reduced the amount of time needed to construct genetic linkage maps of chromosomes. PMID:1598906

  10. Software for analysis and manipulation of genetic linkage data.

    Science.gov (United States)

    Weaver, R; Helms, C; Mishra, S K; Donis-Keller, H

    1992-06-01

    We present eight computer programs written in the C programming language that are designed to analyze genotypic data and to support existing software used to construct genetic linkage maps. Although each program has a unique purpose, they all share the common goals of affording a greater understanding of genetic linkage data and of automating tasks to make computers more effective tools for map building. The PIC/HET and FAMINFO programs automate calculation of relevant quantities such as heterozygosity, PIC, allele frequencies, and informativeness of markers and pedigrees. PREINPUT simplifies data submissions to the Centre d'Etude du Polymorphisme Humain (CEPH) data base by creating a file with genotype assignments that CEPH's INPUT program would otherwise require to be input manually. INHERIT is a program written specifically for mapping the X chromosome: by assigning a dummy allele to males, in the nonpseudoautosomal region, it eliminates falsely perceived noninheritances in the data set. The remaining four programs complement the previously published genetic linkage mapping software CRI-MAP and LINKAGE. TWOTABLE produces a more readable format for the output of CRI-MAP two-point calculations; UNMERGE is the converse to CRI-MAP's merge option; and GENLINK and LINKGEN automatically convert between the genotypic data file formats required by these packages. All eight applications read input from the same types of data files that are used by CRI-MAP and LINKAGE. Their use has simplified the management of data, has increased knowledge of the content of information in pedigrees, and has reduced the amount of time needed to construct genetic linkage maps of chromosomes.

  11. A system for exact and approximate genetic linkage analysis of SNP data in large pedigrees

    OpenAIRE

    Silberstein, Mark; Weissbrod, Omer; Otten, Lars; Tzemach, Anna; Anisenia, Andrei; Shtark, Oren; Tuberg, Dvir; Galfrin, Eddie; Gannon, Irena; Shalata, Adel; Borochowitz, Zvi U.; Dechter, Rina; Thompson, Elizabeth; Geiger, Dan

    2013-01-01

    Motivation: The use of dense single nucleotide polymorphism (SNP) data in genetic linkage analysis of large pedigrees is impeded by significant technical, methodological and computational challenges. Here we describe Superlink-Online SNP, a new powerful online system that streamlines the linkage analysis of SNP data. It features a fully integrated flexible processing workflow comprising both well-known and novel data analysis tools, including SNP clustering, erroneous data filtering, exact an...

  12. Analysis of Linkage Effects among Currency Networks Using REER Data

    Directory of Open Access Journals (Sweden)

    Haishu Qiao

    2015-01-01

    Full Text Available We modeled the currency networks through the use of REER (real effective exchange rate instead of a bilateral exchange rate in order to overcome the confusion in selecting base currencies. Based on the MST (minimum spanning tree approach and the rolling-window method, we constructed time-varying and correlation-based networks with which we investigate the linkage effects among different currencies. In particular, and as the source of empirical data, we chose the monthly REER data for a set of 61 major currencies during the period from 1994 to 2014. The study demonstrated that obvious linkage effects existed among currency networks and the euro (EUR was confirmed as the predominant world currency. Additionally, we used the rolling-window method to investigate the stability of linkage effects, doing so by calculating the mean correlations and mean distances as well as the normalized tree length and degrees of those currencies. The results showed that financial crises during the study period had a great effect on the currency network’s topology structure and led to more clustered currency networks. Our results suggested that it is more appropriate to estimate the linkage effects among currency networks through the use of REER data.

  13. SNP HiTLink: a high-throughput linkage analysis system employing dense SNP data

    OpenAIRE

    Kuwano Ryozo; Miyashita Akinori; Goto Jun; Takahashi Yuji; Date Hidetoshi; Nakahara Yasuo; Fukuda Yoko; Adachi Hiroki; Nakamura Eiji; Tsuji Shoji

    2009-01-01

    Abstract Background During this recent decade, microarray-based single nucleotide polymorphism (SNP) data are becoming more widely used as markers for linkage analysis in the identification of loci for disease-associated genes. Although microarray-based SNP analyses have markedly reduced genotyping time and cost compared with microsatellite-based analyses, applying these enormous data to linkage analysis programs is a time-consuming step, thus, necessitating a high-throughput platform. Result...

  14. Multivariate Stable Isotope Analysis to Determine Linkages between Benzocaine Seizures

    Science.gov (United States)

    Kemp, H. F.; Meier-Augenstein, W.; Collins, M.; Salouros, H.; Cunningham, A.; Harrison, M.

    2012-04-01

    In July 2010, a woman was jailed for nine years in the UK after the prosecution successfully argued that attempting to import a cutting agent was proof of involvement in a conspiracy to supply Cocaine. That landmark ruling provided law enforcement agencies with much greater scope to tackle those involved in this aspect of the drug trade, specifically targeting those importing the likes of benzocaine or lidocaine. Huge quantities of these compounds are imported into the UK and between May and August 2010, four shipments of Benzocaine amounting to more then 4 tons had been seized as part of Operation Kitley, a joint initiative between the UK Border Agency and the Serious Organised Crime Agency (SOCA). By diluting cocaine, traffickers can make it go a lot further for very little cost, leading to huge profits. In recent years, dealers have moved away from inert substances, like sugar and baby milk powder, in favour of active pharmaceutical ingredients (APIs), including anaesthetics like Benzocaine and Lidocaine. Both these mimic the numbing effect of cocaine, and resemble it closely in colour, texture and some chemical behaviours, making it easier to conceal the fact that the drug has been diluted. API cutting agents have helped traffickers to maintain steady supplies in the face of successful interdiction and even expand the market in the UK, particularly to young people aged from their mid teens to early twenties. From importation to street-level, the purity of the drug can be reduced up to a factor of 80 and street level cocaine can have a cocaine content as low as 1%. In view of the increasing use of Benzocaine as cutting agent for Cocaine, a study was carried out to investigate if 2H, 13C, 15N and 18O stable isotope signatures could be used in conjunction with multivariate chemometric data analysis to determine potential linkage between benzocaine exhibits seized from different locations or individuals to assist with investigation and prosecution of drug

  15. Two-trait-locus linkage analysis: A powerful strategy for mapping complex genetic traits

    Energy Technology Data Exchange (ETDEWEB)

    Schork, N.J.; Boehnke, M. (Univ. of Michigan, Ann Arbor, MI (United States)); Terwilliger, J.D.; Ott, J. (Columbia Univ., New York, NY (United States))

    1993-11-01

    Nearly all diseases mapped to date follow clear Mendelian, single-locus segregation patterns. In contrast, many common familial diseases such as diabetes, psoriasis, several forms of cancer, and schizophrenia are familial and appear to have a genetic component but do not exhibit simple Mendelian transmission. More complex models are required to explain the genetics of these important diseases. In this paper, the authors explore two-trait-locus, two-marker-locus linkage analysis in which two trait loci are mapped simultaneously to separate genetic markers. The authors compare the utility of this approach to standard one-trait-locus, one-marker-locus linkage analysis with and without allowance for heterogeneity. The authors also compare the utility of the two-trait-locus, two-marker-locus analysis to two-trait-locus, one-marker-locus linkage analysis. For common diseases, pedigrees are often bilineal, with disease genes entering via two or more unrelated pedigree members. Since such pedigrees often are avoided in linkage studies, the authors also investigate the relative information content of unilineal and bilineal pedigrees. For the dominant-or-recessive and threshold models that the authors consider, the authors find that two-trait-locus, two-marker-locus linkage analysis can provide substantially more linkage information, as measured by expected maximum lod score, than standard one-trait-locus, one-marker-locus methods, even allowing for heterogeneity, while, for a dominant-or-dominant generating model, one-locus models that allow for heterogeneity extract essentially as much information as the two-trait-locus methods. For these three models, the authors also find that bilineal pedigrees provide sufficient linkage information to warrant their inclusion in such studies. The authors discuss strategies for assessing the significance of the two linkages assumed in two-trait-locus, two-marker-locus models. 37 refs., 1 fig., 4 tabs.

  16. Linkage analysis of chromosome 14 and essential hypertension in Chinese population

    Institute of Scientific and Technical Information of China (English)

    ZHAO Wei-yan; HUANG Jian-feng; GE Dong-liang; SU Shao-yong; LI Biao; GU Dong-feng

    2005-01-01

    Background Hypertension is a complex biological trait that influenced by multiple factors. The encouraging results for hypertension research showed that the linkage analysis can be used to replicate other studies and discover new genetic risk factors. Previous studies linked human chromosome 14 to essential hypertension or blood pressure traits. With a Chinese population, we tried to replicate these findings. Methods A linkage scan was performed on chromosome 14 with 14-microsatellite markers with a density of about 10 centi Morgen (cM) in 147 Chinese hypertensive nuclear families. Multipoint non-parametric linkage analysis and exclusion mapping were performed with the GENEHUNTER software, whereas quantitative analysis was performed with the variance component method integrated in the SOLAR package. Results In the qualitative analysis, the highest non-parametric linkage score is 1.0 (P=0.14) at D14S261 in the single point analysis, and no loci achieved non-parametric linkage score more than 1.0 in the multipoint analysis. Maximum-likelihood mapping showed no significant results, either. Subsequently the traditional exclusion criteria of the log-of-the-odds score-2 were adopted, and the chromosome 14 with λs≥2.4 was excluded. In the quantitative analysis of blood pressure with the SOLAR software, two-point analysis and multipoint analysis suggested no evidence for linkage occurred on chromosome 14 for systolic and diastolic blood pressure. Conclusion There was no substantial evidence to support the linkage of chromosome 14 and essential hypertension or blood pressure trait in Chinese hypertensive subjects in this study.

  17. Effect of genetic heterogeneity and assortative mating on linkage analysis: a simulation study.

    OpenAIRE

    Falk, C T

    1997-01-01

    Linkage studies of complex genetic traits raise questions about the effects of genetic heterogeneity and assortative mating on linkage analysis. To further understand these problems, I have simulated and analyzed family data for a complex genetic disease in which disease phenotype is determined by two unlinked disease loci. Two models were studied, a two-locus threshold model and a two-locus heterogeneity model. Information was generated for a marker locus linked to one of the disease-definin...

  18. A FORTRAN program for the calculation and analysis of two-locus linkage disequilibrium coefficients.

    Science.gov (United States)

    Black, W C; Krafsur, E S

    1985-08-01

    A FORTRAN program was written that calculates composite linkage disequilibrium coefficients from genotypic data. Chi-square tests determine whether coefficients calculated for allele and locus pairs are significantly greater than zero. A subroutine is provided that partitions the variance in linkage disequilibrium into within- and between-subpopulation components. Output obtained from analysis of allozyme data collected from natural subpopulations of the house fly (Musca domestica L.) are included to illustrate features of the program.

  19. Linkage analysis with markers on 17q in 29 Swedish breast cancer families.

    OpenAIRE

    Lindblom, A; Rotstein, S; Nordenskjöld, M; Larsson, C.

    1993-01-01

    Recently, a putative breast cancer gene was localized to the long arm of chromosome 17. A collaboration study was undertaken to confirm linkage, to further map the gene, and to determine to what extent breast cancer families are linked to this locus. The Swedish material consisted of 29 breast cancer families in which 68 affected members were studied. Linkage analysis of breast cancer susceptibility was performed with a number of markers on 17q. In this material a weakly positive LOD score in...

  20. FLOSS: flexible ordered subset analysis for linkage mapping of complex traits.

    Science.gov (United States)

    Browning, B L

    2006-02-15

    The FLOSS software package is a flexible framework for ordered subset analysis. FLOSS is specifically designed for use with the Merlin linkage analysis package, but FLOSS can be used with any linkage analysis software package that reports NPL Z-scores for each locus and family. When FLOSS is used with the Merlin linkage analysis package, one can use either non-parametric Z-scores or Kong and Cox linear allele sharing model LOD scores. Monte Carlo P-values are calculated using a permutation test with an efficient Besag-Clifford sequential stopping rule. FLOSS also has a flexible tool for assigning family covariate scores from Merlin input files. FLOSS includes user documentation and is written in Java for easy portability. The FLOSS source code is documented and designed to be extensible.

  1. Linkage analysis of systolic blood pressure: a score statistic and computer implementation

    OpenAIRE

    Peng Yingwei; Wang Kai

    2003-01-01

    Abstract A genome-wide linkage analysis was conducted on systolic blood pressure using a score statistic. The randomly selected Replicate 34 of the simulated data was used. The score statistic was applied to the sibships derived from the general pedigrees. An add-on R program to GENEHUNTER was developed for this analysis and is freely available.

  2. Viral Genetic Linkage Analysis in the Presence of Missing Data.

    Directory of Open Access Journals (Sweden)

    Shelley H Liu

    Full Text Available Analyses of viral genetic linkage can provide insight into HIV transmission dynamics and the impact of prevention interventions. For example, such analyses have the potential to determine whether recently-infected individuals have acquired viruses circulating within or outside a given community. In addition, they have the potential to identify characteristics of chronically infected individuals that make their viruses likely to cluster with others circulating within a community. Such clustering can be related to the potential of such individuals to contribute to the spread of the virus, either directly through transmission to their partners or indirectly through further spread of HIV from those partners. Assessment of the extent to which individual (incident or prevalent viruses are clustered within a community will be biased if only a subset of subjects are observed, especially if that subset is not representative of the entire HIV infected population. To address this concern, we develop a multiple imputation framework in which missing sequences are imputed based on a model for the diversification of viral genomes. The imputation method decreases the bias in clustering that arises from informative missingness. Data from a household survey conducted in a village in Botswana are used to illustrate these methods. We demonstrate that the multiple imputation approach reduces bias in the overall proportion of clustering due to the presence of missing observations.

  3. Linkage analysis of neurofibromatosis type I, using chromosome 17 DNA markers.

    OpenAIRE

    Kittur, S D; Bagdon, M M; Lubs, M L; Phillips, J. A.; Murray, J C; Slaugenhaupt, S A; Chakravarti, A; Adler, W. H.

    1989-01-01

    The gene for von Recklinghausen neurofibromatosis type 1 (NF1) has recently been mapped to the pericentromeric region of human chromosome 17. To further localize the NF1 gene, linkage analysis using chromosome 17 DNA markers was performed on 11 multigeneration families with 175 individuals, 57 of whom were affected. The markers used were D17Z1 (p17H8), D17S58 (EW301), D17S54 (EW203), D17S57 (EW206), D17S73 (EW207), CRI-L946, HOX-2, and growth hormone. Tight linkage was found between NF1 and D...

  4. Genome-Wide Association Study and Linkage Analysis of the Healthy Aging Index

    DEFF Research Database (Denmark)

    Minster, Ryan L; Sanders, Jason L; Singh, Jatinder;

    2015-01-01

    BACKGROUND: The Healthy Aging Index (HAI) is a tool for measuring the extent of health and disease across multiple systems. METHODS: We conducted a genome-wide association study and a genome-wide linkage analysis to map quantitative trait loci associated with the HAI and a modified HAI weighted...

  5. Linkage Analysis of Cement Industry in the Indonesian Economy: Input-Output Analysis

    Directory of Open Access Journals (Sweden)

    Muhammad Mirza

    2015-11-01

    Full Text Available This study aims to determine the relations of backward and forward linkages of cement industry on the various economic sectors in Indonesia. In analyzing the relations, Indonesia’s input-output table of year 2005 isusedwhich is based ontheIndonesian domestic transactions on the basis of the producer price of 175 sectors classification. The results showed that the cement industry has backward linkages to the 43 sectors (5 sectors that have the biggest backward linkage are: the coal sector, electricity and gas sector, natural gas and geothermal sectors,excavation goods and oil refining goods and has forward linkages to 15 sectors (5 sectors that have the biggest forward linkage, namely: agricultural infrastructure sector, roads, bridges and ports, goods from non-metallic materials, residential and non-residental buildings, the building sector and the installation of electricity, gas, water and communication, in the direct linkages, both backward and forward linkages of cement industry are still considered as low, and the total linkages of the cement industry has stronger association with upstream sector when compared to the downstream sector. The conditions of the backward linkages of cement industry in 2014 is assumed to be relatively the same as those in 2005, while the forward linkage in 2014 indicates a shift in the sectors that have the biggest linkage to the cement industry.

  6. QTL linkage analysis of connected populations using ancestral marker and pedigree information.

    Science.gov (United States)

    Bink, Marco C A M; Totir, L Radu; ter Braak, Cajo J F; Winkler, Christopher R; Boer, Martin P; Smith, Oscar S

    2012-04-01

    The common assumption in quantitative trait locus (QTL) linkage mapping studies that parents of multiple connected populations are unrelated is unrealistic for many plant breeding programs. We remove this assumption and propose a Bayesian approach that clusters the alleles of the parents of the current mapping populations from locus-specific identity by descent (IBD) matrices that capture ancestral marker and pedigree information. Moreover, we demonstrate how the parental IBD data can be incorporated into a QTL linkage analysis framework by using two approaches: a Threshold IBD model (TIBD) and a Latent Ancestral Allele Model (LAAM). The TIBD and LAAM models are empirically tested via numerical simulation based on the structure of a commercial maize breeding program. The simulations included a pilot dataset with closely linked QTL on a single linkage group and 100 replicated datasets with five linkage groups harboring four unlinked QTL. The simulation results show that including parental IBD data (similarly for TIBD and LAAM) significantly improves the power and particularly accuracy of QTL mapping, e.g., position, effect size and individuals' genotype probability without significantly increasing computational demand.

  7. Genetic mapping of X-linked ocular albinism: Linkage analysis in a large Newfoundland kindred

    Energy Technology Data Exchange (ETDEWEB)

    Charles, S.J.; Moore, A.T.; Barton, D.E.; Yates, J.R.W. (Addenbrooke' s Hospital, Cambridge (United Kingdom)); Green, J.S. (Memorial Univ. of Newfoundland, St. John' s (Canada))

    1993-04-01

    Genetic linkage studies in a large Newfoundland family affected by X-linked ocular albinism (OA1) showed linkage to markers from Xp22.3. One recombinant mapped the disease proximal to DXS143 (dic56) and two recombinants mapped the disease distal to DXS85 (782). Combining the data with that from 16 British families previously published confirmed close linkage between OA1 and DXS143 (dic56; Z[sub max] = 21.96 at [theta] = 0.01, confidence interval (CI) 0.0005--0.05) and linkage to DXS85 (782; Z[sub max] = 17.60 at [theta] = 0.07, CI = 0.03--0.13) and DXS237 (GMGX9; Z[sub max] = 15.20 at [theta] = 0.08, CI = 0.03--0.15). Multipoint analysis (LINKMAP) gave the most likely order as Xpter-XG-DXS237-DXS143-OA1-DXS85, with odds of 48:1 over the order Xpter-XG-DXS237-OA1-DXS143-DXS85, and odds exceeding 10[sup 10]:1 over other locations for the disease locus. 11 refs., 1 fig., 1 tab.

  8. Linkage Analysis in Familial Non-Lynch Syndrome Colorectal Cancer Families from Sweden

    OpenAIRE

    Vinaykumar Kontham; Susanna von Holst; Annika Lindblom

    2013-01-01

    Family history is a major risk factor for colorectal cancer and many families segregate the disease as a seemingly monogenic trait. A minority of familial colorectal cancer could be explained by known monogenic genes and genetic loci. Familial polyposis and Lynch syndrome are two syndromes where the predisposing genes are known but numerous families have been tested without finding the predisposing gene. We performed a genome wide linkage analysis in 121 colorectal families with an increased ...

  9. Linkage analysis in familial non-Lynch syndrome colorectal cancer families from Sweden.

    Directory of Open Access Journals (Sweden)

    Vinaykumar Kontham

    Full Text Available Family history is a major risk factor for colorectal cancer and many families segregate the disease as a seemingly monogenic trait. A minority of familial colorectal cancer could be explained by known monogenic genes and genetic loci. Familial polyposis and Lynch syndrome are two syndromes where the predisposing genes are known but numerous families have been tested without finding the predisposing gene. We performed a genome wide linkage analysis in 121 colorectal families with an increased risk of colorectal cancer. The families were ascertained from the department of clinical genetics at the Karolinska University Hospital in Stockholm, Sweden and were considered negative for Familial Polyposis and Lynch syndrome. In total 600 subjects were genotyped using single nucleotide polymorphism array chips. Parametric- and non-parametric linkage analyses were computed using MERLIN in all and subsets of families. No statistically significant result was seen, however, there were suggestive positive HLODs above two in parametric linkage analysis. This was observed in a recessive model for high-risk families, at locus 9q31.1 (HLOD=2.2, rs1338121 and for moderate-risk families, at locus Xp22.33 (LOD=2.2 and HLOD=2.5, rs2306737. Using families with early-onset, recessive analysis suggested one locus on 4p16.3 (LOD=2.2, rs920683 and one on 17p13.2 (LOD/HLOD=2.0, rs884250. No NPL score above two was seen for any of the families. Our linkage study provided additional support for the previously suggested region on chromosome 9 and suggested additional loci to be involved in colorectal cancer risk. Sequencing of genes in the regions will be done in future studies.

  10. Linkage analysis in familial non-Lynch syndrome colorectal cancer families from Sweden.

    Science.gov (United States)

    Kontham, Vinaykumar; von Holst, Susanna; Lindblom, Annika

    2013-01-01

    Family history is a major risk factor for colorectal cancer and many families segregate the disease as a seemingly monogenic trait. A minority of familial colorectal cancer could be explained by known monogenic genes and genetic loci. Familial polyposis and Lynch syndrome are two syndromes where the predisposing genes are known but numerous families have been tested without finding the predisposing gene. We performed a genome wide linkage analysis in 121 colorectal families with an increased risk of colorectal cancer. The families were ascertained from the department of clinical genetics at the Karolinska University Hospital in Stockholm, Sweden and were considered negative for Familial Polyposis and Lynch syndrome. In total 600 subjects were genotyped using single nucleotide polymorphism array chips. Parametric- and non-parametric linkage analyses were computed using MERLIN in all and subsets of families. No statistically significant result was seen, however, there were suggestive positive HLODs above two in parametric linkage analysis. This was observed in a recessive model for high-risk families, at locus 9q31.1 (HLOD=2.2, rs1338121) and for moderate-risk families, at locus Xp22.33 (LOD=2.2 and HLOD=2.5, rs2306737). Using families with early-onset, recessive analysis suggested one locus on 4p16.3 (LOD=2.2, rs920683) and one on 17p13.2 (LOD/HLOD=2.0, rs884250). No NPL score above two was seen for any of the families. Our linkage study provided additional support for the previously suggested region on chromosome 9 and suggested additional loci to be involved in colorectal cancer risk. Sequencing of genes in the regions will be done in future studies. PMID:24349560

  11. Clinical features and linkage analysis for a Chinese family with autosomal dominant central areolar choroidal dystrophy

    Institute of Scientific and Technical Information of China (English)

    MA Kai; LIU Ning-pu; YANG Xiu-fen; HAN Cui; ZHANG Ning; XU Jun; LIU Shou-bin; LU Hal; Torkel Snellingen; WANG Ning-li

    2009-01-01

    Background A Chinese family with autosomal dominant central areolar choroidal dystrophy (CACD) was identified.The purpose of this study was to collect the clinical findings from the family and to identify the genetic entity by linkage nalysis.Methods Forty-three individuals from 3 generations of the family underwent ophthalmologic examinations, including best-corrected visual acuity, examination of the anterior segments, and inspection of the ocular fundus after pharmacologic mydriasis. Affected family members further underwent color vision test, color fundus photography,fluorescein angiography, automated perimetry, and electroretinography. The family was followed up for 30 months.Peripheral venous blood or buccal swabs were collected from each family member and genomic DNA was extracted.Linkage analysis was performed for candidate genes or loci using microsatellite markers.Results Seven family members in 3 continuous generations were diagnosed as having autosomal dominant CACD.The family showed progressive development of the disease, affecting both male and female. Age of onset of visual disturbances varied between 11 and 50 years. Phenotypic variability among affected individuals was apparent and ranged from relatively normal-appearing fundus with mild parafoveal pigment mottling to geographic atrophy of the macula. Fluorescein angiography showed hyperfluorescent parafoveal changes in early stage or well-demarcated area of chorioretinal atrophy with enhanced visibility of the residual underlying choroidal vessels in the late stage. Peripheral retina and visual fields were normal in affected individuals. Electroretinogram showed normal or mild reduction in the photopic amplitude. Eight candidate genes (STGD4, RCD1, peripherin/RDS, GUCA1A, RIMS1, UNC119, GUC Y2D, and AIPL1) and two genetic loci (4p15.2-16.3, and 17p13) were excluded to be responsible for the disease by linkage analysis.Conclusions The clinical findings of this Chinese family with CACD shared

  12. A novel classification of planar four-bar linkages and its application to the mechanical analysis of animal systems.

    Science.gov (United States)

    Muller, M

    1996-05-29

    A novel classification of planar four-bar linkages is presented based on the systematical variation of one, two or three bar lengths and studying the transmission properties (input-output curves) of the linkages. This classification is better suited to the study of biological systems than the classical Grashof-classification used in engineering as it considers the change of structural elements, in evolution for example, instead of evaluating the possibilities for the rotation of a particular bar. The mechanical features of a wide range of planar linkages in vertebrates, described by various authors, have been included in this classification. Examples are: skull-levation and jaw-protrusion mechanisms in fishes, reptiles and birds, the coral crushing apparatus of parrotfishes, and catapult-mechanisms in feeding pipefishes. Four-bar replacement mechanisms, e.g., crank-slider mechanisms in feeding systems of fishes and cam-mechanisms in mammalian limb-joints, and more complex linkages than four-bar ones, e.g., six-bar linkages and interconnected four-bar linkages in fish feeding mechanisms are also discussed. In this way, an overview is obtained of the applicability of planar linkage theory in animal mechanics to mechanical functioning and the effect of possible variations of bar lengths and working ranges in evolution. Four-bar system analysis often provides a rigorous method of simplifying the study of complex biological mechanisms. The acceptable width-range of necessary and undesired hysteresis ('play') in biological linkages is also discussed. PMID:8927640

  13. Genetic study of autosomal dominant progressive external ophthalmoplegia and familial myasthenia gravis : linkage analysis, candidate gene cloning and mutation detection

    OpenAIRE

    Li, Fang-Yuan

    2001-01-01

    Identification of genes responsible for familial human diseases is a major task of medical genetics. In this process, linkage analysis, candidate gene screening and mutation detection are the three major steps (Paper I-VI). The purpose of this study was to elucidate the genetic backgrounds of autosomal dominant progressive external ophthalmoplegia (adPEO) and familial inyasthenia gravis (FMG). The methods applied in this study for linkage analysis and repeat expansion we...

  14. A variable age of onset segregation model for linkage analysis, with correction for ascertainment, applied to glioma

    DEFF Research Database (Denmark)

    Sun, Xiangqing; Vengoechea, Jaime; Elston, Robert;

    2012-01-01

    We propose a 2-step model-based approach, with correction for ascertainment, to linkage analysis of a binary trait with variable age of onset and apply it to a set of multiplex pedigrees segregating for adult glioma.......We propose a 2-step model-based approach, with correction for ascertainment, to linkage analysis of a binary trait with variable age of onset and apply it to a set of multiplex pedigrees segregating for adult glioma....

  15. Genome-wide linkage analysis of malaria infection intensity and mild disease.

    Directory of Open Access Journals (Sweden)

    Christian Timmann

    2007-03-01

    Full Text Available Although balancing selection with the sickle-cell trait and other red blood cell disorders has emphasized the interaction between malaria and human genetics, no systematic approach has so far been undertaken towards a comprehensive search for human genome variants influencing malaria. By screening 2,551 families in rural Ghana, West Africa, 108 nuclear families were identified who were exposed to hyperendemic malaria transmission and were homozygous wild-type for the established malaria resistance factors of hemoglobin (HbS, HbC, alpha(+ thalassemia, and glucose-6-phosphate-dehydrogenase deficiency. Of these families, 392 siblings aged 0.5-11 y were characterized for malaria susceptibility by closely monitoring parasite counts, malaria fever episodes, and anemia over 8 mo. An autosome-wide linkage analysis based on 10,000 single-nucleotide polymorphisms was conducted in 68 selected families including 241 siblings forming 330 sib pairs. Several regions were identified which showed evidence for linkage to the parasitological and clinical phenotypes studied, among them a prominent signal on Chromosome 10p15 obtained with malaria fever episodes (asymptotic z score = 4.37, empirical p-value = 4.0 x 10(-5, locus-specific heritability of 37.7%; 95% confidence interval, 15.7%-59.7%. The identification of genetic variants underlying the linkage signals may reveal as yet unrecognized pathways influencing human resistance to malaria.

  16. Linkage analysis suggests a locus of ichthyosis vulgaris on 1q22.

    Science.gov (United States)

    Zhong, Wei; Cui, Bin; Zhang, Yizhi; Jiang, Haisong; Wei, Shengcai; Bu, Lei; Zhao, Guoping; Hu, Landian; Kong, Xiangyin

    2003-01-01

    Ichthyosis vulgaris (IV) is an inherited scaling skin disorder with a prevalence estimated at 2.29% in China. The gene responsible for this disorder has not been elucidated. To find the disease gene, we ascertained two Chinese IV families. Linkage analysis identified an IV locus on chromosome 1q22 with a maximum two-point Lod score of 2.47 at D1S1653 (theta=0.00). Haplotype analysis placed the critical region in a 7-cM interval defined by D1S1653 and D1S2675. These results provide the basis for further identifying the gene responsible for IV disorder.

  17. Evidence of Allopolyploidy in Urochloa humidicola Based on Cytological Analysis and Genetic Linkage Mapping.

    Science.gov (United States)

    Vigna, Bianca B Z; Santos, Jean C S; Jungmann, Leticia; do Valle, Cacilda B; Mollinari, Marcelo; Pastina, Maria M; Pagliarini, Maria Suely; Garcia, Antonio A F; Souza, Anete P

    2016-01-01

    The African species Urochloa humidicola (Rendle) Morrone & Zuloaga (syn. Brachiaria humidicola (Rendle) Schweick.) is an important perennial forage grass found throughout the tropics. This species is polyploid, ranging from tetra to nonaploid, and apomictic, which makes genetic studies challenging; therefore, the number of currently available genetic resources is limited. The genomic architecture and evolution of U. humidicola and the molecular markers linked to apomixis were investigated in a full-sib F1 population obtained by crossing the sexual accession H031 and the apomictic cultivar U. humidicola cv. BRS Tupi, both of which are hexaploid. A simple sequence repeat (SSR)-based linkage map was constructed for the species from 102 polymorphic and specific SSR markers based on simplex and double-simplex markers. The map consisted of 49 linkage groups (LGs) and had a total length of 1702.82 cM, with 89 microsatellite loci and an average map density of 10.6 cM. Eight homology groups (HGs) were formed, comprising 22 LGs, and the other LGs remained ungrouped. The locus that controls apospory (apo-locus) was mapped in LG02 and was located 19.4 cM from the locus Bh027.c.D2. In the cytological analyses of some hybrids, bi- to hexavalents at diakinesis were observed, as well as two nucleoli in some meiocytes, smaller chromosomes with preferential allocation within the first metaphase plate and asynchronous chromosome migration to the poles during anaphase. The linkage map and the meiocyte analyses confirm previous reports of hybridization and suggest an allopolyploid origin of the hexaploid U. humidicola. This is the first linkage map of an Urochloa species, and it will be useful for future quantitative trait locus (QTL) analysis after saturation of the map and for genome assembly and evolutionary studies in Urochloa spp. Moreover, the results of the apomixis mapping are consistent with previous reports and confirm the need for additional studies to search for a co

  18. Markov chain Monte Carlo linkage analysis of a complex qualitative phenotype.

    Science.gov (United States)

    Hinrichs, A; Lin, J H; Reich, T; Bierut, L; Suarez, B K

    1999-01-01

    We tested a new computer program, LOKI, that implements a reversible jump Markov chain Monte Carlo (MCMC) technique for segregation and linkage analysis. Our objective was to determine whether this software, designed for use with continuously distributed phenotypes, has any efficacy when applied to the discrete disease states of the simulated data from the Mordor data from GAW Problem 1. Although we were able to identify the genomic location for two of the three quantitative trait loci by repeated application of the software, the MCMC sampler experienced significant mixing problems indicating that the method, as currently formulated in LOKI, was not suitable for the discrete phenotypes in this data set. PMID:10597502

  19. An approach to incorporate linkage disequilibrium structure into genomic association analysis

    Institute of Scientific and Technical Information of China (English)

    Fengyu Zhang; Diane Wagener

    2008-01-01

    In this study, we propose to use the principal component analysis (PCA) and regression model to incorporate linkage disequilibrium (LD) in genomic association data analysis. To accommodate LD in genomic data and reduce multiple testing, we suggest performing PCA and extracting the PCA score to capture the variation of genomic data, after which regression analysis is used to assess the association of the disease with the principal component score. An empirical analysis result shows that both genotype-basod correlation matrix and haplotype-based LD matrix can produce similar results for PCA. Principal component score seems to be more powerful in detecting genetic association because the principal component score is quantitatively measured and may be able to capture the effect of multiple loci.

  20. Evidence of Allopolyploidy in Urochloa humidicola Based on Cytological Analysis and Genetic Linkage Mapping.

    Science.gov (United States)

    Vigna, Bianca B Z; Santos, Jean C S; Jungmann, Leticia; do Valle, Cacilda B; Mollinari, Marcelo; Pastina, Maria M; Pagliarini, Maria Suely; Garcia, Antonio A F; Souza, Anete P

    2016-01-01

    The African species Urochloa humidicola (Rendle) Morrone & Zuloaga (syn. Brachiaria humidicola (Rendle) Schweick.) is an important perennial forage grass found throughout the tropics. This species is polyploid, ranging from tetra to nonaploid, and apomictic, which makes genetic studies challenging; therefore, the number of currently available genetic resources is limited. The genomic architecture and evolution of U. humidicola and the molecular markers linked to apomixis were investigated in a full-sib F1 population obtained by crossing the sexual accession H031 and the apomictic cultivar U. humidicola cv. BRS Tupi, both of which are hexaploid. A simple sequence repeat (SSR)-based linkage map was constructed for the species from 102 polymorphic and specific SSR markers based on simplex and double-simplex markers. The map consisted of 49 linkage groups (LGs) and had a total length of 1702.82 cM, with 89 microsatellite loci and an average map density of 10.6 cM. Eight homology groups (HGs) were formed, comprising 22 LGs, and the other LGs remained ungrouped. The locus that controls apospory (apo-locus) was mapped in LG02 and was located 19.4 cM from the locus Bh027.c.D2. In the cytological analyses of some hybrids, bi- to hexavalents at diakinesis were observed, as well as two nucleoli in some meiocytes, smaller chromosomes with preferential allocation within the first metaphase plate and asynchronous chromosome migration to the poles during anaphase. The linkage map and the meiocyte analyses confirm previous reports of hybridization and suggest an allopolyploid origin of the hexaploid U. humidicola. This is the first linkage map of an Urochloa species, and it will be useful for future quantitative trait locus (QTL) analysis after saturation of the map and for genome assembly and evolutionary studies in Urochloa spp. Moreover, the results of the apomixis mapping are consistent with previous reports and confirm the need for additional studies to search for a co

  1. Creative Activities in Music – A Genome-Wide Linkage Analysis

    Science.gov (United States)

    Oikkonen, Jaana; Kuusi, Tuire; Peltonen, Petri; Raijas, Pirre; Ukkola-Vuoti, Liisa; Karma, Kai; Onkamo, Päivi; Järvelä, Irma

    2016-01-01

    Creative activities in music represent a complex cognitive function of the human brain, whose biological basis is largely unknown. In order to elucidate the biological background of creative activities in music we performed genome-wide linkage and linkage disequilibrium (LD) scans in musically experienced individuals characterised for self-reported composing, arranging and non-music related creativity. The participants consisted of 474 individuals from 79 families, and 103 sporadic individuals. We found promising evidence for linkage at 16p12.1-q12.1 for arranging (LOD 2.75, 120 cases), 4q22.1 for composing (LOD 2.15, 103 cases) and Xp11.23 for non-music related creativity (LOD 2.50, 259 cases). Surprisingly, statistically significant evidence for linkage was found for the opposite phenotype of creative activity in music (neither composing nor arranging; NCNA) at 18q21 (LOD 3.09, 149 cases), which contains cadherin genes like CDH7 and CDH19. The locus at 4q22.1 overlaps the previously identified region of musical aptitude, music perception and performance giving further support for this region as a candidate region for broad range of music-related traits. The other regions at 18q21 and 16p12.1-q12.1 are also adjacent to the previously identified loci with musical aptitude. Pathway analysis of the genes suggestively associated with composing suggested an overrepresentation of the cerebellar long-term depression pathway (LTD), which is a cellular model for synaptic plasticity. The LTD also includes cadherins and AMPA receptors, whose component GSG1L was linked to arranging. These results suggest that molecular pathways linked to memory and learning via LTD affect music-related creative behaviour. Musical creativity is a complex phenotype where a common background with musicality and intelligence has been proposed. Here, we implicate genetic regions affecting music-related creative behaviour, which also include genes with neuropsychiatric associations. We also propose

  2. Genetic Linkage Map Construction and QTL Analysis of Two Interspecific Reproductive Isolation Traits in Sponge Gourd.

    Science.gov (United States)

    Wu, Haibin; He, Xiaoli; Gong, Hao; Luo, Shaobo; Li, Mingzhu; Chen, Junqiu; Zhang, Changyuan; Yu, Ting; Huang, Wangping; Luo, Jianning

    2016-01-01

    The hybrids between Luffa acutangula (L.) Roxb. and L.cylindrica (L.) Roem. have strong heterosis effects. However, some reproductive isolation traits hindered their normal hybridization and fructification, which was mainly caused by the flowering time and hybrid pollen sterility. In order to study the genetic basis of two interspecific reproductive isolation traits, we constructed a genetic linkage map using an F2 population derived from a cross between S1174 [L. acutangula (L.) Roxb.] and 93075 [L. cylindrica (L.) Roem.]. The map spans 1436.12 CentiMorgans (cM), with an average of 8.11 cM among markers, and consists of 177 EST-SSR markers distributed in 14 linkage groups (LG) with an average of 102.58 cM per LG. Meanwhile, we conducted colinearity analysis between the sequences of EST-SSR markers and the genomic sequences of cucumber, melon and watermelon. On the basis of genetic linkage map, we conducted QTL mapping of two reproductive isolation traits in sponge gourd, which were the flowering time and hybrid male sterility. Two putative QTLs associated with flowering time (FT) were both detected on LG 1. The accumulated contribution of these two QTLs explained 38.07% of the total phenotypic variance (PV), and each QTL explained 15.36 and 22.71% of the PV respectively. Four QTLs for pollen fertility (PF) were identified on LG 1 (qPF1.1 and qPF1.2), LG 3 (qPF3) and LG 7 (qPF7), respectively. The percentage of PF explained by these QTLs varied from 2.91 to 16.79%, and all together the four QTLs accounted for 39.98% of the total PV. Our newly developed EST-SSR markers and linkage map are very useful for gene mapping, comparative genomics and molecular marker-assisted breeding. These QTLs for interspecific reproductive isolation will also contribute to the cloning of genes relating to interspecific reproductive isolation and the utilization of interspecific heterosis in sponge gourd in further studies. PMID:27458467

  3. Genetic Linkage Map Construction and QTL Analysis of Two Interspecific Reproductive Isolation Traits in Sponge Gourd

    Science.gov (United States)

    Wu, Haibin; He, Xiaoli; Gong, Hao; Luo, Shaobo; Li, Mingzhu; Chen, Junqiu; Zhang, Changyuan; Yu, Ting; Huang, Wangping; Luo, Jianning

    2016-01-01

    The hybrids between Luffa acutangula (L.) Roxb. and L.cylindrica (L.) Roem. have strong heterosis effects. However, some reproductive isolation traits hindered their normal hybridization and fructification, which was mainly caused by the flowering time and hybrid pollen sterility. In order to study the genetic basis of two interspecific reproductive isolation traits, we constructed a genetic linkage map using an F2 population derived from a cross between S1174 [L. acutangula (L.) Roxb.] and 93075 [L. cylindrica (L.) Roem.]. The map spans 1436.12 CentiMorgans (cM), with an average of 8.11 cM among markers, and consists of 177 EST-SSR markers distributed in 14 linkage groups (LG) with an average of 102.58 cM per LG. Meanwhile, we conducted colinearity analysis between the sequences of EST-SSR markers and the genomic sequences of cucumber, melon and watermelon. On the basis of genetic linkage map, we conducted QTL mapping of two reproductive isolation traits in sponge gourd, which were the flowering time and hybrid male sterility. Two putative QTLs associated with flowering time (FT) were both detected on LG 1. The accumulated contribution of these two QTLs explained 38.07% of the total phenotypic variance (PV), and each QTL explained 15.36 and 22.71% of the PV respectively. Four QTLs for pollen fertility (PF) were identified on LG 1 (qPF1.1 and qPF1.2), LG 3 (qPF3) and LG 7 (qPF7), respectively. The percentage of PF explained by these QTLs varied from 2.91 to 16.79%, and all together the four QTLs accounted for 39.98% of the total PV. Our newly developed EST-SSR markers and linkage map are very useful for gene mapping, comparative genomics and molecular marker-assisted breeding. These QTLs for interspecific reproductive isolation will also contribute to the cloning of genes relating to interspecific reproductive isolation and the utilization of interspecific heterosis in sponge gourd in further studies. PMID:27458467

  4. Creative Activities in Music--A Genome-Wide Linkage Analysis.

    Science.gov (United States)

    Oikkonen, Jaana; Kuusi, Tuire; Peltonen, Petri; Raijas, Pirre; Ukkola-Vuoti, Liisa; Karma, Kai; Onkamo, Päivi; Järvelä, Irma

    2016-01-01

    Creative activities in music represent a complex cognitive function of the human brain, whose biological basis is largely unknown. In order to elucidate the biological background of creative activities in music we performed genome-wide linkage and linkage disequilibrium (LD) scans in musically experienced individuals characterised for self-reported composing, arranging and non-music related creativity. The participants consisted of 474 individuals from 79 families, and 103 sporadic individuals. We found promising evidence for linkage at 16p12.1-q12.1 for arranging (LOD 2.75, 120 cases), 4q22.1 for composing (LOD 2.15, 103 cases) and Xp11.23 for non-music related creativity (LOD 2.50, 259 cases). Surprisingly, statistically significant evidence for linkage was found for the opposite phenotype of creative activity in music (neither composing nor arranging; NCNA) at 18q21 (LOD 3.09, 149 cases), which contains cadherin genes like CDH7 and CDH19. The locus at 4q22.1 overlaps the previously identified region of musical aptitude, music perception and performance giving further support for this region as a candidate region for broad range of music-related traits. The other regions at 18q21 and 16p12.1-q12.1 are also adjacent to the previously identified loci with musical aptitude. Pathway analysis of the genes suggestively associated with composing suggested an overrepresentation of the cerebellar long-term depression pathway (LTD), which is a cellular model for synaptic plasticity. The LTD also includes cadherins and AMPA receptors, whose component GSG1L was linked to arranging. These results suggest that molecular pathways linked to memory and learning via LTD affect music-related creative behaviour. Musical creativity is a complex phenotype where a common background with musicality and intelligence has been proposed. Here, we implicate genetic regions affecting music-related creative behaviour, which also include genes with neuropsychiatric associations. We also propose

  5. Creative Activities in Music--A Genome-Wide Linkage Analysis.

    Directory of Open Access Journals (Sweden)

    Jaana Oikkonen

    Full Text Available Creative activities in music represent a complex cognitive function of the human brain, whose biological basis is largely unknown. In order to elucidate the biological background of creative activities in music we performed genome-wide linkage and linkage disequilibrium (LD scans in musically experienced individuals characterised for self-reported composing, arranging and non-music related creativity. The participants consisted of 474 individuals from 79 families, and 103 sporadic individuals. We found promising evidence for linkage at 16p12.1-q12.1 for arranging (LOD 2.75, 120 cases, 4q22.1 for composing (LOD 2.15, 103 cases and Xp11.23 for non-music related creativity (LOD 2.50, 259 cases. Surprisingly, statistically significant evidence for linkage was found for the opposite phenotype of creative activity in music (neither composing nor arranging; NCNA at 18q21 (LOD 3.09, 149 cases, which contains cadherin genes like CDH7 and CDH19. The locus at 4q22.1 overlaps the previously identified region of musical aptitude, music perception and performance giving further support for this region as a candidate region for broad range of music-related traits. The other regions at 18q21 and 16p12.1-q12.1 are also adjacent to the previously identified loci with musical aptitude. Pathway analysis of the genes suggestively associated with composing suggested an overrepresentation of the cerebellar long-term depression pathway (LTD, which is a cellular model for synaptic plasticity. The LTD also includes cadherins and AMPA receptors, whose component GSG1L was linked to arranging. These results suggest that molecular pathways linked to memory and learning via LTD affect music-related creative behaviour. Musical creativity is a complex phenotype where a common background with musicality and intelligence has been proposed. Here, we implicate genetic regions affecting music-related creative behaviour, which also include genes with neuropsychiatric associations. We

  6. Creative Activities in Music--A Genome-Wide Linkage Analysis.

    Science.gov (United States)

    Oikkonen, Jaana; Kuusi, Tuire; Peltonen, Petri; Raijas, Pirre; Ukkola-Vuoti, Liisa; Karma, Kai; Onkamo, Päivi; Järvelä, Irma

    2016-01-01

    Creative activities in music represent a complex cognitive function of the human brain, whose biological basis is largely unknown. In order to elucidate the biological background of creative activities in music we performed genome-wide linkage and linkage disequilibrium (LD) scans in musically experienced individuals characterised for self-reported composing, arranging and non-music related creativity. The participants consisted of 474 individuals from 79 families, and 103 sporadic individuals. We found promising evidence for linkage at 16p12.1-q12.1 for arranging (LOD 2.75, 120 cases), 4q22.1 for composing (LOD 2.15, 103 cases) and Xp11.23 for non-music related creativity (LOD 2.50, 259 cases). Surprisingly, statistically significant evidence for linkage was found for the opposite phenotype of creative activity in music (neither composing nor arranging; NCNA) at 18q21 (LOD 3.09, 149 cases), which contains cadherin genes like CDH7 and CDH19. The locus at 4q22.1 overlaps the previously identified region of musical aptitude, music perception and performance giving further support for this region as a candidate region for broad range of music-related traits. The other regions at 18q21 and 16p12.1-q12.1 are also adjacent to the previously identified loci with musical aptitude. Pathway analysis of the genes suggestively associated with composing suggested an overrepresentation of the cerebellar long-term depression pathway (LTD), which is a cellular model for synaptic plasticity. The LTD also includes cadherins and AMPA receptors, whose component GSG1L was linked to arranging. These results suggest that molecular pathways linked to memory and learning via LTD affect music-related creative behaviour. Musical creativity is a complex phenotype where a common background with musicality and intelligence has been proposed. Here, we implicate genetic regions affecting music-related creative behaviour, which also include genes with neuropsychiatric associations. We also propose

  7. Setting up Multiplex Panels for Genetic Testing of Familial Hy¬pertrophic Cardiomyopathy Based on Linkage Analysis

    Directory of Open Access Journals (Sweden)

    Hoorieh SAGHAFI

    2016-03-01

    Full Text Available Background: Familial hypertrophic cardiomyopathy (HCM is caused by mutations in genes encoding cardiac sarcomere proteins. Nowadays genetic testing of HCM plays an important role in clinical practice by contributing to the diagnosis, prognosis, and screening of high-risk individuals. The aim of this study was developing a reliable testing strategy for HCM based on linkage analysis and appropriate for Iranian population.Methods: Six panels of four microsatellite markers surrounding MYH7, MYBPC3, TNNT2, TNNI3, TPM1, and MYL2 genes (24 markers in total were selected for multiplex PCR and fragment length analysis. Characteristics of markers and informativeness of the panels were evaluated in 50 unrelated Iranians. The efficacy of the strategy was verified in a family with HCM.Results: All markers were highly polymorphic. The panels were informative in 96-100% of samples. Multipoint linkage analysis excluded the linkage between the disease and all six genes by obtaining maximum LOD score ≤-2.Conclusion: This study suggests a reliable genetic testing method based on linkage analysis between 6 sarcomere genes and familial HCM. It could be applied for diagnostic, predictive, or screening testing in clinical setting. Keywords: Cardiomyopathy, Hypertrophic, Genetic linkage, Diagnosis 

  8. Genetic diversity and linkage disequilibrium analysis in elite sugar beet breeding lines and wild beet accessions.

    Science.gov (United States)

    Adetunji, Ibraheem; Willems, Glenda; Tschoep, Hendrik; Bürkholz, Alexandra; Barnes, Steve; Boer, Martin; Malosetti, Marcos; Horemans, Stefaan; van Eeuwijk, Fred

    2014-03-01

    Linkage disequilibrium decay in sugar beet is strongly affected by the breeding history, and varies extensively between and along chromosomes, allowing identification of known and unknown signatures of selection. Genetic diversity and linkage disequilibrium (LD) patterns were investigated in 233 elite sugar beet breeding lines and 91 wild beet accessions, using 454 single nucleotide polymorphisms (SNPs) and 418 SNPs, respectively. Principal coordinate analysis suggested the existence of three groups of germplasm, corresponding to the wild beets, the seed parent and the pollen parent breeding pool. LD was investigated in each of these groups, with and without correction for genetic relatedness. Without correction for genetic relatedness, in the pollen as well as the seed parent pool, LD persisted beyond 50 centiMorgan (cM) on four (2, 3, 4 and 5) and three chromosomes (2, 4 and 6), respectively; after correction for genetic relatedness, LD decayed after wild beet accessions, there was a strong LD decay: on average LD disappeared after 1 cM when LD was calculated with a correction for genetic relatedness. Persistence of LD was not only observed between distant SNPs on the same chromosome, but also between SNPs on different chromosomes. Regions on chromosomes 3 and 4 that harbor disease resistance and monogermy loci showed strong genetic differentiation between the pollen and seed parent pools. Other regions, on chromosomes 8 and 9, for which no a priori information was available with respect to their contribution to the phenotype, still contributed to clustering of lines in the elite breeding material.

  9. Fluorescent multiplex linkage analysis and carrier detection for Duchenne/Becker muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, L.S.; Hoffman, E.P. (Univ. of Pittsburgh Schoool of Medicine, Pittsburgh, PA (United States)); Tarleton, J. (Self Memorial Hospital, Greenwood, SC (United States)); Popovich, B. (Children' s Hosptial and Health Center, San Diego, CA (United States)); Seltzer, W.K. (Univ. of Colorado Health Sciences Center, Denver, CO (United States))

    1992-10-01

    The authors have developed a fast and accurate PCR-based linkage and carrier detection protocol for families of Duchenne muscular dystrophy (DMD)/Becker muscular dystrophy (BMD) patients with or without detectable deletions of the dystrophin gene, using fluorescent PCR products analyzed on an automated sequencer. When a deletion is found in the affected male DMD/BMD patient by standard multiplex PCR, fluorescently labeled primers specific for the deleted and nondeleted exon(s) are used to amplify the DNA of at-risk female relatives by using multiplex PCR at low cycle number (20 cycles). The products are then quantitatively analyzed on an automatic sequencer to determine whether they are heterozygous for the deletion and thus are carriers. As a confirmation of the deletion data, and in cases in which a deletion is not found in the proband, fluorescent multiplex PCR linkage is done by using four previously described polymorphic dinucleotide sequences. The four (CA)[sub n] repeats are located throughout the dystrophin gene, making the analysis highly informative and accurate. The authors present the successful application of this protocol in families who proved refractory to more traditional analyses. 22 refs., 3 figs.

  10. Modified distance in average linkage based on M-estimator and MADn criteria in hierarchical cluster analysis

    Science.gov (United States)

    Muda, Nora; Othman, Abdul Rahman

    2015-10-01

    The process of grouping a set of objects into classes of similar objects is called clustering. It divides a large group of observations into smaller groups so that the observations within each group are relatively similar and the observations in different groups are relatively dissimilar. In this study, an agglomerative method in hierarchical cluster analysis is chosen and clusters were constructed by using an average linkage technique. An average linkage technique requires distance between clusters, which is calculated based on the average distance between all pairs of points, one group with another group. In calculating the average distance, the distance will not be robust when there is an outlier. Therefore, the average distance in average linkage needs to be modified in order to overcome the problem of outlier. Therefore, the criteria of outlier detection based on MADn criteria is used and the average distance is recalculated without the outlier. Next, the distance in average linkage is calculated based on a modified one step M-estimator (MOM). The groups of cluster are presented in dendrogram graph. To evaluate the goodness of a modified distance in the average linkage clustering, the bootstrap analysis is conducted on the dendrogram graph and the bootstrap value (BP) are assessed for each branch in dendrogram that formed the group, to ensure the reliability of the branches constructed. This study found that the average linkage technique with modified distance is significantly superior than the usual average linkage technique, if there is an outlier. Both of these techniques are said to be similar if there is no outlier.

  11. Cannabis use and age at onset of schizophrenia

    NARCIS (Netherlands)

    Veen, ND; Selten, JP; Van der Tweel, [No Value; Feller, WG; Hoek, HW; Kahn, RS

    2004-01-01

    Objective: The purpose of the study was to assess the independent influences of gender and cannabis use on milestones of early course in schizophrenia. Method: in this population-based, first-contact incidence study conducted in The Hague, the Netherlands, patients (N=133) were interviewed with the

  12. Cost Analysis of Enhancing Linkages to HIV Care Following Jail: A Cost-Effective Intervention

    OpenAIRE

    Spaulding, Anne C.; Pinkerton, Steven D.; Superak, Hillary; Cunningham, Marc J.; Resch, Stephen; Jordan, Alison O.; Yang, Zhou

    2013-01-01

    We are not aware of published cost-effectiveness studies addressing community transitional programs for HIV-infected jail detainees. To address this gap, data from 9 sites of EnhanceLink, a project that enrolled HIV-infected releasees from jails across the US, were examined. Figures on the number of clients served, cost of linkage services, number of linkages and 6-month sustained linkages to community HIV care, and number of clients achieving viral suppression were assessed for subjects rele...

  13. Linkage analysis of 19 French breast cancer families, with five chromosome 17q markers.

    OpenAIRE

    Mazoyer, S.; Lalle, P.; Narod, S A; Bignon, Y J; Courjal, F.; Jamot, B; Dutrillaux, B; Stoppa-Lyonnett, D; Sobol, H

    1993-01-01

    Nineteen French breast and breast-ovarian cancer families were tested for linkage with five chromosome 17q markers. The five breast-ovarian cancer families as a group give positive evidence for linkage, whereas the 14 breast cancer-only families do not. Heterogeneity of linkage of breast and breast-ovarian cancers is significant in France and supports the existence of more than one susceptibility gene.

  14. Late onset autosomal dominant cerebellar ataxia a family description and linkage analysis with the hla system

    Directory of Open Access Journals (Sweden)

    Walter O. Arruda

    1991-09-01

    Full Text Available A family suffering an autosomal dominant form of late onset hereditary cerebellar ataxia is described. Eight affected family members were personally studied, and data from another four were obtained through anamnesis. The mean age of onset was 37.1±5.4 years (27-47 years. The clinical picture consisted basically of a pure ataxic cerebellar syndrome. CT-scan disclosed diffuse cerebellar atrophy with relative sparing of the brainstem (and no involvement of supratentorial structures. Neurophysiological studies (nerve conduction, VEP and BAEP were normal. Twenty-six individuals were typed for HLA histocompatibility antigens. Lod scores were calculated with the computer program LINKMAP. Close linkage of the ataxia gene with the HLA system in this family could be excluded - 0==0,02, z=(-2,17 - and the overall analysis of the lod scores suggest another chromossomal location than chromosome 6.

  15. Genetic linkage map and comparative genome analysis for the estuarine Atlantic killifish (Fundulus heteroclitus)

    Data.gov (United States)

    U.S. Environmental Protection Agency — Genetic linkage maps are valuable tools in evolutionary biology; however, their availability for wild populations is extremely limited. Fundulus heteroclitus...

  16. Genetic diversity and linkage disequilibrium analysis in elite sugar beet breeding lines and wild beet accessions.

    Science.gov (United States)

    Adetunji, Ibraheem; Willems, Glenda; Tschoep, Hendrik; Bürkholz, Alexandra; Barnes, Steve; Boer, Martin; Malosetti, Marcos; Horemans, Stefaan; van Eeuwijk, Fred

    2014-03-01

    Linkage disequilibrium decay in sugar beet is strongly affected by the breeding history, and varies extensively between and along chromosomes, allowing identification of known and unknown signatures of selection. Genetic diversity and linkage disequilibrium (LD) patterns were investigated in 233 elite sugar beet breeding lines and 91 wild beet accessions, using 454 single nucleotide polymorphisms (SNPs) and 418 SNPs, respectively. Principal coordinate analysis suggested the existence of three groups of germplasm, corresponding to the wild beets, the seed parent and the pollen parent breeding pool. LD was investigated in each of these groups, with and without correction for genetic relatedness. Without correction for genetic relatedness, in the pollen as well as the seed parent pool, LD persisted beyond 50 centiMorgan (cM) on four (2, 3, 4 and 5) and three chromosomes (2, 4 and 6), respectively; after correction for genetic relatedness, LD decayed after wild beet accessions, there was a strong LD decay: on average LD disappeared after 1 cM when LD was calculated with a correction for genetic relatedness. Persistence of LD was not only observed between distant SNPs on the same chromosome, but also between SNPs on different chromosomes. Regions on chromosomes 3 and 4 that harbor disease resistance and monogermy loci showed strong genetic differentiation between the pollen and seed parent pools. Other regions, on chromosomes 8 and 9, for which no a priori information was available with respect to their contribution to the phenotype, still contributed to clustering of lines in the elite breeding material. PMID:24292512

  17. Joint linkage and association analysis with exome sequence data implicates SLC25A40 in hypertriglyceridemia.

    Science.gov (United States)

    Rosenthal, Elisabeth A; Ranchalis, Jane; Crosslin, David R; Burt, Amber; Brunzell, John D; Motulsky, Arno G; Nickerson, Deborah A; Wijsman, Ellen M; Jarvik, Gail P

    2013-12-01

    Hypertriglyceridemia (HTG) is a heritable risk factor for cardiovascular disease. Investigating the genetics of HTG may identify new drug targets. There are ~35 known single-nucleotide variants (SNVs) that explain only ~10% of variation in triglyceride (TG) level. Because of the genetic heterogeneity of HTG, a family study design is optimal for identification of rare genetic variants with large effect size because the same mutation can be observed in many relatives and cosegregation with TG can be tested. We considered HTG in a five-generation family of European American descent (n = 121), ascertained for familial combined hyperlipidemia. By using Bayesian Markov chain Monte Carlo joint oligogenic linkage and association analysis, we detected linkage to chromosomes 7 and 17. Whole-exome sequence data revealed shared, highly conserved, private missense SNVs in both SLC25A40 on chr7 and PLD2 on chr17. Jointly, these SNVs explained 49% of the genetic variance in TG; however, only the SLC25A40 SNV was significantly associated with TG (p = 0.0001). This SNV, c.374A>G, causes a highly disruptive p.Tyr125Cys substitution just outside the second helical transmembrane region of the SLC25A40 inner mitochondrial membrane transport protein. Whole-gene testing in subjects from the Exome Sequencing Project confirmed the association between TG and SLC25A40 rare, highly conserved, coding variants (p = 0.03). These results suggest a previously undescribed pathway for HTG and illustrate the power of large pedigrees in the search for rare, causal variants.

  18. Meta-analysis of genome-wide linkage scans of attention deficit hyperactivity disorder

    NARCIS (Netherlands)

    Zhou, Kaixin; Dempfle, Astrid; Arcos-Burgos, Mauricio; Bakker, Steven C; Banaschewski, Tobias; Biederman, Joseph; Buitelaar, Jan; Castellanos, F Xavier; Doyle, Alysa; Ebstein, Richard P; Ekholm, Jenny; Forabosco, Paola; Franke, Barbara; Freitag, Christine; Friedel, Susann; Gill, Michael; Hebebrand, Johannes; Hinney, Anke; Jacob, Christian; Lesch, Klaus Peter; Loo, Sandra K; Lopera, Francisco; McCracken, James T; McGough, James J; Meyer, Jobst; Mick, Eric; Miranda, Ana; Muenke, Maximilian; Mulas, Fernando; Nelson, Stanley F; Nguyen, T Trang; Oades, Robert D; Ogdie, Matthew N; Palacio, Juan David; Pineda, David; Reif, Andreas; Renner, Tobias J; Roeyers, Herbert; Romanos, Marcel; Rothenberger, Aribert; Schäfer, Helmut; Sergeant, Joseph; Sinke, Richard J; Smalley, Susan L; Sonuga-Barke, Edmund; Steinhausen, Hans-Christoph; van der Meulen, Emma; Walitza, Susanne; Warnke, Andreas; Lewis, Cathryn M; Faraone, Stephen V; Asherson, Philip

    2008-01-01

    Genetic contribution to the development of attention deficit hyperactivity disorder (ADHD) is well established. Seven independent genome-wide linkage scans have been performed to map loci that increase the risk for ADHD. Although significant linkage signals were identified in some of the studies, th

  19. Genetic diversity and linkage disequilibrium analysis in elite sugar beet breeding lines and wild beet accessions

    NARCIS (Netherlands)

    Adetunji, I.; Willems, G.; Tschoep, H.; Bürkholz, A.; Barnes, S.; Boer, M.P.; Malosetti, M.; Horemans, S.; Eeuwijk, van F.

    2014-01-01

    Linkage disequilibrium decay in sugar beet is strongly affected by the breeding history, and varies extensively between and along chromosomes, allowing identification of known and unknown signatures of selection. Genetic diversity and linkage disequilibrium (LD) patterns were investigated in 233 eli

  20. Detection of Duchenne/Becker Muscular Dystrophy Carriers in a Group of Iranian Families by Linkage Analysis

    Directory of Open Access Journals (Sweden)

    Fardeen Ali Malayeri

    2011-03-01

    Full Text Available This study determines the value of linkage analysis using six RFLP markers for carrier detection and prenatal diagnosis in familial DMD/BMD cases and their family members for the first time in the Iranian population. We studied the dystrophin gene in 33 unrelated patients with clinical diagnosis of DMD or BMD. Subsequently, we determined the rate of heterozygosity for six intragenic RFLP markers in the mothers of patients with dystrophin gene deletions. Finally, we studied the efficiency of linkage analysis by using RFLP markers for carrier status detection of DMD/BMD. In 63.6% of the patients we found one or more deletions. The most common heterozygous RFLP marker with 57.1% heterozygosity was pERT87.15Taq1. More than 80% of mothers in two groups of familial or non-familial cases had at least two heterozygous markers. Family linkage analysis was informative in more than 80% of the cases, allowing for accurate carrier detection. We found that linkage analysis using these six RFLP markers for carrier detection and prenatal diagnosis is a rapid, easy, reliable, and inexpensive method, suitable for most routine diagnostic services. The heterozygosity frequency of these markers is high enough in the Iranian population to allow carrier detection and prenatal diagnosis of DMD/BMD in more than 80% of familial cases in Iran.

  1. Construction of high-quality recombination maps with low-coverage genomic sequencing for joint linkage analysis in maize

    Science.gov (United States)

    A genome-wide association study (GWAS) is the foremost strategy used for finding genes that control human diseases and agriculturally important traits, but it often reports false positives. In contrast, its complementary method, linkage analysis, provides direct genetic confirmation, but with limite...

  2. Localization, by linkage analysis, of the cystinuria type III gene to chromosome 19q13.1

    Energy Technology Data Exchange (ETDEWEB)

    Bisceglia, L.; Totaro, A.; Melchionda, S. [and others

    1997-03-01

    Cystinuria is an autosomal recessive aminoaciduria in which three urinary phenotypes (I, II, and III) have been described. An amino acid transporter gene, SLC3A1 (formerly rBAT), was found to be responsible for this disorder. Mutational and linkage analysis demonstrated the presence of genetic heterogeneity in which the SLC3A1 gene is responsible for type I cystinuria but not for type II or type III. In this study, we report the identification of the cystinuria type III locus on the long arm of chromosome 19 (19q13.1), obtained after a genomewide search. Pairwise linkage analysis in a series of type III or type II families previously excluded from linkage to the cystinuria type I locus (SLC3A1 gene) revealed a significant maximum LOD score (Z{sub max}) of 13.11 at a maximum recombination fraction ({theta}{sub max}) of .00, with marker D19S225. Multipoint linkage analysis performed with the use of additional markers from the region placed the cystinuria type III locus between D19S414 and D19S220. Preliminary data on type II families also seem to place the disease locus for this rare type of cystinuria at 19q13.1 (significant Z{sub max} = 3.11 at {theta}{sub max} of .00, with marker D19S225). 33 refs., 2 figs., 1 tab.

  3. Haplotype and linkage disequilibrium analysis of the CRMP1 and EVC genes.

    Science.gov (United States)

    Sivakumaran, Theru A; Lesperance, Marci M

    2004-11-01

    In this report, we present the haplotype and linkage disequilibrium (LD) pattern in the Collapsin Response Mediator Protein 1 (CRMP1) and Ellis-van Creveld syndrome (EVC) gene region. We genotyped eight different single nucleotide polymorphisms (SNPs) in the CRMP1 and EVC genes in 90 control individuals of diverse ethnicity. The minor allele frequencies ranged from 3.3-49.4%, with most having a frequency >25%. A total of 37 haplotypes were derived from these eight polymorphisms, with only one haplotype having a frequency >10%. Pairwise LD analysis showed a weak but significant LD between markers located about 243 kb apart in this region. The LD was significant between markers spaced about 208 kb apart in EVC, whereas no LD was found between a pair of markers located about 5 kb apart in CRMP1. However, in general, LD correlated with the distance between loci. The CRMP1 and EVC genes are located near WFS1, the Wolfram syndrome type 1 gene, in which mutations also cause low frequency sensorineural hearing loss (LFSNHL). The haplotypes obtained from these polymorphisms will be useful to track the segregation of phenotypes in families with Ellis-van Creveld syndrome, Weyers acrodental dysostosis, LFSNHL and Wolfram syndrome type 1.

  4. Genome-wide linkage analysis of inguinal hernia in pigs using affected sib pairs

    Directory of Open Access Journals (Sweden)

    Taubert Helge

    2006-05-01

    Full Text Available Abstract Background Inguinal and scrotal hernias are of great concern to pig producers, and lead to poor animal welfare and severe economic loss. Selection against these conditions is highly preferable, but at this time no gene, Quantitative Trait Loci (QTL, or mode of inheritance has been identified in pigs or in any other species. Therefore, a complete genome scan was performed in order to identify genomic regions affecting inguinal and scrotal hernias in pigs. Records from seedstock breeding farms were collected. No clinical examinations were executed on the pigs and there was therefore no distinction between inguinal and scrotal hernias. The genome scan utilised affected sib pairs (ASP, and the data was analysed using both an ASP test based on Non-parametric Linkage (NPL analysis, and a Transmission Disequilibrium Test (TDT. Results Significant QTLs (p Conclusion For the first time in any species, a genome scan has revealed suggestive QTLs for inguinal and scrotal hernias. While this study permitted the detection of chromosomal regions only, it is interesting to note that several promising candidate genes, including INSL3, MIS, and CGRP, are located within the highly significant QTL regions. Further studies are required in order to narrow down the suggestive QTL regions, investigate the candidate genes, and to confirm the suggestive QTLs in other populations. The haplotype associated with inguinal and scrotal hernias may help in achieving selection against the disorder.

  5. Linkage disequilibrium mapping via cladistic analysis of single-nucleotide polymorphism haplotypes.

    Science.gov (United States)

    Durrant, Caroline; Zondervan, Krina T; Cardon, Lon R; Hunt, Sarah; Deloukas, Panos; Morris, Andrew P

    2004-07-01

    We present a novel approach to disease-gene mapping via cladistic analysis of single-nucleotide polymorphism (SNP) haplotypes obtained from large-scale, population-based association studies, applicable to whole-genome screens, candidate-gene studies, or fine-scale mapping. Clades of haplotypes are tested for association with disease, exploiting the expected similarity of chromosomes with recent shared ancestry in the region flanking the disease gene. The method is developed in a logistic-regression framework and can easily incorporate covariates such as environmental risk factors or additional unlinked loci to allow for population structure. To evaluate the power of this approach to detect disease-marker association, we have developed a simulation algorithm to generate high-density SNP data with short-range linkage disequilibrium based on empirical patterns of haplotype diversity. The results of the simulation study highlight substantial gains in power over single-locus tests for a wide range of disease models, despite overcorrection for multiple testing.

  6. Molecular investigation of mental retardation locus gene PRSS12 by linkage analysis

    Directory of Open Access Journals (Sweden)

    Zafar Ali

    2011-01-01

    Full Text Available The present study was carried out to determine the prevalence of families having mental retardation in Pakistani population. We enrolled seven mentally retarded (MR families with two or more affected individuals. Family history was taken to minimize the chances of other abnormalities. Pedigrees were drawn using the Cyrillic software (version 2.1. The structure of pedigrees shows that all the marriages are consanguineous and the families have recessive mode of inheritance. All the families were studied by linkage analysis to mental retardation locus (MRT1/gene PRSS12. Three STR markers (D4S191, D4S2392, and D4S3024 in vicinity of mental retardation (MR locus (MRT1/gene PRSS12 were amplified on all the sample of each family by PCR. The PCR products were then genotyped on non denaturing polyacrylamide gel electrophoresis (PAGE. The Haplotype were constructed to determine the pattern of inheritance and also to determine that a family was linked or unlinked to gene PRSS12. One out of the seven families was potentially linked to gene PRSS12, while the other six families remain unlinked.

  7. Polymorphisms and linkage analysis for ICAM-1 and the selectin gene cluster

    Energy Technology Data Exchange (ETDEWEB)

    Vora, D.K.; Rosenbloom, C.L.; Cottingham, R.W. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-06-01

    Genetic polymorphisms in leukocyte and endothelial cell adhesion molecules may be important variables with regard to susceptibility to multifactorial disease processes that include an inflammatory component. For this reason, polymorphisms were sought for intercellular adhesion molecule-1 (ICAM-1; gene symbol ICAM1) and for the three genes in the selectin cluster, P-selectin, L-selectin, and E-selectin (gene symbols SELP, SELL, and SELE, respectively). Two amino acid polymorphisms were identified for ICAM-1; Gly or Arg at codon 241 and Lys or Glu at codon 469. Dinucleotide repeat polymorphisms were identified in the 3{prime}-untranslated region for ICAM-1 and in intron 9 for P-selectin. Restriction fragment length polymorphisms were found using cDNAs for each of the three selectin genes as probes; E-selectin with BglII, P-selectin with ScaI, and L-selectin with HincII. Linkage analysis was performed for the selectin gene cluster and for ICAM-1 using the CEPH families; ICAM-1 is very tightly linked to the LDL receptor on chromosome 19, and the selectin cluster is linked to markers at chromosome 1q23. 41 refs., 2 tabs.

  8. SSR based linkage and mapping analysis of C, a yellow cocoon gene in the silkworm, Bombyx mori

    Institute of Scientific and Technical Information of China (English)

    Yun-Po Zhao; Mu-Wang Li; An-Ying Xu; Cheng-Xiang Hou; Ming-Hui Li; Qiu-Hong Guo; Yong-Ping Huang; Xi-Jie Guo

    2008-01-01

    The yellow color of the cocoon of the silkworm Bombyx mori is controlled by three genes, Y ( Yellow haemolymph ), I (Yellow inhibitor) and C (Outer-layer yellow cocoon),which are located on linkage groups 2, 9 and 12, respectively. Taking advantage of a lack of crossing over in females, reciprocal backcrossed F1 (BC1) progeny were used for linkage analysis and mapping of the C gene using silkworm strains C108 and KY, which spin white and yellow cocoons, respectively. DNA was extracted from individual pupae and analyzed for simple sequence repeat (SSR) markers. The C gene was found to be linked to seven SSR markers. All the yellow cocoon individuals from a female heterozygous backcross (BC1F) showed a heterozygous profile for SSR markers on linkage group 12,whereas individuals with light yellow cocoons showed the homozygous profile of the strain C 108. Using a reciprocal heterozygous male backcross (BC1M), we constructed a linkage map of 36.4 cM with the C gene located at the distal end, and the closest SSR marker at a distance of 13.9 cM.

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

    Directory of Open Access Journals (Sweden)

    Weeks Daniel E

    2004-07-01

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

  10. Subsidiary Linkage Patterns

    DEFF Research Database (Denmark)

    Perri, Alessandra; Andersson, Ulf; Nell, Phillip C.;

    competition and subsidiary capabilities. Our theoretical development and the results from the analysis document a far more complex and dynamic relationship between levels of competition and MNCs’ local participation in knowledge intensive activities, i.e. learning and spillovers, than previous studies do. We...... find a curvilinear relationship between the extent of competitive pressure and the quality of local linkages confirming our argument of a trade-off between learning prospects and spillover risks. Furthermore, the level of subsidiary capabilities moderates this relationship.......This paper investigates local vertical linkages of foreign subsidiaries and the dual role of such linkages as conduits for learning as well as potential channels for spillovers to competitors. On the basis of data from 97 subsidiaries, we analyze the quality of such linkages under varying levels of...

  11. A high-resolution linkage map for comparative genome analysis and QTL fine mapping in Asian seabass, Lates calcarifer

    Directory of Open Access Journals (Sweden)

    Feng Felicia

    2011-04-01

    Full Text Available Abstract Background High density linkage maps are essential for comparative analysis of synteny, fine mapping of quantitative trait loci (QTL, searching for candidate genes and facilitating genome sequence assembly. However, in most foodfish species, marker density is still low. We previously reported a first generation linkage map with 240 DNA markers and its application to preliminarily map QTL for growth traits in Asian seabass (Lates calcarifer. Here, we report a high-resolution linkage map with 790 microsatellites and SNPs, comparative analysis of synteny, fine-mapping of QTL and the identification of potential candidate genes for growth traits. Results A second generation linkage map of Asian seabass was developed with 790 microsatellite and SNP markers. The map spanned a genetic length of 2411.5 cM, with an average intermarker distance of 3.4 cM or 1.1 Mb. This high density map allowed for comparison of the map with Tetraodon nigroviridis genome, which revealed 16 synteny regions between the two species. Moreover, by employing this map we refined QTL to regions of 1.4 and 0.2 cM (or 400 and 50 kb in linkage groups 2 and 3 in a population containing 380 progeny; potential candidate genes for growth traits in QTL regions were further identified using comparative genome analysis, whose effects on growth traits were investigated. Interestingly, a QTL cluster at Lca371 underlying growth traits of Asian seabass showed similarity to the cathepsin D gene of human, which is related to cancer and Alzheimer's disease. Conclusions We constructed a high resolution linkage map, carried out comparative mapping, refined the positions of QTL, identified candidate genes for growth traits and analyzed their effects on growth. Our study developed a framework that will be indispensable for further identification of genes and analysis of molecular variation within the refined QTL to enhance understanding of the molecular basis of growth and speed up genetic

  12. An efficient record linkage scheme using graphical analysis for identifier error detection

    Directory of Open Access Journals (Sweden)

    Peto Tim EA

    2011-02-01

    Full Text Available Abstract Background Integration of information on individuals (record linkage is a key problem in healthcare delivery, epidemiology, and "business intelligence" applications. It is now common to be required to link very large numbers of records, often containing various combinations of theoretically unique identifiers, such as NHS numbers, which are both incomplete and error-prone. Methods We describe a two-step record linkage algorithm in which identifiers with high cardinality are identified or generated, and used to perform an initial exact match based linkage. Subsequently, the resulting clusters are studied and, if appropriate, partitioned using a graph based algorithm detecting erroneous identifiers. Results The system was used to cluster over 250 million health records from five data sources within a large UK hospital group. Linkage, which was completed in about 30 minutes, yielded 3.6 million clusters of which about 99.8% contain, with high likelihood, records from one patient. Although computationally efficient, the algorithm's requirement for exact matching of at least one identifier of each record to another for cluster formation may be a limitation in some databases containing records of low identifier quality. Conclusions The technique described offers a simple, fast and highly efficient two-step method for large scale initial linkage for records commonly found in the UK's National Health Service.

  13. Molecular analysis and test of linkage between the FMR-I gene and infantile autism in multiplex families

    Energy Technology Data Exchange (ETDEWEB)

    Hallmayer, J.; Pintado, E.; Lotspeich, L.; Spiker, D.; Kraemer, H.C.; Lee Wong, D.; Lin, A.; Herbert, J.; Cavalli-Sforza, L.L.; Ciaranello, R.D. [Stanford Univ., CA (United States)] [and others

    1994-11-01

    Approximately 2%-5% of autistic children show cytogenetic evidence of the fragile X syndrome. This report tests whether infantile autism in multiplex autism families arises from an unusual manifestion of the fragile X syndrome. This could arise either by expansion of the (CGG)n trinucleotide repeat in FMR-1 or from a mutation elsewhere in the gene. We studied 35 families that met stringent criteria for multiplex autism. Amplification of the trinucleotide repeat and analysis of methylation status were performed in 79 autistic children and in 31 of their unaffected siblings by Southern blot analysis. No examples of amplified repeats were seen in the autistic or control children or in their parents or grandparents. We next examined the hypothesis that there was a mutation elsewhere in the FMR-1 gene, by linkage analysis in 32 of these families. We tested four different dominant models and a recessive model. Linkage to FMR-1 could be excluded (lod score between -24 and -62) in all models by using probes DXS548, FRAXAC1, and FRAXAC2 and the CGG repeat itself. Tests for heterogeneity in this sample were negative, and the occurrence of positive lod scores in this data set could be attributed to chance. Analysis of the data by the affected-sib method also did not show evidence for linkage of any marker to autism. These results enable us to reject the hypothesis that multiplex autism arises from expansion of the (CGG)n trinucleotide repeat in FMR-1. Further, because the overall lod scores for all probes in all models tested were highly negative, linkage to FMR-1 can also be ruled out in multiplex autistic families. 35 refs., 2 figs., 5 tabs.

  14. Single-nucleotide polymorphism versus microsatellite markers in a combined linkage and segregation analysis of a quantitative trait

    OpenAIRE

    Heath Simon C; Daw E Warwick; Lu Yue

    2005-01-01

    Abstract Increasingly, single-nucleotide polymorphism (SNP) markers are being used in preference to microsatellite markers. However, methods developed for microsatellites may be problematic when applied to SNP markers. We evaluated the results of using SNPs vs. microsatellites in Monte Carlo Markov chain (MCMC) oligogenic combined segregation and linkage analysis methods. These methods were developed with microsatellite markers in mind. We selected chromosome 7 from the Collaborative Study on...

  15. Confirmation of Single-Locus Sex Determination and Female Heterogamety in Willow Based on Linkage Analysis

    OpenAIRE

    Yingnan Chen; Tiantian Wang; Lecheng Fang; Xiaoping Li; Tongming Yin

    2016-01-01

    In this study, we constructed high-density genetic maps of Salix suchowensis and mapped the gender locus with an F1 pedigree. Genetic maps were separately constructed for the maternal and paternal parents by using amplified fragment length polymorphism (AFLP) markers and the pseudo-testcross strategy. The maternal map consisted of 20 linkage groups that spanned a genetic distance of 2333.3 cM; whereas the paternal map contained 21 linkage groups that covered 2260 cM. Based on the established ...

  16. Candidate region linkage analysis in twins discordant or concordant for depression symptomatology

    DEFF Research Database (Denmark)

    Christiansen, Lene; Tan, Q; Kruse, T A;

    2009-01-01

    Genetic risk factors contribute considerably to both clinical affective disorders and subsyndromal mood level. There is moreover evidence to suggest that the genetic basis of bipolar disorder and unipolar depression overlap to some extent, and several linkage analyses have suggested evidence...... for a common susceptibility locus in affective disorders on chromosome 12q24. In this study we investigated the chromosome 12 candidate region for linkage to the mean level of depression symptomatology, over a 10-year follow-up, using a highly informative sample of concordant and discordant twin pairs selected...

  17. FBN1 mutation in Chinese patients with Marfan syndrome and its gene diagnosis using haplotype linkage analysis

    Institute of Scientific and Technical Information of China (English)

    王冰; 胡冬煦; 夏家辉; 李崎; 杨进福; 吕国华

    2003-01-01

    Objectives To analyze the FBN1 mutations in Chinese patients with Marfan syndrome (MFS) and to make a genetic diagnosis based on haplotype linkage analysis for MFS. Methods Nine MFS families (17 patients) were analyzed with single strand conformation polymorphism (SSCP) and sequencing. Four primers were designed for the flanking sequences of FBN1 gene and used for haplotype-segregation analysis of MFS (B).Conclusion The combination of mutation detection and chromosome haplotype analysis can provide better evidence for a genetic diagnosis of MFS.

  18. Whole exome sequencing combined with linkage analysis identifies a novel 3 bp deletion in NR5A1.

    Science.gov (United States)

    Eggers, Stefanie; Smith, Katherine R; Bahlo, Melanie; Looijenga, Leendert H J; Drop, Stenvert L S; Juniarto, Zulfa A; Harley, Vincent R; Koopman, Peter; Faradz, Sultana M H; Sinclair, Andrew H

    2015-04-01

    Disorders of sex development (DSDs) encompass a broad spectrum of conditions affecting the development of the gonads and genitalia. The underlying causes for DSDs include gain or loss of function variants in genes responsible for gonad development or steroidogenesis. Most patients with DSD have an unknown genetic etiology and cannot be given an accurate diagnosis. We used whole exome capture and massively parallel sequencing to analyse a large family with 46,XY DSD and 46,XX premature ovarian insufficiency. In addition, we used a recently developed method for linkage analysis using genotypes extracted from the MPS data. This approach identified a unique linkage peak on chromosome 9 and a novel, 3 bp, in-frame deletion in exon six of NR5A1 (steroidogenic factor-1 or SF1) in all affected individuals. We confirmed that the variant disrupts the SF1 protein and its ability to bind and regulate downstream genes. NR5A1 has key roles at multiple points in gonad development and steroidogenic pathways. The variant described here affects the function of SF1 in early testis development and later ovarian function, ultimately leading to the 46,XY DSD and 46,XX premature ovarian insufficiency phenotypes, respectively. This study shows that even at low coverage, whole exome sequencing, when combined with linkage analysis, can be a powerful tool to identify rapidly the disease-causing variant in large pedigrees.

  19. Comparative linkage meta-analysis reveals regionally-distinct, disparate genetic architectures: application to bipolar disorder and schizophrenia.

    Directory of Open Access Journals (Sweden)

    Brady Tang

    Full Text Available New high-throughput, population-based methods and next-generation sequencing capabilities hold great promise in the quest for common and rare variant discovery and in the search for "missing heritability." However, the optimal analytic strategies for approaching such data are still actively debated, representing the latest rate-limiting step in genetic progress. Since it is likely a majority of common variants of modest effect have been identified through the application of tagSNP-based microarray platforms (i.e., GWAS, alternative approaches robust to detection of low-frequency (1-5% MAF and rare (<1% variants are of great importance. Of direct relevance, we have available an accumulated wealth of linkage data collected through traditional genetic methods over several decades, the full value of which has not been exhausted. To that end, we compare results from two different linkage meta-analysis methods--GSMA and MSP--applied to the same set of 13 bipolar disorder and 16 schizophrenia GWLS datasets. Interestingly, we find that the two methods implicate distinct, largely non-overlapping, genomic regions. Furthermore, based on the statistical methods themselves and our contextualization of these results within the larger genetic literatures, our findings suggest, for each disorder, distinct genetic architectures may reside within disparate genomic regions. Thus, comparative linkage meta-analysis (CLMA may be used to optimize low-frequency and rare variant discovery in the modern genomic era.

  20. Genetic Linkage Analysis of the Natural Colored Fiber and Fuzzless Traits in Cotton

    Institute of Scientific and Technical Information of China (English)

    LI Fu-zhen; QIU Xin-mian; WANG Ju-qin; LU Yan-tin; BAO Li-sheng

    2008-01-01

    @@ Genetic linkage relationship of the natural colored fiber and six fuzzless seed germplasms in obsolete backgrounds of Gossypium hirsutum (AD genome) and G.barbadense were analyzed in the past two years.Three lines of natural brown fiber that were controlled by single dominant genes and two lines of green fiber controlled by another single dominant gene.

  1. QTL linkage analysis of connected populations using ancestral marker and pedigree information

    NARCIS (Netherlands)

    Bink, M.C.A.M.; Radu Totir, L.; Braak, ter C.J.F.; Winkler, C.R.; Boer, M.P.; Smith, O.S.

    2012-01-01

    The common assumption in quantitative trait locus (QTL) linkage mapping studies that parents of multiple connected populations are unrelated is unrealistic for many plant breeding programs. We remove this assumption and propose a Bayesian approach that clusters the alleles of the parents of the curr

  2. DNA Marker Transmission and Linkage Analysis in Populations Derived from a Sugarcane (Saccharum spp. x Erianthus arundinaceus Hybrid.

    Directory of Open Access Journals (Sweden)

    Jian-wen Chen

    Full Text Available Introgression of Erianthus arundinaceus has been the focus of several sugarcane breeding programs in the world, because the species has desirable traits such as high biomass production, vigour, ratooning ability and good resistance to environmental stresses and disease. In this study four genetic maps were constructed for two intergeneric populations. The first population (BC1 was generated from a cross between an Erianthus/Saccharum hybrid YC96-40 and a commercial sugarcane variety CP84-1198. The second population (BC2 was generated from a cross between YCE01-116, a progeny of the BC1 cross and NJ57-416, a commercial sugarcane cultivar. Markers across both populations were generated using 35 AFLP and 23 SSR primer pairs. A total of 756 and 728 polymorphic markers were scored in the BC1 and BC2 populations, respectively. In the BC1 population, a higher proportion of markers was derived from the Erianthus ancestor than those from the Saccharum ancestor Badila. In the BC2 population, both the number and proportion of markers derived from Erianthus were approximately half of those in the BC1 population. Linkage analysis led to the construction of 38, 57, 36 and 47 linkage groups (LGs for YC96-40, CP84-1198, YCE01-116, and NJ57-416, encompassing 116, 174, 97 and 159 markers (including single dose, double dose and bi-parental markers, respectively. These LGs could be further placed into four, five, five and six homology groups (HGs, respectively, based on information from multi-allelic SSR markers and repulsion phase linkages detected between LGs. Analysis of repulsion phase linkage indicated that Erianthus behaved like a true autopolyploid.

  3. Two-trait-locus linkage analysis: a powerful strategy for mapping complex genetic traits.

    OpenAIRE

    Schork, N J; Boehnke, M.; Terwilliger, J D; Ott, J.

    1993-01-01

    Recent advances in molecular biology have provided geneticists with ever-increasing numbers of highly polymorphic genetic markers that have made possible linkage mapping of loci responsible for many human diseases. However, nearly all diseases mapped to date follow clear Mendelian, single-locus segregation patterns. In contrast, many common familial diseases such as diabetes, psoriasis, several forms of cancer, and schizophrenia are familial and appear to have a genetic component but do not e...

  4. Genetic linkage analysis of hereditary arthro-ophthalmopathy (Stickler syndrome) and the type II procollagen gene.

    OpenAIRE

    Knowlton, R G; Weaver, E. J.; Struyk, A F; Knobloch, W H; King, R A; Norris, K; Shamban, A; Uitto, J; Jimenez, S A; Prockop, D J

    1989-01-01

    Hereditary arthro-ophthalmopathy (AO), or Stickler syndrome, is a dominantly inherited disorder characterized by vitreo-retinal degeneration and frequently accompanied by epiphyseal dysplasia and premature degenerative joint disease. Three large families with AO were analyzed for clinical manifestations of the disease and for coinheritance of the genetic defect with RFLPs in the type II procollagen gene (COL2A1). Genetic linkage between AO and COL2A1 was demonstrated in the largest family, wi...

  5. Linkages and Interactions Analysis of Major Effect Drought Grain Yield QTLs in Rice

    OpenAIRE

    Prashant Vikram; B P Mallikarjuna Swamy; Shalabh Dixit; Jennylyn Trinidad; Ma Teresa Sta Cruz; Maturan, Paul C.; Modesto Amante; Arvind Kumar

    2016-01-01

    Quantitative trait loci conferring high grain yield under drought in rice are important genomic resources for climate resilient breeding. Major and consistent drought grain yield QTLs usually co-locate with flowering and/or plant height QTLs, which could be due to either linkage or pleiotropy. Five mapping populations used for the identification of major and consistent drought grain yield QTLs underwent multiple-trait, multiple-interval mapping test (MT-MIM) to estimate the significance of pl...

  6. Construction of Commercial Sweet Cherry Linkage Maps and QTL Analysis for Trunk Diameter.

    Directory of Open Access Journals (Sweden)

    Jing Wang

    Full Text Available A cross between the sweet cherry (Prunus avium cultivars 'Wanhongzhu' and 'Lapins' was performed to create a mapping population suitable for the construction of a linkage map. The specific-locus amplified fragment (SLAF sequencing technique used as a single nucleotide polymorphism (SNP discovery platform and generated 701 informative genotypic assays; these, along with 16 microsatellites (SSRs and the incompatibility (S gene, were used to build a map which comprised 8 linkage groups (LGs and covered a genetic distance of 849.0 cM. The mean inter-marker distance was 1.18 cM and there were few gaps > 5 cM in length. Marker collinearity was maintained with the established peach genomic sequence. The map was used to show that trunk diameter (TD is under the control of 4 loci, mapping to 3 different LGs. Different locus influenced TD at a varying stage of the tree's development. The high density 'W×L' genetic linkage map has the potential to enable high-resolution identification of QTLs of agronomically relevant traits, and accelerate sweet cherry breeding.

  7. Genotyping of PCR-based polymorphisms and linkage-disequilibrium analysis at the NF1 locus

    Energy Technology Data Exchange (ETDEWEB)

    Purandare, S.M.; Viskochil, D.H.; Cawthon, R. [Univ. of Utah, Salt Lake City, UT (United States)] [and others

    1996-07-01

    Six polymorphism across the NF1 gene have been adapted for genotyping through application of PCR-based assays. Three exon-based polymorphisms - at positions 702, 2034, and 10647 in the NF1 cDNA - were genotyped by mutagenically separated PCR (MS-PCR). A fourth polymorphism, DV1.9, is an L1 insertion element in intron 30, and the other two polymorphisms, GXAlu and EVI-20, are short tandem repeats in intron 27b. All the polymorphisms were evaluated in a cohort of 110 CEPH individuals who previously had been analyzed by use of eight RFLPs at the NF1 locus. Pairwise linkage-disequilibrium analyses with the six PCR-based polymorphisms and their flanking markers demonstrated disequilibrium between all tested loci. Genotypes of the four diallelic polymorphisms (702, 2034, 10647, and DV1.9) were also evaluated in cohorts from the CEPH, African, and Japanese populations. The CEPH and Japanese cohorts showed similar heterozygosities and linkage-disequilibrium coefficients. The African cohort showed a higher degree of heterozygosity and lower linkage-disequilibrium values, compared with the CEPH and Japanese cohorts. 36 refs., 2 figs., 3 tabs.

  8. Construction of Commercial Sweet Cherry Linkage Maps and QTL Analysis for Trunk Diameter.

    Science.gov (United States)

    Wang, Jing; Zhang, Kaichun; Zhang, Xiaoming; Yan, Guohua; Zhou, Yu; Feng, Laibao; Ni, Yang; Duan, Xuwei

    2015-01-01

    A cross between the sweet cherry (Prunus avium) cultivars 'Wanhongzhu' and 'Lapins' was performed to create a mapping population suitable for the construction of a linkage map. The specific-locus amplified fragment (SLAF) sequencing technique used as a single nucleotide polymorphism (SNP) discovery platform and generated 701 informative genotypic assays; these, along with 16 microsatellites (SSRs) and the incompatibility (S) gene, were used to build a map which comprised 8 linkage groups (LGs) and covered a genetic distance of 849.0 cM. The mean inter-marker distance was 1.18 cM and there were few gaps > 5 cM in length. Marker collinearity was maintained with the established peach genomic sequence. The map was used to show that trunk diameter (TD) is under the control of 4 loci, mapping to 3 different LGs. Different locus influenced TD at a varying stage of the tree's development. The high density 'W×L' genetic linkage map has the potential to enable high-resolution identification of QTLs of agronomically relevant traits, and accelerate sweet cherry breeding. PMID:26516760

  9. Linkage Map Construction and Quantitative Trait Loci Analysis for Bolting Based on a Double Haploid Population of Brassica rapa

    Institute of Scientific and Technical Information of China (English)

    Xu Yang; Yang-Jun Yu; Feng-Lan Zhang; Zhi-Rong Zou; Xiu-Yun Zhao; De-Shuang Zhang; Jia-Bing Xu

    2007-01-01

    Early bolting of Chinese cabbage (Brassica rapa L.) during spring cultivation often has detrimental effects on the yield and quality of the harvested products. Breeding late bolting varieties is a major objective of Chinese cabbage breeding programs. in order to analyze the genetic basis of bolting traits, a genetic map of B. rapa was constructed based on amplified fragment-length polymorphism (AFLP), sequence-related amplified polymorphism (SRAP), simple sequence repeat (SSR), random amplification of polymorphic DNA (RAPD), and isozyme markers. Marker analysis was carried out on 81 double haploid (DH) lines obtained by mlcrospore culture from F1 progeny of two homozygous parents: B. rapa L. ssp. pekinensis (BY) (an extra-early bolting Chinese cabbage line) and B. rapa L. ssp. rapifera (MM) (an extra-late bolting European turnip line). A total of 326 markers including 130 AFLPs, 123 SRAPs, 16 SSRs, 43RAPDs and 14 isozymes were used to construct a linkage map with 10 linkage groups covering 882 cM with an average distance of 2.71 cM between loci. The bolting trait of each DH line was evaluated by the bolting index under controlled conditions. Quantitative trait loci (QTL) analysis was conducted using multiple QTL model mapping with MapQTL5.0 software. Eight QTLs controlling bolting resistance were identified. These QTLs, accounting for 14.1% to 25.2% of the phenotyplc variation with positive additive effects, were distributed into three linkage groups. These results provide useful information for molecular marker-assisted selection of late bolting traits in Chinese cabbage breeding programs.

  10. Examination of X chromosome markers in Rett syndrome: Exclusion mapping with a novel variation on multilocus linkage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Ellison, K.A.; Fill, C.P. (Baylor College of Medicine, Houston, TX (United States)); Terwililger, J.; Percy, A.K.; Zobhbi, H. (Columbia University, NY (United States)); DeGennaro, L.J.; Ott, J. (University of Massachusetts Medical School, Worcester (United States)); Anvret, M.; Martin-Gallardo, A. (National Institutes of Health, Bethesda, MD (United States))

    1992-02-01

    Rett syndrome is a neurologic disorder characterized by early normal development followed by regression, acquired deceleration of head growth, autism, ataxia, and sterotypic hand movements. The exclusive occurrence of the syndrome in females and the occurrence of a few familial cases with inheritance through maternal lines suggest that this disorder is most likely secondary to a mutation on the X chromosome. To address this hypothesis and to identify candidate regions for the Rett syndrome gene locus, genotypic analysis was performed in two families with maternally related affected half-sisters by using 63 DNA markers from the X chromosome. Nineteen of the loci studied were chosen for multipoint linkage analysis because they have been previously genetically mapped using a large number of meioses from reference families. Using the exclusion criterion of a lod score less than [minus]2, the authors were able to exclude the region between the Duchenne muscular dystrophy locus and the DXS456 locus. This region extends from Xp21.2 to Xq21-q23. The use of the multipoint linkage analysis approach outlined in this study should allow the exclusion of additional regions of the X chromosome as new markers are analyzed.

  11. Multicolor in situ hybridization and linkage analysis order Charcot-Marie-Tooth type I (CMTIA) gene-region markers

    Energy Technology Data Exchange (ETDEWEB)

    Lebo, R.V.; Lynch, E.D.; Golbus, M.S. (Univ. of California, San Francisco (United States)); Bird, T.D. (Univ. of Washington, Seattle (United States)); Barker, D.F.; O' Connell, P.; Chance, P.F. (Univ. of Utah, Salt Lake City (United States))

    1992-01-01

    This study demonstrates a clear and current role for multicolor in situ hybridization in expediting positional cloning studies of unknown disease genes. Nine polymorphic DNA cosmids have been mapped to eight ordered locations spanning the Charcot-Marie-Tooth type 1 (CMT1A) disease gene region in distal band 17p11.2, by multicolor in situ hybridization. When used with linkage analysis, these methods have generated a fine physical map and have firmly assigned the CMT1A gene to distal band 17p11.2. Linkage analysis with four CMT1A pedigrees mapped the CMT1A gene with respect to two flanking markers. Additional loci were physically mapped and ordered by in situ hybridization and analysis of phase-known recombinants in CMT1A pedigrees. These data demonstrate the ability of in situ hybridization to resolve loci within 0.5 Mb on early-metaphase chromosomes. Multicolor in situ hybridization also excluded the possibility of pericentric inversions in two unrelated patients with CMT1 and neurofibromatosis type 1. When used with pulsed-field gel electrophoresis, multicolor in situ hybridization can establish physical location, order, and distance in closely spaced chromosome loci.

  12. Quantitative linkage analysis to the autism endophenotype social responsiveness identifies genome-wide significant linkage to two regions on chromosome 8

    Science.gov (United States)

    Lowe, Jennifer K.; Werling, Donna M.; Constantino, John N.; Cantor, Rita M.; Geschwind, Daniel H.

    2015-01-01

    Objective Autism Spectrum Disorder (ASD) is characterized by deficits in social function and the presence of repetitive and restrictive behaviors. Following a previous test of principle, we adopted a quantitative approach to discovering genes contributing to the broader autism phenotype by using social responsiveness as an endophenotype for ASD. Method Linkage analyses using scores from the Social Responsiveness Scale (SRS) were performed in 590 families from AGRE, a largely multiplex ASD cohort. Regional and genome-wide association analyses were performed to search for common variants contributing to social responsiveness. Results SRS is unimodally distributed in male offspring from multiplex autism families, in contrast with a bimodal distribution observed in females. In correlated analyses differing by SRS respondent, genome-wide significant linkage for social responsiveness was identified at chr8p21.3 (multi-point LOD=4.11; teacher/parent scores) and chr8q24.22 (multi-point LOD=4.54; parent-only scores), respectively. Genome-wide or linkage-directed association analyses did not detect common variants contributing to social responsiveness. Conclusions The sex-differential distributions of SRS in multiplex autism families likely reflect mechanisms contributing to the sex ratio for autism observed in the general population and form a quantitative signature of reduced penetrance of inherited liability to ASD among females. The identification of two strong loci for social responsiveness validates the endophenotype approach for the identification of genetic variants contributing to complex traits such as ASD. While causal mutations have yet to be identified, these findings are consistent with segregation of rare genetic variants influencing social responsiveness and underscore the increasingly recognized role of rare inherited variants in the genetic architecture of ASD. PMID:25727539

  13. Genomewide Linkage Analysis of Bipolar Disorder by Use of a High-Density Single-Nucleotide–Polymorphism (SNP) Genotyping Assay: A Comparison with Microsatellite Marker Assays and Finding of Significant Linkage to Chromosome 6q22

    Science.gov (United States)

    Middleton, F. A.; Pato, M. T.; Gentile, K. L.; Morley, C. P.; Zhao, X.; Eisener, A. F.; Brown, A.; Petryshen, T. L.; Kirby, A. N.; Medeiros, H.; Carvalho, C.; Macedo, A.; Dourado, A.; Coelho, I.; Valente, J.; Soares, M. J.; Ferreira, C. P.; Lei, M.; Azevedo, M. H.; Kennedy, J. L.; Daly, M. J.; Sklar, P.; Pato, C. N.

    2004-01-01

    We performed a linkage analysis on 25 extended multiplex Portuguese families segregating for bipolar disorder, by use of a high-density single-nucleotide–polymorphism (SNP) genotyping assay, the GeneChip Human Mapping 10K Array (HMA10K). Of these families, 12 were used for a direct comparison of the HMA10K with the traditional 10-cM microsatellite marker set and the more dense 4-cM marker set. This comparative analysis indicated the presence of significant linkage peaks in the SNP assay in chromosomal regions characterized by poor coverage and low information content on the microsatellite assays. The HMA10K provided consistently high information and enhanced coverage throughout these regions. Across the entire genome, the HMA10K had an average information content of 0.842 with 0.21-Mb intermarker spacing. In the 12-family set, the HMA10K-based analysis detected two chromosomal regions with genomewide significant linkage on chromosomes 6q22 and 11p11; both regions had failed to meet this strict threshold with the microsatellite assays. The full 25-family collection further strengthened the findings on chromosome 6q22, achieving genomewide significance with a maximum nonparametric linkage (NPL) score of 4.20 and a maximum LOD score of 3.56 at position 125.8 Mb. In addition to this highly significant finding, several other regions of suggestive linkage have also been identified in the 25-family data set, including two regions on chromosome 2 (57 Mb, NPL = 2.98; 145 Mb, NPL = 3.09), as well as regions on chromosomes 4 (91 Mb, NPL = 2.97), 16 (20 Mb, NPL = 2.89), and 20 (60 Mb, NPL = 2.99). We conclude that at least some of the linkage peaks we have identified may have been largely undetected in previous whole-genome scans for bipolar disorder because of insufficient coverage or information content, particularly on chromosomes 6q22 and 11p11. PMID:15060841

  14. Improving linkage analysis in outcrossed forest trees - an example from Acacia mangium.

    Science.gov (United States)

    Butcher, A.; Williams, R.; Whitaker, D.; Ling, S.; Speed, P.; Moran, F.

    2002-05-01

    Mapping in forest trees generally relies on outbred pedigrees in which genetic segregation is the result of meiotic recombination from both parents. The currently available mapping packages are not optimal for outcrossed pedigrees as they either cannot order phase-ambiguous data or only use pairwise information when ordering loci within linkage groups. A new package, OUTMAP, has been developed for mapping codominant loci in outcrossed trees. A comparison of maps produced using linkage data from two pedigrees of Acacia mangium Willd demonstrated that the marker orders produced using OUTMAP were consistently of higher likelihood than those produced by JOINMAP. In addition, the maps were produced more efficiently, without the need for recoding data or the detailed investigation of pairwise recombination fractions which was necessary to select the optimal marker order using JOINMAP. Distances between markers often varied from those calculated by JOINMAP, resulting in an increase in the estimated genome length. OUTMAP can be used with all segregation types to determine phase and to calculate the likelihood of alternative marker orders, with a choice of three optimisation methods. PMID:12582629

  15. Effective Linkages of Continuum of Care for Improving Neonatal, Perinatal, and Maternal Mortality: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Kimiyo Kikuchi

    Full Text Available Continuum of care has the potential to improve maternal, newborn, and child health (MNCH by ensuring care for mothers and children. Continuum of care in MNCH is widely accepted as comprising sequential time (from pre-pregnancy to motherhood and childhood and space dimensions (from community-family care to clinical care. However, it is unclear which linkages of care could have a greater effect on MNCH outcomes. The objective of the present study is to assess the effectiveness of different continuum of care linkages for reducing neonatal, perinatal, and maternal mortality in low- and middle-income countries.We searched for randomized and quasi-randomized controlled trials that addressed two or more linkages of continuum of care and attempted to increase mothers' uptake of antenatal care, skilled birth attendance, and postnatal care. The outcome variables were neonatal, perinatal, and maternal mortality.Out of the 7,142 retrieved articles, we selected 19 as eligible for the final analysis. Of these studies, 13 used packages of intervention that linked antenatal care, skilled birth attendance, and postnatal care. One study each used packages that linked antenatal care and skilled birth attendance or skilled birth attendance and postnatal care. Four studies used an intervention package that linked antenatal care and postnatal care. Among the packages that linked antenatal care, skilled birth attendance, and postnatal care, a significant reduction was observed in combined neonatal, perinatal, and maternal mortality risks (RR 0.83; 95% CI 0.77 to 0.89, I2 79%. Furthermore, this linkage reduced combined neonatal, perinatal, and maternal mortality when integrating the continuum of care space dimension (RR 0.85; 95% CI 0.77 to 0.93, I2 81%.Our review suggests that continuous uptake of antenatal care, skilled birth attendance, and postnatal care is necessary to improve MNCH outcomes in low- and middle-income countries. The review was conclusive for the

  16. Cointegration and causality analysis of dynamic linkage between stock market and equity mutual funds in Australia

    Directory of Open Access Journals (Sweden)

    Sasipa Pojanavatee

    2014-12-01

    Full Text Available The existing literature finds conflicting results on the magnitude of price linkages between equity mutual funds and the stock market. The study contends that in an optimal lagged model, the expectations of future prices using knowledge of past price behaviour in a particular equity mutual fund category will improve forecasts of prices of other equity mutual fund categories and the stock market index. The evidence shows that the long-run pricing of equity mutual funds is cointegrated with the stock market index. In the short run, the results indicate that some equity mutual fund categories possess both long-run and short-run exogeneity with the stock market. Therefore, the short-run dynamic indicates short-run Granger causal links running between different equity mutual fund categories.

  17. Identification of a candidate gene for panicle length in rice (Oryza sativa L. via association and linkage analysis

    Directory of Open Access Journals (Sweden)

    Erbao eLiu

    2016-05-01

    Full Text Available Panicle length (PL is an important trait for improving panicle architecture and grain yield in rice (Oryza sativa L.. Three populations were used to identify QTLs and candidate genes associated with PL. Four QTLs for PL were detected on chromosomes 4, 6 and 9 through linkage mapping in the recombinant inbred line population derived from a cross between the cultivars Xiushui79 (short panicle and C-bao (long panicle. Ten SSR markers associated with PL were detected on chromosomes 2, 3, 5, 6, 8, 9 and 10 in the natural population consisting of 540 accessions collected from East and Southeast Asia. A major locus on chromosome 9 with the largest effect was identified via both linkage and association mapping. LONG PANICLE 1 (LP1 locus was delimited to a 90-kb region of the long arm of chromosome 9 through fine mapping using a single segment segregating F2 population. Two single nucleotide polymorphisms (SNPs leading to amino acid changes were detected in the third and fifth exons of LP1. LP1encodes a Remorin_C-containing protein of unknown function with homologs in a variety of species. Sequencing analysis of LP1 in two parents and 103 rice accessions indicated that SNP1 is associated with panicle length. The LP1 allele of Xiushui79 leads to reduced panicle length, whereas the allele of C-bao relieves the suppression of panicle length. LP1 and the elite alleles can be used to improve panicle length in rice.

  18. Mapping a new spontaneous preterm birth susceptibility gene, IGF1R, using linkage, haplotype sharing, and association analysis.

    Directory of Open Access Journals (Sweden)

    Ritva Haataja

    Full Text Available Preterm birth is the major cause of neonatal death and serious morbidity. Most preterm births are due to spontaneous onset of labor without a known cause or effective prevention. Both maternal and fetal genomes influence the predisposition to spontaneous preterm birth (SPTB, but the susceptibility loci remain to be defined. We utilized a combination of unique population structures, family-based linkage analysis, and subsequent case-control association to identify a susceptibility haplotype for SPTB. Clinically well-characterized SPTB families from northern Finland, a subisolate founded by a relatively small founder population that has subsequently experienced a number of bottlenecks, were selected for the initial discovery sample. Genome-wide linkage analysis using a high-density single-nucleotide polymorphism (SNP array in seven large northern Finnish non-consanginous families identified a locus on 15q26.3 (HLOD 4.68. This region contains the IGF1R gene, which encodes the type 1 insulin-like growth factor receptor IGF-1R. Haplotype segregation analysis revealed that a 55 kb 12-SNP core segment within the IGF1R gene was shared identical-by-state (IBS in five families. A follow-up case-control study in an independent sample representing the more general Finnish population showed an association of a 6-SNP IGF1R haplotype with SPTB in the fetuses, providing further evidence for IGF1R as a SPTB predisposition gene (frequency in cases versus controls 0.11 versus 0.05, P = 0.001, odds ratio 2.3. This study demonstrates the identification of a predisposing, low-frequency haplotype in a multifactorial trait using a well-characterized population and a combination of family and case-control designs. Our findings support the identification of the novel susceptibility gene IGF1R for predisposition by the fetal genome to being born preterm.

  19. X-linkage in bipolar affective illness. Perspectives on genetic heterogeneity, pedigree analysis and the X-chromosome map.

    Science.gov (United States)

    Baron, M; Rainer, J D; Risch, N

    1981-06-01

    The search for genetic markers is a powerful strategy in psychiatric genetics. The present article examines four areas relevant to discrepancies among X-linkage studies in bipolar affective disorder. These are questions of ascertainment, analytic methods, the X-chromosome map and genetic heterogeneity. The following conclusions are reached: (a) Positive linkage findings cannot be attributed to ascertainment bias or association between affective illness and colorblindness. (b) The possibility that falsely positive linkage results were obtained by using inappropriate analytic methods is ruled out. (c) Reported linkages of bipolar illness to colorblind and G6PD loci are compatible with known map distances between X-chromosome loci. Linkage to the Xg antigen remains uncertain. (d) The discrepancy among the various data sets on affective illness and colorblindness is best explained by significant linkage heterogeneity among pedigrees informative for the two traits. PMID:6454708

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    dominantly inherited colorectal cancer risk. Recently, a locus on chromosome 9q22.2-31.2 was identified by linkage analysis in sib pairs with colorectal cancer or adenoma. METHODS: Linkage analysis for the suggested locus on chromosome 9 was carried out in an extended Swedish family. This family had...... previously been investigated but following the identification of adenomas in several previously unaffected family members, these subjects were now considered to be gene carriers. RESULTS: In the present study, we found linkage of adenoma and colorectal cancer to chromosome 9q22.32-31.1 with a multipoint LOD...... score of 2.4. We were also able to define the region for this locus to 7.9 cM between the markers D9S280 and D9S277. CONCLUSIONS: Our result supports the presence of a susceptibility locus predisposing to adenoma and colorectal cancer in this chromosomal region....

  1. A Novel Method to Magnetic Flux Linkage Optimization of Direct-Driven Surface-Mounted Permanent Magnet Synchronous Generator Based on Nonlinear Dynamic Analysis

    Directory of Open Access Journals (Sweden)

    Qian Xie

    2016-07-01

    Full Text Available This paper pays attention to magnetic flux linkage optimization of a direct-driven surface-mounted permanent magnet synchronous generator (D-SPMSG. A new compact representation of the D-SPMSG nonlinear dynamic differential equations to reduce system parameters is established. Furthermore, the nonlinear dynamic characteristics of new D-SPMSG equations in the process of varying magnetic flux linkage are considered, which are illustrated by Lyapunov exponent spectrums, phase orbits, Poincaré maps, time waveforms and bifurcation diagrams, and the magnetic flux linkage stable region of D-SPMSG is acquired concurrently. Based on the above modeling and analyses, a novel method of magnetic flux linkage optimization is presented. In addition, a 2 MW D-SPMSG 2D/3D model is designed by ANSYS software according to the practical design requirements. Finally, five cases of D-SPMSG models with different magnetic flux linkages are simulated by using the finite element analysis (FEA method. The nephograms of magnetic flux density are agreement with theoretical analysis, which both confirm the correctness and effectiveness of the proposed approach.

  2. Genetic linkage analysis excludes HLA and several other potential candidates as being responsible for familial dilated cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Durand, J.B.; Bachinski, L.L.; Beiling, L. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-09-01

    Familial dilated cardiomyopthy (FDCM), manifested by ventricular dilation and decreased systolic function, is inherited as an autosomal dominant trait. We identified a family segregating DCM with 11 affected living individuals in whom the diagnosis was confirmed by echocardiography (EF <50%, left ventricular volume >80 ml/m{sup 2}). DNA was extracted and analyzed with highly polymorphmic microsatellite markers (STRs). In view of the high frequency of antibodies to specific HLA proteins in FDCM, this region was selected as a possible candidate locus. Genes whose products are sarcomeric proteins were also selected as candidates. Genetic linkage of FDCM to these candidate genes was excluded on the basis of a LOD score of <= -2. Subsequent to the candidate gene approach we pursued random mapping and completed analysis of a total of 93 chromosomal markers excluding 1000 cM.

  3. Analysis of biomarkers for the cross-linkage of formaldehyde with bovine serum albumin peptides

    Institute of Scientific and Technical Information of China (English)

    AHMAD Waqar; DENG YuLin; LI Bo; LI LiLi; AHAMD Manzoor; IQBAL Zafar; PARVEEN Zahida

    2008-01-01

    Formaldehyde, a well-known environmental toxic hazard, has been found to produce endogenously via semicarbazide-sensitive amine oxidase-catalyzed oxidative deamination of methylamine. In diabetes,the activity of SSAO has been found to increase with a subsequent increase in endogenous formalde-hyde production. It has been postulated that SSAO-induced production of formaldehyde may be in-volved in the alteration of protein structure, which may subsequently cause protein deposition associ-ated with chronic pathological disorders. Formaldehyde has also been found to react (cross-link) withamino group of the N-terminal amino acid residue and with the side-chains of arginine, cysteine, his-tidine and lysine residues. Therefore, formaldehyde may be responsible, at least in part, for protein cross-linkage, oxidative stress and cytotoxicity. The cross-linking of formaldehyde with bovine serum albumin was studied using LC-MS and Mascot database. The peptides sequence for control BSA (un-treated) digested with trypsin was matched in the online database search query by exporting the MS/MS data to online MASCOT database. In this way, a total of twenty-seven peptides were matched in the database search query. These twenty-seven peptides were then searched manually in all of the tryptic BSA samples treated with different concentrations of FA that were incubated in different time intervals.Six formaldehyde-treated BSA peptides (FKDLGEEHFK, HLVDEPQNLIK, KVPQVSTPTLVEVSR,RPCFSALTPDETYVPK, LVNELTEFAK, DAFLGSFLYEYSR) were found to be the possible markers for formaldehyde-protein/peptides adducts.

  4. Power of non-parametric linkage analysis in mapping genes contributing to human longevity in long-lived sib-pairs

    DEFF Research Database (Denmark)

    Tan, Qihua; Zhao, J H; Iachine, I;

    2004-01-01

    This report investigates the power issue in applying the non-parametric linkage analysis of affected sib-pairs (ASP) [Kruglyak and Lander, 1995: Am J Hum Genet 57:439-454] to localize genes that contribute to human longevity using long-lived sib-pairs. Data were simulated by introducing a recently...... developed statistical model for measuring marker-longevity associations [Yashin et al., 1999: Am J Hum Genet 65:1178-1193], enabling direct power comparison between linkage and association approaches. The non-parametric linkage (NPL) scores estimated in the region harboring the causal allele are evaluated...... in case of a dominant effect. Although the power issue may depend heavily on the true genetic nature in maintaining survival, our study suggests that results from small-scale sib-pair investigations should be referred with caution, given the complexity of human longevity....

  5. Construction of a linkage map of the Rennell Island Tall coconut type (Cocos nucifera L.) and QTL analysis for yield characters.

    Science.gov (United States)

    Lebrun, P; Baudouin, L; Bourdeix, R; Konan, J L; Barker, J H; Aldam, C; Herrán, A; Ritter, E

    2001-12-01

    AFLP and SSR DNA markers were used to construct a linkage map in the coconut (Cocos nucifera L.; 2n = 32) type Rennell Island Tall (RIT). A total of 227 markers were arranged into 16 linkage groups. The total genome length corresponded to 1971 cM for the RIT map, with 5-23 markers per linkage group. QTL analysis for yield characters in two consecutive sampling periods identified nine loci. Three and two QTLs were detected for number of bunches and one and three QTLs for number of nuts. The correlation of trait values between characters and evaluation periods is partially reflected in identical QTLs. The QTLs represent characters that are important in coconut breeding. The cosegregation of markers with these QTLs provides an opportunity for marker-assisted selection in coconut breeding programmes.

  6. Joint Modeling of Linkage and Association: Identifying SNPs Responsible for a Linkage Signal

    OpenAIRE

    Li, Mingyao; Boehnke, Michael; Abecasis, Gonçalo R

    2005-01-01

    Once genetic linkage has been identified for a complex disease, the next step is often association analysis, in which single-nucleotide polymorphisms (SNPs) within the linkage region are genotyped and tested for association with the disease. If a SNP shows evidence of association, it is useful to know whether the linkage result can be explained, in part or in full, by the candidate SNP. We propose a novel approach that quantifies the degree of linkage disequilibrium (LD) between the candidate...

  7. Analysis of molecular diversity, population structure and linkage disequilibrium in a worldwide survey of cultivated barley germplasm (Hordeum vulgare L.

    Directory of Open Access Journals (Sweden)

    Ganal Martin W

    2006-01-01

    Full Text Available Abstract Background The goal of our study was a systematic survey of the molecular diversity in barley genetic resources. To this end 953 cultivated barley accessions originating from all inhabited continents except Australia were genotyped with 48 SSR markers. Molecular diversity was evaluated with routine statistics (allelic richness, gene diversity, allele frequency, heterozygosity and unique alleles, Principal Coordinate Analysis (PCoA, and analysis of genome-wide linkage disequilibrium. Results A genotyping database for 953 cultivated barley accessions profiled with 48 SSR markers was established. The PCoA revealed structuring of the barley population with regard to (i geographical regions and (ii agronomic traits. Geographic origin contributed most to the observed molecular diversity. Genome-wide linkage disequilibrium (LD was estimated as squared correlation of allele frequencies (r2. The values of LD for barley were comparable to other plant species (conifers, poplar, maize. The pattern of intrachromosomal LD with distances between the genomic loci ranging from 1 to 150 cM revealed that in barley LD extended up to distances as long as 50 cM with r2 > 0.05, or up to 10 cM with r2 > 0.2. Few loci mapping to different chromosomes showed significant LD with r2 > 0.05. The number of loci in significant LD as well as the pattern of LD were clearly dependent on the population structure. The LD in the homogenous group of 207 European 2-rowed spring barleys compared to the highly structured worldwide barley population was increased in the number of loci pairs with r2 > 0.05 and had higher values of r2, although the percentage of intrachromosomal loci pairs in significant LD based on P 0.80 provided higher LD values as compared to 19 low polymorphic loci (PIC Conclusion A global population of cultivated barley accessions was highly structured. Clustering highlighted the accessions with the same geographic origin, as well as accessions possessing

  8. Population genomic structure and linkage disequilibrium analysis of South African goat breeds using genome-wide SNP data.

    Science.gov (United States)

    Mdladla, K; Dzomba, E F; Huson, H J; Muchadeyi, F C

    2016-08-01

    The sustainability of goat farming in marginal areas of southern Africa depends on local breeds that are adapted to specific agro-ecological conditions. Unimproved non-descript goats are the main genetic resources used for the development of commercial meat-type breeds of South Africa. Little is known about genetic diversity and the genetics of adaptation of these indigenous goat populations. This study investigated the genetic diversity, population structure and breed relations, linkage disequilibrium, effective population size and persistence of gametic phase in goat populations of South Africa. Three locally developed meat-type breeds of the Boer (n = 33), Savanna (n = 31), Kalahari Red (n = 40), a feral breed of Tankwa (n = 25) and unimproved non-descript village ecotypes (n = 110) from four goat-producing provinces of the Eastern Cape, KwaZulu-Natal, Limpopo and North West were assessed using the Illumina Goat 50K SNP Bead Chip assay. The proportion of SNPs with minor allele frequencies >0.05 ranged from 84.22% in the Tankwa to 97.58% in the Xhosa ecotype, with a mean of 0.32 ± 0.13 across populations. Principal components analysis, admixture and pairwise FST identified Tankwa as a genetically distinct population and supported clustering of the populations according to their historical origins. Genome-wide FST identified 101 markers potentially under positive selection in the Tankwa. Average linkage disequilibrium was highest in the Tankwa (r(2)  = 0.25 ± 0.26) and lowest in the village ecotypes (r(2) range = 0.09 ± 0.12 to 0.11 ± 0.14). We observed an effective population size of 100 kb with the exception of those in Savanna and Tswana populations. This study highlights the high level of genetic diversity in South African indigenous goats as well as the utility of the genome-wide SNP marker panels in genetic studies of these populations. PMID:27306145

  9. Linkage disequilibrium analysis in young populations: Pseudo-vitamin D-deficiency rickets and the founder effect in French Canadians

    Energy Technology Data Exchange (ETDEWEB)

    Labuda, M.; Glorieux, F.H. [McGill Univ., Montreal (Canada); Labuda, D.; Korab-Laskowska, M. [Universite de Montreal (Canada)] [and others

    1996-09-01

    Pseudo-vitamin D-deficiency rickets (PDDR) was mapped close to D12S90 and between proximal D12S312 and distal (D12S305, D12S104) microsatellites that were subsequently found on a single YAC clone. Analysis of a complex haplotype in linkage disequilibrium (LD) with the disease discriminated among distinct founder effects in French Canadian populations in Acadia and in Charlevoix-Saguenay-Lac-Saint-Jean (Ch-SLSJ), as well as an earlier one in precolonial Europe. A simple demographic model suggested the historical age of the founder effect in Ch-SLSJ to be {approximately}12 generations. The corresponding LD data are consistent with this figure when they are analyzed within the framework of Luria-Delbruck model, which takes into account the population growth. Population sampling due to a limited number of first settlers and the rapid demographic expansion appear to have played a major role in the founding of PDDR in Ch-SLSJ and, presumably, other genetic disorders endemic to French Canada. Similarly, the founder effect in Ashkenazim, coinciding with their early settlement in medieval Poland and subsequent expansion eastward, could explain the origin of frequent genetic diseases in this population. 48 refs., 5 figs., 2 tabs.

  10. Linkage analysis in a family with Stickler syndrome leads to the exclusion of the COL2A1 locus

    Energy Technology Data Exchange (ETDEWEB)

    Mottes, M.; Zolezzi, F.; Pignatti, P.F. [Univ. of Verona (Italy)

    1994-09-01

    Hereditary arthro-ophtalmopathy (AO) or Stickler Syndrome (MIM No. 10830) is a dominantly inherited disorder characterized by vitro-retinal degeneration and other connective tissue disturbances. Mutations in the COL2A1 gene, coding for type II collagen chains, have been described in a few patients. The wide spectrum of clinical manifestations is presumably due to genetic heterogeneity, since only about 50% of the Stickler families so far studied show cosegregation of the disease with the COL2A1 locus. We have investigated a large pedigree (19 individuals of whom 9 are affected) in which severe myopia with vitro-retinal degeneration consegregated with joint laxity, recurrent inguinal hernias, and degenerative changes of the hip and the knee. The 3{prime} end COL2A1 VNTR polymorphism was utilized for linkage analysis. In order to get the maximum informativity, we have analyzed the allelic microheterogeneity of this VNTR, due to the repeat sequence variation, by means of a single strand polymorphism. Mendelian inheritance of the different single strands was observed as expected. Discordance of segregation between the disease and the COL2A1 locus was thus established inequivocally in this family.

  11. Potential chromosomal introgression barriers revealed by linkage analysis in a hybrid of Pinus massoniana and P. hwangshanensis

    Directory of Open Access Journals (Sweden)

    Yin Tongming

    2010-02-01

    Full Text Available Abstract Background Exploring the genetic mechanisms underlying speciation is a hot topic in modern genetics and evolutionary studies. Distortion of marker transmission ratio is frequently ascribed to selection against alleles that cause hybrid incompatibility. The natural introgression between P. massoniana and P. hwangshanensis and their distribution ranges lead to the emergence of the two species as desirable organisms to study the genetic mechanisms for speciation. Results Using seeds sampled from trees at different elevations, we consistently detected sharp decreases in seed germination rates of trees in the hybrid zone, which might be due largely to the hybrid incompatibility. A genetic map was established using 192 megagametophytes from a single tree in the hybrid zone of the two species. Segregation distortion analysis revealed that the percentage of significant-segregation-distortion (SSD markers was extremely high, accounting for more than 25% of the segregating markers. The extension range, the distortion direction, and the distortion intensity of SSD markers also varied dramatically on different linkage groups. Conclusions In this study, we display the potential chromosomal introgression barriers between P. massoniana and P. hwangshanensis. Our study provides a valuable platform for conducting genome-wide association of hybrid incompatible QTLs and/or candidate genes with marker transmission ratio distortion in the hybrid.

  12. Impact Analysis of Economic Linkages of South Korea with North Korea Using a CGE Model

    OpenAIRE

    Kim, Euijune; Shin, Hyewon

    2014-01-01

    The purpose of this paper is to estimate impacts of core infrastructure investments in North Korea on South and North Koreas. The investment expenditures of core infrastructure projects in North Korea are calibrated as 9.35 billion US$ including highway, railroad and industrial complex. Since South and North Koreas are based on market and planned economies respectively, the Computable General Equilibrium model is applied to the economic analysis of South Korea and an Input-Output Model for th...

  13. Linkage and Segregation Analysis of Black and Brindle Coat Color in Domestic Dogs

    OpenAIRE

    Kerns, Julie A.; Cargill, Edward J; Clark, Leigh Anne; Candille, Sophie I.; Berryere, Tom G.; Olivier, Michael; Lust, George; Todhunter, Rory J.; Schmutz, Sheila M.; Murphy, Keith E; Barsh, Gregory S

    2007-01-01

    Mutations of pigment type switching have provided basic insight into melanocortin physiology and evolutionary adaptation. In all vertebrates that have been studied to date, two key genes, Agouti and Melanocortin 1 receptor (Mc1r), encode a ligand-receptor system that controls the switch between synthesis of red–yellow pheomelanin vs. black–brown eumelanin. However, in domestic dogs, historical studies based on pedigree and segregation analysis have suggested that the pigment type-switching sy...

  14. Investigating fault propagation and segment linkage using throw distribution analysis within the Agbada formation of Ewan and Oloye fields, northwestern Niger delta

    Science.gov (United States)

    Durogbitan, Abimbola Adewole

    2016-08-01

    Throw distribution analysis of the key stratigraphic surfaces (sequence boundaries and maximum flooding surfaces) across faults has allowed detailed investigation of the tectonic history within the Ewan and Oloye fields, northwestern Niger delta. The structure in the studied area is dominated by growth fault systems which are listric in cross section and concave to the basin in plan-view. Generally, the faults are active down to 2000 m depth before they die out or sole into the underlying shale. The hanging-wall blocks of growth faults are deformed into broad rollover anticlines, with some synthetic and antithetic faults initiated from the anticline crests, and fault splays off major faults, further complicating these structures. Stratigraphic key surfaces within the syn-faulting succession range in age from 16.7 to 10.35 Ma. Periods of maximum and minimum throw are established from 2-Dimensional throw distribution on the growth fault plane. Throw distribution allows analysis of growth fault nucleation, propagation and linkage. Each fault nucleated at different and a distinct interval within the stratigraphic section, as a result of the paleo-stress distribution between the interacting faults. Nucleation and linkage positions can be identified at points of maximum and minimum throw respectively. Following nucleation, faults propagated radially and linked to form the present geometry. Within the study area, fault propagation and segment linkage (lateral and vertical) are important features of the fault system. Understanding of growth fault evolution and linkage has greatly improved prediction of seal potential, trap geometry and migration. The accurate timing of the segment linkage has helped to evaluate the seal risk.

  15. Enhanced understanding of ectoparasite–host trophic linkages on coral reefs through stable isotope analysis

    Directory of Open Access Journals (Sweden)

    Amanda W.J. Demopoulos

    2015-04-01

    Full Text Available Parasitism, although the most common type of ecological interaction, is usually ignored in food web models and studies of trophic connectivity. Stable isotope analysis is widely used in assessing the flow of energy in ecological communities and thus is a potentially valuable tool in understanding the cryptic trophic relationships mediated by parasites. In an effort to assess the utility of stable isotope analysis in understanding the role of parasites in complex coral-reef trophic systems, we performed stable isotope analysis on three common Caribbean reef fish hosts and two kinds of ectoparasitic isopods: temporarily parasitic gnathiids (Gnathia marleyi and permanently parasitic cymothoids (Anilocra. To further track the transfer of fish-derived carbon (energy from parasites to parasite consumers, gnathiids from host fish were also fed to captive Pederson shrimp (Ancylomenes pedersoni for at least 1 month. Parasitic isopods had δ13C and δ15N values similar to their host, comparable with results from the small number of other host–parasite studies that have employed stable isotopes. Adult gnathiids were enriched in 15N and depleted in 13C relative to juvenile gnathiids, providing insights into the potential isotopic fractionation associated with blood-meal assimilation and subsequent metamorphosis. Gnathiid-fed Pedersen shrimp also had δ13C values consistent with their food source and enriched in 15N as predicted due to trophic fractionation. These results further indicate that stable isotopes can be an effective tool in deciphering cryptic feeding relationships involving parasites and their consumers, and the role of parasites and cleaners in carbon transfer in coral-reef ecosystems specifically.

  16. Genome-wide Linkage Disequilibrium Linkage Analysis (LDLA) of Body Fat Traits in an F2 Porcine Model for Human Obesity

    DEFF Research Database (Denmark)

    Pant, Sameer Dinkar; Karlskov-Mortensen, Peter; Cirera Salicio, Susanna;

    . Subsequently bioinformatic analysis was performed to identify genes in close proximity of chromosomal positions where statistically significant QTLs were identified. Several important genes previously linked to obesity (e.g. BBS4, CHRNA2, DLK1), along with other novel genes were identified, that together......ABSTRACT: Purebred Duroc and Yorkshire sows were crossed with Göttingen minipig boars to obtain two separate F2 intercross resource populations (n=287 and 279 respectively). Several obesity, metabolic and slaughter measurements were recorded from birth to slaughter (220 ± 45 days). In addition...... provide novel insights that may further the current understanding of the molecular mechanisms underlying human obesity....

  17. Robust Group Linkage

    OpenAIRE

    Li, Pei; Dong, Xin Luna; Guo, Songtao; Maurino, Andrea; Srivastava, Divesh

    2015-01-01

    We study the problem of group linkage: linking records that refer to entities in the same group. Applications for group linkage include finding businesses in the same chain, finding conference attendees from the same affiliation, finding players from the same team, etc. Group linkage faces challenges not present for traditional record linkage. First, although different members in the same group can share some similar global values of an attribute, they represent different entities so can also...

  18. A sugar beet (Beta vulgaris L.) reference FISH karyotype for chromosome and chromosome-arm identification, integration of genetic linkage groups and analysis of major repeat family distribution.

    Science.gov (United States)

    Paesold, Susanne; Borchardt, Dietrich; Schmidt, Thomas; Dechyeva, Daryna

    2012-11-01

    We developed a reference karyotype for B. vulgaris which is applicable to all beet cultivars and provides a consistent numbering of chromosomes and genetic linkage groups. Linkage groups of sugar beet were assigned to physical chromosome arms by FISH (fluorescent in situ hybridization) using a set of 18 genetically anchored BAC (bacterial artificial chromosome) markers. Genetic maps of sugar beet were correlated to chromosome arms, and North-South orientation of linkage groups was established. The FISH karyotype provides a technical platform for genome studies and can be applied for numbering and identification of chromosomes in related wild beet species. The discrimination of all nine chromosomes by BAC probes enabled the study of chromosome-specific distribution of the major repetitive components of sugar beet genome comprising pericentromeric, intercalary and subtelomeric satellites and 18S-5.8S-25S and 5S rRNA gene arrays. We developed a multicolor FISH procedure allowing the identification of all nine sugar beet chromosome pairs in a single hybridization using a pool of satellite DNA probes. Fiber-FISH was applied to analyse five chromosome arms in which the furthermost genetic marker of the linkage group was mapped adjacently to terminal repetitive sequences on pachytene chromosomes. Only on two arms telomere arrays and the markers are physically linked, hence these linkage groups can be considered as terminally closed making the further identification of distal informative markers difficult. The results support genetic mapping by marker localization, the anchoring of contigs and scaffolds for the annotation of the sugar beet genome sequence and the analysis of the chromosomal distribution patterns of major families of repetitive DNA.

  19. A sugar beet (Beta vulgaris L.) reference FISH karyotype for chromosome and chromosome-arm identification, integration of genetic linkage groups and analysis of major repeat family distribution.

    Science.gov (United States)

    Paesold, Susanne; Borchardt, Dietrich; Schmidt, Thomas; Dechyeva, Daryna

    2012-11-01

    We developed a reference karyotype for B. vulgaris which is applicable to all beet cultivars and provides a consistent numbering of chromosomes and genetic linkage groups. Linkage groups of sugar beet were assigned to physical chromosome arms by FISH (fluorescent in situ hybridization) using a set of 18 genetically anchored BAC (bacterial artificial chromosome) markers. Genetic maps of sugar beet were correlated to chromosome arms, and North-South orientation of linkage groups was established. The FISH karyotype provides a technical platform for genome studies and can be applied for numbering and identification of chromosomes in related wild beet species. The discrimination of all nine chromosomes by BAC probes enabled the study of chromosome-specific distribution of the major repetitive components of sugar beet genome comprising pericentromeric, intercalary and subtelomeric satellites and 18S-5.8S-25S and 5S rRNA gene arrays. We developed a multicolor FISH procedure allowing the identification of all nine sugar beet chromosome pairs in a single hybridization using a pool of satellite DNA probes. Fiber-FISH was applied to analyse five chromosome arms in which the furthermost genetic marker of the linkage group was mapped adjacently to terminal repetitive sequences on pachytene chromosomes. Only on two arms telomere arrays and the markers are physically linked, hence these linkage groups can be considered as terminally closed making the further identification of distal informative markers difficult. The results support genetic mapping by marker localization, the anchoring of contigs and scaffolds for the annotation of the sugar beet genome sequence and the analysis of the chromosomal distribution patterns of major families of repetitive DNA. PMID:22775355

  20. Waardenburg syndrome (WS): the analysis of a single family with a WS1 mutation showing linkage to RFLP markers on human chromosome 2q.

    OpenAIRE

    Asher, J H; Morell, R; Friedman, T B

    1991-01-01

    Waardenburg syndrome type I (WS1; MIM 19350) is caused by a pleiotropic, autosomal dominant mutation with variable penetrance and expressivity. Of individuals with this mutation, 20%-25% are hearing impaired. A multilocus linkage analysis of RFLP data from a single WS1 family with 11 affected individuals indicates that the WS1 mutation in this family is linked to the following four marker loci located on the long arm of chromosome 2: ALPP (alkaline phosphatase, placental), FN1 (fibronectin 1)...

  1. An Interspecific Backcross of Lycopersicon Esculentum X L. Hirsutum: Linkage Analysis and a Qtl Study of Sexual Compatibility Factors and Floral Traits

    OpenAIRE

    Bernacchi, D.; Tanksley, S D

    1997-01-01

    A BC(1) population of the self-compatible tomato Lycopersicon esculentum and its wild self-incompatible relative L. hirsutum f. typicum was used for restriction fragment length polymorphism linkage analysis and quantitative trait loci (QTL) mapping of reproductive behavior and floral traits. The self-incompatibility locus, S, on chromosome 1 harbored the only QTL for self-incompatibility indicating that the transition to self-compatibility in the lineage leading to the cultivated tomato was p...

  2. Amphibian Sex Determination: Segregation and Linkage Analysis Using Members of the Tiger Salamander Species Complex (Ambystoma mexicanum and A. t. tigrinum)

    OpenAIRE

    Smith, Jeramiah J.; Voss, S. Randal

    2009-01-01

    Little is known about the genetic basis of sex determination in vertebrates though considerable progress has been made in recent years. In this study, segregation analysis and linkage mapping were performed to localize an amphibian sex-determining locus (ambysex) in the tiger salamander (Ambystoma) genome. Segregation of sex phenotypes (male, female) among 2nd generation individuals of interspecific crosses (A. mexicanum x A. t. tigrinum) was consistent with Mendelian expectations, although a...

  3. Cost-Utility Analysis of Three U.S. HIV Linkage and Re-engagement in Care Programs from Positive Charge.

    Science.gov (United States)

    Jain, Kriti M; Zulliger, Rose; Maulsby, Cathy; Kim, Jeeyon Janet; Charles, Vignetta; Riordan, Maura; Holtgrave, David

    2016-05-01

    Linking and retaining people living with HIV in ongoing, HIV medical care is vital for ending the U.S. HIV epidemic. Yet, 41-44 % of HIV+ individuals are out of care. In response, AIDS United initiated Positive Charge, a series of five HIV linkage and re-engagement projects around the U.S. This paper investigates whether three Positive Charge programs were cost effective and calculates a return on investment for each program. It uses standard methods of cost utility analysis and WHO-CHOICE thresholds. All three projects were found to be cost effective, and two were highly cost effective. Cost utility ratios ranged from $4439 to $137,271. These results suggest that HIV linkage to care programs are a productive and efficient use of public health funds. PMID:26563760

  4. Cost-Utility Analysis of Three U.S. HIV Linkage and Re-engagement in Care Programs from Positive Charge.

    Science.gov (United States)

    Jain, Kriti M; Zulliger, Rose; Maulsby, Cathy; Kim, Jeeyon Janet; Charles, Vignetta; Riordan, Maura; Holtgrave, David

    2016-05-01

    Linking and retaining people living with HIV in ongoing, HIV medical care is vital for ending the U.S. HIV epidemic. Yet, 41-44 % of HIV+ individuals are out of care. In response, AIDS United initiated Positive Charge, a series of five HIV linkage and re-engagement projects around the U.S. This paper investigates whether three Positive Charge programs were cost effective and calculates a return on investment for each program. It uses standard methods of cost utility analysis and WHO-CHOICE thresholds. All three projects were found to be cost effective, and two were highly cost effective. Cost utility ratios ranged from $4439 to $137,271. These results suggest that HIV linkage to care programs are a productive and efficient use of public health funds.

  5. Localization of the CYP2D gene locus to human chromosome 22q13. 1 by polymerase chain reaction, in situ hybridization, and linkage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Gouch, A.C.; Howell, S.M.; Bryant, S.P.; Spurr, N.K. (Clare Hall Lab., Hertfordshire (United Kingdom)); Smith, C.A.D.; Wolf, C.R. (Cancer Research Fund, Edinburgh (United Kingdom))

    1993-02-01

    Using a combination of somatic cell hybrids, in situ hybridization, and linkage mapping, we have been able to localize the cytochrome P450 CYP2D6 gene to chromosome 22 in the region q13.1. Linkage analysis, using locus-specific primers, showed a maximum sex-average lod score of 8.12 ([theta] = 0.00) between the marker pH130 (D22S64) and CYPsD6, of 6.92 ([theta] - 0.00) between the marker KI839 (D22S95) and CYP2D6, and 4.80 ([theta] = 0.036) between the platelet-derived growth factor [beta] subunit gene (PDGFB) and CYP2D6. 16 refs., 2 figs.

  6. Refining the localization of the PKD2 locus on chromosome 4q by linkage analysis in Spanish families with autosomal dominant polycystic kidney disease type 2

    Energy Technology Data Exchange (ETDEWEB)

    San Millan, J.L.; Viribay, M.; Peral, B.; Moreno, F. [Unidad de Genetica Molecular, Madrid (Spain); Martinez, I. [Hospital de Galdacano (Spain); Weissenbach, J. [Genethon, Evry (France)

    1995-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disorder. At least two distinct forms of ADPKD are now well defined. In {approximately}86% of affected European families, a gene defect localized to 16p13.3 was responsible for ADPKD, while a second locus has been recently localized to 4q13-q23 as candidate for the disease in the remaining families. We present confirmation of linkage to microsatellite markers on chromosome 4q in eight Spanish families with ADPKD, in which the disease was not linked to 16p13.3. By linkage analysis with marker D4S423, a maximum lod score of 9.03 at a recombination fraction of .00 was obtained. Multipoint linkage analysis, as well as a study of recombinant haplotypes, placed the PKD2 locus between D4S1542 and D4S1563, thereby defining a genetic interval of {approximately}1 cM. The refined map will serve as a genetic framework for additional genetic and physical mapping of the region and will improve the accuracy of presymptomatic diagnosis of PKD2. 25 refs., 4 figs., 1 tab.

  7. Linkage Disequilibrium Mapping of Meat Quality QTL

    Science.gov (United States)

    Previous studies based on linkage analysis have identified broad areas in the bovine genome associated with meat quality. Linkage disequilibrium (LD) analyses have the potential to identify narrower regions and point towards candidate genes. Tenderness and marbling were chosen to be evaluated in a ...

  8. Parent-of-origin effects in autism identified through genome-wide linkage analysis of 16,000 SNPs.

    Directory of Open Access Journals (Sweden)

    Delphine Fradin

    Full Text Available BACKGROUND: Autism is a common heritable neurodevelopmental disorder with complex etiology. Several genome-wide linkage and association scans have been carried out to identify regions harboring genes related to autism or autism spectrum disorders, with mixed results. Given the overlap in autism features with genetic abnormalities known to be associated with imprinting, one possible reason for lack of consistency would be the influence of parent-of-origin effects that may mask the ability to detect linkage and association. METHODS AND FINDINGS: We have performed a genome-wide linkage scan that accounts for potential parent-of-origin effects using 16,311 SNPs among families from the Autism Genetic Resource Exchange (AGRE and the National Institute of Mental Health (NIMH autism repository. We report parametric (GH, Genehunter and allele-sharing linkage (Aspex results using a broad spectrum disorder case definition. Paternal-origin genome-wide statistically significant linkage was observed on chromosomes 4 (LOD(GH = 3.79, empirical p<0.005 and LOD(Aspex = 2.96, p = 0.008, 15 (LOD(GH = 3.09, empirical p<0.005 and LOD(Aspex = 3.62, empirical p = 0.003 and 20 (LOD(GH = 3.36, empirical p<0.005 and LOD(Aspex = 3.38, empirical p = 0.006. CONCLUSIONS: These regions may harbor imprinted sites associated with the development of autism and offer fruitful domains for molecular investigation into the role of epigenetic mechanisms in autism.

  9. Linkage, evaluation and analysis of national electronic healthcare data: application to providing enhanced blood-stream infection surveillance in paediatric intensive care.

    Directory of Open Access Journals (Sweden)

    Katie Harron

    these data need to take account of biases due to ascertainment and linkage error. This study provides a generalisable guide for linkage, evaluation and analysis of complex electronic healthcare data.

  10. 任意角度的RRP杆组的运动分析%Motion Analysis of RRP Linkage Group at Arbitrary Angle

    Institute of Scientific and Technical Information of China (English)

    张小琴

    2012-01-01

    运用转换坐标系的方法对任意角度的RRP杆组的运动进行分析,用解析法推导出RRP杆组的位置解的个数及机构的运动趋势的判别,并且给出任意角度曲柄滑块机构的曲柄存在条件。最后用MATLAB软件编写出RRP杆组在实际运用中的运动分析程序,分析杆组的位置、速度、加速度。%In this paper,the motion analysis of arbitrary angle RRP Linkage Group is carried out based on the conversion coordinate method.The analytical method is used to derive the number of solution of the RRP linkage group and to identify the location of the motion trend.The conditions for having a crank of the arbitrary angle slider-crank mechanism are also proposed.Finally,an application program has been developed with MATLAB to analyze RRP linkage group's position,velocity and acceleration.

  11. Using Linkage Analysis to Detect Gene-Gene Interactions. 2. Improved Reliability and Extension to More-Complex Models.

    Directory of Open Access Journals (Sweden)

    Susan E Hodge

    Full Text Available Detecting gene-gene interaction in complex diseases has become an important priority for common disease genetics, but most current approaches to detecting interaction start with disease-marker associations. These approaches are based on population allele frequency correlations, not genetic inheritance, and therefore cannot exploit the rich information about inheritance contained within families. They are also hampered by issues of rigorous phenotype definition, multiple test correction, and allelic and locus heterogeneity. We recently developed, tested, and published a powerful gene-gene interaction detection strategy based on conditioning family data on a known disease-causing allele or a disease-associated marker allele4. We successfully applied the method to disease data and used computer simulation to exhaustively test the method for some epistatic models. We knew that the statistic we developed to indicate interaction was less reliable when applied to more-complex interaction models. Here, we improve the statistic and expand the testing procedure. We computer-simulated multipoint linkage data for a disease caused by two interacting loci. We examined epistatic as well as additive models and compared them with heterogeneity models. In all our models, the at-risk genotypes are "major" in the sense that among affected individuals, a substantial proportion has a disease-related genotype. One of the loci (A has a known disease-related allele (as would have been determined from a previous analysis. We removed (pruned family members who did not carry this allele; the resultant dataset is referred to as "stratified." This elimination step has the effect of raising the "penetrance" and detectability at the second locus (B. We used the lod scores for the stratified and unstratified data sets to calculate a statistic that either indicated the presence of interaction or indicated that no interaction was detectable. We show that the new method is robust

  12. Structure-Function Analysis of a Mixed-linkage β-Glucanase/Xyloglucanase from the Key Ruminal Bacteroidetes Prevotella bryantii B(1)4.

    Science.gov (United States)

    McGregor, Nicholas; Morar, Mariya; Fenger, Thomas Hauch; Stogios, Peter; Lenfant, Nicolas; Yin, Victor; Xu, Xiaohui; Evdokimova, Elena; Cui, Hong; Henrissat, Bernard; Savchenko, Alexei; Brumer, Harry

    2016-01-15

    The recent classification of glycoside hydrolase family 5 (GH5) members into subfamilies enhances the prediction of substrate specificity by phylogenetic analysis. However, the small number of well characterized members is a current limitation to understanding the molecular basis of the diverse specificity observed across individual GH5 subfamilies. GH5 subfamily 4 (GH5_4) is one of the largest, with known activities comprising (carboxymethyl)cellulases, mixed-linkage endo-glucanases, and endo-xyloglucanases. Through detailed structure-function analysis, we have revisited the characterization of a classic GH5_4 carboxymethylcellulase, PbGH5A (also known as Orf4, carboxymethylcellulase, and Cel5A), from the symbiotic rumen Bacteroidetes Prevotella bryantii B14. We demonstrate that carboxymethylcellulose and phosphoric acid-swollen cellulose are in fact relatively poor substrates for PbGH5A, which instead exhibits clear primary specificity for the plant storage and cell wall polysaccharide, mixed-linkage β-glucan. Significant activity toward the plant cell wall polysaccharide xyloglucan was also observed. Determination of PbGH5A crystal structures in the apo-form and in complex with (xylo)glucan oligosaccharides and an active-site affinity label, together with detailed kinetic analysis using a variety of well defined oligosaccharide substrates, revealed the structural determinants of polysaccharide substrate specificity. In particular, this analysis highlighted the PbGH5A active-site motifs that engender predominant mixed-linkage endo-glucanase activity vis à vis predominant endo-xyloglucanases in GH5_4. However the detailed phylogenetic analysis of GH5_4 members did not delineate particular clades of enzymes sharing these sequence motifs; the phylogeny was instead dominated by bacterial taxonomy. Nonetheless, our results provide key enzyme functional and structural reference data for future bioinformatics analyses of (meta)genomes to elucidate the biology of

  13. Comparative analysis of premature mortality among urban immigrants in Bremen, Germany: a retrospective register-based linkage study

    OpenAIRE

    Makarova, Nataliya; Brand, Tilman; Brünings-Kuppe, Claudia; Pohlabeln, Hermann; Luttmann, Sabine

    2016-01-01

    Objectives The main objective of this study was to explore differences in mortality patterns among two large immigrant groups in Germany: one from Turkey and the other from the former Soviet Union (FSU). To this end, we investigated indicators of premature mortality. Design This study was conducted as a retrospective population-based study based on mortality register linkage. Using mortality data for the period 2004–2010, we calculated age-standardised death rates (SDR) and standardised morta...

  14. Inheritance of 15 microsatellites in the Pacific oyster Crassostrea gigas: segregation and null allele identification for linkage analysis

    Institute of Scientific and Technical Information of China (English)

    LI Li; GUO Ximing; ZHANG Guofan

    2009-01-01

    Microsatellites were screened in a backcross family of the Pacific oyster, Crassostrea gigas. Fifteen microsatellite loci were distinguishable and polymorphic with 6 types of allele-combinations. Null alleles were detected in 46.7% of loci, accounting for 11.7% of the total alleles. Four loci did not segregate in Mendelian Ratios. Three linkage groups were identified among 7 of the 15 segregating loci. Fluorescence-based automated capillary electrophoresis (ABI 310 Genetic Analyzer) that used to detect the microsatellite loci, has been proved a fast, precise, and reliable method in microsatellite genotyping.

  15. Construction of a genetic linkage map and QTL analysis for some leaf traits in pear (Pyrus L .)

    Institute of Scientific and Technical Information of China (English)

    Wenying SUN; Yuxing ZHANG; Wenquan LE; Hai'e ZHANG

    2009-01-01

    The major incompatibility barriers to specific inbred lines and the long generation duration in Pyrus L. May hinder the Pyrus breeding process. A genetic linkage map provides the foundation for quantitative trait loci (QTL) mapping and molecular marker-assisted breeding. In this study, we constructed a genetic map with 145 F1 populations from a cross of two cultivars, Yali and Jingbaili, using AFLP and SSR markers. The map consisted of 18 linkage groups which included 402 genetic markers and covered 1395.9 cM, with an average genetic distance of 3.8 cM. The interval mapping was used to identify quantitative trait loci associated with four leaf agronomic traits in the F1 population. The results indicated that four QTLs were associated with leaf length, two QTLs with leaf width, two with leaf length/leaf width, and three with petiole length. The eleven QTLs were associated with 9.9%-48.5% of the phenotypic variation in different traits. It is considered that the map covers almost the whole genome, and molecular markers will be greatly helpful to the related breeding.

  16. Comparison of serum creatine kinase estimation with short tandem repeats based linkage analysis in carriers and affected children of duchenne muscular dystrophy

    International Nuclear Information System (INIS)

    Background: Duchenne Muscular Dystrophy (DMD) is an X-linked recessive lethal, genetic disorder characterised by progressive weakness of skeletal muscles which is untreatable and transmitted to males by carrier females. Advances in laboratory techniques now focus direct mutational analysis as the most reliable and indirect analysis based on Short Tandem Repeats (STR) based linkage analysis as feasible, inexpensive, and efficient method for carrier detection and prenatal diagnosis. The objective of this study was to compare the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic efficiency of Serum Creatine Kinase (SCK) with Short Tandem Repeats (STR based linkage analysis in carriers and affected children of Duchenne Muscular Dystrophy. Methods: The study was carried out from Dec 2006 to Dec 2007 in families having index clinical cases of DMD who were referred from different hospitals for evaluation/workup of DMD. SCK was done as a preliminary investigation in all index cases. The PCR assay with STR based linkage analysis with Intron 44, 45, 49 and 50 of DMD gene were performed in all families. Six families were informative with Intron 44 of DMD gene and one family was non-informative with all four intronic markers of DMD. SCK analyses were done in all the family members and compared with PCR analysis in informative families. SCK was not performed on Chorionic villous sample (CVS) done for prenatal diagnosis of DMD, and CVS and non-informative family members were excluded from the study. Results: In carriers of DMD, the sensitivity and negative predictive value of SCK were 33.3%, and specificity and positive predictive were 100% with diagnostic efficiency of 50%. In affected cases of DMD the sensitivity and negative predictive value of SCK were 100%, and specificity and positive predictive were 91% and 88.8% respectively and diagnostic efficiency of 94.1%. Conclusion: The SCK is an excellent screening test for

  17. Review on the Application of Web Linkage-analysis%网络链接分析应用研究综述

    Institute of Scientific and Technical Information of China (English)

    文庭孝; 王尧; 杨雅惟; 刘璇

    2011-01-01

    Web linkage-analysis is an important method in Webometrics research,and it has extensive application.Now Web linkage-analysis was used in following fields: web information resourse assessment,website impact evaluation,university evaluation,discovery of co%网络链接分析法是网络信息计量学研究的重要研究方法,具有广泛的应用。目前国内外主要将网络链接分析方法用于网络信息资源评价、网站网络影响力评价、大学评价、核心网络与核心作者发现、竞争情报与竞争对手分析、网站关联分析、期刊评价以及搜索引擎优化等方面。

  18. Analysis of four families with the Stickler syndrome by linkage studies. Identification of a new premature stop codon in the COL2A1 gene in a family

    Energy Technology Data Exchange (ETDEWEB)

    Bonaventure, J.; Lasselin, C. [Hopital Necker, Paris (France); Toutain, A. [CHU Bretonneau, Tours (France)] [and others

    1994-09-01

    The Stickler syndrome is an arthro-ophthalmopathy which associates progressive myopia with vitreal degeneration and retinal detachment. Cleft palate, cranio-facial abnormalities, deafness and osteoarthritis are often associated symptoms. Genetic heterogeneity of this autosomal dominant disease was consistent with its large clinical variability. Linkage studies have provided evidence for cosegregation of the disease with COL2A1, the gene coding for type II collagen, in about 50% of the families. Four additional families are reported here. Linkage analyses by using a VNTR located in the 3{prime} region of the gene were achieved. In three families, positive lod scores were obtained with a cumulative maximal value of 3.5 at a recombination fraction of 0. In one of these families, single strand conformation analysis of 25 exons disclosed a new mutation in exon 42. Codon for glutamic acid at position a1-803 was converted into a stop codon. The mutation was detected in DNA samples from all the affected members of the family but not in the unaffected. This result confirms that most of the Stickler syndromes linked to COL2A1 are due to premature stop codons. In a second family, an abnormal SSCP pattern of exon 34 was detected in all the affected individuals. The mutation is likely to correspond to a splicing defect in the acceptor site of intron 33. In one family the disease did not segregate with the COL2A1 locus. Further linkage studies with intragenic dimorphic sites in the COL10A1 gene and highly polymorphic markers close to the COL9A1 locus indicated that this disorder did not result from defects in these two genes.

  19. Chromosomal differences between European and North American Atlantic salmon discovered by linkage mapping and supported by fluorescence in situ hybridization analysis

    Directory of Open Access Journals (Sweden)

    Brenna-Hansen Silje

    2012-08-01

    Full Text Available Abstract Background Geographical isolation has generated a distinct difference between Atlantic salmon of European and North American Atlantic origin. The European Atlantic salmon generally has 29 pairs of chromosomes and 74 chromosome arms whereas it has been reported that the North American Atlantic salmon has 27 chromosome pairs and an NF of 72. In order to predict the major chromosomal rearrangements causing these differences, we constructed a dense linkage map for Atlantic salmon of North American origin and compared it with the well-developed map for European Atlantic salmon. Results The presented male and female genetic maps for the North American subspecies of Atlantic salmon, contains 3,662 SNPs located on 27 linkage groups. The total lengths of the female and male linkage maps were 2,153 cM and 968 cM respectively, with males characteristically showing recombination only at the telomeres. We compared these maps with recently published SNP maps from European Atlantic salmon, and predicted three chromosomal reorganization events that we then tested using fluorescence in situ hybridization (FISH analysis. The proposed rearrangements, which define the differences in the karyotypes of the North American Atlantic salmon relative to the European Atlantic salmon, include the translocation of the p arm of ssa01 to ssa23 and polymorphic fusions: ssa26 with ssa28, and ssa08 with ssa29. Conclusions This study identified major chromosomal differences between European and North American Atlantic salmon. However, while gross structural differences were significant, the order of genetic markers at the fine-resolution scale was remarkably conserved. This is a good indication that information from the International Cooperation to Sequence the Atlantic salmon Genome, which is sequencing a European Atlantic salmon, can be transferred to Atlantic salmon from North America.

  20. Linkage disequilibrium mapping via cladistic analysis of phase-unknown genotypes and inferred haplotypes in the Genetic Analysis Workshop 14 simulated data.

    Science.gov (United States)

    Durrant, Caroline; Morris, Andrew P

    2005-01-01

    We recently described a method for linkage disequilibrium (LD) mapping, using cladistic analysis of phased single-nucleotide polymorphism (SNP) haplotypes in a logistic regression framework. However, haplotypes are often not available and cannot be deduced with certainty from the unphased genotypes. One possible two-stage approach is to infer the phase of multilocus genotype data and analyze the resulting haplotypes as if known. Here, haplotypes are inferred using the expectation-maximization (EM) algorithm and the best-guess phase assignment for each individual analyzed. However, inferring haplotypes from phase-unknown data is prone to error and this should be taken into account in the subsequent analysis. An alternative approach is to analyze the phase-unknown multilocus genotypes themselves. Here we present a generalization of the method for phase-known haplotype data to the case of unphased SNP genotypes. Our approach is designed for high-density SNP data, so we opted to analyze the simulated dataset. The marker spacing in the initial screen was too large for our method to be effective, so we used the answers provided to request further data in regions around the disease loci and in null regions. Power to detect the disease loci, accuracy in localizing the true site of the locus, and false-positive error rates are reported for the inferred-haplotype and unphased genotype methods. For this data, analyzing inferred haplotypes outperforms analysis of genotypes. As expected, our results suggest that when there is little or no LD between a disease locus and the flanking region, there will be no chance of detecting it unless the disease variant itself is genotyped.

  1. Topology of randon linkages

    OpenAIRE

    Farber, Michael

    2007-01-01

    Betti numbers of configuration spaces of mechanical linkages (known also as polygon spaces) depend on a large number of parameters -- the lengths of the bars of the linkage. Motivated by applications in topological robotics, statistical shape theory and molecular biology, we view these lengths as random variables and study asymptotic values of the average Betti numbers as the number of links n tends to infinity. We establish a surprising fact that for a reasonably ample class of sequences of ...

  2. Risk factors for weight faltering in infancy according to age at onset

    DEFF Research Database (Denmark)

    Olsen, Else Marie; Skovgaard, Anne M; Weile, Birgitte;

    2010-01-01

    and gestational age, with single parenthood and with mother having smoked during pregnancy. Onset between 2 weeks and 4 months was associated with congenital disorders and serious somatic illness, and with deviant mother-child relationship, whereas, onset between 4 and 8 months seemed to represent a group...... of children with feeding problems arising de novo in otherwise healthy children. In conclusion, weight faltering in infancy is clearly associated with contemporary measured feeding problems, but the risk mechanisms involved differ in early vs. late onset....

  3. Substance use in bipolar disorder : associations with age at onset, treatment delay and outcome

    OpenAIRE

    2011-01-01

    The overall aim of this thesis was to investigate the relationship between substance use and central aspects of bipolar disorder (BD); the development or onset of the disorder, the clinical and functional characteristics, and the initiation of adequate treatment. The prevalence of substance use disorders (abuse or dependence) among patients with BD are generally high, but also vary widely. Furthermore, to what degree and in which outcome areas substance use disorders have a negative impac...

  4. Predictors of age at onset of tobacco and cannabis use in Danish adolescents

    DEFF Research Database (Denmark)

    Wium-Andersen, Ida Kim; Wium-Andersen, Marie Kim; Becker, Ulrik;

    2010-01-01

    Early onset of tobacco and cannabis use predicts later substance abuse and risk behaviour and has large health consequences.......Early onset of tobacco and cannabis use predicts later substance abuse and risk behaviour and has large health consequences....

  5. Cigarette Smoking among Adolescents in Northwest Ohio: Correlates of Prevalence and Age at Onset

    Directory of Open Access Journals (Sweden)

    James H. Price

    2008-12-01

    Full Text Available This study examined the prevalence and correlates of smoking initiation among adolescents. We have used data from adolescents (n=5,392 ages 10-18 who participated in the 2003 Tobacco Survey, a representative sample of adolescents in Northwest Ohio. A selfreport of cigarette smoking was obtained using a questionnaire administered in classrooms. Data were analyzed using weighted chi-square and multiple logistic regressions in SAS that accounted for the survey design. The prevalence rates for adolescents that ever tried smoking were 7.4% in elementary (grades 4-5; 17.7% in middle (grades 6-8, and 41.4% in high (grades 9-12 schools, respectively. The highest prevalence rate was among Hispanics. Having a close friend that smoked and a smoker at home correlated significantly with both initiation of smoking and smoking at an earlier age. Smoking was correlated with low academic achievement among adolescents in all grades. Students who reported smoking by parents or siblings were significantly more likely to start smoking at an earlier age, compared to other students living in a non-smoking home environment. Smoking prevention program should include components focused on adolescents’ home environment and should start as early as the 4th grade.

  6. Risk factors for weight faltering in infancy according to age at onset

    DEFF Research Database (Denmark)

    Olsen, Else Marie; Skovgaard, Anne M; Weile, Birgitte;

    2010-01-01

    and gestational age, with single parenthood and with mother having smoked during pregnancy. Onset between 2 weeks and 4 months was associated with congenital disorders and serious somatic illness, and with deviant mother-child relationship, whereas, onset between 4 and 8 months seemed to represent a...

  7. Microsatellite isolation and marker development in carrot - genomic distribution, linkage mapping, genetic diversity analysis and marker transferability across Apiaceae

    Directory of Open Access Journals (Sweden)

    Yildiz Mehtap

    2011-08-01

    Full Text Available Abstract Background The Apiaceae family includes several vegetable and spice crop species among which carrot is the most economically important member, with ~21 million tons produced yearly worldwide. Despite its importance, molecular resources in this species are relatively underdeveloped. The availability of informative, polymorphic, and robust PCR-based markers, such as microsatellites (or SSRs, will facilitate genetics and breeding of carrot and other Apiaceae, including integration of linkage maps, tagging of phenotypic traits and assisting positional gene cloning. Thus, with the purpose of isolating carrot microsatellites, two different strategies were used; a hybridization-based library enrichment for SSRs, and bioinformatic mining of SSRs in BAC-end sequence and EST sequence databases. This work reports on the development of 300 carrot SSR markers and their characterization at various levels. Results Evaluation of microsatellites isolated from both DNA sources in subsets of 7 carrot F2 mapping populations revealed that SSRs from the hybridization-based method were longer, had more repeat units and were more polymorphic than SSRs isolated by sequence search. Overall, 196 SSRs (65.1% were polymorphic in at least one mapping population, and the percentage of polymophic SSRs across F2 populations ranged from 17.8 to 24.7. Polymorphic markers in one family were evaluated in the entire F2, allowing the genetic mapping of 55 SSRs (38 codominant onto the carrot reference map. The SSR loci were distributed throughout all 9 carrot linkage groups (LGs, with 2 to 9 SSRs/LG. In addition, SSR evaluations in carrot-related taxa indicated that a significant fraction of the carrot SSRs transfer successfully across Apiaceae, with heterologous amplification success rate decreasing with the target-species evolutionary distance from carrot. SSR diversity evaluated in a collection of 65 D. carota accessions revealed a high level of polymorphism for these

  8. An estimating function approach to linkage heterogeneity

    Indian Academy of Sciences (India)

    He Gao; Ying Zhou; Weijun Ma; Haidong Liu; Linan Zhao

    2013-12-01

    Testing linkage heterogeneity between two loci is an important issue in genetics. Currently, there are four methods (K-test, A-test, B-test and D-test) for testing linkage heterogeneity in linkage analysis, which are based on the likelihood-ratio test. Among them, the commonly used methods are the K-test and A-test. In this paper, we present a novel test method which is different from the above four tests, called G-test. The new test statistic is based on estimating function, possessing a theoretic asymptotic distribution, and therefore demonstrates its own advantages. The proposed test is applied to analyse a real pedigree dataset. Our simulation results also indicate that the G-test performs well in terms of power of testing linkage heterogeneity and outperforms the current methods to some degree.

  9. Genome-wide SNP discovery and linkage analysis in barley based on genes responsive to abiotic stress.

    Science.gov (United States)

    Rostoks, Nils; Mudie, Sharon; Cardle, Linda; Russell, Joanne; Ramsay, Luke; Booth, Allan; Svensson, Jan T; Wanamaker, Steve I; Walia, Harkamal; Rodriguez, Edmundo M; Hedley, Peter E; Liu, Hui; Morris, Jenny; Close, Timothy J; Marshall, David F; Waugh, Robbie

    2005-12-01

    More than 2,000 genome-wide barley single nucleotide polymorphisms (SNPs) were developed by resequencing unigene fragments from eight diverse accessions. The average genome-wide SNP frequency observed in 877 unigenes was 1 SNP per 200 bp. However, SNP frequency was highly variable with the least number of SNP and SNP haplotypes observed within European cultivated germplasm reflecting effects of breeding history on genetic diversity. More than 300 SNP loci were mapped genetically in three experimental mapping populations which allowed the construction of an integrated SNP map incorporating a large number of RFLP, AFLP and SSR markers (1,237 loci in total). The genes used for SNP discovery were selected based on their transcriptional response to a variety of abiotic stresses. A set of known barley abiotic stress QTL was positioned on the linkage map, while the available sequence and gene expression information facilitated the identification of genes potentially associated with these traits. Comparison of the sequenced SNP loci to the rice genome sequence identified several regions of highly conserved gene order providing a framework for marker saturation in barley genomic regions of interest. The integration of genome-wide SNP and expression data with available genetic and phenotypic information will facilitate the identification of gene function in barley and other non-model organisms. PMID:16244872

  10. Genome-wide linkage meta-analysis identifies susceptibility loci at 2q34 and 13q31.3 for genetic generalized epilepsies

    DEFF Research Database (Denmark)

    Leu, Costin; de Kovel, Carolien G F; Zara, Federico;

    2012-01-01

    Purpose: Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% with heritability estimates of 80%. A considerable proportion of families with siblings affected by GGEs presumably display an oligogenic inheritance. The present genome-wide linkage meta-analysis aimed to map: (1...... ancestry including 982 relatives with GGEs. To dissect out seizure type-related susceptibility genes, two family subgroups were stratified comprising 235 families with predominantly genetic absence epilepsies (GAEs) and 118 families with an aggregation of juvenile myoclonic epilepsy (JME). To map shared....... Phenotype-genotype strategies applying narrow trait definitions in phenotypic homogeneous subgroups of families improve the prospects of disentangling the genetic basis of common familial GGE syndromes....

  11. Caution in interpreting results from imputation analysis when linkage disequilibrium extends over a large distance: a case study on venous thrombosis.

    Directory of Open Access Journals (Sweden)

    Marine Germain

    Full Text Available By applying an imputation strategy based on the 1000 Genomes project to two genome-wide association studies (GWAS, we detected a susceptibility locus for venous thrombosis on chromosome 11p11.2 that was missed by previous GWAS analyses that had been conducted on the same datasets. A comprehensive linkage disequilibrium and haplotype analysis of the whole locus where twelve SNPs exhibited association p-values lower than 2.23 10(-11 and the use of independent case-control samples demonstrated that the culprit variant was a rare variant located ~1 Mb away from the original hits, not tagged by current genome-wide genotyping arrays and even not well imputed in the original GWAS samples. This variant was in fact the rs1799963, also known as the FII G20210A prothrombin mutation. This work may be of major interest not only for its scientific impact but also for its methodological findings.

  12. A consensus microsatellite-based linkage map for the hermaphroditic bay scallop (Argopecten irradians and its application in size-related QTL analysis.

    Directory of Open Access Journals (Sweden)

    Hongjun Li

    Full Text Available Bay scallop (Argopecten irradians is one of the most economically important aquaculture species in China. In this study, we constructed a consensus microsatellite-based genetic linkage map with a mapping panel containing two hybrid backcross-like families involving two subspecies of bay scallop, A. i. irradians and A. i. concentricus. One hundred sixty-one microsatellite and one phenotypic (shell color markers were mapped to 16 linkage groups (LGs, which corresponds to the haploid chromosome number of bay scallop. The sex-specific map was 779.2 cM and 781.6 cM long in female and male, respectively, whereas the sex-averaged map spanned 849.3 cM. The average resolution of integrated map was 5.9 cM/locus and the estimated coverage was 81.3%. The proportion of distorted markers occurred more in the hybrid parents, suggesting that the segregation distortion was possibly resulted from heterospecific interaction between genomes of two subspecies of bay scallop. The overall female-to-male recombination rate was 1.13:1 across all linked markers in common to both parents, and considerable differences in recombination also existed among different parents in both families. Four size-related traits, including shell length (SL, shell height (SH, shell width (SW and total weight (TW were measured for quantitative trait loci (QTL analysis. Three significant and six suggestive QTL were detected on five LGs. Among the three significant QTL, two (qSW-10 and qTW-10, controlling SW and TW, respectively were mapped on the same region near marker AiAD121 on LG10 and explained 20.5% and 27.7% of the phenotypic variance, while the third (qSH-7, controlling SH was located on LG7 and accounted for 15.8% of the phenotypic variance. Six suggestive QTL were detected on four different LGs. The linkage map and size-related QTL obtained in this study may facilitate marker-assisted selection (MAS in bay scallop.

  13. A Linkage Learning Genetic Algorithm with Linkage Matrix

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The goal of linkage learning, or building block identification, is the creation of a more effective Genetic Algorithm (GA). This paper proposes a new Linkage Learning Genetic Algorithms, named m-LLGA. With the linkage learning module and the linkage-based genetic operation, m-LLGA is not only able to learn and record the linkage information among genes without any prior knowledge of the function being optimized. It also can use the linkage information stored in the linkage matrix to guide the selection of crossover point. The preliminary experiments on two kinds of bounded difficulty problems and a TSP problem validated the performance of m-LLGA. The m-LLGA learns the linkage of different building blocks parallel and therefore solves these problems effectively; it can also reasonably reduce the probability of building blocks being disrupted by crossover at the same time give attention to getting away from local minimum.

  14. Cosmopolitan linkage disequilibrium maps

    Directory of Open Access Journals (Sweden)

    Gibson Jane

    2005-03-01

    Full Text Available Abstract Linkage maps have been invaluable for the positional cloning of many genes involved in severe human diseases. Standard genetic linkage maps have been constructed for this purpose from the Centre d'Etude du Polymorphisme Humain and other panels, and have been widely used. Now that attention has shifted towards identifying genes predisposing to common disorders using linkage disequilibrium (LD and maps of single nucleotide polymorphisms (SNPs, it is of interest to consider a standard LD map which is somewhat analogous to the corresponding map for linkage. We have constructed and evaluated a cosmopolitan LD map by combining samples from a small number of populations using published data from a 10-megabase region on chromosome 20. In support of a pilot study, which examined a number of small genomic regions with a lower density of markers, we have found that a cosmopolitan map, which serves all populations when appropriately scaled, recovers 91 to 95 per cent of the information within population-specific maps. Recombination hot spots appear to have a dominant role in shaping patterns of LD. The success of the cosmopolitan map might be attributed to the co-localisation of hot spots in all populations. Although there must be finer scale differences between populations due to other processes (mutation, drift, selection, the results suggest that a whole-genome standard LD map would indeed be a useful resource for disease gene mapping.

  15. Equivalent Linkages of Compressor Mechanisms

    OpenAIRE

    Bukac, Hubert

    2014-01-01

    Frequently, the dynamics of a compressor’s mechanism can be simplified and better understood by analyzing compressor’s equivalent linkage. Although the equivalent linkage of a reciprocating piston compressor is well known, the equivalent linkages of other types of compressors are not. For example, it is not well understood that the equivalent linkage of a rolling piston compressor is also the same slider-crank mechanism as the one of a reciprocating piston compressor. The difference between r...

  16. Coulomb Control of Polygonal Linkages

    NARCIS (Netherlands)

    Khimshiashvili, Giorgi N.; Panina, Gaiane Yu; Siersma, Dirk

    2014-01-01

    Equilibria of polygonal linkage with respect to Coulomb potential of point charges placed at the vertices of linkage are considered. It is proved that any convex configuration of a quadrilateral linkage is the point of global minimum of Coulomb potential for appropriate values of charges of vertices

  17. A Turkish family with Ellis-van Creveld syndrome in six siblings; linkage analysis on 4p16 region (D4S3360-D4S2366).

    Science.gov (United States)

    Cağdaş, D N; Parlar, A I; Pac, A; Tutun, U; Balci, S

    2008-01-01

    We present a Turkish family and their 6 children, consecutively affected by Ellis-van Creveld (EVC) Syndrome. Four of the affected children died in the postnatal period, and 2 of them had been admitted to the pediatric cardiology department for their cardiologic evaluation. Since they had the features of the EVC Syndrome, linkage analysis was performed with the polymorphic markers, D4S3360-D4S2366, selected from 4p 16 locus. There was complete segregation between the disease and marker allels and the two affected siblings were homozygote for the polymorphic markers, as expected in autosomal recessive inheritance. The diagnosis of EVC Syndrome was confirmed by this molecular analysis. Two cases with EVC were presented in this report. Case 1 had partial abnormal pulmonary venous return and pulmonary stenosis additional to ostium primum atrial septal defect and mitral cleft. Partial abnormal pulmonary venous return and pulmonary stenosis were previously not reported with EVC Syndrome. Postaxial polydactyly phenotype of the Case 2 differs from her brother's. There is bifid 5th metacarpal and unilateral (L) bifid middle and distal phalanges resembling syndactyly.

  18. Mapping one form of autosomal dominant postaxial polydactyly type A to chromosome 7p15-q11.23 by linkage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Radhakrishna, U.; Mehenni, H.; Antonarakis, S.E. [Geneva Medical School (Switzerland)] [and others

    1997-03-01

    Postaxial polydactyly type-A (PAP-A) in humans is an autosomal dominant trait characterized by an extra digit in the ulnar and/or fibular side of the upper and/or lower extremities. The extra digit is well formed and articulates with the fifth, or extra, metacarpal/metatarsal, and thus it is usually functional. In order to map the gene responsible for PAP-A, we studied a five-generation Indian family of 37 individuals (15 of whom were affected). A genomewide search with highly informative polymorphic markers on part of the pedigree showed linkage between the PAP-A phenotype and markers on chromosome 7p15-q11.23 (no crossovers were found with D7S526, D7S795, D7S528, D7S521, D7S691, D7S667, D7S478, D7S1830, D7S803, D7S801, or ELN). The highest LOD score was obtained with marker D7S801 (Z{sub max} = 4.21; {theta} = 0). Haplotype analysis enabled the mapping of the PAP-A phenotype in this family between markers D7S2848 and D7S669. Analysis of additional families with PAP-A will narrow down the critical genomic region, facilitate positional cloning of the PAP-A gene, and/or uncover potential genetic heterogeneity. 42 refs., 4 figs., 1 tab.

  19. 中国产业间关联程度及经济距离分析%An Analysis of China's Industrial Linkage and Economic Distance

    Institute of Scientific and Technical Information of China (English)

    赵素萍; 林玲; 葛明

    2014-01-01

    应用改进的投入产出分析方法研究各产业部门间的经济联系程度和经济距离。结果表明:就与整体国民经济的经济联系而言,农业、采选业、商业服务业的推动作用较强,轻工业、建筑业的拉动作用明显,重工业和电力热力业两方面作用都很显著。应用产业间关联程度分析方法后发现:采选业的供给推动作用明显,轻工业的需求拉动作用较强,重工业成为国民经济的关键部门,其它产业表现出明显的依赖性。应用产业间经济距离分析方法后发现:采选业、农业前向经济联系距离较大,轻工业、建筑业后向经济联系距离较长,重工业、电力热力业位于产业链的中心位置,商业服务业和其它服务业前、后向经济联系距离都较短。%Based on input-output tables of China in 2005 and 2010 ,this paper gives a deep insight of China's industrial linkage and economic distance by the methods of modified input-output analysis,industrial linkage and economic distance analysis. The results show that:from the viewpoint of linkage with whole na-tional economy,the economic status of each industry is relatively stable,agriculture,mining industry,busi-ness services play a strong role in promoting,and light industry,construction industry in obviously pulling, while heavy industry and electricity and heat sector in both. By comparison between two industries,mining in-dustry plays an obvious role in supply promoting,light industry is adept at driving demand,and other indus-tries show significant dependence on heavy industry,which is a key sector of national economy. From the viewpoint of industrial economic distance,mining industry and agriculture have a longer economic distance to upstream industry,light industry and construction industry have a longer economic distance to downstream in-dustry,heavy industry and electricity and heat sector play a key role in industry chain,while business

  20. Linkage, evaluation and analysis of national electronic healthcare data: application to providing enhanced blood-stream infection surveillance in paediatric intensive care.

    OpenAIRE

    Katie Harron; Harvey Goldstein; Angie Wade; Berit Muller-Pebody; Roger Parslow; Ruth Gilbert

    2013-01-01

    Background: Linkage of risk-factor data for blood-stream infection (BSI) in paediatric intensive care (PICU) withbacteraemia surveillance data to monitor risk-adjusted infection rates in PICU is complicated by a lack of uniqueidentifiers and under-ascertainment in the national surveillance system. We linked, evaluated and performedpreliminary analyses on these data to provide a practical guide on the steps required to handle linkage of suchcomplex data sources.Methods: Data on PICU admissions...

  1. Genomewide high-density SNP linkage analysis of non-BRCA1/2 breast cancer families identifies various candidate regions and has greater power than microsatellite studies

    Directory of Open Access Journals (Sweden)

    Gonzalez-Neira Anna

    2007-08-01

    Full Text Available Abstract Background The recent development of new high-throughput technologies for SNP genotyping has opened the possibility of taking a genome-wide linkage approach to the search for new candidate genes involved in heredity diseases. The two major breast cancer susceptibility genes BRCA1 and BRCA2 are involved in 30% of hereditary breast cancer cases, but the discovery of additional breast cancer predisposition genes for the non-BRCA1/2 breast cancer families has so far been unsuccessful. Results In order to evaluate the power improvement provided by using SNP markers in a real situation, we have performed a whole genome screen of 19 non-BRCA1/2 breast cancer families using 4720 genomewide SNPs with Illumina technology (Illumina's Linkage III Panel, with an average distance of 615 Kb/SNP. We identified six regions on chromosomes 2, 3, 4, 7, 11 and 14 as candidates to contain genes involved in breast cancer susceptibility, and additional fine mapping genotyping using microsatellite markers around linkage peaks confirmed five of them, excluding the region on chromosome 3. These results were consistent in analyses that excluded SNPs in high linkage disequilibrium. The results were compared with those obtained previously using a 10 cM microsatellite scan (STR-GWS and we found lower or not significant linkage signals with STR-GWS data compared to SNP data in all cases. Conclusion Our results show the power increase that SNPs can supply in linkage studies.

  2. Restricted maximum likelihood analysis of linkage between genetic markers and quantitative trait loci for a granddaughter design.

    NARCIS (Netherlands)

    Arendonk, van J.A.M.; Tier, B.; Bink, M.C.A.M.; Bovenhuis, H.

    1998-01-01

    REML for the estimation of location and variance of a single quantitative trait locus, together with polygenic and residual variance, is described for the analysis of a granddaughter design. The method is based on a mixed linear model that includes the allelic effects of the quantitative trait locus

  3. Improved linkage analysis of Quantitative Trait Loci using bulk segregants unveils a novel determinant of high ethanol tolerance in yeast

    NARCIS (Netherlands)

    Duitama, Jorge; Sánchez-Rodríguez, Aminael; Goovaerts, Annelies; Pulido-Tamayo, Sergio; Hubmann, Georg; Foulquié-Moreno, María R.; Thevelein, Johan M.; Verstrepen, Kevin J.; Marchal, Kathleen

    2014-01-01

    Background: Bulk segregant analysis (BSA) coupled to high throughput sequencing is a powerful method to map genomic regions related with phenotypes of interest. It relies on crossing two parents, one inferior and one superior for a trait of interest. Segregants displaying the trait of the superior p

  4. An interspecific backcross of Lycopersicon esculentum x L. hirsutum: linkage analysis and a QTL study of sexual compatibility factors and floral traits.

    Science.gov (United States)

    Bernacchi, D; Tanksley, S D

    1997-10-01

    A BC1 population of the self-compatible tomato Lycopersicon esculentum and its wild self-incompatible relative L. hirsutum f. typicum was used for restriction fragment length polymorphism linkage analysis and quantitative trait loci (QTL) mapping of reproductive behavior and floral traits. The self-incompatibility locus, S, on chromosome 1 harbored the only QTL for self-incompatibility indicating that the transition to self-compatibility in the lineage leading to the cultivated tomato was primarily the result of mutations at the S locus. Moreover, the major QTL controlling unilateral incongruity also mapped to the S locus, supporting the hypothesis that self-incompatibility and unilateral incongruity are not independent mechanisms. The mating behavior of near-isogenic lines carrying the L. hirsutum allele for the S locus on chromosome 1 in an otherwise L. esculentum background support these conclusions. The S locus region of chromosome 1 also harbors most major QTL for several floral traits important to pollination biology (e.g., number and size of flowers), suggesting a gene complex controlling both genetic and morphological mechanisms of reproduction control. Similar associations in other flowering plants suggest that such complex may have been conserved since early periods of plant evolution or else reflect a convergent evolutionary process. PMID:9335620

  5. Automation of High-Throughput Mass Spectrometry-Based Plasma N-Glycome Analysis with Linkage-Specific Sialic Acid Esterification.

    Science.gov (United States)

    Bladergroen, Marco R; Reiding, Karli R; Hipgrave Ederveen, Agnes L; Vreeker, Gerda C M; Clerc, Florent; Holst, Stephanie; Bondt, Albert; Wuhrer, Manfred; van der Burgt, Yuri E M

    2015-09-01

    Glycosylation is a post-translational modification of key importance with heterogeneous structural characteristics. Previously, we have developed a robust, high-throughput MALDI-TOF-MS method for the comprehensive profiling of human plasma N-glycans. In this approach, sialic acid residues are derivatized with linkage-specificity, namely the ethylation of α2,6-linked sialic acid residues with parallel lactone formation of α2,3-linked sialic acids. In the current study, this procedure was used as a starting point for the automation of all steps on a liquid-handling robot system. This resulted in a time-efficient and fully standardized procedure with throughput times of 2.5 h for a first set of 96 samples and approximately 1 h extra for each additional sample plate. The mass analysis of the thus-obtained glycans was highly reproducible in terms of relative quantification, with improved interday repeatability as compared to that of manual processing. PMID:26179816

  6. Definition of the locus responsible for systemic carnitine deficiency within a 1.6-cM region of mouse chromosome 11 by detailed linkage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Okita, Kohei; Tokino, Takashi; Nishimori, Hiroyuki [Univ. of Tokyo (Japan)] [and others

    1996-04-15

    Carnitine is an essential cofactor for oxidation of mitochondrial fatty acids. Carnitine deficiency results in failure of energy production by mitochondria and leads to metabolic encephalopathy, lipid-storage myopathy, and cardiomyopathy. The juvenile visceral steatosis (JVS) mouse, an animal model of systemic carnitine deficiency, inherits the JVS phenotype in autosomal recessive fashion, through a mutant allele mapped to mouse chromosome 11. As a step toward identifying the gene responsible for JVS by positional cloning, we attempted to refine the jvs locus in the mouse by detailed linkage analysis with 13 microsatellite markers, using 190 backcross progeny. Among the 13 loci tested, 5 (defined by markers D11Mit24, D11Mit111,D11Nds9, D11Mit86, and D11Mit23) showed no recombination, with a maximum lod score of 52.38. Our results implied that the jvs gene can be sought on mouse chromosome 11 within a genetic distance no greater than about 1.6 cM. 21 refs., 2 figs.

  7. A gene-based linkage map for Bicyclus anynana butterflies allows for a comprehensive analysis of synteny with the lepidopteran reference genome.

    Directory of Open Access Journals (Sweden)

    Patrícia Beldade

    2009-02-01

    Full Text Available Lepidopterans (butterflies and moths are a rich and diverse order of insects, which, despite their economic impact and unusual biological properties, are relatively underrepresented in terms of genomic resources. The genome of the silkworm Bombyx mori has been fully sequenced, but comparative lepidopteran genomics has been hampered by the scarcity of information for other species. This is especially striking for butterflies, even though they have diverse and derived phenotypes (such as color vision and wing color patterns and are considered prime models for the evolutionary and developmental analysis of ecologically relevant, complex traits. We focus on Bicyclus anynana butterflies, a laboratory system for studying the diversification of novelties and serially repeated traits. With a panel of 12 small families and a biphasic mapping approach, we first assigned 508 expressed genes to segregation groups and then ordered 297 of them within individual linkage groups. We also coarsely mapped seven color pattern loci. This is the richest gene-based map available for any butterfly species and allowed for a broad-coverage analysis of synteny with the lepidopteran reference genome. Based on 462 pairs of mapped orthologous markers in Bi. anynana and Bo. mori, we observed strong conservation of gene assignment to chromosomes, but also evidence for numerous large- and small-scale chromosomal rearrangements. With gene collections growing for a variety of target organisms, the ability to place those genes in their proper genomic context is paramount. Methods to map expressed genes and to compare maps with relevant model systems are crucial to extend genomic-level analysis outside classical model species. Maps with gene-based markers are useful for comparative genomics and to resolve mapped genomic regions to a tractable number of candidate genes, especially if there is synteny with related model species. This is discussed in relation to the identification of

  8. Phylogenetic and functional analysis of metagenome sequence from high-temperature archaeal habitats demonstrate linkages between metabolic potential and geochemistry

    Directory of Open Access Journals (Sweden)

    William P. Inskeep

    2013-05-01

    Full Text Available Geothermal habitats in Yellowstone National Park (YNP provide an unparalled opportunity to understand the environmental factors that control the distribution of archaea in thermal habitats. Here we describe, analyze and synthesize metagenomic and geochemical data collected from seven high-temperature sites that contain microbial communities dominated by archaea relative to bacteria. The specific objectives of the study were to use metagenome sequencing to determine the structure and functional capacity of thermophilic archaeal-dominated microbial communities across a pH range from 2.5 to 6.4 and to discuss specific examples where the metabolic potential correlated with measured environmental parameters and geochemical processes occurring in situ. Random shotgun metagenome sequence (~40-45 Mbase Sanger sequencing per site was obtained from environmental DNA extracted from high-temperature sediments and/or microbial mats and subjected to numerous phylogenetic and functional analyses. Analysis of individual sequences (e.g., MEGAN and G+C content and assemblies from each habitat type revealed the presence of dominant archaeal populations in all environments, 10 of whose genomes were largely reconstructed from the sequence data. Analysis of protein family occurrence, particularly of those involved in energy conservation, electron transport and autotrophic metabolism, revealed significant differences in metabolic strategies across sites consistent with differences in major geochemical attributes (e.g., sulfide, oxygen, pH. These observations provide an ecological basis for understanding the distribution of indigenous archaeal lineages across high temperature systems of YNP.

  9. Phylogenetic and Functional Analysis of Metagenome Sequence from High-Temperature Archaeal Habitats Demonstrate Linkages between Metabolic Potential and Geochemistry.

    Science.gov (United States)

    Inskeep, William P; Jay, Zackary J; Herrgard, Markus J; Kozubal, Mark A; Rusch, Douglas B; Tringe, Susannah G; Macur, Richard E; Jennings, Ryan deM; Boyd, Eric S; Spear, John R; Roberto, Francisco F

    2013-01-01

    Geothermal habitats in Yellowstone National Park (YNP) provide an unparalleled opportunity to understand the environmental factors that control the distribution of archaea in thermal habitats. Here we describe, analyze, and synthesize metagenomic and geochemical data collected from seven high-temperature sites that contain microbial communities dominated by archaea relative to bacteria. The specific objectives of the study were to use metagenome sequencing to determine the structure and functional capacity of thermophilic archaeal-dominated microbial communities across a pH range from 2.5 to 6.4 and to discuss specific examples where the metabolic potential correlated with measured environmental parameters and geochemical processes occurring in situ. Random shotgun metagenome sequence (∼40-45 Mb Sanger sequencing per site) was obtained from environmental DNA extracted from high-temperature sediments and/or microbial mats and subjected to numerous phylogenetic and functional analyses. Analysis of individual sequences (e.g., MEGAN and G + C content) and assemblies from each habitat type revealed the presence of dominant archaeal populations in all environments, 10 of whose genomes were largely reconstructed from the sequence data. Analysis of protein family occurrence, particularly of those involved in energy conservation, electron transport, and autotrophic metabolism, revealed significant differences in metabolic strategies across sites consistent with differences in major geochemical attributes (e.g., sulfide, oxygen, pH). These observations provide an ecological basis for understanding the distribution of indigenous archaeal lineages across high-temperature systems of YNP.

  10. Signature analysis of satellite derived SSHa, SST and chlorophyll concentration and their linkage with marine fishery resources

    Science.gov (United States)

    Solanki, H. U.; Bhatpuria, Dhyey; Chauhan, Prakash

    2015-10-01

    This study aims to understand patterns, persistence and interrelationship between satellite derived oceanic variables. Time series near-synchronous sea surface height anomaly (SSHa), chlorophyll-a concentration (CC) and sea surface temperature (SST) derived from Topex/Poseidon altimeter, Oceansat-OCM and NOAA-AVHRR, respectively, were used for integrative signature analysis. Three dimensional surface and two dimensional spatial profiles of these variables were generated to understand the spatio-temporal variability. SST and SSHa were co-varying and CC shows an inverse correlation. The time series data analysis indicated bio-physical closely coupled processes. The patterns of variability in CC signatures were found to be associated with SSHa and SST signatures. High fish catch in terms of CPUE (catch-per-unit-effort) were found in low SSHa and corresponding high chlorophyll concentration area during the year 1998-2004 in the Northern Arabian Sea. SSHa signatures were detected earlier than CC and SST. Lower SSHa signatures were inferred as advanced information of the occurrence of productive sites in near future. This study would be useful to understand large scale bio-physical coupled processes for fishery resources exploration.

  11. A whole transcriptomal linkage analysis of gene co-regulation in insecticide resistant house flies, Musca domestica

    DEFF Research Database (Denmark)

    Li, Ming; Reid, William R; Zhang, Lee;

    2013-01-01

    Background Studies suggest that not only is insecticide resistance conferred via multiple gene up-regulation, but it is mediated through the interaction of regulatory factors. However, no regulatory factors in insecticide resistance have yet been identified, and there has been no examination...... of the regulatory interaction of resistance genes. Our current study generated the first reference transcriptome from the adult house fly and conducted a whole transcriptome analysis for the multiple insecticide resistant strain ALHF (wild-type) and two insecticide susceptible strains: aabys (with morphological...... recessive markers) and CS (wild type) to gain valuable insights into the gene interaction and complex regulation in insecticide resistance of house flies, Musca domestica. Results Over 56 million reads were used to assemble the adult female M. domestica transcriptome reference and 14488 contigs were...

  12. A scoping analysis of peer-reviewed literature about linkages between aquaculture and determinants of human health.

    Science.gov (United States)

    Burns, Theresa E; Wade, Joy; Stephen, Craig; Toews, Lorraine

    2014-06-01

    For many of the world's poor, aquatic products are critical for food security and health. Because the global population is increasing as wild aquatic stocks are declining, aquaculture is an increasingly important source of aquatic products. We undertook a scoping review of the English-language peer-reviewed literature to evaluate how the research community has examined the impacts of aquaculture on four key determinants of human health: poverty, food security, food production sustainability, and gender equality. The review returned 156 primary research articles. Most research (75%) was focused in Asia, with limited research from Africa (10%) and South America (2%). Most research (80%) focused on freshwater finfish and shrimp production. We used qualitative content analysis of records which revealed 11 themes: famer income; the common environment; shared resources; integrated farming/ polyculture; employment; extensive vs. intensive production; local vs. distant ownership; food security; income equity; gender equality; and input costs. We used quantitative content analysis of records and full-text publications about freshwater finfish and shrimp aquaculture to record the frequency with which themes were represented and the positive or negative impacts of aquaculture associated with each theme. Scatter plots showed that no theme was identified in more than half of all articles and publications for both production types. Farmer income was a theme that was identified commonly and was positively impacted by both shrimp and fresh water finfish aquaculture. Polyculture, employment, and local ownership were identified less often as themes, but were also associated with positive impacts. The common environment and shared resources were more common themes in shrimp aquaculture than freshwater finfish aquaculture research, while polyculture and local ownership were more common themes in freshwater finfish aquaculture than shrimp aquaculture. Gender equality, employment, and

  13. Genome-wide linkage analysis of global gene expression in loin muscle tissue identifies candidate genes in pigs.

    Directory of Open Access Journals (Sweden)

    Juan Pedro Steibel

    Full Text Available BACKGROUND: Nearly 6,000 QTL have been reported for 588 different traits in pigs, more than in any other livestock species. However, this effort has translated into only a few confirmed causative variants. A powerful strategy for revealing candidate genes involves expression QTL (eQTL mapping, where the mRNA abundance of a set of transcripts is used as the response variable for a QTL scan. METHODOLOGY/PRINCIPAL FINDINGS: We utilized a whole genome expression microarray and an F(2 pig resource population to conduct a global eQTL analysis in loin muscle tissue, and compared results to previously inferred phenotypic QTL (pQTL from the same experimental cross. We found 62 unique eQTL (FDR <10% and identified 3 gene networks enriched with genes subject to genetic control involved in lipid metabolism, DNA replication, and cell cycle regulation. We observed strong evidence of local regulation (40 out of 59 eQTL with known genomic position and compared these eQTL to pQTL to help identify potential candidate genes. Among the interesting associations, we found aldo-keto reductase 7A2 (AKR7A2 and thioredoxin domain containing 12 (TXNDC12 eQTL that are part of a network associated with lipid metabolism and in turn overlap with pQTL regions for marbling, % intramuscular fat (% fat and loin muscle area on Sus scrofa (SSC chromosome 6. Additionally, we report 13 genomic regions with overlapping eQTL and pQTL involving 14 local eQTL. CONCLUSIONS/SIGNIFICANCE: Results of this analysis provide novel candidate genes for important complex pig phenotypes.

  14. 维基百科链接网络实证分析%Structural analysis on Wikipedia linkage network

    Institute of Scientific and Technical Information of China (English)

    王辉; 徐晓旻; 施佺

    2012-01-01

    理解维基百科词条链接网络的结构特征是深入而有效地应用维基百科的前提.基于2010年1月的数据,从度分布、权分布、宏观结构特征等角度对维基百科词条链接网络的结构特征展开实证分析.相关结果与2006年之前的维基百科词条链接网络展开对比,发现当前的维基百科网络仍然具有无标度网络特性;其宏观结构总体上满足bow-tie模型,但模型中的各组成部分比例发生了显著变化.因此,该研究对深入解析维基百科词条链接网络的结构特性具有理论和现实意义.%In order to make better use of Wikipedia, it is necessary to have a clear understanding of the structural features of word entry hyperlink network of Wikipedia. This paper conducted brief experimental analysis in aspects of degree distribution, weight distribution and marco structural analysis on Wikipedia crawled on January 2010. By comparing these characteristic with previous works done before 2006, it found that the Wikipedia hyperlink network still followed power-law distribution on degree and the marco structure still obeyed bow-tie model, however, the proportion of different components defined in bow-tie model varied significantly.

  15. Molecular studies of linkage group XIX of Chlamydomonas reinhardtii: evidence against a basal body location

    OpenAIRE

    1991-01-01

    Linkage group XIX (also known as the UNI linkage group) in the green alga, Chlamydomonas reinhardtii, exhibits a number of unusual properties that have lead to the suggestion that it represents a basal body-associated chromosome. To begin a molecular analysis of this linkage group, we have identified DNA sequences from it and used them to determine the copy number of linkage group XIX within the cell. We find that linkage group XIX is present in the same copy number per cell as nuclear linkag...

  16. Toward the Integrated Framework Analysis of Linkages among Agrobiodiversity, Livelihood Diversification, Ecological Systems, and Sustainability amid Global Change

    Directory of Open Access Journals (Sweden)

    Karl S. Zimmerer

    2016-04-01

    Full Text Available Scientific and policy interest in the biological diversity of agriculture (agrobiodiversity is expanding amid global socioeconomic and environmental changes and sustainability interests. The majority of global agrobiodiversity is produced in smallholder food-growing. We use meta-analyses in an integrated framework to examine the interactions of smallholder agrobiodiversity with: (1 livelihood processes, especially migration, including impacts on agrobiodiversity as well as the interconnected resource systems of soil, water, and uncultivated habitats; and (2 plant-soil ecological systems. We hypothesize these interactions depend on: (1 scope of livelihood diversification and type resource system; and (2 plant residues and above-/belowground component ecological specificity. Findings show: (1 livelihood diversification is linked to varied environmental factors that range from rampant degradation to enhancing sustainability; and (2 significant ecological coupling of aboveground and soil agrobiodiversity (AGSOBIO assemblages. The environmental impacts of livelihood interactions correspond to variation of diversification (migration, on-farm diversification and resource system (i.e., agrobiodiversity per se, soil, water. Our findings also reveal mutually dependent interactions of aboveground and soil agrobiodiversity. Results identify livelihood diversification-induced reduction of environmental resource quality with lagged agrobiodiversity declines as a potentially major avenue of global change. Our contribution re-frames livelihood interactions to include both agrobiodiversity and ecological systems. We discuss this integrated social-environmental re-framing through the proposed spatial geographic schema of regional agri-food spaces with distinctive matrices of livelihood strategies and relations to biodiversity and resources. This re-framing can be used to integrate livelihood, agrobiodiversity, and ecological analysis and to guide policy and

  17. Genome-wide meta-analysis of myopia and hyperopia provides evidence for replication of 11 loci.

    Directory of Open Access Journals (Sweden)

    Claire L Simpson

    Full Text Available Refractive error (RE is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness and hyperopia (farsightedness, which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p = 1.25×10(-8, which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE refractive error. We observed two genome-wide significant associations with hyperopia. These regions overlapped with loci on 15q14 (minimum p value = 9.11×10(-11 and 8q12 (minimum p value 1.82×10(-11 previously reported for MSE and myopia age at onset. We also used an intermarker linkage- disequilibrium-based method for calculating the effective number of tests in targeted regional replication analyses. We analyzed myopia (which represents the closest phenotype in our data to the one used by Kiefer et al. and showed replication of 10 additional loci associated with myopia previously reported by Kiefer et al. This is the first replication of these loci using myopia as the trait under analysis. "Replication-level" association was also seen between hyperopia and 12 of Kiefer et al.'s published loci. For the loci that show evidence of association to both myopia and hyperopia, the estimated effect of the risk alleles were in opposite directions for the two traits. This suggests that these loci are important contributors to variation of

  18. Genome-wide linkage and association analysis identifies major gene loci for guttural pouch tympany in Arabian and German warmblood horses.

    Directory of Open Access Journals (Sweden)

    Julia Metzger

    Full Text Available Equine guttural pouch tympany (GPT is a hereditary condition affecting foals in their first months of life. Complex segregation analyses in Arabian and German warmblood horses showed the involvement of a major gene as very likely. Genome-wide linkage and association analyses including a high density marker set of single nucleotide polymorphisms (SNPs were performed to map the genomic region harbouring the potential major gene for GPT. A total of 85 Arabian and 373 German warmblood horses were genotyped on the Illumina equine SNP50 beadchip. Non-parametric multipoint linkage analyses showed genome-wide significance on horse chromosomes (ECA 3 for German warmblood at 16-26 Mb and 34-55 Mb and for Arabian on ECA15 at 64-65 Mb. Genome-wide association analyses confirmed the linked regions for both breeds. In Arabian, genome-wide association was detected at 64 Mb within the region with the highest linkage peak on ECA15. For German warmblood, signals for genome-wide association were close to the peak region of linkage at 52 Mb on ECA3. The odds ratio for the SNP with the highest genome-wide association was 0.12 for the Arabian. In conclusion, the refinement of the regions with the Illumina equine SNP50 beadchip is an important step to unravel the responsible mutations for GPT.

  19. Genomewide high-density SNP linkage analysis of non-BRCA1/2 breast cancer families identifies various candidate regions and has greater power than microsatellite studies

    NARCIS (Netherlands)

    A. González-Neira (Anna); J.M. Rosa-Rosa; A. Osorio (Ana); E. Gonzalez (Emilio); M.C. Southey (Melissa); O. Sinilnikova (Olga); H. Lynch (Henry); R.A. Oldenburg (Rogier); C.J. van Asperen (Christi); N. Hoogerbrugge (Nicoline); G. Pita (G.); P. Devilee (Peter); D. Goldgar (David); J. Benítez (Javier)

    2007-01-01

    textabstractBackground: The recent development of new high-throughput technologies for SNP genotyping has opened the possibility of taking a genome-wide linkage approach to the search for new candidate genes involved in heredity diseases. The two major breast cancer susceptibility genes BRCA1 and BR

  20. Construction of an intra-specific sweet cherry (Prunus avium L.) genetic linkage map and synteny analysis with the Prunus reference map

    Science.gov (United States)

    Linkage maps of the sweet cherry cultivar ‘Emperor Francis’ (EF) and the wild forest cherry ‘New York 54’ (NY) were constructed using primarily simple sequence repeat (SSR) markers and gene-derived markers with known positions on the Prunus reference map. The success rate for identifying SSR markers...

  1. How home HIV testing and counselling with follow-up support achieves high testing coverage and linkage to treatment and prevention: a qualitative analysis from Uganda

    Directory of Open Access Journals (Sweden)

    Norma C Ware

    2016-06-01

    Full Text Available Introduction: The successes of HIV treatment scale-up and the availability of new prevention tools have raised hopes that the epidemic can finally be controlled and ended. Reduction in HIV incidence and control of the epidemic requires high testing rates at population levels, followed by linkage to treatment or prevention. As effective linkage strategies are identified, it becomes important to understand how these strategies work. We use qualitative data from The Linkages Study, a recent community intervention trial of community-based testing with linkage interventions in sub-Saharan Africa, to show how lay counsellor home HIV testing and counselling (home HTC with follow-up support leads to linkage to clinic-based HIV treatment and medical male circumcision services. Methods: We conducted 99 semi-structured individual interviews with study participants and three focus groups with 16 lay counsellors in Kabwohe, Sheema District, Uganda. The participant sample included both HIV+ men and women (N=47 and HIV-uncircumcised men (N=52. Interview and focus group audio-recordings were translated and transcribed. Each transcript was summarized. The summaries were analyzed inductively to identify emergent themes. Thematic concepts were grouped to develop general constructs and framing propositional statements. Results: Trial participants expressed interest in linking to clinic-based services at testing, but faced obstacles that eroded their initial enthusiasm. Follow-up support by lay counsellors intervened to restore interest and inspire action. Together, home HTC and follow-up support improved morale, created a desire to reciprocate, and provided reassurance that services were trustworthy. In different ways, these functions built links to the health service system. They worked to strengthen individuals’ general sense of capability, while making the idea of accessing services more manageable and familiar, thus reducing linkage barriers. Conclusions

  2. How home HIV testing and counselling with follow-up support achieves high testing coverage and linkage to treatment and prevention: a qualitative analysis from Uganda

    Science.gov (United States)

    Ware, Norma C; Wyatt, Monique A; Asiimwe, Stephen; Turyamureeba, Bosco; Tumwesigye, Elioda; van Rooyen, Heidi; Barnabas, Ruanne V; Celum, Connie L

    2016-01-01

    Introduction The successes of HIV treatment scale-up and the availability of new prevention tools have raised hopes that the epidemic can finally be controlled and ended. Reduction in HIV incidence and control of the epidemic requires high testing rates at population levels, followed by linkage to treatment or prevention. As effective linkage strategies are identified, it becomes important to understand how these strategies work. We use qualitative data from The Linkages Study, a recent community intervention trial of community-based testing with linkage interventions in sub-Saharan Africa, to show how lay counsellor home HIV testing and counselling (home HTC) with follow-up support leads to linkage to clinic-based HIV treatment and medical male circumcision services. Methods We conducted 99 semi-structured individual interviews with study participants and three focus groups with 16 lay counsellors in Kabwohe, Sheema District, Uganda. The participant sample included both HIV+ men and women (N=47) and HIV-uncircumcised men (N=52). Interview and focus group audio-recordings were translated and transcribed. Each transcript was summarized. The summaries were analyzed inductively to identify emergent themes. Thematic concepts were grouped to develop general constructs and framing propositional statements. Results Trial participants expressed interest in linking to clinic-based services at testing, but faced obstacles that eroded their initial enthusiasm. Follow-up support by lay counsellors intervened to restore interest and inspire action. Together, home HTC and follow-up support improved morale, created a desire to reciprocate, and provided reassurance that services were trustworthy. In different ways, these functions built links to the health service system. They worked to strengthen individuals’ general sense of capability, while making the idea of accessing services more manageable and familiar, thus reducing linkage barriers. Conclusions Home HTC with follow

  3. Emergency Linkage Mode of Power Enterprise

    OpenAIRE

    Feng Jie; Yu Zhen; Liu Chao

    2016-01-01

    Power emergency disposal needs take full advantage of the power enterprise within the external emergency power and resources. Based on analyzing and summarizing the relevant experience of domestic and foreign emergency linkage, this paper draws the Emergency Linkage subjects, Emergency Linkage contents, Emergency Linkage level, which are three key elements if power enterprise Emergency Linkage. Emergency Linkage subjects are divided into the two types of inner subjects and the external body; ...

  4. The first-generation Daphnia magna linkage map

    Directory of Open Access Journals (Sweden)

    De Meester Luc

    2010-09-01

    Full Text Available Abstract Background Daphnia magna is a well-established model species in ecotoxicology, ecology and evolution. Several new genomics tools are presently under development for this species; among them, a linkage map is a first requirement for estimating the genetic background of phenotypic traits in quantitative trait loci (QTL studies and is also very useful in assembling the genome. It also enables comparative studies between D. magna and D. pulex, for which a linkage map already exists. Results Here we describe the first genetic linkage map of D. magna. We generated 214 F2 (intercross clonal lines as the foundation of the linkage analysis. The linkage map itself is based on 109 microsatellite markers, which produced ten major linkage groups ranging in size from 31.1 cM to 288.5 cM. The total size of this linkage map extends to 1211.6 Kosambi cM, and the average interval for the markers within linkage groups is 15.1 cM. The F2 clones can be used to map QTLs for traits that differ between the parental clones. We successfully mapped the location of two loci with infertility alleles, one inherited from the paternal clone (Iinb1 and the other from the maternal clone (Xinb3. Conclusions The D. magna linkage map presented here provides extensive coverage of the genome and a given density of markers that enable us to detect QTLs of moderate to strong effects. It is similar in size to the linkage map of D. pulex.

  5. POC CD4 Testing Improves Linkage to HIV Care and Timeliness of ART Initiation in a Public Health Approach: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Lara Vojnov

    Full Text Available CD4 cell count is an important test in HIV programs for baseline risk assessment, monitoring of ART where viral load is not available, and, in many settings, antiretroviral therapy (ART initiation decisions. However, access to CD4 testing is limited, in part due to the centralized conventional laboratory network. Point of care (POC CD4 testing has the potential to address some of the challenges of centralized CD4 testing and delays in delivery of timely testing and ART initiation. We conducted a systematic review and meta-analysis to identify the extent to which POC improves linkages to HIV care and timeliness of ART initiation.We searched two databases and four conference sites between January 2005 and April 2015 for studies reporting test turnaround times, proportion of results returned, and retention associated with the use of point-of-care CD4. Random effects models were used to estimate pooled risk ratios, pooled proportions, and 95% confidence intervals.We identified 30 eligible studies, most of which were completed in Africa. Test turnaround times were reduced with the use of POC CD4. The time from HIV diagnosis to CD4 test was reduced from 10.5 days with conventional laboratory-based testing to 0.1 days with POC CD4 testing. Retention along several steps of the treatment initiation cascade was significantly higher with POC CD4 testing, notably from HIV testing to CD4 testing, receipt of results, and pre-CD4 test retention (all p<0.001. Furthermore, retention between CD4 testing and ART initiation increased with POC CD4 testing compared to conventional laboratory-based testing (p = 0.01. We also carried out a non-systematic review of the literature observing that POC CD4 increased the projected life expectancy, was cost-effective, and acceptable.POC CD4 technologies reduce the time and increase patient retention along the testing and treatment cascade compared to conventional laboratory-based testing. POC CD4 is, therefore, a useful tool

  6. North-South Business Linkages

    DEFF Research Database (Denmark)

    Sørensen, Olav Jull; Kuada, John

    2006-01-01

    Based on empirical studies of linkages between TNCs and local firms in India, Malaysia, Vietnam, Ghana and South Africa, five themes are discussed and related to present theoretical perspectives. The themes are (1) Linakge Governance; (2) Globalisation and the dynamics in developing countries (the...... TNC-driven markets in developing countries); (3) The upgrading impact of FDI; (4) Non-equity linkages as a platform for business development, and (5) The learning perspective on international business linakges. The chapter offers at the end a three-dimanional model for impacts of business linkages....

  7. Linkage analysis of congenital nuclear cataract and DLAD locus%先天性核性白内障家系DLAD基因的连锁分析

    Institute of Scientific and Technical Information of China (English)

    陈琳琳; 唐爱兰; 张学; 张劲松

    2005-01-01

    目的:为进一步确定DLAD基因缺陷与人类白内障发生的关系.方法:对6个先天性白内障家系进行临床遗传学分析,然后进行连锁分析.结果:D1 S551和D1 S3471(GATA65B07)引物两点LOD值均为负值.结论:该6个家系的先天性白内障的发生与DLAD基因缺陷无关.%· AIM: DLAD (DnaseII-like acid Dnase) is an acid DNase that is highly expressed in human and murine lens fibre cells. Recently, the DLAD-/- mice with a deficience in DLAD gene were reported to develop nuclear cataract.To elucidate whether a deficient DLAD gene can cause some human cataract, we studied autosomal dominant nuclear catarat in 6 families and analysed linkage between cataract and DLAD locus.·METHODS: Two-point Lod score values were obtained for markers D1S551 and GATA65B07.· RESULTS: The results show negative Lod scores (z=-∞ at θ =0), so linkage was excluded between the defect and DLAD locus in these families.·CONCLUSION: no evidence for cataracts in these families linkage to chromosome 1p22.3, the DLAD locus.

  8. Resource linkages and sustainable development

    Science.gov (United States)

    Anouti, Yahya

    prices we estimate that the demand for gasoline could be reduced by 7.8 percent and that of diesel by 5.9 percent. This would lead to not only reduction in the associated negative externalities, but also to the generation of more than USD400 billion in revenues for governments. However, the partial equilibrium analysis in essay one ignores the general equilibrium effects that will be mainly driven by how the government spends the subsidy. In essay 2, we build the case for phasing out these subsidies and accompanying that by a welfare compensating cash transfer. In order to evaluate the impact of that on consumer's welfare, we develop a numerical model for Saudi Arabia in a general equilibrium setting to discuss a phase out of transport fuel subsidies that is. Results show that the Saudi government can increase its consumers' welfare up to five percentage points. In case the cash transfer is adjusted to keep consumers' utility at the pre-reform level, the required compensating transfer would leave the government with three percentage points of additional revenues. Finally, we highlight policy implications of phasing out the transport fuel subsidies. Finally, in essay 3 we turn our focus to the application of local content policies in the oil and gas sector. There is limited literature that investigates economic linkages from the extractive industries, assesses intertemporal tradeoffs, and guides the design of efficient and sustainable policies. Our contribution in this essay is three-fold. First, we present the first comprehensive analysis of economic linkages from the oil and gas sector across 48 countries. Then, we analyze the economic distortions from applying local content policies using a Hotelling type optimal control model with an international oil company maximizing its profits subject to a local content requirement. Finally, we investigate the presence of a socially optimal local content level when the social planner maximizing the net benefits from the

  9. Emergency Linkage Mode of Power Enterprise

    Directory of Open Access Journals (Sweden)

    Feng Jie

    2016-01-01

    Full Text Available Power emergency disposal needs take full advantage of the power enterprise within the external emergency power and resources. Based on analyzing and summarizing the relevant experience of domestic and foreign emergency linkage, this paper draws the Emergency Linkage subjects, Emergency Linkage contents, Emergency Linkage level, which are three key elements if power enterprise Emergency Linkage. Emergency Linkage subjects are divided into the two types of inner subjects and the external body; Emergency Linkage contents are in accordance with four phases of prevention, preparedness, response and recovery; Emergency Linkage level is divided into three levels of enterprise headquarter, provincial enterprise and incident unite. Binding power enterprise emergency management practice, this paper studies the internal Emergency Linkage modes (including horizontal mode and vertical mode, external Emergency Linkage mode and comprehensive Emergency Linkage Mode of power enterprise based on Fishbone Diagram and Process Management Technology.

  10. From Enclave to Linkage Economies?

    DEFF Research Database (Denmark)

    Hansen, Michael W.

    If African developing countries are to benefit fully from the current boom in foreign direct investment (FDI) in extractives (i.e. mining and oil/gas), it is essential that the foreign investors foster linkages to the local economy. Traditionally, extractive FDI in Africa has been seen as the enc......If African developing countries are to benefit fully from the current boom in foreign direct investment (FDI) in extractives (i.e. mining and oil/gas), it is essential that the foreign investors foster linkages to the local economy. Traditionally, extractive FDI in Africa has been seen...... as the enclave economy par excellence, moving in with fully integrated value chains, extracting resources and exporting them as commodities having virtually no linkages to the local economy. However, new opportunities for promoting linkages are offered by changing business strategies of local African enterprises...

  11. A linkage study of candidate loci in familial Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Westerberg Lisa

    2003-07-01

    Full Text Available Abstract Background Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease. Most cases are sporadic, however familial cases do exist. We examined 12 families with familial Parkinson's disease ascertained at the Movement Disorder clinic at the Oregon Health Sciences University for genetic linkage to a number of candidate loci. These loci have been implicated in familial Parkinson's disease or in syndromes with a clinical presentation that overlaps with parkinsonism, as well as potentially in the pathogenesis of the disease. Methods The examined loci were PARK3, Parkin, DRD (dopa-responsive dystonia, FET1 (familial essential tremor, BDNF (brain-derived neurotrophic factor, GDNF (glial cell line-derived neurotrophic factor, Ret, DAT1 (the dopamine transporter, Nurr1 and Synphilin-1. Linkage to the α-synuclein gene and the Frontotemporal dementia with parkinsonism locus on chromosome 17 had previously been excluded in the families included in this study. Using Fastlink, Genehunter and Simwalk both parametric and model-free non-parametric linkage analyses were performed. Results In the multipoint parametric linkage analysis lod scores were below -2 for all loci except FET1 and Synphilin-1 under an autosomal dominant model with incomplete penetrance. Using non-parametric linkage analysis there was no evidence for linkage, although linkage could not be excluded. A few families showed positive parametric and non-parametric lod scores indicating possible genetic heterogeneity between families, although these scores did not reach any degree of statistical significance. Conclusions We conclude that in these families there was no evidence for linkage to any of the loci tested, although we were unable to exclude linkage with both parametric and non-parametric methods.

  12. JLIN: A java based linkage disequilibrium plotter

    Directory of Open Access Journals (Sweden)

    McCaskie Pamela A

    2006-02-01

    Full Text Available Abstract Background A great deal of effort and expense are being expended internationally in attempts to detect genetic polymorphisms contributing to susceptibility to complex human disease. Techniques such as Linkage Disequilibrium mapping are being increasingly used to examine and compare markers across increasingly large datasets. Visualisation techniques are becoming essential to analyse the ever-growing volume of data and results available with any given analysis. Results JLIN (Java LINkage disequilibrium plotter is a software package designed for customisable, intuitive visualisation of Linkage Disequilibrium (LD across all common computing platforms. Customisation allows the user to choose particular visualisations, statistical measures and measurement ranges. JLIN also allows the user to export images of the LD visualisation in several common document formats. Conclusion JLIN allows the user to visually compare and contrast the results of a range of statistical measures on the input dataset(s. These measures include the commonly used D' and r2 statistics and empirical p-values. JLIN has a number of unique and novel features that improve on existing LD visualisation tools.

  13. HLA-B27 predicts a more extended disease with increasing age at onset in boys with juvenile idiopathic arthritis

    DEFF Research Database (Denmark)

    Berntson, Lillemor; Damgård, Michael; Andersson-Gäre, Boel;

    2008-01-01

    : HLA-B27 is of increasing importance with older age at disease onset in boys with JIA, predicting more active joints within the first 3 years of disease, and also involving small joints in the lower extremity to a greater degree than in HLA-B27-negative boys. During the first 3 years of disease......OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a heterogeneous condition with very few clinical and laboratory signs that can help predict the course and severity of the disease in the individual patient. The cell-surface antigen HLA-B27 is well known to be associated with spondyloarthropathies......, reactive arthritis, and enthesitis. HLA-B27 plays an important role in the classification of JIA, since evidence of sacroiliitis most often evolves after years of arthritis in other joints. We investigated the associations of HLA-B27 and the clinical manifestations of JIA using a method as close...

  14. Clinical characteristics and long-term response to mood stabilizers in patients with bipolar disorder and different age at onset

    OpenAIRE

    Bernardo Dell’Osso; Massimiliano Buoli; Riccardo Riundi; Nazario D’Urso; et al, ...

    2009-01-01

    Bernardo Dell’Osso1, Massimiliano Buoli1, Riccardo Riundi2, Nazario D’Urso1, Sara Pozzoli1, Roberta Bassetti2, Emanuela Mundo1,  A Carlo Altamura11Department of Psychiatry, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milano, Italy; 2Department of Clinical Sciences, Luigi Sacco, Milano, ItalyIntroduction: Bipolar disorder (BD) is a prevalent, comorbid, and impairing condition. Potential predictors of response to ...

  15. Association and linkage analysis of COL1A1 and AHSG gene polymorphisms with femoral neck bone geometric parameters in both Caucasian and Chinese nuclear families

    Institute of Scientific and Technical Information of China (English)

    Hui JIANG; Shu-feng LEI; Su-mei XIAO; Yuan CHEN; Xiao SUN; Fang YANG; Li-ming LI; Shun WU; Hong-wen DENC

    2007-01-01

    Aim: To simultaneously investigate the contribution of the alpha 1 chain of col-lagen type 1 (COL1A1) and alpha2-HS-glycoprotein (AHSG) genes to the varia-tion of bone geometric parameters in both Caucasians and Chinese. Methods: Six hundred and five Caucasian individuals from 157 nuclear families and 1228 Chi-nese subjects from 400 nuclear families were genotyped at the AHSG-Sacl, COL1A1-PCOL2 and Sp1 polymorphisms using polymerase chain reaction (PCR)-restric-tion fragment length polymorphism (RFLP). 5 FN bone geometric parameters were calculated based on bone mineral density and bone area of femoral neck (FN)measured by dual energy X-ray absorptiometry. Population stratification, total family association, within-family association, and linkage tests were performed by the quantitative transmission disequilibrium test program. Results: The t-test showed the significant differences of all bone geometric phenotypes (except ED)between Caucasians and Chinese in the offspring using both unadjusted and adjusted (by age, height, weight, and gender) data. In Caucasians, we found significant within-family association results between the COL1A1-Sp1 polymor-phism (rs1800012) and cross sectional area (CSA), cortical thickness (CT),endocortical diameter (ED), buckling ratio (BR) (P=0.018, 0.002, 0.023, and 0.001,respectively); the COL1A1-Sp1 polymorphism also detected significant linkage with BR (P=0.039). In the population of China, the within-family associations between the COL1A1-PCOL2 polymorphism (rs1107946) and CT, BR were signifi-cant (P=0.012 and 0.008, respectively). Furthermore, evidence of linkage were observed between the AHSG-SacI polymorphism (rs4918) and CT, BR (P--0.042 and 0.014, respectively) in Caucasians, but not in Chinese. Conclusion: Our results suggest that the COL1A1 gene may have significantly association with bone geometry in both Caucasians and Chinese, and the AHSG gene may be linked to bone geometry in Caucasians, but not in Chinese. This study

  16. Comprehensive analysis of APOE and selected proximate markers for late-onset Alzheimer's disease: patterns of linkage disequilibrium and disease/marker association.

    Science.gov (United States)

    Yu, Chang-En; Seltman, Howard; Peskind, Elaine R; Galloway, Nichole; Zhou, Peter X; Rosenthal, Elisabeth; Wijsman, Ellen M; Tsuang, Debby W; Devlin, Bernie; Schellenberg, Gerard D

    2007-06-01

    The epsilon(4) allele of APOE confers a two- to fourfold increased risk for late-onset Alzheimer's disease (LOAD), but LOAD pathology does not all fit neatly around APOE. It is conceivable that genetic variation proximate to APOE contributes to LOAD risk. Therefore, we investigated the degree of linkage disequilibrium (LD) for a comprehensive set of 50 SNPs in and surrounding APOE using a substantial Caucasian sample of 1100 chromosomes. SNPs in APOE were further molecularly haplotyped to determine their phases. One set of SNPs in TOMM40, roughly 15 kb upstream of APOE, showed intriguing LD with the epsilon(4) allele and was strongly associated with the risk for developing LOAD. However, when all the SNPs were entered into a logit model, only the effect of APOE epsilon(4) remained significant. These observations diminish the possibility that loci in the TOMM40 gene may have a major effect on the risk for LOAD in Caucasians.

  17. Comprehensive Analysis of APOE and Selected Proximate Markers for Late-onset Alzheimer Disease: Pattern of Linkage Disequilibrium and Disease/Marker Association

    Science.gov (United States)

    Yu, Chang-En; Seltman, Howard; Peskind, Elaine R.; Galloway, Nichole; Zhou, Peter X.; Rosenthal, Elisabeth; Wijsman, Ellen M.; Tsuang, Debby W.; Devlin, Bernie; Schellenberg, Gerard D.

    2007-01-01

    The ε4 allele of APOE confers a two- to four-fold increased risk for late-onset Alzheimer’s disease (LOAD), but LOAD pathology does not all fit neatly around APOE. It is conceivable that genetic variation proximate to APOE contributes to LOAD risk. Therefore, we investigated the degree of linkage disequilibrium (LD) for a comprehensive set of 50 SNPs in and surrounding the APOE using a substantial Caucasian sample of 1100 chromosomes. SNPs in APOE were further molecular haplotyped to determine their phases. One set of SNPs in TOMM40, roughly 15 Kb upstream of APOE, showed intriguing LD with the ε4 allele, and were strongly associated with the risk for developing AD. However, when all the SNPs were entered into a logit model, only the effect of APOE ε4 remained significant. These observations diminish the possibility that loci in the TOMM40 may have a major effect on the risk of LOAD in Caucasians. PMID:17434289

  18. Data Linkage: A powerful research tool with potential problems

    Directory of Open Access Journals (Sweden)

    Scott Ian

    2010-12-01

    Full Text Available Abstract Background Policy makers, clinicians and researchers are demonstrating increasing interest in using data linked from multiple sources to support measurement of clinical performance and patient health outcomes. However, the utility of data linkage may be compromised by sub-optimal or incomplete linkage, leading to systematic bias. In this study, we synthesize the evidence identifying participant or population characteristics that can influence the validity and completeness of data linkage and may be associated with systematic bias in reported outcomes. Methods A narrative review, using structured search methods was undertaken. Key words "data linkage" and Mesh term "medical record linkage" were applied to Medline, EMBASE and CINAHL databases between 1991 and 2007. Abstract inclusion criteria were; the article attempted an empirical evaluation of methodological issues relating to data linkage and reported on patient characteristics, the study design included analysis of matched versus unmatched records, and the report was in English. Included articles were grouped thematically according to patient characteristics that were compared between matched and unmatched records. Results The search identified 1810 articles of which 33 (1.8% met inclusion criteria. There was marked heterogeneity in study methods and factors investigated. Characteristics that were unevenly distributed among matched and unmatched records were; age (72% of studies, sex (50% of studies, race (64% of studies, geographical/hospital site (93% of studies, socio-economic status (82% of studies and health status (72% of studies. Conclusion A number of relevant patient or population factors may be associated with incomplete data linkage resulting in systematic bias in reported clinical outcomes. Readers should consider these factors in interpreting the reported results of data linkage studies.

  19. Resource linkages and sustainable development

    Science.gov (United States)

    Anouti, Yahya

    prices we estimate that the demand for gasoline could be reduced by 7.8 percent and that of diesel by 5.9 percent. This would lead to not only reduction in the associated negative externalities, but also to the generation of more than USD400 billion in revenues for governments. However, the partial equilibrium analysis in essay one ignores the general equilibrium effects that will be mainly driven by how the government spends the subsidy. In essay 2, we build the case for phasing out these subsidies and accompanying that by a welfare compensating cash transfer. In order to evaluate the impact of that on consumer's welfare, we develop a numerical model for Saudi Arabia in a general equilibrium setting to discuss a phase out of transport fuel subsidies that is. Results show that the Saudi government can increase its consumers' welfare up to five percentage points. In case the cash transfer is adjusted to keep consumers' utility at the pre-reform level, the required compensating transfer would leave the government with three percentage points of additional revenues. Finally, we highlight policy implications of phasing out the transport fuel subsidies. Finally, in essay 3 we turn our focus to the application of local content policies in the oil and gas sector. There is limited literature that investigates economic linkages from the extractive industries, assesses intertemporal tradeoffs, and guides the design of efficient and sustainable policies. Our contribution in this essay is three-fold. First, we present the first comprehensive analysis of economic linkages from the oil and gas sector across 48 countries. Then, we analyze the economic distortions from applying local content policies using a Hotelling type optimal control model with an international oil company maximizing its profits subject to a local content requirement. Finally, we investigate the presence of a socially optimal local content level when the social planner maximizing the net benefits from the

  20. Linkage analysis of water use among industrial sectors in China%我国行业水资源消耗的关联度分析

    Institute of Scientific and Technical Information of China (English)

    和夏冰; 王媛; 张宏伟; 王文琴; 王丽丽

    2012-01-01

    The aim of this paper was to study the behaviour of the productive sectors of the Chinese economy as direct and indirect consumers of water. Industrial water consumption linkages analysis was empolyed, based on hypothetical extraction method. By comparing the direct water consumption with vertical integrated water consumption based on the input-output data of water utilization in 2007 in China, direct water consumption of each sector was not equal to water required to meet final demand of itself. In view of the economy, the total of direct water consumption of all sectors was equivalent to the total of water required to meet final demand of themselves. Water resource transferred among productive sectors. In the supply-chain, upstream sectors such as agriculture and basic industry, met their final demand by the internal exchange of production, and transferred a large number of water resource to their downstream sectors by intermediate input. On the contrary, downstream sectors such as light industry and high-technology industry, transferred a great quantity of water resource from their upstream sectors, because their direct water consumption was unable to meet the final demand. In this way, water resource was transferred from upstream to downstream step by step to maintain the production and exchange in economy. If the final demand did not have a change, industrial restructuring was just to divert the sector with a high-water-consumption from a place to the other. Therefore, the total water consumption of the economy did not have a change. This paper revealed the regular of industrial water consumption so as to provide a fresh perspective of structure adjustment and more scientific basis of policy-making.%选取2007年相关数据进行整理分析,应用基于假设抽取法的水资源消耗产业关联度计量模型,比较各行业水资源的直接消耗和纵向集成消耗,定量测算出我国行业间水资源的流动转移情况.通过分析得到:不同

  1. 实用新型收割机切割机构的运动分析与仿真%Kinematics Analysis and Simulation of A New Spatial Linkages Cutter

    Institute of Scientific and Technical Information of China (English)

    孙书民; 柯坚; 王进戈; 王强

    2012-01-01

    A new spatial linkage mechanism was designed for three dimensional modeling construction and motion mechanism analysis in terms of current defects in traditional cutter transmission device which adopted gear mechanism combining with planar crank-rocker mechanism. The output displacement, speed and acceleration equation of motion were obtained, and the motion diagrams of cutter using spatial linkages mechanism were simulated. The simulation results showed that the mechanism could achieve the smooth output of the cutter, it would establish the basis for the next dimensional synthesis.%针对传统切割器传动装置采用齿轮机构和平面曲柄摇杆机构相结合方式的缺点,提出了采用实用空间连杆机构,对机构进行了三维建模和运动分析,得到了输出的位移、速度、加速度运动方程,并通过仿真得到了运动曲线.仿真结果显示,该机构可以实现割刀的平稳输出,为以后的机构尺寸综合打下了基础.

  2. Record-linkage for pharmacovigilance in Scotland

    OpenAIRE

    Evans, Josie M M; MacDonald, Thomas M

    1999-01-01

    Record-linkage is the linkage of patient-specific information that is stored separately. Recent advances in computerization have meant that record-linkage techniques in medical research are increasingly being used and refined. In particular, they have made a significant contribution to pharmacovigilance, which involves linking drug exposure to outcomes data. In this article, the contribution of record-linkage in Scotland to medical research is described. The two organizations that utilize rec...

  3. Genotyping by Sequencing for SNP-Based Linkage Map Construction and QTL Analysis of Chilling Requirement and Bloom Date in Peach [Prunus persica (L. Batsch].

    Directory of Open Access Journals (Sweden)

    Douglas Gary Bielenberg

    Full Text Available Low-cost, high throughput genotyping methods are crucial to marker discovery and marker-assisted breeding efforts, but have not been available for many 'specialty crops' such as fruit and nut trees. Here we apply the Genotyping-By-Sequencing (GBS method developed for cereals to the discovery of single nucleotide polymorphisms (SNPs in a peach F2 mapping population. Peach is a genetic and genomic model within the Rosaceae and will provide a template for the use of this method with other members of this family. Our F2 mapping population of 57 genotypes segregates for bloom time (BD and chilling requirement (CR and we have extensively phenotyped this population. The population derives from a selfed F1 progeny of a cross between 'Hakuho' (high CR and 'UFGold' (low CR. We were able to successfully employ GBS and the TASSEL GBS pipeline without modification of the original methodology using the ApeKI restriction enzyme and multiplexing at an equivalent of 96 samples per Illumina HiSeq 2000 lane. We obtained hundreds of SNP markers which were then used to construct a genetic linkage map and identify quantitative trait loci (QTL for BD and CR.

  4. The clinical characteristics of a pedigree with incompletely penetrated autosomal dominant hereditary spastic paraplegia and its exclusion analysis of genetic loci%不完全外显的遗传性痉挛性截瘫一家系临床与致病基因排除定位分析

    Institute of Scientific and Technical Information of China (English)

    赵国华; 任志军; 刘小民; 李书剑; 郭鹏; 沈璐; 夏昆; 唐北沙

    2008-01-01

    Objective To describe the clinical features of a big family with ineompletely penetrated autosomal dominant hereditary spastic paraplegia(SPG) and perform the exclusion analysis of genetic loci.Methods The clinical information of this SPG family was analyzed retmspecfively.Exclusion analysis of the known autosomal dominant SPG loci was performed by using rnltiplex fluorescence PCR, capillary electrophoresis and Linkage package. Results There were eleven affected members available in this SPG family and the age at onset ranged from 2 to 10 years.The first symptoms were a bilateral,symmetrical,progressive lower limb weakness and spasticity.Patients presented with spastieity and hyperrdlexia,positive Babinski sign and scissors gait,and the upper limbs were involved more seveiely than the lower limbs.No urinary inconsistence,sensory impairment,nystagmus and dementia were found.Genetic analyfis showed that this family was consistent with autosomal dominant inheritance.The linkage analysis and mutation analysis revealed this family was not linked to the known autosomal dominant loci.Conclusion This SPG family had typical"pure"clinical symptoms.The age at onset Was early and the signs in the upper limbs were more obvious than those in the lower limbs.The result of linkage analysis shows that this family represents a new SPG subtype.%目的 描述一个遗传了4代的不完全外显的遗传性痉挛性截瘫(hereditary spastic paraplegia,SPG)大家系的临床特征,并进行致病基因排除定位分析.方法 对SPG家系内11例患者的临床资料进行回顾性分析,并采用荧光多重PCR、毛细管凝胶电泳、Linkage软件包,选择对已定位常染色体显性遗传致病基因位点附近微卫星标记进行连锁分析.结果 该SPG家系的11例患者的发病年龄2~10岁,表现为缓慢进展的双下肢僵硬无力,四肢肌张力轻度增高,双上肢为主的腱反射亢进,剪刀步态和病理征阳性,无小便失禁或尿频、感觉障

  5. Linkage of PRA models. Phase 1, Results

    International Nuclear Information System (INIS)

    The goal of the Phase I work of the ''Linkage of PRA Models'' project was to postulate methods of providing guidance for US Nuclear Regulator Commission (NRC) personnel on the selection and usage of probabilistic risk assessment (PRA) models that are best suited to the analysis they are performing. In particular, methods and associated features are provided for (a) the selection of an appropriate PRA model for a particular analysis, (b) complementary evaluation tools for the analysis, and (c) a PRA model cross-referencing method. As part of this work, three areas adjoining ''linking'' analyses to PRA models were investigated: (a) the PRA models that are currently available, (b) the various types of analyses that are performed within the NRC, and (c) the difficulty in trying to provide a ''generic'' classification scheme to groups plants based upon a particular plant attribute

  6. The EU’s Trade Relations with China (1975-2008): A Linkage Power at Work?

    OpenAIRE

    Zhang, Xiaotong

    2010-01-01

    The EU’s Trade Relations with China (1975-2008): A Linkage Power at Work?(Summary)The central aim of this thesis is to improve our understanding of the EU’s power, in particular in its external trade relations/negotiations. Our hypothesis is that the EU is a distinctive kind of linkage power, defined as an actor relying on linkage as a crucial modus operandi in its external relations. We explored how, to what extent and in which distinctive ways the EU is such a linkage power. Our analysis wa...

  7. Synthesis of Intermittent-Motion Linkages with Slight Difference in Length Between Links

    Institute of Scientific and Technical Information of China (English)

    CHEN Xin-bo; YU Zhen

    2006-01-01

    The design of intermittent-motion linkages using traditional methods iS usually complicated.In this paper,(1)a new method for realizing intermittent motion,using linkages with a slight difference in length between links,is studied;(2)some new types of intermittent-motion linkages and their software for visual analysis and design are developed;and(3)influences of some design parameters on intermittent.motion characteristics are clarifled.Results confirmed that the theory and the software are useful,making the synthesis of intermittent-motion linkages clear and easy.

  8. 家族性高甘油三酯血症家系的候选基因位点连锁分析%Linkage analysis of a family with familial hypertriglyceriridemia

    Institute of Scientific and Technical Information of China (English)

    唐新; 林婴; 刘兵; 马誓; 杨洋; 杨正林

    2009-01-01

    Objective To perform linkage analysis and mutation screening in a Chinese family with familial hpertriglyceridemia (FHTG). Method Thirty two family members including 12 hypertriglyceridemia patients participated in the study. Genotyping and haplotype analysis for 22 subjects were performed using short tandem repeat (STR) microsatellite polymorphism markers on 16 candidate genes and/or loci related to lipid metabolism. Two of the sixteen known candidate genes, APOA2 and USF1 were screened for mutation by direct DNA sequencing. Result No linkage was found between the candidate genes/loci of APOA5, LIPI, RP1, APOC2, ABC1, LMF1, APOA1-APOC3-APOA4, LPL, APOB,CETP, LCAT, LDLR, APOE and the phenotype in this family. The two-point Lod scores (θ=0) were all less than-1.0 for all the markers tested. Linkage analysis suggested linkage to chromosome 1q23.3-24.2 between the disease phenotype and STR marker D1S194 with a two-point maximum Lod score of 2.44 at θ=0. Fine mapping indicated that the disease gene was localized to a 5.87 cM interval between D1S104 and D1S196. No disease-causing mutation was detected in the APOA2 and USF1 genes. Conclusion The above mentioned candidate genes were excluded as the disease causing genes for this family. The results implied that there might be a novel gene/locus for FHTG on chromosome 1q23.3-1q24.2.%目的 对一个家族性高甘油三酯血症(familial hypertriglyceridemia,FHTG)家系进行遗传连锁定位及基因突变分析.方法 32名家系成员,其中12例为高甘油三酯血症(hypertriglyceridemia)患者.应用短串联重复(short tandem repeat,STR)片段微卫星标记物对其中的22名成员进行了16个与脂代谢有关的候选基因和(或)位点的遗传连锁分析和单倍型分析,并对其中的两个候选基因APOA2和USF1直接测序以筛查突变.结果 APOA5、LIPI、RP1、APOC2、ABC1,LMF1、APOA1-APOC3-APOA4、LPL,APOB、CETP、LCAT,LDLR,APOE等候选基因位点与该家

  9. A genetic linkage map of the Durum x Triticum dicoccoides backcross population based on SSRs and AFLP markers, and QTL analysis for milling traits.

    Science.gov (United States)

    Elouafi, I; Nachit, M M

    2004-02-01

    Durum wheat ( Triticum turgidum L. var durum) is mainly produced and consumed in the Mediterranean region; it is used to produce several specific end-products; such as local pasta, couscous and burghul. To study the genetics of grain-milling quality traits, chromosomal locations, and interaction with the environment, a genetic linkage map of durum was constructed and the quantitative trait loci QTLs for the milling-related traits, test weight (TW) and thousand-kernel weight (TKW), were identified. The population constituted 114 recombinant inbred lines derived from the cross: Omrabi 5 /Triticum dicoccoides 600545// Omrabi 5. TW and TKW were analyzed over 18 environments (sites x years). Single-sequence-repeat markers (SSRs), Amplified-fragment-length-polymorphism markers (AFLPs), and seed storage proteins (SSPs) showed a high level of polymorphism (>60%). The map was constructed with 124 SSRs, 149 AFLPs and 6 SSPs; its length covered 2,288.8 cM (8.2 cM/marker). The map showed high synteny with previous wheat maps, and both SSRs and AFLPs mapped evenly across the genome, with more markers in the B genome. However, some rearrangements were observed. For TW, a high genotypic effect was detected and two QTLs with epistasic effect were identified on 7AS and 6BS, explaining 30% of the total variation. The TKW showed a significant transgressive inheritance and five QTLs were identified, explaining 32% of the total variation, out of which 25% was of a genetic nature, and showing QTLxE interaction. The major TKW-QTLs were around the centromere region of 6B. For both traits, Omrabi 5 alleles had a significant positive effect. This population will be used to determine other QTLs of interest, as its parents are likely to harbor different genes for diseases and drought tolerance. PMID:14676946

  10. Presentation, heritability, and genome-wide linkage analysis of the midchildhood growth spurt in healthy children from the Fels Longitudinal Study.

    Science.gov (United States)

    Towne, Bradford; Williams, Kimberly D; Blangero, John; Czerwinski, Stefan A; Demerath, Ellen W; Nahhas, Ramzi W; Dyer, Thomas D; Cole, Shelley A; Lee, Miryoung; Choh, Audrey C; Duren, Dana L; Sherwood, Richard J; Chumlea, William Cameron; Siervogel, Roger M

    2008-12-01

    Growth is a complex process composed of distinct phases over the course of childhood. Although the pubertal growth spurt has received the most attention from auxologists and pediatricians, the midchildhood growth spurt has been less well studied. The midchildhood growth spurt refers to a relatively small increase in growth velocity observed in some, but not necessarily all, children in early to middle childhood. If present, the midchildhood growth spurt typically occurs sometime between the ages of 4 and 8 years, well before the onset of the far more pronounced pubertal growth spurt. In this study we used a triple logistic curve-fitting method to fit individual growth curves to serial stature data from 579 healthy participants in the Fels Longitudinal Study, 479 of whom have been genotyped for about 400 short tandem repeat (STR) markers spanning the genome. We categorized individuals according to the presence or absence of a midchildhood growth spurt and then conducted heritability and genome-wide linkage analyses on the dichotomous trait. In the total sample of 579 individuals, 336 (58%) were found to have evidence of having had a midchildhood growth spurt. There was a marked sex difference in presence of the midchildhood growth spurt, however, with 232 of the 293 males (79%) having had a midchildhood growth spurt but just 104 of the 286 females (36%) having had one. Presence of a midchildhood growth spurt was found to have a significant heritability of 0.37 +/- 0.14 (p = 0.003). Two quantitative trait loci with suggestive LOD scores were found: one at 12 cM on chromosome 17p13.2 (LOD = 2.13) between markers D17S831 and D17S938 and one at 85 cM on chromosome 12q14 (LOD = 2.06) between markers D12S83 and D12S326. PMID:19728540

  11. 插床六杆机构运动学和静力学分析%Kinematics and statics analysis for six bar linkage in slotting machine

    Institute of Scientific and Technical Information of China (English)

    叶素娣; 徐敬华

    2015-01-01

    In the slotting machine the slotting tool moved up and down which is directly related to the cutting efficiency for work-piece. The vector model of slotting machine six bar linkage is established,matlab/simulink integral module method is used to establish the simulation diagram,reasonable initial conditions are set up to visualize displacement,velocity and acceleration curve. The friction force is always tangent to the friction circle,and its moment to hinge center is contrary to the relative angular velocity,the static equi-librium equations are solved of each components. Ultimately the active parts should be applied to the driving moment on the law of the change over time.%插床中插刀的上下往复运动直接关系到工件切削的效率。建立插床六杆机构的矢量模型,用Matlab/Simulink中的积分模块建立仿真框图,设置合理的初始条件,将插刀的位移、速度和加速度曲线规律可视化。对机构作计及摩擦力的静力分析,通过摩擦圆和相对角速度判断运动副所受摩擦总反力的方向,依次求解各个构件的静力平衡方程式,得出主动件上所能克服的等效阻力矩,并用Matlab软件得出等效阻力矩随时间变化的规律。

  12. Changes in satellite-derived spring vegetation green-up date and its linkage to climate in China from 1982 to 2010: a multimethod analysis.

    Science.gov (United States)

    Cong, Nan; Wang, Tao; Nan, Huijuan; Ma, Yuecun; Wang, Xuhui; Myneni, Ranga B; Piao, Shilong

    2013-03-01

    The change in spring phenology is recognized to exert a major influence on carbon balance dynamics in temperate ecosystems. Over the past several decades, several studies focused on shifts in spring phenology; however, large uncertainties still exist, and one understudied source could be the method implemented in retrieving satellite-derived spring phenology. To account for this potential uncertainty, we conducted a multimethod investigation to quantify changes in vegetation green-up date from 1982 to 2010 over temperate China, and to characterize climatic controls on spring phenology. Over temperate China, the five methods estimated that the vegetation green-up onset date advanced, on average, at a rate of 1.3 ± 0.6 days per decade (ranging from 0.4 to 1.9 days per decade) over the last 29 years. Moreover, the sign of the trends in vegetation green-up date derived from the five methods were broadly consistent spatially and for different vegetation types, but with large differences in the magnitude of the trend. The large intermethod variance was notably observed in arid and semiarid vegetation types. Our results also showed that change in vegetation green-up date is more closely correlated with temperature than with precipitation. However, the temperature sensitivity of spring vegetation green-up date became higher as precipitation increased, implying that precipitation is an important regulator of the response of vegetation spring phenology to change in temperature. This intricate linkage between spring phenology and precipitation must be taken into account in current phenological models which are mostly driven by temperature.

  13. Genome-Wide SNP Linkage Mapping and QTL Analysis for Fiber Quality and Yield Traits in the Upland Cotton Recombinant Inbred Lines Population.

    Science.gov (United States)

    Li, Cong; Dong, Yating; Zhao, Tianlun; Li, Ling; Li, Cheng; Yu, En; Mei, Lei; Daud, M K; He, Qiuling; Chen, Jinhong; Zhu, Shuijin

    2016-01-01

    It is of significance to discover genes related to fiber quality and yield traits and tightly linked markers for marker-assisted selection (MAS) in cotton breeding. In this study, 188 F8 recombinant inbred lines (RILs), derived from a intraspecific cross between HS46 and MARCABUCAG8US-1-88 were genotyped by the cotton 63K single nucleotide polymorphism (SNP) assay. Field trials were conducted in Sanya, Hainan Province, during the 2014-2015 cropping seasons under standard conditions. Results revealed significant differences (P < 0.05) among RILs, environments and replications for fiber quality and yield traits. Broad-sense heritabilities of all traits including fiber length, fiber uniformity, micronaire, fiber elongation, fiber strength, boll weight, and lint percentage ranged from 0.26 to 0.66. A 1784.28 cM (centimorgans) linkage map, harboring 2618 polymorphic SNP markers, was constructed, which had 0.68 cM per marker density. Seventy-one quantitative trait locus (QTLs) for fiber quality and yield traits were detected on 21 chromosomes, explaining 4.70∼32.28% phenotypic variance, in which 16 were identified as stable QTLs across two environments. Meanwhile, 12 certain regions were investigated to be involved in the control of one (hotspot) or more (cluster) traits, mainly focused on Chr05, Chr09, Chr10, Chr14, Chr19, and Chr20. Nineteen pairs of epistatic QTLs (e-QTLs) were identified, of which two pairs involved in two additive QTLs. These additive QTLs, e-QTLs, and QTL clusters were tightly linked to SNP markers, which may serve as target regions for map-based cloning, gene discovery, and MAS in cotton breeding. PMID:27660632

  14. Genome-Wide SNP Linkage Mapping and QTL Analysis for Fiber Quality and Yield Traits in the Upland Cotton Recombinant Inbred Lines Population

    Science.gov (United States)

    Li, Cong; Dong, Yating; Zhao, Tianlun; Li, Ling; Li, Cheng; Yu, En; Mei, Lei; Daud, M. K.; He, Qiuling; Chen, Jinhong; Zhu, Shuijin

    2016-01-01

    It is of significance to discover genes related to fiber quality and yield traits and tightly linked markers for marker-assisted selection (MAS) in cotton breeding. In this study, 188 F8 recombinant inbred lines (RILs), derived from a intraspecific cross between HS46 and MARCABUCAG8US-1-88 were genotyped by the cotton 63K single nucleotide polymorphism (SNP) assay. Field trials were conducted in Sanya, Hainan Province, during the 2014–2015 cropping seasons under standard conditions. Results revealed significant differences (P < 0.05) among RILs, environments and replications for fiber quality and yield traits. Broad-sense heritabilities of all traits including fiber length, fiber uniformity, micronaire, fiber elongation, fiber strength, boll weight, and lint percentage ranged from 0.26 to 0.66. A 1784.28 cM (centimorgans) linkage map, harboring 2618 polymorphic SNP markers, was constructed, which had 0.68 cM per marker density. Seventy-one quantitative trait locus (QTLs) for fiber quality and yield traits were detected on 21 chromosomes, explaining 4.70∼32.28% phenotypic variance, in which 16 were identified as stable QTLs across two environments. Meanwhile, 12 certain regions were investigated to be involved in the control of one (hotspot) or more (cluster) traits, mainly focused on Chr05, Chr09, Chr10, Chr14, Chr19, and Chr20. Nineteen pairs of epistatic QTLs (e-QTLs) were identified, of which two pairs involved in two additive QTLs. These additive QTLs, e-QTLs, and QTL clusters were tightly linked to SNP markers, which may serve as target regions for map-based cloning, gene discovery, and MAS in cotton breeding. PMID:27660632

  15. Linkage mapping bovine EST-based SNP

    Directory of Open Access Journals (Sweden)

    Bennett Gary L

    2005-05-01

    Full Text Available Abstract Background Existing linkage maps of the bovine genome primarily contain anonymous microsatellite markers. These maps have proved valuable for mapping quantitative trait loci (QTL to broad regions of the genome, but more closely spaced markers are needed to fine-map QTL, and markers associated with genes and annotated sequence are needed to identify genes and sequence variation that may explain QTL. Results Bovine expressed sequence tag (EST and bacterial artificial chromosome (BACsequence data were used to develop 918 single nucleotide polymorphism (SNP markers to map genes on the bovine linkage map. DNA of sires from the MARC reference population was used to detect SNPs, and progeny and mates of heterozygous sires were genotyped. Chromosome assignments for 861 SNPs were determined by twopoint analysis, and positions for 735 SNPs were established by multipoint analyses. Linkage maps of bovine autosomes with these SNPs represent 4585 markers in 2475 positions spanning 3058 cM . Markers include 3612 microsatellites, 913 SNPs and 60 other markers. Mean separation between marker positions is 1.2 cM. New SNP markers appear in 511 positions, with mean separation of 4.7 cM. Multi-allelic markers, mostly microsatellites, had a mean (maximum of 216 (366 informative meioses, and a mean 3-lod confidence interval of 3.6 cM Bi-allelic markers, including SNP and other marker types, had a mean (maximum of 55 (191 informative meioses, and were placed within a mean 8.5 cM 3-lod confidence interval. Homologous human sequences were identified for 1159 markers, including 582 newly developed and mapped SNP. Conclusion Addition of these EST- and BAC-based SNPs to the bovine linkage map not only increases marker density, but provides connections to gene-rich physical maps, including annotated human sequence. The map provides a resource for fine-mapping quantitative trait loci and identification of positional candidate genes, and can be integrated with other

  16. 一种磁链轨迹跟踪的PWM方法及其特性分析%PWM method of flux linkage trajectory tracking and analysis of its characteristics

    Institute of Scientific and Technical Information of China (English)

    吴德会; 柳振凉; 夏晓昊; 张忠远

    2013-01-01

    A frequency control underlying implementation of induction motor was suggested based on flux linkage trajectory tracking.By changing the operate mode of inverter,the actual flux linkage was produced to tracking the reference flux linkage circle,and the corresponding pulse width modulation (PWM) waveform was also generated.The basic theoretical computing equation was deduced,a specific control strategy was suggested,and the characteristics of the PWM waveform generated was analyzed.Simulations and experimental results show that the modulation index is up to 1,and the voltage utilization is same as SVPWM,while 15.47% higher than SPWM.Furthermore,the existence of error upper limit was verified,which provides a quantitative basis for further analysis of the accuracy.%提出一种基于磁链轨迹跟踪策略的电动机变频调速方法.该方法不通过空间电压矢量的合成,而直接通过实际磁链矢量来跟踪基准磁链圆轨迹,再由跟踪的结果决定逆变器的开关状态模式,从而实现对脉冲宽度调制(PWM)波的调制输出.对该方法的基本原理进行推导,给出具体的控制策略,并对其产生的PWM波形特性进行系统分析.仿真及物理实验结果表明,该方法幅度调制比可达到1,电压利用率与空间矢量脉宽调制(SVPWM)方法相同,比正弦波脉宽调制(SPWM)提高15.47%;同时验证了其跟踪误差上限的存在性,为进一步分析该方法精确度提供了定量依据.该方法为变频调速的底层实现提供了另一种可行的途径.

  17. Constructing Linkage Disequilibrium Map with Iterative Approach

    Science.gov (United States)

    Ao, S. I.

    2008-05-01

    With recent advance of the genotyping single nucleotide polymorphisms (SNPs) in mass scale of high density in a candidate region of the human genome, the linkage disequilibrium analysis can offer a much higher resolution of the biological samples than the traditional linkage maps. We have formulated this LD mapping problem as a constrained unidimensional scaling problem. Our method, which is directly based on the measurement of LD among SNPs, is non-parametric. Therefore it is different from LD maps derived from the given Malecot model. We have formulated with the quadratic programming approach for solving this constrained unidimensional scaling problem. Different from the classical metric unidimensional scaling problem, the constrained problem is not an NP-hard combinatorial problem. The optimal solution is determined by using the quadratic programming solver. Nevertheless, because of the large requirement for memory during the running time that may cause the out of memory problems, and the high computational time of the quadratic programming algorithm, the iterative algorithm has been developed for solving this LD constrained unidimensional scaling problem.

  18. A linkage study of bipolar disorder

    Energy Technology Data Exchange (ETDEWEB)

    Kelsoe, J.R. [Univ. of California, San Diego (United States); Sadovnick, A.D.; Remick, R.A. [Univ. of British Columbia, Vancouver (Canada)] [and others

    1994-09-01

    We are currently surveying the genome with polymorphic DNA markers in search of loci linked to bipolar disorder (manic-depressive illness) in three populations: 20 families (175 subjects) from the general North American population from San Diego (UCSD) and Vancouver (UBC); 3 Icelandic families (55 subjects); and an Old Order Amish pedigree 110 (118 subjects). Over 50 markers on chromosomes 1, 2, 5, 11, 17, 18, 20 and 21 have been examined. All markers have been tested in the Amish and Icelandic families, and a portion of them in the UCSD/UBC families, which we have only recently begun genotyping. The following candidate genes have been examined: {beta}-TSH, dopamine transporter (HDAT), {beta}2 adrenergic receptor (ADRB2), glucocorticoid type II receptor (GRL), D2 dopamine receptor, serotonin transporter (HSERT), and G{alpha}s G protein subunit (GNAS1). Linkage analysis was conducted using an autosomal dominant model with age-dependent reduced penetrance. Subjects with bipolar, schizoaffective, or recurrent major depressive disorders were considered affected. No significant evidence for linkage was obtained. Mildly positive lods ranging between 1.1 and 1.6 were obtained for three loci: D11S29, HDAT, and GRL.

  19. Linkages between NAMA - LEDS - MRV

    DEFF Research Database (Denmark)

    Agyemang-Bonsu, William; Benioff, Ron; Cox, Sadie;

    Low Emission Development Strategies (LEDS), Nationally Appropriate Mitigation Actions (NAMAs) and Monitoring, Reporting and Verification (MRV) are three of the key conceptual components emerging as part of the global architecture for a new climate agreement by 2015. The three components are...... how the three components are conceptually interlinked. Identifying the linkages can inform the work on each component and strengthen coordination of work in the context of the three big partnerships; the International Partnership on Mitigation and MRV, the LEDS Global Partnership and the NAMA...

  20. Synthesis of deoxycytidine oligomers containing phosphorodithioate linkages

    DEFF Research Database (Denmark)

    Grandas, Ana; Marshall, William S.; Nielsen, John;

    1989-01-01

    Deoxydicytidine phosphoramidite, 4-chlorobenzylmercaptan and tetrazole reacted to form dinucleoside thiophosphite. Oxidation with sulfur yields phosphorodithioates which were used to synthesize pentadecadeoxyoligonucleotides containing nuclease resistant phosphorodithioate internucleotide linkages...

  1. Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and age of onset in schizophrenia: A combined analysis of independent samples

    DEFF Research Database (Denmark)

    Saetre, Peter; Vares, Maria; Werge, Thomas;

    2011-01-01

    Methylenetetrahydrofolate reductase (MTHFR) is involved in the one-carbon cycle, which is of importance for nucleotide synthesis and methylation of DNA, membranes, proteins and lipids. The MTHFR gene includes two common polymorphisms (rs1801133 or C677T; rs1801131 or A1298C) which both alter enzyme...... activity. The T-allele of the C677T polymorphism has recently been associated with earlier age at onset of schizophrenia. In the present study we examined the association between the MTHFR C677T and A1298C polymorphisms and age at onset of schizophrenia in twelve samples consisting of 3,213 unrelated...... schizophrenia patients, including the original Scandinavian sample. There was no consistent relationship between MTHFR C677T, A1298C or combined 677T/1298C carriers and age of onset in schizophrenia when the results of each study were combined using meta-analysis. The present results suggest that the...

  2. Automated generation of linkage loop equations for planar 1-DOF linkages, demonstrated up to 8-bar

    OpenAIRE

    Parrish, BE; McCarthy, JM; Eppstein, D

    2014-01-01

    Copyright © 2014 by ASME. In this paper we present an algorithm that automatically creates the linkage loop equations for planar 1-DoF linkages of any topology with rotating joints, demonstrated up to 8-bars. The algorithm derives the linkage loop equations from the linkage graph by establishing a cycle basis through a single common edge. Divergent and convergent loops are identified and used to establish the fixed angles of the ternary and higher links. Results demonstrate the automated gene...

  3. Validation of an instrument to measure inter-organisational linkages in general practice

    Directory of Open Access Journals (Sweden)

    Cheryl Amoroso

    2007-11-01

    Full Text Available Purpose: Linkages between general medical practices and external services are important for high quality chronic disease care. The purpose of this research is to describe the development, evaluation and use of a brief tool that measures the comprehensiveness and quality of a general practice’s linkages with external providers for the management of patients with chronic disease. In this study, clinical linkages are defined as the communication, support, and referral arrangements between services for the care and assistance of patients with chronic disease. Methods: An interview to measure surgery-level (rather than individual clinician-level clinical linkages was developed, piloted, reviewed, and evaluated with 97 Australian general practices. Two validated survey instruments were posted to patients, and a survey of locally available services was developed and posted to participating Divisions of General Practice (support organisations. Hypotheses regarding internal validity, association with local services, and patient satisfaction were tested using factor analysis, logistic regression and multilevel regression models. Results: The resulting General Practice Clinical Linkages Interview (GP-CLI is a nine-item tool with three underlying factors: referral and advice linkages, shared care and care planning linkages, and community access and awareness linkages. Local availability of chronic disease services has no affect on the comprehensiveness of services with which practices link, however comprehensiveness of clinical linkages has an association with patient assessment of access, receptionist services, and of continuity of care in their general practice. Conclusions: The GP-CLI may be useful to researchers examining comparable health care systems for measuring the comprehensiveness and quality of linkages at a general practice-level with related services, possessing both internal and external validity. The tool can be used with large samples

  4. A genetic linkage map of hexaploid naked oat constructed with SSR markers

    Institute of Scientific and Technical Information of China (English)

    Gaoyuan; Song; Pengjie; Huo; Bin; Wu; Zongwen; Zhang

    2015-01-01

    Naked oat is a unique health food crop in China. Using 202 F2 individuals derived from a hybrid between the variety 578 and the landrace Sanfensan, we constructed a genetic linkage map consisting of 22 linkage groups covering 2070.50 c M and including 208 simple sequence repeat(SSR) markers. The minimum distance between adjacent markers was0.01 c M and the average was 9.95 c M. Each linkage group contained 2–22 markers. The largest linkage group covered 174.40 c M and the shortest one covered 36.80 c M, with an average of 94.11 c M. Thirty-six markers(17.3%) showing distorted segregation were distributed across linkage groups LG5 to LG22. This map complements published oat genetic maps and is applicable for quantitative trait locus analysis, gene cloning and molecular marker-assisted selection.

  5. A genetic linkage map of hexaploid naked oat constructed with SSR markers

    Institute of Scientific and Technical Information of China (English)

    Gaoyuan Song; Pengjie Huo; Bin Wu; Zongwen Zhang

    2015-01-01

    Naked oat is a unique health food crop in China. Using 202 F2 individuals derived from a hybrid between the variety 578 and the landrace Sanfensan, we constructed a genetic linkage map consisting of 22 linkage groups covering 2070.50 cM and including 208 simple sequence repeat (SSR) markers. The minimum distance between adjacent markers was 0.01 cM and the average was 9.95 cM. Each linkage group contained 2–22 markers. The largest linkage group covered 174.40 cM and the shortest one covered 36.80 cM, with an average of 94.11 cM. Thirty-six markers (17.3%) showing distorted segregation were distributed across linkage groups LG5 to LG22. This map complements published oat genetic maps and is applicable for quantitative trait locus analysis, gene cloning and molecular marker-assisted selection.

  6. Empirical aspects of record linkage across multiple data sets using statistical linkage keys: the experience of the PIAC cohort study

    Directory of Open Access Journals (Sweden)

    Gibson Diane

    2010-02-01

    Full Text Available Abstract Background In Australia, many community service program data collections developed over the last decade, including several for aged care programs, contain a statistical linkage key (SLK to enable derivation of client-level data. In addition, a common SLK is now used in many collections to facilitate the statistical examination of cross-program use. In 2005, the Pathways in Aged Care (PIAC cohort study was funded to create a linked aged care database using the common SLK to enable analysis of pathways through aged care services. Linkage using an SLK is commonly deterministic. The purpose of this paper is to describe an extended deterministic record linkage strategy for situations where there is a general person identifier (e.g. an SLK and several additional variables suitable for data linkage. This approach can allow for variation in client information recorded on different databases. Methods A stepwise deterministic record linkage algorithm was developed to link datasets using an SLK and several other variables. Three measures of likely match accuracy were used: the discriminating power of match key values, an estimated false match rate, and an estimated step-specific trade-off between true and false matches. The method was validated through examining link properties and clerical review of three samples of links. Results The deterministic algorithm resulted in up to an 11% increase in links compared with simple deterministic matching using an SLK. The links identified are of high quality: validation samples showed that less than 0.5% of links were false positives, and very few matches were made using non-unique match information (0.01%. There was a high degree of consistency in the characteristics of linked events. Conclusions The linkage strategy described in this paper has allowed the linking of multiple large aged care service datasets using a statistical linkage key while allowing for variation in its reporting. More widely, our

  7. Development of 304 new microsatellite markers for carrot. Analysis of their potential for linkage mapping, assessment of genetic diversity and cross-taxa utilization

    Science.gov (United States)

    Two different approaches were used to isolate carrot SSRs: 1) Construction and analysis of a genomic DNA library enriched for SSR loci (GSSRs) and 2) Bioinformatic mining for SSR motifs in a 1.7 Mb BAC-end sequence database (BSSR). The SSR-enriched library yielded microsatellites with more repeats b...

  8. Hereditary spastic paraplegia: LOD-score considerations for confirmation of linkage in a heterogeneous trait

    Energy Technology Data Exchange (ETDEWEB)

    Dube, M.P.; Kibar, Z.; Rouleau, G.A. [McGill Univ., Quebec (Canada)] [and others

    1997-03-01

    Hereditary spastic paraplegia (HSP) is a degenerative disorder of the motor system, defined by progressive weakness and spasticity of the lower limbs. HSP may be inherited as an autosomal dominant (AD), autosomal recessive, or an X-linked trait. AD HSP is genetically heterogeneous, and three loci have been identified so far: SPG3 maps to chromosome 14q, SPG4 to 2p, and SPG4a to 15q. We have undertaken linkage analysis with 21 uncomplicated AD families to the three AD HSP loci. We report significant linkage for three of our families to the SPG4 locus and exclude several families by multipoint linkage. We used linkage information from several different research teams to evaluate the statistical probability of linkage to the SPG4 locus for uncomplicated AD HSP families and established the critical LOD-score value necessary for confirmation of linkage to the SPG4 locus from Bayesian statistics. In addition, we calculated the empirical P-values for the LOD scores obtained with all families with computer simulation methods. Power to detect significant linkage, as well as type I error probabilities, were evaluated. This combined analytical approach permitted conclusive linkage analyses on small to medium-size families, under the restrictions of genetic heterogeneity. 19 refs., 1 fig., 1 tab.

  9. 乡村旅游中土地流转与开发策略的联动博弈分析%Rural Tourism in the Land Transfer and Development Strategy of the Linkage Game Analysis

    Institute of Scientific and Technical Information of China (English)

    刘赟

    2014-01-01

    The introduction of a new land transfer policy had a significant impact on rural land use and promoted to achieve scale effects of land-use basis. This paper set rural tourism as a research object, used the application of game analysis method to analyze the rural tourism industry development process of land transfer and linkage, analysed the demand of stake-holders in the different demands of the land transfer, and made the effective suggestion for rural tourism development strategy and sustainable development.%新型土地流转政策的出台对农村土地利用产生了重大影响,为实现土地利用的规模化效应奠定了基础。以乡村旅游作为研究对象,应用博弈分析法分析乡村旅游产业发展过程中土地流转和旅游开发策略的联动关系,剖析利益相关者在土地流转中的不同诉求,为乡村旅游的土地开发策略和可持续发展提供有效建议。

  10. A genome-wide linkage study of bipolar disorder and co-morbid migraine

    DEFF Research Database (Denmark)

    Oedegaard, K. J.; Greenwood, T. A.; Lunde, Asger;

    2010-01-01

    and migraine have shown overlapping regions of linkage on chromosomes, and two functionally similar voltage-dependent calcium channels CACNA1A and CACNA1C have been identified in familial hemiplegic migraine and recently implicated in two whole genome BPAD association studies, respectively.We hypothesized...... Genetics Initiative wave 4 data set. In this analysis we selected only those families in which at least two members were diagnosed with migraine by a doctor according to patients' reports. Nonparametric linkage analysis performed on 31 families segregating both BPAD and migraine identified a linkage signal...

  11. An international collaborative family-based whole genome quantitative trait linkage scan for myopic refractive error

    DEFF Research Database (Denmark)

    Abbott, Diana; Li, Yi-Ju; Guggenheim, Jeremy A;

    2012-01-01

    To investigate quantitative trait loci linked to refractive error, we performed a genome-wide quantitative trait linkage analysis using single nucleotide polymorphism markers and family data from five international sites....

  12. Using Improved Linkage Analysis to Screen Candidate Gene of Familial Hypercholesterolemia%应用改良连锁分析初筛家族性高胆固醇血症的候选基因

    Institute of Scientific and Technical Information of China (English)

    张筠婷; 王绿娅

    2015-01-01

    知致病基因存在。%Objective Improved linkage analysis was applied to screen candidate gene of two homozygous familial hypercholesterolemia families,providing a clear subsequent sequencing direction for early detection of pathogenic gene. Methods 2 probands of FH were enrolled in Beijing Anzhen Hospital,Capital Medical University in June 2010 and July 2010. All the family members underwent serum lipid determination,electrocardiogram,echocardiogram and carotid artery ultrasound,and other clinical informations(age,gender,age of onset,course of disease,family history and treatment)of family memberswere recorded. We selected the new microsatellite markers and capillary electrophoresis for linkage analysis of screening,and then sequenced the high linkaged one to confirm the pathogenic gene. Results The ECG of proband 1 showed left ventricular hypertrophy. The ECG of proband 2 was generally normal. The echocardiography of proband 1 showed aortic regurgitationwhile that of proband 2 showed left atrioventricular valve regurgitation. The ultrasonography of carotid artery in proband 1 found intima -media thickening and plaque formation,while that in proband 2 found carotid intima - media thickening. In family 1 the level of TC〔(6. 98 ± 1. 99) mmol/ L〕in subjects with high cholesterol level was significantly higher than that〔(3. 20 ± 1. 02) mmol/ L〕in subjects with normal blood lipid level( t = 7. 023,P < 0. 001),and the level of LDL - C〔(3. 02 ± 2. 26) mmol/ L〕in subjects with high cholesterol level was significantly higher than that〔(1. 98 ± 0. 93)mmol/ L〕in subjects with normal blood lipid level(t = 3. 497,P = 0. 004). In family 2 the level of TC〔(8. 12 ± 3. 65)mmol/ L〕in subjects with high cholesterol level was significantly higher than that〔(4. 37 ± 1. 01) mmol/ L〕in subjects with normal blood lipid level( t= 4. 355,P = 0. 001),and the level of LDL - C〔(5. 72 ± 3. 92)mmol/ L〕in subjects with high cholesterol level was higher than that〔(2. 72 ± 0. 62) mmol/ L

  13. Integrative Pathway Analysis of Metabolic Signature in Bladder Cancer: A Linkage to The Cancer Genome Atlas Project and Prediction of Survival

    Science.gov (United States)

    von Rundstedt, Friedrich-Carl; Rajapakshe, Kimal; Ma, Jing; Arnold, James M.; Gohlke, Jie; Putluri, Vasanta; Krishnapuram, Rashmi; Piyarathna, D. Badrajee; Lotan, Yair; Gödde, Daniel; Roth, Stephan; Störkel, Stephan; Levitt, Jonathan M.; Michailidis, George; Sreekumar, Arun; Lerner, Seth P.; Coarfa, Cristian; Putluri, Nagireddy

    2016-01-01

    Purpose We used targeted mass spectrometry to study the metabolic fingerprint of urothelial cancer and determine whether the biochemical pathway analysis gene signature would have a predictive value in independent cohorts of patients with bladder cancer. Materials and Methods Pathologically evaluated, bladder derived tissues, including benign adjacent tissue from 14 patients and bladder cancer from 46, were analyzed by liquid chromatography based targeted mass spectrometry. Differential metabolites associated with tumor samples in comparison to benign tissue were identified by adjusting the p values for multiple testing at a false discovery rate threshold of 15%. Enrichment of pathways and processes associated with the metabolic signature were determined using the GO (Gene Ontology) Database and MSigDB (Molecular Signature Database). Integration of metabolite alterations with transcriptome data from TCGA (The Cancer Genome Atlas) was done to identify the molecular signature of 30 metabolic genes. Available outcome data from TCGA portal were used to determine the association with survival. Results We identified 145 metabolites, of which analysis revealed 31 differential metabolites when comparing benign and tumor tissue samples. Using the KEGG (Kyoto Encyclopedia of Genes and Genomes) Database we identified a total of 174 genes that correlated with the altered metabolic pathways involved. By integrating these genes with the transcriptomic data from the corresponding TCGA data set we identified a metabolic signature consisting of 30 genes. The signature was significant in its prediction of survival in 95 patients with a low signature score vs 282 with a high signature score (p = 0.0458). Conclusions Targeted mass spectrometry of bladder cancer is highly sensitive for detecting metabolic alterations. Applying transcriptome data allows for integration into larger data sets and identification of relevant metabolic pathways in bladder cancer progression. PMID:26802582

  14. The phenotypic difference discards sib-pair QTL linkage information

    Energy Technology Data Exchange (ETDEWEB)

    Wright, F.A. [Univ. of California, San Diego, CA (United States)]|[Univ. of Texas, El Paso, TX (United States)

    1997-03-01

    Kruglyak and Lander provide an important synthesis of methods for (IBD) sib-pair linkage mapping, with an emphasis on the use of complete multipoint inheritance information for each sib pair. These procedures are implemented in the computer program MAPMAKER/SIBS, which performs interval mapping for dichotomous and quantitative traits. The authors present three methods for mapping quantitative trait loci (QTLs): a variant of the commonly used Haseman-Elston regression approach, a maximum-likelihood procedure involving variance components, and a rank-based nonparametric procedure. These approaches and related work use the magnitude of the difference in the sibling phenotype values for each sib pair as the observation for analysis. Linkage is detected if siblings sharing more alleles IBD have similar phenotypes (i.e., a small difference in the phenotype values), while siblings sharing fewer alleles IBD have less similar phenotypes. Such techniques have been used to detect linkage for a number of quantitative traits. However, the exclusive reliance on the phenotypic differences may be due in large part to historical inertia. A likelihood argument is presented here to show that, under certain classical assumptions, the phenotypic differences do not contain the full likelihood information for QTL mapping. Furthermore, considerable gains in power to detect linkage can be achieved with an expanded likelihood model. The development here is related to previous work, which incorporates the full set of phenotypic data using likelihood and robust quasi-likelihood methods. The purpose of this letter is not to endorse a particular approach but to spur research in alternative and perhaps more powerful linkage tests. 17 refs.

  15. Cat3vl and Cat3vao cataract mutations on mouse chromosome 10: phenotypic characterization, linkage studies and analysis of candidate genes.

    Science.gov (United States)

    Löster, J; Immervoll, T; Schmitt-John, T; Graw, J

    1997-12-01

    Cat3vl and Cat3vao are two allelic, dominant cataract mutations that arose independently in the F1 generation after gamma-irradiation of male mice. The cataracts are already present at birth. Examination of the eyes with a slit lamp revealed completely vacuolated lenses in Cat3vl mutants and anteriorly located opacity in Cat3vao mutants. The appearance of the opacities does not differ between the individuals or between heterozygotes and homozygotes. Penetrance of the mutations is complete. Viability and fertility of the mutants are normal except in the case of the Cat3vl homozygotes. Cat3vao was assigned to the distal part of mouse chromosome 10, 3.2 +/- 0.9 cM away from the visible marker Steel (SlgbH). Using polymorphic markers the following locus order was found: D10Mit230-(0.2 +/- 0.1 cM)-Cat3vao-(2.5 +/- 0.6 cM)-D10Mit70. No recombinants were found between Cat3vao and the markers D10Mit4l and D10Mit95 among 921 offspring. The results exclude allelism of Cat3vao with CatLop or To2, which also map to chromosome 10. Candidate genes were tested by examination of their expression in the eye of newborn mice and by analysis of cDNA sequences. So far, negative results have been obtained for the genes encoding the proteoglycans lumican and decorin, the nuclear orphan receptor Tr2-11 and the transcription factor Elk3. Based on syntenic homology of the Cat3 region to the human chromosome 12q, the Cat3 mutants are discussed as mouse models for cornea plana congenita in man. The recovery of the Cat3 mutations demonstrates the importance of the corresponding locus for proper eye development. PMID:9439574

  16. DYNAMIC DESIGN OF VARIABLE SPEED PLANAR LINKAGES

    Institute of Scientific and Technical Information of China (English)

    Yao Yanan; Yan Hongsen; Zou Huijun

    2005-01-01

    A method for improving dynamic characteristics of planar linkages by actively varying the speed function of the input link is presented. Design criteria and constraints for the dynamic design of variable speed planar linkages are developed. Both analytical and optimization approaches for determining suitable input speed functions to minimize the driving torque, the shaking moment, or both simultaneously of planar linkages, subject to various design requirements and constraints, are derived.Finally, some examples are given to illustrate the design procedure and to verify its feasibility.

  17. Farm production diversity and dietary quality: Linkages and measurement issues

    OpenAIRE

    Sibhatu, Kibrom T.; Qaim, Matin

    2016-01-01

    Recent research has analyzed whether higher levels of farm production diversity contribute to improved dietary quality in smallholder households. We add to this literature by using different indicators, thus testing the robustness of previous findings and helping to better understand the underlying linkages. The analysis builds on data from Indonesia, Kenya, and Uganda. Farm diversity measured through a simple species count has a small positive effect on dietary quality, either expressed in t...

  18. Linkage between productivity and innovation in different service sectors

    OpenAIRE

    Rõigas, Kärt

    2011-01-01

    The purpose of the paper is to find out whether linkages between productivity and innovation are different among Estonian service sector sub-sectors. In this paper productivity is measured as value added per employee. An original approach toward measurement of productivity is used, decomposing it into three components: labour costs, depreciation and gross profit per employee. Four types of innovation are studied: product, process, organizational and marketing innovation. The empirical analysi...

  19. Linkage disequilibrium in wild mice.

    Directory of Open Access Journals (Sweden)

    Cathy C Laurie

    2007-08-01

    Full Text Available Crosses between laboratory strains of mice provide a powerful way of detecting quantitative trait loci for complex traits related to human disease. Hundreds of these loci have been detected, but only a small number of the underlying causative genes have been identified. The main difficulty is the extensive linkage disequilibrium (LD in intercross progeny and the slow process of fine-scale mapping by traditional methods. Recently, new approaches have been introduced, such as association studies with inbred lines and multigenerational crosses. These approaches are very useful for interval reduction, but generally do not provide single-gene resolution because of strong LD extending over one to several megabases. Here, we investigate the genetic structure of a natural population of mice in Arizona to determine its suitability for fine-scale LD mapping and association studies. There are three main findings: (1 Arizona mice have a high level of genetic variation, which includes a large fraction of the sequence variation present in classical strains of laboratory mice; (2 they show clear evidence of local inbreeding but appear to lack stable population structure across the study area; and (3 LD decays with distance at a rate similar to human populations, which is considerably more rapid than in laboratory populations of mice. Strong associations in Arizona mice are limited primarily to markers less than 100 kb apart, which provides the possibility of fine-scale association mapping at the level of one or a few genes. Although other considerations, such as sample size requirements and marker discovery, are serious issues in the implementation of association studies, the genetic variation and LD results indicate that wild mice could provide a useful tool for identifying genes that cause variation in complex traits.

  20. 四连杆曲柄飞剪机剪切力测试与分析%Test and analysis of sthar force of four-bar linkage crank flying shear

    Institute of Scientific and Technical Information of China (English)

    李彦峰; 李强; 贝律仁; 姚伟峰

    2001-01-01

    The article presents through a test and an analysis of shearforce of four-bar linkage crank flying shear, the reality relation between the shear force and technical parameters, offering a vital basis for production plan and safe operation, and the determination of maximum productive capacity and valid evaluation of work condition of the flying shear. We have solved many difficult technical problems in the test. For example, the conversion of static instability system of stress of shearing edge, the improvement of shearing edge, the imitation of real shearing condition in calibration, the way how to get the signal of shear force, compensation of temperature during stress measurement and protection of heat and so on.%通过对四连杆曲柄飞剪机剪切力的测试与分析,弄清了剪切力与工艺参数之间的定量关系,为合理安排生产,确保飞剪机安全运行,掌握飞剪机的最大生产能力,正确评估飞剪机的工作状态提供了重要依据。在测试中,解决了不少技术难题,如剪刃受力静不定系统的转化、剪刃的技术改造方法、标定时实际剪切状态的模拟、剪切力信号的获取方法、应力测量时的温度补偿与导线的热辐射防护等。

  1. Connectivity and Linkages Between Isolated Habitat

    Data.gov (United States)

    California Department of Resources — Proposed areas where connectiviy and linkages between isolated habitat on the San Joaquin Valley floor and natural lands in the surrounding foothills should be...

  2. Identifying nanotechnological linkages in the Finnish economy

    OpenAIRE

    Nikulainen, Tuomo

    2007-01-01

    Nanotechnology, as an emerging science-based technology, is seen to have great potential both in scientific as well as economic terms. In this paper the focus is on identifying the technological linkages between the Finnish nanotechnology community and the industrial incumbents. These technological link-ages are first observed at a broader level in comparison with the technological strengths of the Finnish industries, and then in greater detail at the level of companies. In addition, the abso...

  3. Linkage of health and aged care service events: comparing linkage and event selection methods

    OpenAIRE

    Rosman Diana; Karmel Rosemary

    2008-01-01

    Abstract Background Data linkage is a technique that has long been used to connect information across several disparate data sources – most commonly for medical and population health research. Often the purpose is to connect data for individuals over extended time periods or across different service settings, and so person-based linkage using detailed personal information is preferred. Linkage which aims to link connected events, on the other hand, requires information about the time and plac...

  4. Whole genome linkage disequilibrium maps in cattle

    Directory of Open Access Journals (Sweden)

    Mannen Hideyuki

    2007-10-01

    Full Text Available Abstract Background Bovine whole genome linkage disequilibrium maps were constructed for eight breeds of cattle. These data provide fundamental information concerning bovine genome organization which will allow the design of studies to associate genetic variation with economically important traits and also provides background information concerning the extent of long range linkage disequilibrium in cattle. Results Linkage disequilibrium was assessed using r2 among all pairs of syntenic markers within eight breeds of cattle from the Bos taurus and Bos indicus subspecies. Bos taurus breeds included Angus, Charolais, Dutch Black and White Dairy, Holstein, Japanese Black and Limousin while Bos indicus breeds included Brahman and Nelore. Approximately 2670 markers spanning the entire bovine autosomal genome were used to estimate pairwise r2 values. We found that the extent of linkage disequilibrium is no more than 0.5 Mb in these eight breeds of cattle. Conclusion Linkage disequilibrium in cattle has previously been reported to extend several tens of centimorgans. Our results, based on a much larger sample of marker loci and across eight breeds of cattle indicate that in cattle linkage disequilibrium persists over much more limited distances. Our findings suggest that 30,000–50,000 loci will be needed to conduct whole genome association studies in cattle.

  5. SSR and EST-SSR-based genetic linkage map of cassava (Manihot esculenta Crantz).

    Science.gov (United States)

    Sraphet, Supajit; Boonchanawiwat, Athipong; Thanyasiriwat, Thanwanit; Boonseng, Opas; Tabata, Satoshi; Sasamoto, Shigemi; Shirasawa, Kenta; Isobe, Sachiko; Lightfoot, David A; Tangphatsornruang, Sithichoke; Triwitayakorn, Kanokporn

    2011-04-01

    Simple sequence repeat (SSR) markers provide a powerful tool for genetic linkage map construction that can be applied for identification of quantitative trait loci (QTL). In this study, a total of 640 new SSR markers were developed from an enriched genomic DNA library of the cassava variety 'Huay Bong 60' and 1,500 novel expressed sequence tag-simple sequence repeat (EST-SSR) loci were developed from the Genbank database. To construct a genetic linkage map of cassava, a 100 F(1) line mapping population was developed from the cross Huay Bong 60 by 'Hanatee'. Polymorphism screening between the parental lines revealed that 199 SSRs and 168 EST-SSRs were identified as novel polymorphic markers. Combining with previously developed SSRs, we report a linkage map consisted of 510 markers encompassing 1,420.3 cM, distributed on 23 linkage groups with a mean distance between markers of 4.54 cM. Comparison analysis of the SSR order on the cassava linkage map and the cassava genome sequences allowed us to locate 284 scaffolds on the genetic map. Although the number of linkage groups reported here revealed that this F(1) genetic linkage map is not yet a saturated map, it encompassed around 88% of the cassava genome indicating that the map was almost complete. Therefore, sufficient markers now exist to encompass most of the genomes and efficiently map traits in cassava.

  6. Clinical study and linkage analysis for a Chinese Marfan syndrome family%马凡综合征一家系的临床研究及致病基因连锁分析

    Institute of Scientific and Technical Information of China (English)

    布娟; 张莹; 刘敬; 庞红蕾; 林淑芳; 王乐今

    2012-01-01

    Objective To study the clinical phenotype in a Chinese family with Marfan syndrome ( MFS) and determine the candidate gene using linkage analysis. Methods A detailed clinical ophthalmic and complete physical examinations were performed for all patients in the MFS family. The microsatellite markers which near known MFS candidate genes (FBN1, TGFBR1, TGFBR2) were used as genetic markers after determining the clinical phenotype and the mode of inheritance. Multiple amplitude of microsatellite sequence was performed using PCR. Two-point LOD scores were calculated using the Linkage program. Results The affected members in the pedigree had classical phenotype of MFS,they were inherited as an autosomal dominant trait. All patients in this family had various bilateral lens dislocation, high myopia and skeletal features. Only 2 patients had cardiovascular malformations. The disease phenotype co-segregated with the markers D3S1609 and D3S2432 which were near from TGFBR2 gene, the maximum LOD score was 3.22. Conclusion This family has autosomal dominant trait,the candidate gene locate in D3S1609 and D3S2432 near from TGFBR2 gene, the known TGFBR2 gene mutation may be the molecular basis for MFS.%目的 研究一个中国人马凡综合征( Marian sydrome,MFS)家系的临床特点,并通过基因连锁分析的方法对该家系的致病基因进行定位研究.方法 收集一个MFS家系,对家系所有成员进行全面详细的眼科及全身临床检查.确定其临床表型及遗传方式后,在位于MFS的已知基因FBN1、TGFBR1、TGFBR2附近选取微卫星标记物进行连锁分析.经ABI3130型遗传分析仪、Genscan 2.1收集数据,Genotyper 2.1进行基因分型,Linkage软件计算两点LOD值.结果 该家系的遗传方式为常染色体显性遗传,家系中所有患者均具有典型的晶状体脱位、高度近视及MFS的特征性骨骼改变.仅有2例患者表现为心血管系统的异常.与该家系连锁的染色体微卫星标记物为D3S1609

  7. 家族性不宁腿综合征候选基因的连锁分析%Linkage Analysis of the Candidate Genes of Familial Restless Legs Syndrome

    Institute of Scientific and Technical Information of China (English)

    李靖; 胡兰靛; 王维郡; 陈宇光; 孔祥银

    2003-01-01

    This research was performed to investigate the relationship between 16 candidate genes responsible for dopaminergic transmission or iron metabolism and familial restless legs syndrome.Genotyping was performed in a Han restless legs syndrome family using the technique of fluorescence-based genescan with the microsatellite markers selected in chromosomal regions flanking the candidate genes.Classical linkage analysis was conducted under the autosomal dominant genetic mode.Results showed that all of the LOD scores at recombination fraction 0.00 are smaller than -2.00,which indicated that these loci were not linked to familial restless legs syndrome.No linkage was found between the candidate genes and RLS in this family.Familial restless legs syndrome may be caused by another gene related to dopaminergic transmission and iron metabolism or there is new mechanism involved in this disease.%不宁腿综合征(restless legs syndrome,RLS)是以下肢部出现蚁行样及酸、麻、胀等不适感而使肢体不得休息为特征的一组病症.由于症状常在晚间发作并导致运动不安,患者长期入睡困难,经受严重的继发性失眠.作为一种常见的神经系统疾病,RLS发病率高达5%,其中原发性RLS多呈阳性家族史,表现为单基因决定的常染色体显性遗传.现在,人们普遍认为RLS的发生很可能与神经系统内多巴胺能功能异常和脑内铁缺乏有关,并初步建立了脑铁-多巴胺能系统的致病模型.为了探求脑铁-多巴胺能系统在RLS中的作用,选择了与脑铁-多巴胺能系统相关的16个疾病候选基因,在每个候选基因附近染色体区域内选取若干个微卫星多态标记,应用微卫星引物荧光标记-基因扫描技术,对一个汉族家族性不宁腿综合征家系进行了基因分型和常染色体显性遗传模式下的连锁分析,试图从分子遗传学层面上确认或排除一些可能与RLS相关的重要候选基因.结果显示,当重组系数θ=0.00

  8. High-resolution gene mapping using admixture linkage disequilibrium

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    This note reports simulation study on the rate of decay in linkage dis equilibrium (LD) in mixed populations over multiple discrete generations and explores the usefulness of the LD analysis in high-resolution gene mapping. The results indicate that the smaller the recombination fraction and the fewer generati ons since admixtureevent, the higher power of the approach in gene mapping. The expected estimate of recombination fraction would give an estimate that is slig htly biased upwards, if relevant genes are in tight linkage. The estimated recom bination fraction is usually larger than the true value within 2-5 generations. From generations 10-20, the mean estimates are in good agreement with the true value. The method presented here enables estimation of means and corresponding confidence intervals of the recombination fraction at any number of generations.

  9. Hybrid reuteransucrase enzymes reveal regions important for glucosidic linkage specificity and the transglucosylation/hydrolysis ratio

    OpenAIRE

    Kralj, S.; van Leeuwen, S.S.; Valk, Vincent; Eeuwema, W.; Kamerling, J P; Dijkhuizen, L.

    2008-01-01

    The reuteransucrase enzymes of Lactobacillus reuteri strain 121 (GTFA) and L. reuteri strain ATCC 55730 (GTFO) convert sucrose into alpha-d-glucans (labelled reuterans) with mainly alpha-(1 -> 4) glucosidic linkages (50% and 70%, respectively), plus alpha-(1 -> 6) linkages. In the present study, we report a detailed analysis of various hybrid GTFA/O enzymes, resulting in the identification of specific regions in the N-termini of the catalytic domains of these proteins as the main determinants...

  10. Quantitative linkage genome scan for atopy in a large collection of Caucasian families

    DEFF Research Database (Denmark)

    Webb, BT; van den Oord, E; Akkari, A;

    2007-01-01

    Quantitative phenotypes correlated with a complex disorder offer increased power to detect linkage in comparison to affected-unaffected classifications. Asthma is a complex disorder characterized by periods of bronchial obstruction and increased bronchial hyper reactivity. In childhood and early...... report represents one of the biggest genome scans so far reported for asthma related phenotypes. This study also demonstrates the utility of increased sample sizes and quantitative phenotypes in linkage analysis of complex disorders....

  11. How Strong are the Linkages between Real Estate and Other Sectors in China?

    OpenAIRE

    Wenlang Zhang; Gaofeng Han; Steven Chan

    2014-01-01

    International experience points to the critical role of stable property markets in maintaining financial stability. In China, the real estate sector has become increasingly important for the economy, but existing evidence has likely understated its importance as its linkages with other sectors have not been taken into account. This paper attempts to shed some light on these linkages which occur through both real and financial channels. Our analysis based on input-output tables shows that the ...

  12. 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

    linkage could exist in different ethnic populations. BMI was measured from 126 dizygotic twins in Qingdao municipality who were genotyped using high-resolution Affymetrix Genome-Wide Human SNP arrays containing about 1 million single-nucleotide polymorphisms (SNPs). Nonparametric linkage analysis...

  13. 西瓜遗传图谱构建及果实相关性状QTL分析%Construction of a Genetic Linkage Map and QTL Analysis of Fruit-Associated Traits in Watermelon

    Institute of Scientific and Technical Information of China (English)

    刘传奇; 高鹏; 栾非时

    2014-01-01

    electrophoresis was used to detect the digestion products. SSR markers in this experiment were come from the published literature. The products of SSR-PCR were detected by polyacrylamid gel electrophoresis. All the molecular data were tested by chi-square. Markers which were confirmed the proportion 1﹕2﹕1 were chosen for the genetic linkage map. The genetic linkage map was constructed by Mapmaker/Exp version 3.0. The markers were grouped with the order ‘Group’. The number of the markers in the group which was less than 8 was sequenced faultlessly with the order ‘Compare’, which was more than 8 was ordered with the order ‘Try’. Map Chart 2.1 was used for drawing this genetic linkage map. QTL Network 2.0 was used for QTL analysis. 1 000 times repeats were done with the replacement testing, the critical threshold was P=0.005, and the method of constructing the map was composite interval mapping. The whole genome was scanned on every chromosome with 1 cM walking speed. QTL additive effect and epistatic effect were analyzed by the software.[Result]This genetic linkage map contained 16 linkage groups and included 87 CAPS markers and SSR markers. The map was 1 484.3 cM and the average distance between two makers was 15.46 cM. Mapping the QTL of the fruit-associated traits and analyzed by software QTL Network 2.0, and a total of 8 additive QTL and one pair of epistatic QTL were detected. Among the additive loci, 1 is for fruit shape index(QFSI 1), 1 for center brix (QCBR), 1 for center flesh firmness(QCFF), 1 for edge flesh firmness(QEFF), 1 for seed length(QSL), and 3 for seed width(QSWD 1,QSWD 2,QSWD 3). The epistatic loci,FSI 2 andFSI 3arefor fruit shape index. Phenotypic contribution rate of 10% or more have six QTL, which explained 11.7% -18.8% of the genetic variation. All of the QTL explained 7.12%-18.8% of the phenotypic variation.[Conclusion]A molecular genetic linkage map composed mainly of CAPS markers was constructed. Eight additive QTL and one pair of

  14. Construction of a Genetic Linkage Map and QTL Analysis of Fruit-Associated Traits in Watermelon%西瓜遗传图谱构建及果实相关性状QTL分析

    Institute of Scientific and Technical Information of China (English)

    刘传奇; 高鹏; 栾非时

    2014-01-01

    electrophoresis was used to detect the digestion products. SSR markers in this experiment were come from the published literature. The products of SSR-PCR were detected by polyacrylamid gel electrophoresis. All the molecular data were tested by chi-square. Markers which were confirmed the proportion 1﹕2﹕1 were chosen for the genetic linkage map. The genetic linkage map was constructed by Mapmaker/Exp version 3.0. The markers were grouped with the order ‘Group’. The number of the markers in the group which was less than 8 was sequenced faultlessly with the order ‘Compare’, which was more than 8 was ordered with the order ‘Try’. Map Chart 2.1 was used for drawing this genetic linkage map. QTL Network 2.0 was used for QTL analysis. 1 000 times repeats were done with the replacement testing, the critical threshold was P=0.005, and the method of constructing the map was composite interval mapping. The whole genome was scanned on every chromosome with 1 cM walking speed. QTL additive effect and epistatic effect were analyzed by the software.[Result]This genetic linkage map contained 16 linkage groups and included 87 CAPS markers and SSR markers. The map was 1 484.3 cM and the average distance between two makers was 15.46 cM. Mapping the QTL of the fruit-associated traits and analyzed by software QTL Network 2.0, and a total of 8 additive QTL and one pair of epistatic QTL were detected. Among the additive loci, 1 is for fruit shape index(QFSI 1), 1 for center brix (QCBR), 1 for center flesh firmness(QCFF), 1 for edge flesh firmness(QEFF), 1 for seed length(QSL), and 3 for seed width(QSWD 1,QSWD 2,QSWD 3). The epistatic loci,FSI 2 andFSI 3arefor fruit shape index. Phenotypic contribution rate of 10% or more have six QTL, which explained 11.7% -18.8% of the genetic variation. All of the QTL explained 7.12%-18.8% of the phenotypic variation.[Conclusion]A molecular genetic linkage map composed mainly of CAPS markers was constructed. Eight additive QTL and one pair of

  15. Genome scan for linkage to Gilles de la Tourette syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Barr, C.L.; Livingston, J.; Williamson, R. [and others

    1994-09-01

    Gilles de la Tourette Syndrome (TS) is a familial, neuropsychiatric disorder characterized by chronic, intermittent motor and vocal tics. In addition to tics, affected individuals frequently display symptoms such as attention-deficit hyperactivity disorder and/or obsessive compulsive disorder. Genetic analyses of family data have suggested that susceptibility to the disorder is most likely due to a single genetic locus with a dominant mode of transmission and reduced penetrance. In the search for genetic linkage for TS, we have collected well-characterized pedigrees with multiple affected individuals on whom extensive diagnostic evaluations have been done. The first stage of our study is to scan the genome systematically using a panel of uniformly spaced (10 to 20 cM), highly polymorphic, microsatellite markers on 5 families segregating TS. To date, 290 markers have been typed and 3,660 non-overlapping cM of the genome have been excluded for possible linkage under the assumption of genetic homogeneity. Because of the possibility of locus heterogeneity overall summed exclusion is not considered tantamount to absolute exclusion of a disease locus in that region. The results from each family are carefully evaluated and a positive lod score in a single family is followed up by typing closely linked markers. Linkage to TS was examined by two-point analysis using the following genetic model: single autosomal dominant gene with gene frequency .003 and maximum penetrance of .99. An age-of-onset correction is included using a linear function increasing from age 2 years to 21 years. A small rate of phenocopies is also incorporated into the model. Only individuals with TS or CMT according to DSM III-R criteria were regarded as affected for the purposes of this summary. Additional markers are being tested to provide coverage at 5 cM intervals. Moreover, we are currently analyzing the data non-parametrically using the Affected-Pedigree-Member Method of linkage analysis.

  16. A High-Density SNP Genetic Linkage Map and QTL Analysis of Growth-Related Traits in a Hybrid Family of Oysters (Crassostrea gigas × Crassostrea angulata Using Genotyping-by-Sequencing

    Directory of Open Access Journals (Sweden)

    Jinpeng Wang

    2016-05-01

    Full Text Available Oysters are among the most important species in global aquaculture. Crassostrea gigas, and its subspecies C. angulata, are the major cultured species. To determine the genetic basis of growth-related traits in oysters, we constructed a second-generation linkage map from 3367 single-nucleotide polymorphisms (SNPs based on genotyping-by-sequencing, genotyped from a C. gigas × C. angulata hybrid family. These 3367 SNPs were distributed on 1695 markers, which were assigned to 10 linkage groups. The genetic linkage map had a total length of 1084.3 cM, with an average of 0.8 cM between markers; it thus represents the densest genetic map constructed for oysters to date. Twenty-seven quantitative trait loci (QTL for five growth-related traits were detected. These QTL could explain 4.2–7.7% (mean = 5.4% of the phenotypic variation. In total, 50.8% of phenotypic variance for shell width, 7.7% for mass weight, and 34.1% for soft tissue weight were explained. The detected QTL were distributed among eight linkage groups, and more than half (16 were concentrated within narrow regions in their respective linkage groups. Thirty-eight annotated genes were identified within the QTL regions, two of which are key genes for carbohydrate metabolism. Other genes were found to participate in assembly and regulation of the actin cytoskeleton, signal transduction, and regulation of cell differentiation and development. The newly developed high-density genetic map, and the QTL and candidate genes identified provide a valuable genetic resource and a basis for marker-assisted selection for C. gigas and C. angulata.

  17. Genetic linkage heterogeneity in the fragile X syndrome.

    Science.gov (United States)

    Brown, W T; Gross, A C; Chan, C B; Jenkins, E C

    1985-01-01

    Genetic linkage between a factor IX DNA restriction fragment length polymorphism (RFLP) and the fragile X chromosome marker was analyzed in eight fragile X pedigrees and compared to eight previously reported pedigrees. A large pedigree with apparently full penetrance in all male members showed a high frequency of recombination. A lod score of -7.39 at theta = 0 and a maximum score of 0.26 at theta = 0.32 were calculated. A second large pedigree with a nonpenetrant male showed tight linkage with a maximum lod score of 3.13 at theta = 0, a result similar to one large pedigree with a nonpenetrant male previously reported. The differences in lod scores seen in these large pedigrees suggested there was genetic heterogeneity in linkage between families which appeared to relate to the presence of nonpenetrant males. The combined lod score for the three pedigrees with nonpenetrant males was 6.84 at theta = 0. For the 13 other pedigrees without nonpenetrant males the combined lod score was -21.81 at theta = 0, with a peak of 0.98 at theta = 0.28. When lod scores from all 16 families were combined, the value was -15.14 at theta = 0 and the overall maximum was 5.13 at theta = 0.17. To determine whether genetic heterogeneity was present, three statistical tests for heterogeneity were employed. First, a "predivided-sample" test was used. The 16 pedigrees were divided into two classes, NP and P, based upon whether or not any nonpenetrant males were detected in the pedigree. This test gave evidence for significant genetic heterogeneity whether the three large pedigrees with seven or more informative males (P less than 0.005), the eight pedigrees with three informative males (P less than 0.001), or all 16 pedigrees (P less than 0.001) were included in the analysis. Second, Morton's large sample test was employed. Significant heterogeneity was present when the analysis was restricted to the three large pedigrees (P less than 0.025), or to the eight pedigrees with informative males

  18. Evolution of zygotic linkage disequilibrium in a finite local population.

    Directory of Open Access Journals (Sweden)

    Xin-Sheng Hu

    Full Text Available One crucial feature of zygotic linkage disequilibrium (LD analysis is its direct use of diploid genotyping data, irrespective of the type of mating system. Previous theories from an evolutionary perspective mainly focus on gametic LD, but the equivalent development for zygotic LD is not available. Here I study the evolution of zygotic LD and the covariances between gametic and zygotic LDs or between distinct zygotic LDs in a finite local population under constant immigration from a continent population. I derive the analytical theory under genetic hitchhiking effects or in a neutral process. Results indicate that zygotic LDs (diploid level are more informative than gametic LD (haploid level in indicating the effects of different evolutionary forces. Zygotic LDs may be greater than or comparable to gametic LD under the epistatic selection process, but smaller than gametic LD under the non epistatic selection process. The covariances between gametic and zygotic LDs are strongly affected by the mating system, linkage distance, and genetic drift effects, but weakly affected by seed and pollen flow and natural selection. The covariances between different zygotic LDs are generally robust to the effects of gene flow, selection, and linkage distance, but sensitive to the effects of genetic drift and mating system. Consistent patterns exist for the covariances between the zygotic LDs for the two-locus genotypes with one common genotype at one locus or without any common genotype at each locus. The results highlight that zygotic LDs can be applied to detecting natural population history.

  19. Linear models for joint association and linkage QTL mapping

    Directory of Open Access Journals (Sweden)

    Fernando Rohan L

    2009-09-01

    Full Text Available Abstract Background Populational linkage disequilibrium and within-family linkage are commonly used for QTL mapping and marker assisted selection. The combination of both results in more robust and accurate locations of the QTL, but models proposed so far have been either single marker, complex in practice or well fit to a particular family structure. Results We herein present linear model theory to come up with additive effects of the QTL alleles in any member of a general pedigree, conditional to observed markers and pedigree, accounting for possible linkage disequilibrium among QTLs and markers. The model is based on association analysis in the founders; further, the additive effect of the QTLs transmitted to the descendants is a weighted (by the probabilities of transmission average of the substitution effects of founders' haplotypes. The model allows for non-complete linkage disequilibrium QTL-markers in the founders. Two submodels are presented: a simple and easy to implement Haley-Knott type regression for half-sib families, and a general mixed (variance component model for general pedigrees. The model can use information from all markers. The performance of the regression method is compared by simulation with a more complex IBD method by Meuwissen and Goddard. Numerical examples are provided. Conclusion The linear model theory provides a useful framework for QTL mapping with dense marker maps. Results show similar accuracies but a bias of the IBD method towards the center of the region. Computations for the linear regression model are extremely simple, in contrast with IBD methods. Extensions of the model to genomic selection and multi-QTL mapping are straightforward.

  20. Motion Analysis for Vegetable Potted Seedling Pick-up Mechanism with Double Crank Geared Linkages%蔬菜钵苗取苗机构运动分析与参数优化

    Institute of Scientific and Technical Information of China (English)

    金鑫; 李树君; 杨学军; 颜华; 吴俭敏; 孙星; 张萌

    2014-01-01

    In the present process of vegetable transplanting operation in China , the dibble-type semi-automatic trans-planter is the best available technology of applying mulch film with holes to transplanting vegetable potted seedlings . However , the dibble-type transplanter has very low efficiency because of the artificial feeding seedlings .Aiming at this problem , a new automatic transplanter for vegetable potted seedling was designed while the working principle of it was ex -pounded .It has the potted seedling pick-up mechanism with double crank geared five-bar linkages .The kinematics model of the pick-up mechanism was established by using the mathematical analysis method .The influence law of the structural parameters on the motion trajectory and relative velocity of the seedling pick-up arm cusp were obtained .The design of optimization objective for picking vegetable potted seedling was proposed .Meanwhile , the optimal parameter combination of the pick-up mechanism was obtained by using MATLAB based on the objective .With it, the path of the seedling pick-up arm inserting and pulling out the seedling pot were almost straight line , and were nearly perpendicular to potted seedling .Furthermore , the velocity of seedling taking and dropping cusps were very low .Then , the demands of picking and feeding potted seedling for vegetable automatic transplanter could be met .%针对目前吊篮式半自动蔬菜移栽机手工喂入效率低的问题,设计了一种具有双曲柄齿轮-五杆式钵苗取苗机构的蔬菜自动移栽机。同时,建立了该机取苗机构的运动数学模型,并对机构的运动学特性进行了分析,得出了取苗机构主要参数对取苗臂尖点轨迹和速度的影响规律;提出了蔬菜移栽自动取苗的设计优化目标,利用MATLAB优化软件,优选出了取苗机构的一组最佳参数组合。在此组合下,取苗机构取苗、拔苗段的运动轨迹几乎是直线且与钵苗的垂直度较高

  1. Genome-wide significance for a modifier of age at neurological onset in Huntington's Disease at 6q23-24: the HD MAPS study

    Directory of Open Access Journals (Sweden)

    Gillis Tammy

    2006-08-01

    Full Text Available Abstract Background Age at onset of Huntington's disease (HD is correlated with the size of the abnormal CAG repeat expansion in the HD gene; however, several studies have indicated that other genetic factors also contribute to the variability in HD age at onset. To identify modifier genes, we recently reported a whole-genome scan in a sample of 629 affected sibling pairs from 295 pedigrees, in which six genomic regions provided suggestive evidence for quantitative trait loci (QTL, modifying age at onset in HD. Methods In order to test the replication of this finding, eighteen microsatellite markers, three from each of the six genomic regions, were genotyped in 102 newly recruited sibling pairs from 69 pedigrees, and data were analyzed, using a multipoint linkage variance component method, in the follow-up sample and the combined sample of 352 pedigrees with 753 sibling pairs. Results Suggestive evidence for linkage at 6q23-24 in the follow-up sample (LOD = 1.87, p = 0.002 increased to genome-wide significance for linkage in the combined sample (LOD = 4.05, p = 0.00001, while suggestive evidence for linkage was observed at 18q22, in both the follow-up sample (LOD = 0.79, p = 0.03 and the combined sample (LOD = 1.78, p = 0.002. Epistatic analysis indicated that there is no interaction between 6q23-24 and other loci. Conclusion In this replication study, linkage for modifier of age at onset in HD was confirmed at 6q23-24. Evidence for linkage was also found at 18q22. The demonstration of statistically significant linkage to a potential modifier locus opens the path to location cloning of a gene capable of altering HD pathogenesis, which could provide a validated target for therapeutic development in the human patient.

  2. Inter-organizational linkages and resource dependence

    Directory of Open Access Journals (Sweden)

    Rod B. McNaughton

    2014-12-01

    Full Text Available Few studies have examined the relationship between inter-industry, inter-corporate ownership (ICO patterns and inter-industry resource exchange patterns. Using data from Statistics Canada, this paper reveals a positive association between the degree of ICO linkages and the degree of input–output dependence among Canadian industry groups. This provides empirical support for the primary assertion of resource dependence theory: that corporations employ ICO linkages to manage their input–output dependence resulting from recurrent resource exchanges. This research differs from extant tests of resource dependence in that it uses data for the population of firms (over a size threshold in Canada and includes all forms of interdependence between enterprises. The findings suggest scenarios in which corporations can adopt ICO linkages to manage resource dependence and reduce transaction costs.

  3. Intragroup emotions: physiological linkage and social presence

    Directory of Open Access Journals (Sweden)

    Simo eJärvelä

    2016-02-01

    Full Text Available We investigated how technologically mediating two different components of emotion – communicative expression and physiological state – to group members affects physiological linkage and self-reported feelings in a small group during video viewing. In different conditions the availability of second screen text chat (communicative expression and visualization of group level physiological heart rates and their dyadic linkage (physiology was varied. Within this four person group two participants formed a physically co-located dyad and the other two were individually situated in two separate rooms. We found that text chat always increased heart rate synchrony but HR visualization only with non-co-located dyads. We also found that physiological linkage was strongly connected to self-reported social presence. The results encourage further exploration of the possibilities of sharing group member’s physiological components of emotion by technological means to enhance mediated communication and strengthen social presence.

  4. Some methods for blindfolded record linkage

    Directory of Open Access Journals (Sweden)

    Christen Peter

    2004-06-01

    Full Text Available Abstract Background The linkage of records which refer to the same entity in separate data collections is a common requirement in public health and biomedical research. Traditionally, record linkage techniques have required that all the identifying data in which links are sought be revealed to at least one party, often a third party. This necessarily invades personal privacy and requires complete trust in the intentions of that party and their ability to maintain security and confidentiality. Dusserre, Quantin, Bouzelat and colleagues have demonstrated that it is possible to use secure one-way hash transformations to carry out follow-up epidemiological studies without any party having to reveal identifying information about any of the subjects – a technique which we refer to as "blindfolded record linkage". A limitation of their method is that only exact comparisons of values are possible, although phonetic encoding of names and other strings can be used to allow for some types of typographical variation and data errors. Methods A method is described which permits the calculation of a general similarity measure, the n-gram score, without having to reveal the data being compared, albeit at some cost in computation and data communication. This method can be combined with public key cryptography and automatic estimation of linkage model parameters to create an overall system for blindfolded record linkage. Results The system described offers good protection against misdeeds or security failures by any one party, but remains vulnerable to collusion between or simultaneous compromise of two or more parties involved in the linkage operation. In order to reduce the likelihood of this, the use of last-minute allocation of tasks to substitutable servers is proposed. Proof-of-concept computer programmes written in the Python programming language are provided to illustrate the similarity comparison protocol. Conclusion Although the protocols described in

  5. The Barley Chromosome 5 Linkage Map

    DEFF Research Database (Denmark)

    Jensen, J.; Jørgensen, Jørgen Helms

    1975-01-01

    The distances between nine loci on barley chromosome 5 have been studied in five two-point tests, three three-point tests, and one four-point test. Our previous chromosome 5 linkage map, which contained eleven loci mapped from literature data (Jensen and Jørgensen 1975), is extended with four loci......-position is fixed on the map by a locus (necl), which has a good marker gene located centrally in the linkage group. The positions of the other loci are their distances in centimorgans from the 0-position; loci in the direction of the short chromosome arm are assigned positive values and those...

  6. Fine mapping quantitative trait loci under selective phenotyping strategies based on linkage and linkage disequilibrium criteria

    DEFF Research Database (Denmark)

    Ansari-Mahyari, S; Berg, P; Lund, M S

    2009-01-01

    In fine mapping of a large-scale experimental population where collection of phenotypes are very expensive, difficult to record or time-demanding, selective phenotyping could be used to phenotype the most informative individuals. Linkage analyses based sampling criteria (LAC) and linkage disequil......In fine mapping of a large-scale experimental population where collection of phenotypes are very expensive, difficult to record or time-demanding, selective phenotyping could be used to phenotype the most informative individuals. Linkage analyses based sampling criteria (LAC) and linkage...... disequilibrium-based sampling criteria (LDC) for selecting individuals to phenotype are compared to random phenotyping in a quantitative trait loci (QTL) verification experiment using stochastic simulation. Several strategies based on LAC and LDC for selecting the most informative 30%, 40% or 50% of individuals...... for phenotyping to extract maximum power and precision in a QTL fine mapping experiment were developed and assessed. Linkage analyses for the mapping was performed for individuals sampled on LAC within families and combined linkage disequilibrium and linkage analyses was performed for individuals...

  7. Comparative analysis of features phenotype limb-girdle muscular dystrophy 2А and 2I types

    Directory of Open Access Journals (Sweden)

    I. V. Sharkova

    2013-01-01

    Full Text Available A comparative analysis of the frequency of occurrence of 36 clinical symptoms in the three groups of patients with LGMD 2A and LGMD 2Itypes and LGMD those patients who have mutations in CAPN3 and FKRP was detected. The absence of a particular symptom, allowing for thedifferentiation of these genetic variants on clinical level. An algorithm for molecular genetic investigation of patients according to age at onset and some clinical symptoms. The proposed algorithm can significantly reduce the economic and time costs during expensive standing DNA analysis.

  8. Effectiveness of service linkages in primary mental health care: a narrative review part 1

    Directory of Open Access Journals (Sweden)

    Parker Sharon

    2011-04-01

    Full Text Available Abstract Background With the move to community care and increased involvement of generalist health care providers in mental health, the need for health service partnerships has been emphasised in mental health policy. Within existing health system structures the active strategies that facilitate effective partnership linkages are not clear. The objective of this study was to examine the evidence from peer reviewed literature regarding the effectiveness of service linkages in primary mental health care. Methods A narrative and thematic review of English language papers published between 1998 and 2009. Studies of analytic, descriptive and qualitative designs from Australia, New Zealand, UK, Europe, USA and Canada were included. Data were extracted to examine what service linkages have been used in studies of collaboration in primary mental health care. Findings from the randomised trials were tabulated to show the proportion that demonstrated clinical, service delivery and economic benefits. Results A review of 119 studies found ten linkage types. Most studies used a combination of linkage types and so the 42 RCTs were grouped into four broad linkage categories for meaningful descriptive analysis of outcomes. Studies that used multiple linkage strategies from the suite of "direct collaborative activities" plus "agreed guidelines" plus "communication systems" showed positive clinical (81%, service (78% and economic (75% outcomes. Most evidence of effectiveness came from studies of depression. Long term benefits were attributed to medication concordance and the use of case managers with a professional background who received expert supervision. There were fewer randomised trials related to collaborative care of people with psychosis and there were almost none related to collaboration with the wider human service sectors. Because of the variability of study types we did not exclude on quality or attempt to weight findings according to power or effect

  9. Hybrid reuteransucrase enzymes reveal regions important for glucosidic linkage specificity and the transglucosylation/hydrolysis ratio.

    Science.gov (United States)

    Kralj, Slavko; van Leeuwen, Sander S; Valk, Vincent; Eeuwema, Wieger; Kamerling, Johannis P; Dijkhuizen, Lubbert

    2008-12-01

    The reuteransucrase enzymes of Lactobacillus reuteri strain 121 (GTFA) and L. reuteri strain ATCC 55730 (GTFO) convert sucrose into alpha-d-glucans (labelled reuterans) with mainly alpha-(1-->4) glucosidic linkages (50% and 70%, respectively), plus alpha-(1-->6) linkages. In the present study, we report a detailed analysis of various hybrid GTFA/O enzymes, resulting in the identification of specific regions in the N-termini of the catalytic domains of these proteins as the main determinants of glucosidic linkage specificity. These regions were divided into three equal parts (A1-3; O1-3), and used to construct six additional GTFA/O hybrids. All hybrid enzymes were able to synthesize alpha-glucans from sucrose, and oligosaccharides from sucrose plus maltose or isomaltose as acceptor substrates. Interestingly, not only the A2/O2 regions, with the three catalytic residues, affect glucosidic linkage specificity, but also the upstream A1/O1 regions make a strong contribution. Some GTFO derived hybrid/mutant enzymes displayed strongly increased transglucosylation/hydrolysis activity ratios. The reduced sucrose hydrolysis allowed the much improved conversion of sucrose into oligo- and polysaccharide products. Thus, the glucosidic linkage specificity and transglucosylation/hydrolysis ratios of reuteransucrase enzymes can be manipulated in a relatively simple manner. This engineering approach has yielded clear changes in oligosaccharide product profiles, as well as a range of novel reuteran products differing in alpha-(1-->4) and alpha-(1-->6) linkage ratios. PMID:19016850

  10. Closed-chain principal vector linkages

    NARCIS (Netherlands)

    Wijk, van der V.; Flores, Paulo; Viadero, Fernando

    2015-01-01

    For high-speed robotics dynamic balance is an important property for low base vibrations and short cycle times. To consider dynamic balance in the beginning of the design process of a manipulator, mechanism solutions can be synthesized from principal vector linkages, which are fundamental kinematic

  11. Regional Workshops on CETA/Educational Linkages.

    Science.gov (United States)

    McGough, Robert; And Others

    This document presents a summary of the proceedings of five regional workshops in Virginia which focused on planning for future involvement and linkages, as well as giving an orientation to the capabilities and operational philosophies of both Comprehensive Employment and Training Act (CETA) programs and educational organizations. Following…

  12. Past CETA Linkages: Models for the Future.

    Science.gov (United States)

    Lapin, Joel D.

    1982-01-01

    Examines lessons learned from successful linkages between community colleges and Comprehensive Employment and Training Act (CETA) sponsors as the basis for future occupational training and employment programs. Reviews research examining CETA funding patterns in California and exemplary arrangements between community colleges and CETA nationwide.…

  13. Whole genome linkage disequilibrium maps in cattle

    Science.gov (United States)

    Bovine whole genome linkage disequilibrium maps were constructed for eight breeds of cattle. These data provide fundamental information concerning bovine genome organization which will allow the design of studies to associate genetic variation with economically important traits and also provides bac...

  14. A RAD-based linkage map and comparative genomics in the gudgeons (genus Gnathopogon, Cyprinidae

    Directory of Open Access Journals (Sweden)

    Kakioka Ryo

    2013-01-01

    Full Text Available Abstract Background The construction of linkage maps is a first step in exploring the genetic basis for adaptive phenotypic divergence in closely related species by quantitative trait locus (QTL analysis. Linkage maps are also useful for comparative genomics in non-model organisms. Advances in genomics technologies make it more feasible than ever to study the genetics of adaptation in natural populations. Restriction-site associated DNA (RAD sequencing in next-generation sequencers facilitates the development of many genetic markers and genotyping. We aimed to construct a linkage map of the gudgeons of the genus Gnathopogon (Cyprinidae for comparative genomics with the zebrafish Danio rerio (a member of the same family as gudgeons and for the future QTL analysis of the genetic architecture underlying adaptive phenotypic evolution of Gnathopogon. Results We constructed the first genetic linkage map of Gnathopogon using a 198 F2 interspecific cross between two closely related species in Japan: river-dwelling Gnathopogon elongatus and lake-dwelling Gnathopogon caerulescens. Based on 1,622 RAD-tag markers, a linkage map spanning 1,390.9 cM with 25 linkage groups and an average marker interval of 0.87 cM was constructed. We also identified a region involving female-specific transmission ratio distortion (TRD. Synteny and collinearity were extensively conserved between Gnathopogon and zebrafish. Conclusions The dense SNP-based linkage map presented here provides a basis for future QTL analysis. It will also be useful for transferring genomic information from a “traditional” model fish species, zebrafish, to screen candidate genes underlying ecologically important traits of the gudgeons.

  15. Use of linkage disequilibrium approaches to map genes for bipolar disorder in the Costa Rican population

    Energy Technology Data Exchange (ETDEWEB)

    Escamilla, M.A.; Reus, V.I.; Smith, L.B.; Freimer, N.B. [Univ. of California, San Francisco, CA (United States)] [and others

    1996-05-31

    Linkage disequilibrium (LD) analysis provides a powerful means for screening the genome to map the location of disease genes, such as those for bipolar disorder (BP). As described in this paper, the population of the Central Valley of Costa Rica, which is descended from a small number of founders, should be suitable for LD mapping; this assertion is supported by reconstruction of extended haplotypes shared by distantly related individuals in this population suffering low-frequency hearing loss (LFHL1), which has previously been mapped by linkage analysis. A sampling strategy is described for applying LD methods to map genes for BP, and clinical and demographic characteristics of an initially collected sample are discussed. This sample will provide a complement to a previously collected set of Costa Rican BP families which is under investigation using standard linkage analysis. 42 refs., 4 figs., 2 tabs.

  16. 北京市生产性土地的部门关联效应分析%Analysis of Linkage Effects of Beijing Productive Land Resource among Sector Blocks

    Institute of Scientific and Technical Information of China (English)

    王亚菲

    2011-01-01

    本文基于生态足迹的投入产出模型,利用改进的HEM方法和北京市2007年投入产出表及相关数据,计算生产性土地的部门关联效应指标,对北京市9部门块土地资源关联效应进行了分析.研究结果表明:土地资源纵向总效应超过直接消耗的部门块主要由制造业、建筑业和服务业等部门构成;采选业部门块有更大的土地资源转让潜力;其他部门块都要从本部门块以外获取土地资源,导致各部门块的外部后向关联及外部前向关联都很大.本文认为:生产性土地的关联效应实际上是经济系统部门间土地资源需求的转移,最终需求总量不变,其结构调整就不会对土地资源总量产生影响;改进的HEM方法结合生态足迹最终需求,分析直接土地资源消耗数量,分解影响部门土地资源的组成因素,可以更直接、明确地量化部门间以及部门内部土地资源的关联关系;如果能够以实物型投入产出表代替货币型投入产出表,可以更加科学地反映经济系统中各产业部门土地资源的关联特性.%Based on the input-output model on ecological footprint, the modified hypothetical extraction method and input-output table 2007 of Beijing are applied to compute indicators and analyze the linkage effects of Beijing productive land resource among 9 sector blocks. The results show that the sector blocks, whose vertically integrated production outnumbers direct consumption, consist of manufacturing, construction and services. Mining sector block has a greater potential for the transfer of land resources, while other sector blocks must get part of land resources from the outside, which leads to a large external backward linkage and external forward linkage. This paper argues that linkage effects of productive land resources among different sectors are actually the demand that transfers from one sector to another. If the total final demand unchanged, the structure adjustment

  17. Mutation analysis of ATP13A2 in early-onset parkinsonism patients

    Institute of Scientific and Technical Information of China (English)

    Yuping Ning; Hiroyuki Tomiyama; Yuanzhe Li; Manabu Funayama; Hiroyo Yoshino; Shigeto Sato; Yoshikuni Mizuno; Nobutaka Hattori

    2008-01-01

    BACKGROUND: A recent study has found that ATP13A2 is the causative gene for PARK9-linked autosomal recessive early-onset parkinsonism, described previously in Jordanian and Chilean families (Kufor-Rakeb syndrome). OBJECTIVE: To screen eastern Asian patients with early-onset parkinsonism for mutations in ATP13A2 and to describe positron emission tomography (PET) findings of PARK9-linked parkinsonism.DESIGN, TIME AND SETTING: In total, 117 patients were selected from the Department of Neurology, Juntendo University, from February 2003 to October 2006, for this molecular genetics and case-control study.PARTICIPANTS: The patients with parkinsonism consist of two cohorts. Ninety four patients with onset age of less than 30 years were selected for the first cohort. They included 49 males and 44 females, comprising 73 Japanese, 9 Korean, 8 Taiwanese, and 4 Mainland Chinese. Eleven patients had parkinsonism complicated with dementia, 15 patients had family histories of parkinsonism (including 2 families), and 5 patients were from consanguineous parents (including one family). The second cohort of 23 patients was composed of patients with consanguineous parents (n = 15) or who had affected siblings (n = 6) or both (n = 2), but the age at onset ranged from 30 to 50 years.METHODS: In 117 patients with parkinsonism, direct sequencing of ATP13A2 exons 13, 16, and 26, in which mutations had been reported previously, were performed. Sequencing was also performed in all 29 exons, including splice sites, in 28 probands who showed homozygosity at the PARK9 locus by haplotype analysis. Mutation analysis was also performed in 150 normal people. Linkage analysis was performed on all 3 parkinsonism families using short tandem repeat markers flanking the PARK9 locus. For patients who had ATP13A2 mutation, we performed brain MRI and 18F-dopa PET scans.MAIN OUTCOME MEASURES: ATP13A2 DNA sequence, 18F-dopa PET scan and brain MRI findings.RESULTS: A novel F182L mutation in a consanguineous

  18. Availability of Insurance Linkage Programs in U.S. Emergency Departments

    Directory of Open Access Journals (Sweden)

    Mia Kanak

    2014-07-01

    Full Text Available Introduction: As millions of uninsured citizens who use emergency department (ED services are now eligible for health insurance under the Affordable Care Act, the ED is ideally situated to facilitate linkage to insurance. Forty percent of U.S. EDs report having an insurance linkage program. This is the first national study to examine the characteristics of EDs that offer or do not offer these programs. Methods: This was a secondary analysis of data from the National Survey for Preventive Health Services in U.S. EDs conducted in 2008-09. We compared EDs with and without insurance programs across demographic and operational factors using univariate analysis. We then tested our hypotheses using multivariable logistic regression. We also further examined program capacity and priority among the sub-group of EDs with no insurance linkage program. Results: After adjustment, ED-insurance linkage programs were more likely to be located in the West (RR= 2.06, 95% CI = 1.33 – 2.72. The proportion of uninsured patients in an ED, teaching hospital status, and public ownership status were not associated with insurance linkage availability. EDs with linkage programs also offer more preventive services (RR = 1.87, 95% CI = 1.37–2.35 and have greater social worker availability (RR = 1.71, 95% CI = 1.12–2.33 than those who do not. Four of five EDs with a patient mix of ≥25% uninsured and no insurance linkage program reported that they could not offer a program with existing staff and funding. Conclusion: Availability of insurance linkage programs in the ED is not associated with the proportion of uninsured patients served by an ED. Policy or hospital-based interventions to increase insurance linkage should first target the 27% of EDs with high rates of uninsured patients that lack adequate program capacity. Further research on barriers to implementation and cost effectiveness may help to facilitate increased adoption of insurance linkage programs. [West J

  19. Molecular characterization of Blau syndrome: Genetic linkage to chromosome 16

    Energy Technology Data Exchange (ETDEWEB)

    Tromp, G.; Duivaniemi, H.; Christiano, A. [Thomas Jefferson Univ., Philadelphia, PA (United States)] [and others

    1994-09-01

    The Blau syndrome is an autosomal, dominantly-inherited disease characterized by multi-organ, tissue-specific inflammation. Its clinical phenotype includes granulomatous uveitis, arthritis and skin rash. The syndrome is unique in that it is the sole human model for a variety of multi-system inflammatory diseases that afflict a significant percentage of the population. Karyotypic analysis of the large, three generation kindred whose disease originally characterized the syndrome was unremarkable. Following exclusion of a number of extracellular matrix candidates genes, a genome-wide search was undertaken of the Blau susceptibility locus. Fifty-seven members of the family were genotyped for about 200 highly polymorphic dinucleotide repeat markers. Linkage analysis was performed using the LINKAGE package of programs under a model of dominant inheritance with reduced penetrance. Five liability classes were used to specify penetrances and phenocopy rates for those affected the arthritis, uveitis, skin rash and combinations thererof. In addition, five age-dependent penetrance classes were used for unaffected individuals. The marker D16S298 gave a maximum lod score of 3.6 at {theta} = 0.05 with two-point analysis. Lod scores for flanking markers were consistent. These data provide convincing evidence that the Blau susceptibility locus is situated within the 16p12-q21 interval. Fine mapping of the candidate interval with additional families exhibiting the Blau phenotype, as well as with more polymorphic markers, is underway.

  20. SNPs discovery and linkage disequilibrium analysis of BSG in Chinese Han population%中国汉族人群BSG基因SNPs发掘与连锁不平衡分析

    Institute of Scientific and Technical Information of China (English)

    郑杰; 李慕鹏; 孙涛; 呼晓雷; 李元建; 陈小平

    2013-01-01

    Objective:To identify BSG single nucleotide polymorphisms (SNPs) in Chinese Han population. Methods:Peripheral blood samples were collected from 48 unrelated healthy Chinese Han subjects. Sequences at the BSG locus, including the promoter region, all exons and exon-intron boundaries were ampliifed, sequenced and followed by Hardy-Weinberg equilibrium test and linkage disequilibrium (LD) analysis. Results:A total of 19 SNPs were identiifed, 2 of which two were novel. Genotype distributions of all SNPs were consistent with Hardy-Weinberg equilibrium. Four haplotype blocks were constructed throughout the gene locus, and 9 haplotype tag SNPs (htSNPs) were inferred. Distribution of SNPs was in accordance with the neutrality theory in Chinese Han population. Conclusion:For the ifrst time, systematic identiifcation of BSG SNPs in the Chinese Han population has been done, and 9 htSNPs are identified. Our study has provided basis for further genetic association studies for related diseases as wel as pharmacogenetics study for drug response in Chinese Han population.%目的:探讨健康中国汉族人群中basigin(BSG)基因的单核苷酸多态性(single nucleotide polymorphisms,SNPs)发生情况。方法:随机收集48例健康、无亲缘关系的中国汉族人外周血液并提取基因组DNA,设计引物对所有个体BSG基因的启动子区、外显子区和外显子内含子交界区的序列进行PCR扩增和正反向测序,通过判读测序峰图,明确SNPs的发生情况及其频率;通过Hardy-Weinberg平衡分析、单倍型推测和连锁不平衡分析,确定BSG基因位点的单倍型标签SNPs(haplotype tag SNPs,htSNPs);中性理论检验查明该基因位点SNPs频率分布是否符合选择中性。结果:共发现19个SNPs,其中包括2个新发现的SNPs;所有SNPs位点基因型分布均符合Hardy-Weinberg平衡。该基因位点共推测出4种常见单倍型域,确定9个SNPs为htSNPs。中性理论检验结果提示

  1. The effect of data cleaning on record linkage quality

    OpenAIRE

    Randall, Sean M; Ferrante, Anna M; Boyd, James H.; Semmens, James B

    2013-01-01

    Background Within the field of record linkage, numerous data cleaning and standardisation techniques are employed to ensure the highest quality of links. While these facilities are common in record linkage software packages and are regularly deployed across record linkage units, little work has been published demonstrating the impact of data cleaning on linkage quality. Methods A range of cleaning techniques was applied to both a synthetically generated dataset and a large administrative data...

  2. Variants Located Upstream of CHRNB4 on Chromosome 15q25.1 Are Associated with Age at Onset of Daily Smoking and Habitual Smoking

    OpenAIRE

    Kapoor, Manav; Wang, Jen-Chyong; Bertelsen, Sarah; Bucholz, Kathy; Budde, John P; Hinrichs, Anthony; Agrawal, Arpana; Brooks, Andrew; Chorlian, David; Dick, Danielle; Hesselbrock, Victor; Foroud, Tatiana; Kramer, John; Kuperman, Samuel; Manz, Niklas

    2012-01-01

    Several genome-wide association and candidate gene studies have linked chromosome 15q24–q25.1 (a region including the CHRNA5-CHRNA3-CHRNB4 gene cluster) with alcohol dependence, nicotine dependence and smoking-related illnesses such as lung cancer and chronic obstructive pulmonary disease. To further examine the impact of these genes on the development of substance use disorders, we tested whether variants within and flanking the CHRNA5-CHRNA3-CHRNB4 gene cluster affect the transition to dail...

  3. Loss of Y-chromosome does not correlate with age at onset of head and neck carcinoma: a case-control study

    Energy Technology Data Exchange (ETDEWEB)

    Silva Veiga, L.C. [Departamento de Genética, Instituto de Biociências, Universidade Estadual Paulista, Botucatu, SP (Brazil); Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Bérgamo, N.A. [Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, GO (Brazil); Reis, P.P. [Departamento de Cirurgia e Ortopedia, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu, SP (Brazil); Kowalski, L.P. [Departamento de Cirurgia de Cabeça e Pescoço e Otorrinolaringologia, Hospital A.C. Camargo, São Paulo, SP (Brazil); Rogatto, S.R. [Laboratório NeoGene, Departamento de Urologia, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu, SP (Brazil); Departamento de Pesquisa, Hospital A.C. Camargo,Fundação Antônio Prudente, São Paulo, SP (Brazil)

    2012-01-20

    Loss of Y-chromosome has been correlated with older age in males. Furthermore, current evidence indicates that Y-chromosome loss also occurs in several human tumors, including head and neck carcinomas. However, the association between Y nullisomy and the occurrence of neoplasias in elderly men has not been well established. In the present study, the association between Y-chromosome loss and head and neck carcinomas was evaluated by comparison to cells from peripheral blood lymphocytes and normal mucosa of cancer-free individuals matched for age using dual-color fluorescence in situ hybridization. Twenty-one patients ranging in age from 28 to 68 years were divided into five-year groups for comparison with 16 cancer-free individuals matched for age. The medical records of all patients were examined to obtain clinical and histopathological data. None of the patients had undergone radiotherapy or chemotherapy before surgery. In all groups, the frequency of Y-chromosome loss was higher among patients than among normal reference subjects (P < 0.0001) and was not age-dependent. These data suggest that Y-chromosome loss is a tumor-specific alteration not associated with advanced age in head and neck carcinomas.

  4. Loss of Y-chromosome does not correlate with age at onset of head and neck carcinoma: a case-control study

    International Nuclear Information System (INIS)

    Loss of Y-chromosome has been correlated with older age in males. Furthermore, current evidence indicates that Y-chromosome loss also occurs in several human tumors, including head and neck carcinomas. However, the association between Y nullisomy and the occurrence of neoplasias in elderly men has not been well established. In the present study, the association between Y-chromosome loss and head and neck carcinomas was evaluated by comparison to cells from peripheral blood lymphocytes and normal mucosa of cancer-free individuals matched for age using dual-color fluorescence in situ hybridization. Twenty-one patients ranging in age from 28 to 68 years were divided into five-year groups for comparison with 16 cancer-free individuals matched for age. The medical records of all patients were examined to obtain clinical and histopathological data. None of the patients had undergone radiotherapy or chemotherapy before surgery. In all groups, the frequency of Y-chromosome loss was higher among patients than among normal reference subjects (P < 0.0001) and was not age-dependent. These data suggest that Y-chromosome loss is a tumor-specific alteration not associated with advanced age in head and neck carcinomas

  5. Prioritizing tiger conservation through landscape genetics and habitat linkages.

    Directory of Open Access Journals (Sweden)

    Bibek Yumnam

    Full Text Available Even with global support for tiger (Panthera tigris conservation their survival is threatened by poaching, habitat loss and isolation. Currently about 3,000 wild tigers persist in small fragmented populations within seven percent of their historic range. Identifying and securing habitat linkages that connect source populations for maintaining landscape-level gene flow is an important long-term conservation strategy for endangered carnivores. However, habitat corridors that link regional tiger populations are often lost to development projects due to lack of objective evidence on their importance. Here, we use individual based genetic analysis in combination with landscape permeability models to identify and prioritize movement corridors across seven tiger populations within the Central Indian Landscape. By using a panel of 11 microsatellites we identified 169 individual tigers from 587 scat and 17 tissue samples. We detected four genetic clusters within Central India with limited gene flow among three of them. Bayesian and likelihood analyses identified 17 tigers as having recent immigrant ancestry. Spatially explicit tiger occupancy obtained from extensive landscape-scale surveys across 76,913 km(2 of forest habitat was found to be only 21,290 km(2. After accounting for detection bias, the covariates that best explained tiger occupancy were large, remote, dense forest patches; large ungulate abundance, and low human footprint. We used tiger occupancy probability to parameterize habitat permeability for modeling habitat linkages using least-cost and circuit theory pathway analyses. Pairwise genetic differences (FST between populations were better explained by modeled linkage costs (r>0.5, p<0.05 compared to Euclidean distances, which was in consonance with observed habitat fragmentation. The results of our study highlight that many corridors may still be functional as there is evidence of contemporary migration. Conservation efforts should

  6. Co-movements of and Linkages between Asian Stock Markets

    Directory of Open Access Journals (Sweden)

    Joe H. Kim,

    2012-01-01

    Full Text Available International marketers may be interested in stock market linkages for various reasons: the co-movements of equity prices appear to reflect not only market globalization but also the globalization of capital resources. The co-movements can affect the balancing strategies of country market portfolios as they indicate opportunities and risks. The strategic choice of alternative market presence, such as market entry via export marketing or a full ownership and marketing may need to match with the type of financial resources. The co-movements of and the linkages between the U.S. stock market and Asian stock markets have been studied extensively. However, little attention has been given to the co-movements of Asian stock markets and the lead/lag linkages between them. In this paper, we study this issue with the principal components analysis (PCA and Granger-causality (G-C statistical techniques. We find that the contemporaneous co-movements of Asian stock markets have become closer and portfolio diversification benefits with Asian stock markets have diminished over time during the January 1, 2001-January 1, 2011 period. We find that the Singapore, Indian, and Japanese stock markets are the most influential stock markets and the Philippine and South Korean stock markets are the least influential stock markets in Asia. The Japanese, Singapore, and New Zealand stock markets are the least affected stock markets and the Shanghai, Australian, and South Korean stock markets are the most affected stock markets by the movements in the other Asian stock markets.

  7. Data Mining Applied to Linkage Disequilibrium Mapping

    OpenAIRE

    Toivonen, H T T; Onkamo, P.; Vasko, K; Ollikainen, V; Sevon, P; Mannila, H.; Herr, M; Kere, J

    2000-01-01

    We introduce a new method for linkage disequilibrium mapping: haplotype pattern mining (HPM). The method, inspired by data mining methods, is based on discovery of recurrent patterns. We define a class of useful haplotype patterns in genetic case-control data and use the algorithm for finding disease-associated haplotypes. The haplotypes are ordered by their strength of association with the phenotype, and all haplotypes exceeding a given threshold level are used for prediction of disease susc...

  8. Measuring the Success of Wildlife Linkage Efforts

    OpenAIRE

    Servheen, Christopher; Shoemaker, Rebecca; Basting, Pat

    2007-01-01

    Successful movement of wildlife across highways to effectively provide population-level wildlife linkage is usually viewed in one dimension - movement either exists or it does not. We believe that there are multiple ways to measure both the existence and value of such movement opportunities to better demonstrate success or failure of these efforts. The use of multiple methods to measure success will provide quantitative and qualitative values that can be used to better judge the effectiveness...

  9. How Population Growth Affects Linkage Disequilibrium

    OpenAIRE

    Alan R Rogers

    2014-01-01

    The “LD curve” relates the linkage disequilibrium (LD) between pairs of nucleotide sites to the distance that separates them along the chromosome. The shape of this curve reflects natural selection, admixture between populations, and the history of population size. This article derives new results about the last of these effects. When a population expands in size, the LD curve grows steeper, and this effect is especially pronounced following a bottleneck in population size. When a population ...

  10. Structure and apoprotein linkages of phycourobilin.

    Science.gov (United States)

    Killilea, S D; O'Carra, P

    1985-03-15

    R-Phycoerythrin contains two covalently bound bilin prosthetic groups, phycoerythrobilin and phycourobilin. The two chromophore types were separated as their peptide-bound derivatives by subjecting tryptic digests of R-phycoerythrin to adsorption chromatography on Sephadex G-25. The structure and apoprotein linkages of the bound phycoerythrobilin were found to be identical with those previously reported for this phycobilin [Killilea, O'Carra & Murphy (1980) Biochem. J. 187, 311-320]. Phycourobilin is a tetrapyrrole, containing no oxo bridges and has the same order of side chains as IX alpha bilins. The chromophore is linked to the peptide through two and possibly three of its pyrrole rings. One linkage possibly consists of an ester bond between the hydroxy group of a serine residue and the propionic acid side chain of one of the inner rings. The second linkage is a labile thioether bond between a cysteine residue and the C2 side chain of pyrrole ring A. The third linkage is a stable thioether bond between a cysteine residue and the alpha-carbon atom of the C2 side chain of pyrrole ring D. Ring D is unsaturated and is attached to ring C through a saturated carbon bridge. Rings B and C have a conjugated system of five bonds, as found in other urobilinoid pigments. Ring A is attached to ring B via a saturated carbon bridge. Both of the alpha-positions of ring A are in the reduced state, but the ring does contain an unsaturated centre (probably a double bond between the beta-carbon and the ring nitrogen atom). The presence of this double bond and its isomerization into the bridge position between rings A and B would explain the extension of the conjugated system of phycourobilin to that of a phycoerythrobilinoid/rhodenoid pigment in acid or alkali. PMID:3838665

  11. Genomic risk profiling of ischemic stroke: results of an international genome-wide association meta-analysis.

    Directory of Open Access Journals (Sweden)

    James F Meschia

    Full Text Available INTRODUCTION: Familial aggregation of ischemic stroke derives from shared genetic and environmental factors. We present a meta-analysis of genome-wide association scans (GWAS from 3 cohorts to identify the contribution of common variants to ischemic stroke risk. METHODS: This study involved 1464 ischemic stroke cases and 1932 controls. Cases were genotyped using the Illumina 610 or 660 genotyping arrays; controls, with Illumina HumanHap 550Kv1 or 550Kv3 genotyping arrays. Imputation was performed with the 1000 Genomes European ancestry haplotypes (August 2010 release as a reference. A total of 5,156,597 single-nucleotide polymorphisms (SNPs were incorporated into the fixed effects meta-analysis. All SNPs associated with ischemic stroke (P<1×10(-5 were incorporated into a multivariate risk profile model. RESULTS: No SNP reached genome-wide significance for ischemic stroke (P<5×10(-8. Secondary analysis identified a significant cumulative effect for age at onset of stroke (first versus fifth quintile of cumulative profiles based on SNPs associated with late onset, ß = 14.77 [10.85,18.68], P = 5.5×10(-12, as well as a strong effect showing increased risk across samples with a high propensity for stroke among samples with enriched counts of suggestive risk alleles (P<5×10(-6. Risk profile scores based only on genomic information offered little incremental prediction. DISCUSSION: There is little evidence of a common genetic variant contributing to moderate risk of ischemic stroke. Quintiles based on genetic loading of alleles associated with a younger age at onset of ischemic stroke revealed a significant difference in age at onset between those in the upper and lower quintiles. Using common variants from GWAS and imputation, genomic profiling remains inferior to family history of stroke for defining risk. Inclusion of genomic (rare variant information may be required to improve clinical risk profiling.

  12. Structural synthesis of linkages for quadruped bio-robot legs

    Science.gov (United States)

    Antonescu, O.; Robu, C.; Antonescu, P.

    2016-08-01

    The paper presents a few kinematic schemes of planar mechanisms with bars (linkages) used as part of the quadruped robot legs. The Dunshee linkage having only four elements as crank-rocker mechanism is analyzed. Further, the Klann linkage, which is accomplished by amplifying the crank-rocker mechanism with a dyadic kinematic chain, is also presented. More than that, the Jansen linkage, which is obtained by extending and amplifying the crank-rocker mechanism with two dyadic kinematic chains, is also analyzed. At the end of the paper, the authors present a novel linkage application consisting of a quadric kinematic chain.

  13. Preliminary genetic linkage maps of Chinese herb Dendrobium nobile and D. moniliforme

    Indian Academy of Sciences (India)

    Shangguo Feng; Hongyan Zhao; Jiangjie Lu; Junjun Liu; Bo Shen; Huizhong Wang

    2013-08-01

    Dendrobium is an endangered genus in the orchid family with medicinal and horticultural value. Two preliminary genetic linkage maps were constructed using 90 F1 progeny individuals derived from an interspecific cross between D. nobile and D. moniliforme (both, $2n = 38$), using random amplified polymorphic DNA (RAPD) and intersimple sequence repeat (ISSR). A total of 286 RAPD loci and 68 ISSR loci were identified and used for genetic linkage analysis. Maps were constructed by double pseudo-testcross mapping strategy using the software Mapmaker/EXP ver. 3.0, and Kosambi map distances were constructed using a LOD score ≥4 and a recombination threshold of 0.4. The resulting frame map of D. nobile was 1474 cM in total length with 116 loci distributed in 15 linkage groups; and the D. moniliforme linkage map had 117 loci placed in 16 linkage groups spanning 1326.5 cM. Both maps showed 76.91% and 73.59% genome coverage for D. nobile and D. moniliforme, respectively. These primary maps provide an important basis for genetic studies and further medicinal and horticultural traits mapping and marker-assisted selection in Dendrobium breeding programmes.

  14. Irish study of high-density Schizophrenia families: Field methods and power to detect linkage

    Energy Technology Data Exchange (ETDEWEB)

    Kendler, K.S.; Straub, R.E.; MacLean, C.J. [Virginia Commonwealth Univ., Richmond, VA (United States)] [and others

    1996-04-09

    Large samples of multiplex pedigrees will probably be needed to detect susceptibility loci for schizophrenia by linkage analysis. Standardized ascertainment of such pedigrees from culturally and ethnically homogeneous populations may improve the probability of detection and replication of linkage. The Irish Study of High-Density Schizophrenia Families (ISHDSF) was formed from standardized ascertainment of multiplex schizophrenia families in 39 psychiatric facilities covering over 90% of the population in Ireland and Northern Ireland. We here describe a phenotypic sample and a subset thereof, the linkage sample. Individuals were included in the phenotypic sample if adequate diagnostic information, based on personal interview and/or hospital record, was available. Only individuals with available DNA were included in the linkage sample. Inclusion of a pedigree into the phenotypic sample required at least two first, second, or third degree relatives with non-affective psychosis (NAP), one of whom had schizophrenia (S) or poor-outcome schizoaffective disorder (PO-SAD). Entry into the linkage sample required DNA samples on at least two individuals with NAP, of whom at least one had S or PO-SAD. Affection was defined by narrow, intermediate, and broad criteria. 75 refs., 6 tabs.

  15. Drought susceptibility of modern rice varieties: an effect of linkage of drought tolerance with undesirable traits.

    Science.gov (United States)

    Vikram, Prashant; Swamy, B P Mallikarjuna; Dixit, Shalabh; Singh, Renu; Singh, Bikram P; Miro, Berta; Kohli, Ajay; Henry, Amelia; Singh, N K; Kumar, Arvind

    2015-01-01

    Green Revolution (GR) rice varieties are high yielding but typically drought sensitive. This is partly due to the tight linkage between the loci governing plant height and drought tolerance. This linkage is illustrated here through characterization of qDTY1.1, a QTL for grain yield under drought that co-segregates with the GR gene sd1 for semi-dwarf plant height. We report that the loss of the qDTY1.1 allele during the GR was due to its tight linkage in repulsion with the sd1 allele. Other drought-yield QTLs (qDTY) also showed tight linkage with traits rejected in GR varieties. Genetic diversity analysis for 11 different qDTY regions grouped GR varieties separately from traditional drought-tolerant varieties, and showed lower frequency of drought tolerance alleles. The increased understanding and breaking of the linkage between drought tolerance and undesirable traits has led to the development of high-yielding drought-tolerant dwarf lines with positive qDTY alleles and provides new hope for extending the benefits of the GR to drought-prone rice-growing regions. PMID:26458744

  16. Thiocyanate linkage isomerism in a ruthenium polypyridyl complex.

    Science.gov (United States)

    Brewster, Timothy P; Ding, Wendu; Schley, Nathan D; Hazari, Nilay; Batista, Victor S; Crabtree, Robert H

    2011-12-01

    Ruthenium polypyridyl complexes have seen extensive use in solar energy applications. One of the most efficient dye-sensitized solar cells produced to date employs the dye-sensitizer N719, a ruthenium polypyridyl thiocyanate complex. Thiocyanate complexes are typically present as an inseparable mixture of N-bound and S-bound linkage isomers. Here we report the synthesis of a new complex, [Ru(terpy)(tbbpy)SCN][SbF(6)] (terpy = 2,2';6',2''-terpyridine, tbbpy = 4,4'-di-tert-butyl-2,2'-bipyridine), as a mixture of N-bound and S-bound thiocyanate linkage isomers that can be separated based on their relative solubility in ethanol. Both isomers have been characterized spectroscopically and by X-ray crystallography. At elevated temperatures the isomers equilibrate, the product being significantly enriched in the more thermodynamically stable N-bound form. Density functional theory analysis supports our experimental observation that the N-bound isomer is thermodynamically preferred, and provides insight into the isomerization mechanism. PMID:22066656

  17. Linkage of familial dilated cardiomyopathy to chromosome 9

    Energy Technology Data Exchange (ETDEWEB)

    Krajinovic, M.; Vatta, M.; Milasin, J. [Univ. of Trieste (Italy)] [and others

    1995-10-01

    Idiopathic dilated cardiomyopathy is a heart muscle disease of unknown etiology, characterized by impaired myocardial contractility and ventricular dilatation. The disorder is an important cause of morbidity and mortality and represents the chief indication for heart transplantation. Familial transmission is often recognized (familial dilated cardiomyopathy, or FDC), mostly with autosomal dominant inheritance. In order to understand the molecular genetic basis of the disease, a large six-generation kindred with autosomal dominant FDC was studied for linkage analysis. A genome-wide search was undertaken after a large series of candidate genes were excluded and was then extended to two other families with autosomal dominant pattern of transmission and identical clinical features. Coinheritance of the disease gene was excluded for >95% of the genome, after 251 polymorphic markers were analyzed. Linkage was found for chromosome 9q13-q22, with a maximum multipoint lod score of 4.2. There was no evidence of heterogeneity. The FDC locus was placed in the interval between loci D9S153 and D9S152. Several candidate genes for causing dilated cardiomyopathy map in this region. 33 refs., 3 figs., 1 tab.

  18. Genetic linkage analysis of susceptible gene of congenital dislocation of the hip with chromosome 7, 22 in four Yunnan pedigrees%云南地区先天性髋关节脱位4个家系22号与7号染色体易感基因连锁分析

    Institute of Scientific and Technical Information of China (English)

    鲁宁; 张宝华; 胡侦明; 浦波; 王迎松; 虞弘; 曹有良; 王少飞; 杨庆秋; 劳汉昌

    2008-01-01

    Objective To investigate genetic linkage between the phenotype of congenital dislocation of the hip (CDH) and genes located in chromosome 22,7, and attempt initially process of the genome-wide scan for searching disease-susceptibility loci.Methods According to epidemiological data,we studied 4 kindred with CDH in yunna,which include 65 persons in 5 generations.the affected status of 17 individuals had been established on the basis of their clinical and radiological presentation of the disorder.44 blood specimens were collected from those members who could be followed trail, and their nucleus DNA was extracted from peripheral leukocytes as phenol method.35 Tetnuc or Trinuc repeat microsatellite markers exploited by CHLC were chosen.8 markers distributed on chromosome 22, and 10 markers distributed on 7chromosome with an average interval of 10 cm.Genimic DNA were amplified by PCR technique.The PCR products were subjected to vertical electrophoresis in PAGE gel with continous buffer system, followed by siliver staining.graphic analysis system was used to define each allele.Parametric linkage analysi using maximum likelihood estimation were computed by the linkage package for various recombination fraction valus, with a disease gene grequency of 0.02.Results 18 STR loci are showen to provide good discrimination power by highly polymorphism and heterozygosity.Gnotype dated were obtained and conformed to Mendel law.Linkage analysis with those markers gave minus two-point LOD score values (Z<1), which the markers in 22and 7 chromosome indicated that there no linkage between the markers and CDH gene in those pedigrees.Conclusions CDH susceptibility genes are not likely located on chromosome 22, 7.The approach to geno-wide scan using highly density STR markers would play an important role in map the gene responsible for CDH.%目的 探讨先天性髋关节脱位 (CDH) 与22、7号染色体之间的连锁关系.方法 以4个云南地区CDH家系为研究对象,提取所有

  19. 企业间协调联动机制影响因素分析——基于结构方程模型的分析%Analysis on Influential Factors of the Coordination and Linkage Mechanism Between Enterprises—Based on the SEM

    Institute of Scientific and Technical Information of China (English)

    徐娜; 王锐; 王辉

    2012-01-01

    Affected by multiple factors,the coordination and linkage mechanism shows characteristics of diversity and complexity.This paper puts forwords six key factors:interdependence and trust,uncertainty,enterprise culture,information communication and sharing,benefit-sharing,policy and legal environment.Using the structural equation model,through an analysis of the complex interactions of different factors on the pathway and the linkage between factors,the corresponding countermeasures are proposed to improve the cooperative relationship.%企业间协调联动机制受多因素综合影响,体现出多元化与复杂性特征。利用结构方程模型,针对影响协调联动机制的6个关键因素:相互依赖与信任、不确定性、企业文化、信息沟通与共享、利益分享和政策法律环境,分析验证不同因素对协调联动的作用路径及各因素间的复杂交互关系,并提出改进合作关系的相应对策。

  20. 制造业与物流业联动发展模式选择研究--微观视角下的比较分析%Research on the Mode Selection of Linkage Development of Manufacturing and Logistics Industry-the Micro Perspective of Comparative Analysis

    Institute of Scientific and Technical Information of China (English)

    云程浩; 李严锋; 王永峰; 司银元

    2014-01-01

    With the acceleration of linkage development of manufacturing and logistics industry ,more and more studies are being carried out in this field .By using the method of comparative analysis , the article researches on the mode of linkage development of manufacturing and logistics industry from the micro perspective .We elaborate three modes which are self -run logistics,principal-agent,strategic alliance mainly from the perspective of organization form ,and then put forward the qualitative decision-making model of mode selection by comparing the advantages ,disadvantages and applicable conditions .%随着制造业与物流业联动发展的逐步深入,有关两业联动的研究越来越多。文中站在微观视角,运用比较分析的方法对制造业与物流业联动发展的模式进行研究。重点从两业联动的组织形式的角度阐述自营物流、委托代理、战略联盟三种模式及其子模式。进而比较各模式的优势、劣势和适用条件,最终提出定性的模式选择决策模型。

  1. Genetic linkage map of Brassica campestris L. Using AFLP and RAPD markers

    Institute of Scientific and Technical Information of China (English)

    卢钢; 曹家树; 陈杭

    2002-01-01

    A genetic linkage map comprised of 131 loci was constructed with an F2 population derived from an inter-subspecific cross between Brassica 'qisihai'. The genetic map included 93 RAPD loci, 36 AFLP loci and 2 morphological loci organized into 10 main linkage groups (LGs) and 2 small groups, covering 1810.9cM with average distance between adjacent markers being approximately 13.8cM. The map is suitable for identification of molecular markers linked to important agronomic traits, QTL analysis, and even for marker-assisted selection in breeding programs of Chinese cabbage and turnip.

  2. Extensional hard linkages, eastern Gulf of Suez, Egypt

    Science.gov (United States)

    McClay, Ken; Khalil, Samir

    1998-06-01

    The Araba Abu Durba area on the eastern margin of the Gulf of Suez exhibits two superb outcrop examples of extensional hard linkages in a rift basin. Here, three large, domino-style, basement-cored, northeast-dipping fault blocks are formed by a series of major northwest-trending normal faults. These are offset by two north-northeast trending sinistral oblique-slip transfer faults that terminate in horsetail normal fault splays. The transfer faults do not extend across the entire rift basin. Detailed mapping and structural analysis show that they developed by breakage of initial low-strain relay ramps along reactivated north-northeast trending basement fabrics between overlapping northwest-trending normal fault segments. Paleostrain analysis of fault-slip indicators shows that both the normal and the sinistral oblique-slip transfer faults were formed synchronously in response to northeast-southwest extension, perpendicular to the main northwest rift trend.

  3. Multiple Resonance and Stability of a Motor-elastic Linkage Mechanism System

    Institute of Scientific and Technical Information of China (English)

    LI Zhao-jun; CAI Gan-wei; DAI Wen-zheng

    2006-01-01

    The dynamics of a three-phase AC motor-elastic linkage mechanism system is considered. Taking the drive motor and the linkage mechanism as an integrated system, the coupling dynamic equations of the system are established by the finite element method. The multiple resonance and its stability of the system are studied using the method of multiple scales. The first order approximate solutions of the multiple resonance of the system are obtained. An algorithm for determining the stability of resonance is derived. The studies show that the multiple resonance and its stability of the system are not only related to the structure parameters of the linkage mechanism, but also to the electromagnetism parameters of the motor. At last, an experiment is given to verify the results of the theoretical analysis.

  4. Linkage between sexual orientation and chromosome Xq28 in males but not in females.

    Science.gov (United States)

    Hu, S; Pattatucci, A M; Patterson, C; Li, L; Fulker, D W; Cherny, S S; Kruglyak, L; Hamer, D H

    1995-11-01

    We have extended our analysis of the role of the long arm of the X chromosome (Xq28) in sexual orientation by DNA linkage analyses of two newly ascertained series of families that contained either two gay brothers or two lesbian sisters as well as heterosexual siblings. Linkage between the Xq28 markers and sexual orientation was detected for the gay male families but not for the lesbian families or for families that failed to meet defined inclusion criteria for the study of sex-linked sexual orientation. Our results corroborate the previously reported linkage between Xq28 and male homosexuality in selected kinships and suggest that this region contains a locus that influences individual variations in sexual orientation in men but not in women. PMID:7581447

  5. Effective population size of an indigenous Swiss cattle breed estimated from linkage disequilibrium

    Science.gov (United States)

    Effective population size is an important parameter for the assessment of genetic diversity within a livestock population and its development over time. If pedigree information is not available, linkage disequilibrium (LD) analysis might offer an alternative perspective for the estimation of effecti...

  6. University-Industry Linkages in Developing Countries: Perceived Effect on Innovation

    Science.gov (United States)

    Vaaland, Terje I.; Ishengoma, Esther

    2016-01-01

    Purpose: The purpose of this paper is to assess the perceptions of both universities and the resource-extractive companies on the influence of university-industry linkages (UILs) on innovation in a developing country. Design/Methodology/Approach: A total of 404 respondents were interviewed. Descriptive analysis and multinomial logistic regression…

  7. Influence of Ti–O–Si hetero-linkages in the photocatalytic degradation of Rhodamine B

    NARCIS (Netherlands)

    Rasalingam, S; Kibombo, H.S.; Wu, C.M.; Budhi, S.; Peng, R.; Baltrusaitis, J.; Koodali, R.T.

    2013-01-01

    The influence of Ti–O–Si hetero-linkages in the degradation of Rhodamine B (RhB) dye over TiO2–SiO2 xerogels is exemplified by XPS analysis. We demonstrate a relationship between the percentage surface content of Ti–O–Si and the rate of photocatalytic degradation of RhB. Our detailed surface investi

  8. Trade-FDI linkages in a simultaneous equations system of gravity models for german regional data

    DEFF Research Database (Denmark)

    Mitze, Timo Friedel; Alecke, Björn; Untiedt, Gerhard

    2010-01-01

    Abstract. Using regional data, we analyze the nature of German trade-FDI linkages within the EU27 for a system of gravity equations. Starting from a macroeconomic perspective, our analysis supports earlier empirical evidence for Germany in finding substitutive links between trade and outward FDI...... between trade and FDI....

  9. Linkage localization of X-linked Charcot-Marie-Tooth disease

    Energy Technology Data Exchange (ETDEWEB)

    Bergoffen, J. (Children' s Hospital, Philadelphia, PA (United States) Univ. of Pennsylvania, Philadelphia (United States)); Trofatter, J.; Haines, J.L. (Massachusetts General Hospital, Boston (United States)); Pericak-Vance, M.A. (Duke Univ., Durham, NC (United States)); Chance, P.F. (Univ. of Utah, Salt Lake City (United States)); Fischbeck, K.H. (Univ. of Pennsylvania, Philadelphia (United States))

    1993-02-01

    Charcot-Marie-Tooth disease (CMT), also known as hereditary motor and sensory neuropathy, is a heterogeneous group of slowly progressive, degenerative disorders of peripheral nerve. X-linked CMT (CMTX) (McKusick 302800), a subdivision of type I, or demyelinating, CMT is an X-linked dominant condition with variable penetrance. Previous linkage analysis using RFLPs demonstrated linkage to markers on the proximal long and short arms of the X chromosome, with the more likely localization on the proximal long arm of the X chromosome. Available variable simple-sequence repeats (VSSRs) broaden the possibilities for linkage analysis. This paper presents new linkage data and recombination analysis derived from work with four VSSR markers - AR, PGKP1, DXS453, and DXYS1X - in addition to analysis using RFLP markers described elsewhere. These studies localize the CMTX gene to the proximal Xq segment between PGKP1 (Xq11.2-12) and DXS72 (Xq21.1), with a combined maximum multipoint lod score of 15.3 at DXS453 ([theta] = 0). 32 refs., 3 figs., 2 tabs.

  10. An integrated resource for barley linkage map and malting quality QTL alignment

    Science.gov (United States)

    Barley (Hordeum vulgare subsp. vulgare) is an economically important model plant for genetics research that is currently served by a comprehensive set of tools for genetic analysis. High density genetic linkage maps constructed from the inheritance of robust gene-based Single Nucleotide Polymorphism...

  11. Transformational leadership climate : Performance linkages, mechanisms, and boundary conditions at the organizational level

    NARCIS (Netherlands)

    Menges, J.; Walter, F.; Vogel, B.; Bruch, H.

    2011-01-01

    Transformational leadership (TFL) climate describes the degree to which leaders throughout an organization engage in TFL behaviors. In this study, we investigate performance linkages, mechanisms, and boundary conditions of TFL climate at the organizational level of analysis. In a sample of 158 indep

  12. HIV-1 transmission linkage in an HIV-1 prevention clinical trial

    Energy Technology Data Exchange (ETDEWEB)

    Leitner, Thomas [Los Alamos National Laboratory; Campbell, Mary S [UNIV OF WASHINGTON; Mullins, James I [UNIV OF WASHINGTON; Hughes, James P [UNIV OF WASHINGTON; Wong, Kim G [UNIV OF WASHINGTON; Raugi, Dana N [UNIV OF WASHINGTON; Scrensen, Stefanie [UNIV OF WASHINGTON

    2009-01-01

    HIV-1 sequencing has been used extensively in epidemiologic and forensic studies to investigate patterns of HIV-1 transmission. However, the criteria for establishing genetic linkage between HIV-1 strains in HIV-1 prevention trials have not been formalized. The Partners in Prevention HSV/HIV Transmission Study (ClinicaITrials.gov NCT00194519) enrolled 3408 HIV-1 serodiscordant heterosexual African couples to determine the efficacy of genital herpes suppression with acyclovir in reducing HIV-1 transmission. The trial analysis required laboratory confirmation of HIV-1 linkage between enrolled partners in couples in which seroconversion occurred. Here we describe the process and results from HIV-1 sequencing studies used to perform transmission linkage determination in this clinical trial. Consensus Sanger sequencing of env (C2-V3-C3) and gag (p17-p24) genes was performed on plasma HIV-1 RNA from both partners within 3 months of seroconversion; env single molecule or pyrosequencing was also performed in some cases. For linkage, we required monophyletic clustering between HIV-1 sequences in the transmitting and seroconverting partners, and developed a Bayesian algorithm using genetic distances to evaluate the posterior probability of linkage of participants sequences. Adjudicators classified transmissions as linked, unlinked, or indeterminate. Among 151 seroconversion events, we found 108 (71.5%) linked, 40 (26.5%) unlinked, and 3 (2.0%) to have indeterminate transmissions. Nine (8.3%) were linked by consensus gag sequencing only and 8 (7.4%) required deep sequencing of env. In this first use of HIV-1 sequencing to establish endpoints in a large clinical trial, more than one-fourth of transmissions were unlinked to the enrolled partner, illustrating the relevance of these methods in the design of future HIV-1 prevention trials in serodiscordant couples. A hierarchy of sequencing techniques, analysis methods, and expert adjudication contributed to the linkage

  13. 区域产业关联经济距离模型的构建及实证分析%A model construction and empirical analysis of regional industrial linkage and economic distance

    Institute of Scientific and Technical Information of China (English)

    唐志鹏; 邓志国; 刘红光

    2013-01-01

    There are both a linkage relationship and economic distances between sectors in the national economic system.The linkages between sectors show their interconnection,and their economic distance reflects their intermediate production links.This paper synthesizes the advantages of the average production lengths model and relevancy of input-output method,and constructs a regional industrial linkage and economic distance model,including the forward linkage and economic distance index and the backward linkage and economic distance index.Then,we calculate these indexes according to eight-regional-input-output table for China in 1997,in 2002 and in 2007.The results show,from the viewpoint of the primary inputs of upstream industry,that the greatest interconnection and the minimum economic distance is from the sector of mining to the sector of electricity and heating power production and supply; and from the point of the final demand of the downstream industry,that the greatest interconnection and the minimum economic distance is from the sector of electricity and heating power production and supply mining to the sector of heavy industry or the sector of construction during the period from 1997 to 2007 either intra-region or inter-region.We find there are greater interconnections in intra-region than inter-region for the upstream and downstream industries of the sector of electricity and heating power production and supply,and the greatest spatial energy interconnection takes place in the vicinity of most of the eight regions because of spatial costs.%国民经济系统中产业之间既存在关联,又存在经济距离.关联反映产业之间联系程度的紧密,经济距离反映产业之间中间生产环节的多少.本文结合投入产出关联度和APL模型两种方法各自的优点,创建了区域产业关联经济距离模型,包括前向关联经济距离指数和后向关联经济距离指数,并采用1997-2007中国区域间投入产出表的电力热力

  14. Population-environment linkages in international law

    Energy Technology Data Exchange (ETDEWEB)

    Babor, D.D.M.

    1999-03-31

    This article explores population-environment linkages both within developed and developing nations, and considers the consequences of a population growth rate which, as one hectare of arable land is simultaneously lost or destroyed, currently results in eight live births every three seconds. In order to better comprehend the forces governing their perceptions, Part 1 of this article will discuss eight interactive variables which inform decision-making. Part 2 will examine the existence of legal duties under international law to limit or constrain the level of consumption and the right to freely reproduce, particularly as applicable in states considered free of a population problem.

  15. Ethnicity and the ethics of data linkage

    Directory of Open Access Journals (Sweden)

    Boyd Kenneth M

    2007-11-01

    Full Text Available Abstract Linking health data with census data on ethnicity has potential benefits for the health of ethnic minority groups. Ethical objections to linking these data however include concerns about informed consent and the possibility of the findings being misused against the interests of ethnic minority groups. While consent concerns may be allayed by procedures to safeguard anonymity and respect privacy, robust procedures to demonstrate public approval of data linkage also need to be devised. The possibility of findings being misused against the interests of ethnic minority groups may be diminished by informed and open public discussion in mature democracies, but remain a concern in the international context.

  16. 考虑风储参与的电力市场联动博弈分析%Analysis on Electricity Market Linkage Game Considering Participation of Wind Power and Energy Storage

    Institute of Scientific and Technical Information of China (English)

    李丹; 刘俊勇; 刘友波; 戴松灵; 江润洲

    2015-01-01

    研究了考虑风电与储能参与的电力市场联动博弈问题。首先,在含有传统发电、供电、风电、储能商及用户的多方电力市场联动博弈模型中,针对风电与储能服务商的特点,设计了独立和联营2种运营模式,并分别建立了考虑投标风险的最佳风电投标量及储能充放电决策模型;然后,建立了基于多代理的电力市场联动博弈模型,对比和分析了2种模式下风电投标及储能充放电行为的差异,以及联营模式下考虑网络约束前后各方利润和线路负载等技术经济指标。仿真结果表明:风电商能够优化决策自身投标电量,获得合理的利润;风-储联营模式能够对风能进行合理转移,增加两者总利润;网络约束对市场中参与方的利润有重要影响。%The electricity market linkage game, in which the wind power provider and energy storage provider participate, is researched. Firstly, in multipartite electricity market linkage game model including traditional gencos, power supply enterprises, wind power provider and energy storage provider, according to the characteristics of wind power provider and energy storage provider, two operating modes, namely independent operation and joint operation, are designed, and the optimal wind power bidding decision model and optimal charging/discharging decision model, in which the risk of bidding is taken into account, are established respectively; secondly, a multi-agent based electricity market linkage game model is built, and the differences between wind power bidding and charging/discharging behavior of energy storage provider as well as the benefits of different aspects and techno- economical indices such as line load and so on before and after considering network constraints under the joint operation mode are compared and analyzed. Simulation results show that the wind power provider can optimize and decide its own electricity quantity

  17. Analysis on Electricity Market Linkage Game Considering Participation of Wind Power and Energy Storage%考虑风储参与的电力市场联动博弈分析

    Institute of Scientific and Technical Information of China (English)

    李丹; 刘俊勇; 刘友波; 戴松灵; 江润洲

    2015-01-01

    The electricity market linkage game, in which the wind power provider and energy storage provider participate, is researched. Firstly, in multipartite electricity market linkage game model including traditional gencos, power supply enterprises, wind power provider and energy storage provider, according to the characteristics of wind power provider and energy storage provider, two operating modes, namely independent operation and joint operation, are designed, and the optimal wind power bidding decision model and optimal charging/discharging decision model, in which the risk of bidding is taken into account, are established respectively; secondly, a multi-agent based electricity market linkage game model is built, and the differences between wind power bidding and charging/discharging behavior of energy storage provider as well as the benefits of different aspects and techno- economical indices such as line load and so on before and after considering network constraints under the joint operation mode are compared and analyzed. Simulation results show that the wind power provider can optimize and decide its own electricity quantity participating the bidding to achieve reasonable revenue; the joint operation mode of wind power provider with energy storage provider can transfer the wind energy reasonably to increase the benefits of both sides; there is important impact of network constraints on the benefits of the participants.%研究了考虑风电与储能参与的电力市场联动博弈问题。首先,在含有传统发电、供电、风电、储能商及用户的多方电力市场联动博弈模型中,针对风电与储能服务商的特点,设计了独立和联营2种运营模式,并分别建立了考虑投标风险的最佳风电投标量及储能充放电决策模型;然后,建立了基于多代理的电力市场联动博弈模型,对比和分析了2种模式下风电投标及储能充放电行为的差异,以及联营模式下考虑网络约

  18. Linkage results on 11q21-22 in Eastern Quebec pedigrees densely affected by schizophrenia

    Energy Technology Data Exchange (ETDEWEB)

    Maziade, M.; Raymond, V.; Cliche, D. [Universite Laval Robert Giffard, Beauport, Quebec (Canada)] [and others

    1995-12-18

    The 11q21-22 region is of interest for schizophrenia because several candidate genes are located in this section of the genome. The 11q21-22 region, including DRD2, was surveyed by linkage analysis in a sample (N = 242) made of four large multigenerational pedigrees densely affected by schizophrenia (SZ) and eight others by bipolar disorder (BP). These pedigrees were ascertained in a large area of Eastern Quebec and Northern New Brunswick and are still being extended. Family members were administered a {open_quotes}consensus best-estimate diagnosis procedure{close_quotes} (DSM-III-R criteria) blind to probands and relatives` diagnosis and to pedigree assignment (SZ or BP). For linkage analysis, 11 microsatellite polymorphism (CA repeat) markers, located at 11q21-22, and comprising DRD2, were genotyped. Results show no evidence of a major gene for schizophrenia. However, a maximum lod score of 3.41 at the D11S35 locus was observed in an affected-only analysis of one large SZ family, pedigree 255. Whether or not the positive linkage trend in pedigree 255 reflects a true linkage for a small proportion of SZ needs to be confirmed through the extension of this kindred and through replication. 36 refs., 2 tabs.

  19. A SSR-based composite genetic linkage map for the cultivated peanut (Arachis hypogaea L. genome

    Directory of Open Access Journals (Sweden)

    Li Shaoxiong

    2010-01-01

    Full Text Available Abstract Background The construction of genetic linkage maps for cultivated peanut (Arachis hypogaea L. has and continues to be an important research goal to facilitate quantitative trait locus (QTL analysis and gene tagging for use in a marker-assisted selection in breeding. Even though a few maps have been developed, they were constructed using diploid or interspecific tetraploid populations. The most recently published intra-specific map was constructed from the cross of cultivated peanuts, in which only 135 simple sequence repeat (SSR markers were sparsely populated in 22 linkage groups. The more detailed linkage map with sufficient markers is necessary to be feasible for QTL identification and marker-assisted selection. The objective of this study was to construct a genetic linkage map of cultivated peanut using simple sequence repeat (SSR markers derived primarily from peanut genomic sequences, expressed sequence tags (ESTs, and by "data mining" sequences released in GenBank. Results Three recombinant inbred lines (RILs populations were constructed from three crosses with one common female parental line Yueyou 13, a high yielding Spanish market type. The four parents were screened with 1044 primer pairs designed to amplify SSRs and 901 primer pairs produced clear PCR products. Of the 901 primer pairs, 146, 124 and 64 primer pairs (markers were polymorphic in these populations, respectively, and used in genotyping these RIL populations. Individual linkage maps were constructed from each of the three populations and a composite map based on 93 common loci were created using JoinMap. The composite linkage maps consist of 22 composite linkage groups (LG with 175 SSR markers (including 47 SSRs on the published AA genome maps, representing the 20 chromosomes of A. hypogaea. The total composite map length is 885.4 cM, with an average marker density of 5.8 cM. Segregation distortion in the 3 populations was 23.0%, 13.5% and 7.8% of the markers

  20. Linkage of morphological markers in brassica

    International Nuclear Information System (INIS)

    Morphological markers play a pivotal role in selection of desirable traits in all plant breeding programs. The genetic linkage maps provide the basic information about the nature and place of genes on genetic maps. Two plant introduction (PI) germplasm of Brassica napus i.e. PI409024 and PI 535850 were inter specifically hybridized to 366 and 1203 lines of B. campestris. The hybrids i.e. 409024 x 1203 and crusher x 1203 were grown to produce F1 generation. The F1 populations were evaluated for genetic nature of four morphological qualitative traits like plant color, flower color, leaf shape and leaf pubescence at the KPK Agricultural University, Peshawar. In F1 generation dark green plant color (C), dark yellow flower color (Y), entire leaf shape (E1) and non-hairiness of leaf (h) were expressed as dominant traits. In F2 generation the hybrids segregated and were classified into their respective phenotypic classes. Linkages were detected between Y and H, and E1 and H, pairs of loci. The recombination frequency between Y and H loci was 17.7+- 10.3 cM, and between E1 and H was 32.3 +- 9.9 cM. (author)

  1. Mechanical Design of Step-Climbing Vehicle with Passive Linkages

    OpenAIRE

    Chugo, Daisuke; Kawabata, Kuniaki; Kaetsu, Hayato; Asama, Hajime; Mishima, Taketoshi

    2007-01-01

    In this paper, we proposed the mechanical design for passive linkages. We discuss the moment force which is applied on the vehicle body when the vehicle contacts the step and we derive the moment force using the position of free joint point. From the derivation, we design new passive linkage mechanism and utilize it to our prototype. We verified the effectiveness of our proposed design on passive linkages by computer simulations and experiments. Utilizing our proposed mechanical design on the...

  2. Molecular Cytogenetic Maps of Sorghum Linkage Groups 2 and 8

    OpenAIRE

    Kim, Jeong-Soon; Klein, Patricia E; Klein, Robert R.; Price, H. James; Mullet, John E.; Stelly, David M.

    2005-01-01

    To integrate genetic, physical, and cytological perspectives of the Sorghum bicolor genome, we selected 40 landed bacterial artificial chromosome (BAC) clones that contain different linkage map markers, 21 from linkage group 2 (LG-02) and 19 from linkage group 8 (LG-08). Multi-BAC probe cocktails were constructed for each chromosome from the landed BACs, which were also preevaluated for FISH signal quality, relative position, and collective chromosome coverage. Comparison to the corresponding...

  3. 人民币与欧元、美元、日元之间的汇率联动分析%Dynamic Linkage Analysis to the Exchange Rates of RMB,the Euro,the Dollar and the Yen

    Institute of Scientific and Technical Information of China (English)

    郭珺; 滕柏华

    2011-01-01

    利用向量自回归模型和多变量GARCH模型,对人民币汇率改革以来人民币、欧元、美元和日元之间的收益溢出效应和波动溢出效应进行了研究。结果显示欧元、美元和日元对人民币存在显著的收益溢出效应和波动溢出效应,但是人民币对其他几种货币的收益溢出效应和波动溢出效应并不显著。研究结果表明,人民币汇率形成机制改革以来,人民币汇率正在融入世界主要货币汇率市场,但是人民币汇率市场尚不成熟,目前我国仍然应该实行有管理的浮动汇率制度。%This paper analyzes the dynamic linkages among exchange rates of Chinese Yuan euro,USA dollar and Japanese yen.Using vector autoregressive model and multivariate generalized autoregressive conditional heteroskedasticity model,we have found that the spillo

  4. Further evidence for clustering of human GABA[sub A] receptor subunit genes: Localization of the [alpha][sub 6]-subunit gene (GABRA6) to distal chromosome 5q by linkage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Hicks, A.A.; Kamphuis, W.; Darlison, M.G. (MRC Molecular Neurobiology Unit, Cambride (United Kingdom)); Bailey, M.E.S.; Johnson, K.J. (Charing Cross and Westminster Medical School, London (United Kingdom)); Riley, B.P. (St. Mary' s Hospital Medical School, London (United Kingdom)); Siciliano, M.J. (Univ. of Texas M.D. Anderson Cancer Center, Houston, TX (United States))

    1994-03-15

    GABA[sub A] receptors are hetero-oligomeric ion-channel complexes that are composed of combinations of [alpha], [beta], [gamma], and [delta] subunits and play a major role in inhibitory neurotransmission in the mammalian brain. The authors report here a microsatellite polymorphism within the human [alpha][sub 6]-subunit gene (GABRA6). Mapping of this marker in a human-hamster hybrid cell-line panel and typing of the repeat in the Centre d'Etude du Polymorphisme Humain (CEPH) reference families enabled the localization of this gene to chromosome 5q and established its linkage to the GABA[sub A] receptor [alpha][sub 1]-subunit gene (GA-BRA1) with a maximum lod score (Z[sub max]) of 39.87 at a [theta] of 0.069 (males) and 0.100 (females). These results reveal the clustering of GABRA6, GABRA1, and the GABA[sub A] receptor [gamma][sub 2]-subunit gene (GABRG2) on distal chromosome 5q. 17 refs., 1 fig., 1 tab.

  5. Accuracy of probabilistic and deterministic record linkage: the case of tuberculosis

    Science.gov (United States)

    de Oliveira, Gisele Pinto; Bierrenbach, Ana Luiza de Souza; de Camargo, Kenneth Rochel; Coeli, Cláudia Medina; Pinheiro, Rejane Sobrino

    2016-01-01

    ABSTRACT OBJECTIVE To analyze the accuracy of deterministic and probabilistic record linkage to identify TB duplicate records, as well as the characteristics of discordant pairs. METHODS The study analyzed all TB records from 2009 to 2011 in the state of Rio de Janeiro. A deterministic record linkage algorithm was developed using a set of 70 rules, based on the combination of fragments of the key variables with or without modification (Soundex or substring). Each rule was formed by three or more fragments. The probabilistic approach required a cutoff point for the score, above which the links would be automatically classified as belonging to the same individual. The cutoff point was obtained by linkage of the Notifiable Diseases Information System – Tuberculosis database with itself, subsequent manual review and ROC curves and precision-recall. Sensitivity and specificity for accurate analysis were calculated. RESULTS Accuracy ranged from 87.2% to 95.2% for sensitivity and 99.8% to 99.9% for specificity for probabilistic and deterministic record linkage, respectively. The occurrence of missing values for the key variables and the low percentage of similarity measure for name and date of birth were mainly responsible for the failure to identify records of the same individual with the techniques used. CONCLUSIONS The two techniques showed a high level of correlation for pair classification. Although deterministic linkage identified more duplicate records than probabilistic linkage, the latter retrieved records not identified by the former. User need and experience should be considered when choosing the best technique to be used. PMID:27556963

  6. Spin Transfer in Polymer Degradation of Abnormal Linkage

    Science.gov (United States)

    Yu, Tianrong; Tian, Chuanjin; Liu, Xizhe; Wang, Jia; Gao, Yang; Wang, Zhigang

    2016-09-01

    The degradation of polymer materials plays an important role in production and life. In this work, the degradation mechanism of poly-α-methylstyrene (PAMS) tetramers with abnormal linkage was investigated by using density functional theory (DFT). Calculated results indicate that the head-to-head and the tail-to-tail reactions needed to overcome the energy barriers are about 0.15 eV and about 1.26 eV, respectively. The broken C-C bond at the unsaturated end of the chain leads to the dissociation of alpha-methylstyrene (AMS) monomers one by one. Furthermore, the analyses of bond characteristics are in good agreement with the results of energy barriers. In addition, the spin population analysis presents an interesting net spin transfer process in depolymerization reactions. We hope that the current theoretical results provide useful help to understand the degradation mechanism of polymers.

  7. Automated Generation of Kempe Linkage and Its Complexity

    Institute of Scientific and Technical Information of China (English)

    高小山; 朱长才

    1999-01-01

    It is a famous result of Kempe that a linkage can be designed to generate any given plane algebraic curve.In this paper,Kempe's result is improved to give a precise algorithm for generating Kempe linkage.We proved that for an algebraic plane curve of degrenn n,Kempe linkage uses at most O(n4) links.Efforts to implement a program which may generate Kempe linkage and simulation of the generation process of the plane curves are presented in the paper.

  8. ECONOMIC GROWTH AND SECTORAL LINKAGES: EMPIRICAL EVIDENCE FROM ODISHA

    OpenAIRE

    Behera, Deepak Kumar

    2012-01-01

    The present paper analyses the trends in sectoral shares in state domestic product and inter-sectoral linkages in Odisha for the period 1980-81 to 2011-12. Results drawn from Granger causality test suggest that there is a weak linkage between primary and secondary sectors in the growth process. In the case of primary and tertiary sector services, though the primary sector does not show linkages with the tertiary sector as a whole, it does have linkages with some important sub-services like tr...

  9. Quantifying landscape linkages among giant panda subpopulations in regional scale conservation.

    Science.gov (United States)

    Qi, Dunwu; Hu, Yibo; Gu, Xiaodong; Yang, Xuyi; Yang, Guang; Wei, Fuwen

    2012-06-01

    Understanding habitat requirements and identifying landscape linkages are essential for the survival of isolated populations of endangered species. Currently, some of the giant panda populations are isolated, which threatens their long-term survival, particularly in the Xiaoxiangling mountains. In the present study, we quantified niche requirements and then identified potential linkages of giant panda subpopulations in the most isolated region, using ecological niche factor analysis and a least-cost path model. Giant pandas preferred habitat with conifer forest and gentle slopes (>20 to ≤30°). Based on spatial distribution of suitable habitat, linkages were identified for the Yele subpopulation to 4 other subpopulations (Liziping, Matou, Xinmin and Wanba). Their lengths ranged from 15 to 54 km. The accumulated cost ranged from 693 to 3166 and conifer forest covered over 31%. However, a variety of features (e.g. major roads, human settlements and large unforested areas) might act as barriers along the linkages for giant panda dispersal. Our analysis quantified giant panda subpopulation connectivity to ensure long-term survival.

  10. The Barley Chromosome 5 Linkage Map

    DEFF Research Database (Denmark)

    Jensen, J.; Jørgensen, Jørgen Helms

    1975-01-01

    The literature is surveyed for data on recombination between loci on chromosome 5 of barley; 13 loci fall into the category “mapped” loci, more than 20 into the category “associated” loci and nine into the category “loci once suggested to be on chromosome 5”. A procedure was developed...... for estimating a linkage map; it involves (1) transformation by the Kosambi mapping function of the available recombination percentages to additive map distances, (2) calculations of a set of map distances from the transformed recombination percentages by a maximum likelihood method in which all the available...... data are utilized jointly, and (3) omission of inconsistent data and determination of the most likely order of the loci. This procedure was applied to the 42 recombination percentages available for the 13 “mapped” loci. Due to inconsistencies 14 of the recombination percentages and, therefore, two...

  11. LD2SNPing: linkage disequilibrium plotter and RFLP enzyme mining for tag SNPs

    OpenAIRE

    Chang, Hsueh-Wei; Chuang, Li-Yeh; Chang, Yan-Jhu; Cheng, Yu-Huei; Hung, Yu-Chen; Chen, Hsiang-Chi; Yang, Cheng-Hong

    2009-01-01

    Background Linkage disequilibrium (LD) mapping is commonly used to evaluate markers for genome-wide association studies. Most types of LD software focus strictly on LD analysis and visualization, but lack supporting services for genotyping. Results We developed a freeware called LD2SNPing, which provides a complete package of mining tools for genotyping and LD analysis environments. The software provides SNP ID- and gene-centric online retrievals for SNP information and tag SNP selection from...

  12. Construction of a genetic linkage map of black gram, Vigna mungo (L.) Hepper, based on molecular markers and comparative studies.

    Science.gov (United States)

    Gupta, S K; Souframanien, J; Gopalakrishna, T

    2008-08-01

    A genetic linkage map of black gram, Vigna mungo (L.) Hepper, was constructed with 428 molecular markers using an F9 recombinant inbred population of 104 individuals. The population was derived from an inter-subspecific cross between a black gram cultivar, TU94-2, and a wild genotype, V. mungo var. silvestris. The linkage analysis at a LOD score of 5.0 distributed all 428 markers (254 AFLP, 47 SSR, 86 RAPD, and 41 ISSR) into 11 linkage groups. The map spanned a total distance of 865.1 cM with an average marker density of 2 cM. The largest linkage group spanned 115 cM and the smallest linkage group was of 44.9 cM. The number of markers per linkage group ranged from 11 to 86 and the average distance between markers varied from 1.1 to 5.6 cM. Comparison of the map with other published azuki bean and black gram maps showed high colinearity of markers, with some inversions. The current map is the most saturated map for black gram to date and will provide a useful tool for identification of QTLs and for marker-assisted selection of agronomically important characters in black gram.

  13. Fine mapping of multiple interacting quantitative trait loci using combined linkage disequilibrium and linkage information

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Quantitative trait loci (QTL) and their additive, dominance and epistatic effects play a critical role in complex trait variation. It is often infeasible to detect multiple interacting QTL due to main effects often being confounded by interaction effects.Positioning interacting QTL within a small region is even more difficult. We present a variance component approach nested in an empirical Bayesian method, which simultaneously takes into account additive, dominance and epistatic effects due to multiple interacting QTL. The covariance structure used in the variance component approach is based on combined linkage disequilibrium and linkage (LDL) information. In a simulation study where there are complex epistatic interactions between QTL, it is possible to simultaneously fine map interacting QTL using the proposed approach. The present method combined with LDL information can efficiently detect QTL and their dominance and epistatic effects, making it possible to simultaneously fine map main and epistatic QTL.

  14. SYNTHESIS OF GUIDED CHAIN DRIVE MECHANISM WITH LINKAGE

    Institute of Scientific and Technical Information of China (English)

    1998-01-01

    A method of designing guided chain drive mechanism with linkage basing on the given motion track is expounded. The method consists of two steps that are synthesizing four-bar linkage approximately first and then deducing guide track, removing crank and jointing free end with chain. An example of synthesis that can realize the given motion track precisely is provided.

  15. Urban-rural linkages enhancing European territorial competitiveness: background paper

    OpenAIRE

    Davidson, Gill

    2008-01-01

    This background paper provides the context for the seminar on urban-rural linkages enhancing European territorial competitiveness, to be held by DG REGIO on 17th September 2008. This seminar forms part of an ongoing debate at European level on the importance of urban-rural linkages for territorial competitiveness, and on appropriate support mechanisms to assist these developments in Member States.

  16. A microsatellite genetic linkage map of black rockfish ( Sebastes schlegeli)

    Science.gov (United States)

    Chu, Guannan; Jiang, Liming; He, Yan; Yu, Haiyang; Wang, Zhigang; Jiang, Haibin; Zhang, Quanqi

    2014-12-01

    Ovoviviparous black rockfish ( Sebastes schlegeli) is an important marine fish species for aquaculture and fisheries in China. Genetic information of this species is scarce because of the lack of microsatellite markers. In this study, a large number of microsatellite markers of black rockfish were isolated by constructing microsatellite-enriched libraries. Female- and male-specific genetic linkage maps were constructed using 435 microsatellite markers genotyped in a full-sib family of the fish species. The female linkage map contained 140 microsatellite markers, in which 23 linkage groups had a total genetic length of 1334.1 cM and average inter-marker space of 13.3 cM. The male linkage map contained 156 microsatellite markers, in which 25 linkage groups had a total genetic length of 1359.6 cM and average inter-marker distance of 12.4 cM. The genome coverage of the female and male linkage maps was 68.6% and 69.3%, respectively. The female-to-male ratio of the recombination rate was approximately 1.07:1 in adjacent microsatellite markers. This paper presents the first genetic linkage map of microsatellites in black rockfish. The collection of polymorphic markers and sex-specific linkage maps of black rockfish could be useful for further investigations on parental assignment, population genetics, quantitative trait loci mapping, and marker-assisted selection in related breeding programs.

  17. Privacy-preserving record linkage on large real world datasets.

    Science.gov (United States)

    Randall, Sean M; Ferrante, Anna M; Boyd, James H; Bauer, Jacqueline K; Semmens, James B

    2014-08-01

    Record linkage typically involves the use of dedicated linkage units who are supplied with personally identifying information to determine individuals from within and across datasets. The personally identifying information supplied to linkage units is separated from clinical information prior to release by data custodians. While this substantially reduces the risk of disclosure of sensitive information, some residual risks still exist and remain a concern for some custodians. In this paper we trial a method of record linkage which reduces privacy risk still further on large real world administrative data. The method uses encrypted personal identifying information (bloom filters) in a probability-based linkage framework. The privacy preserving linkage method was tested on ten years of New South Wales (NSW) and Western Australian (WA) hospital admissions data, comprising in total over 26 million records. No difference in linkage quality was found when the results were compared to traditional probabilistic methods using full unencrypted personal identifiers. This presents as a possible means of reducing privacy risks related to record linkage in population level research studies. It is hoped that through adaptations of this method or similar privacy preserving methods, risks related to information disclosure can be reduced so that the benefits of linked research taking place can be fully realised.

  18. Building and Strengthening Linkages between CETA and Community Colleges.

    Science.gov (United States)

    Lapin, Joel D.

    A study was conducted by Catonsville Community College (Maryland) to identify those factors that foster successful linkages between Comprehensive Employment and Training Act (CETA) sponsors and community colleges. The study involved: (1) identifying exemplary CETA/college linkages through consultation with experts in academe and government; (2)…

  19. Construction variants for linkage of overcast combinations - part 2

    Energy Technology Data Exchange (ETDEWEB)

    Goehring, H.

    1988-04-01

    Continues the review of linkage designs between bucket wheel excavators and boom spreaders in surface mine overburden removal. Boom linkage with three linkage points comes in two versions, with and without auxiliary boom support. The TAKRAF manufacturer's ARs 8800.195 spreader with suspended receiving boom and no auxiliary support crawler on which the boom may rest is given as an example. The version with three linkage points incorporating an auxiliary boom support crawler is further explained. This version (SRs 1400 bucket wheel excavator combined with ARs 5200.165.spreader) operates at the Visonta coal surface mine in Hungary. Boom linkage at four points is outlined as a further technological possibility. This design requires an additional mobile transfer conveyor between excavator and spreader, rather than an auxiliary support crawler. This version is preferred in surface mines with a large distance between excavator and spreader or where equipment must be positioned on different mine bench levels. 2 refs.

  20. Automated assembly of oligosaccharides containing multiple cis-glycosidic linkages

    Science.gov (United States)

    Hahm, Heung Sik; Hurevich, Mattan; Seeberger, Peter H.

    2016-09-01

    Automated glycan assembly (AGA) has advanced from a concept to a commercial technology that rapidly provides access to diverse oligosaccharide chains as long as 30-mers. To date, AGA was mainly employed to incorporate trans-glycosidic linkages, where C2 participating protecting groups ensure stereoselective couplings. Stereocontrol during the installation of cis-glycosidic linkages cannot rely on C2-participation and anomeric mixtures are typically formed. Here, we demonstrate that oligosaccharides containing multiple cis-glycosidic linkages can be prepared efficiently by AGA using monosaccharide building blocks equipped with remote participating protecting groups. The concept is illustrated by the automated syntheses of biologically relevant oligosaccharides bearing various cis-galactosidic and cis-glucosidic linkages. This work provides further proof that AGA facilitates the synthesis of complex oligosaccharides with multiple cis-linkages and other biologically important oligosaccharides.

  1. 织机四连杆打纬机构对主墙板的动应力分析%Dynamic stress analysis of four-bar linkage beating-up mechanism on loom wallboard

    Institute of Scientific and Technical Information of China (English)

    沈丹峰; 赵宁; 张华安; 叶国铭

    2013-01-01

    织机的墙板具有尺寸大、结构复杂的特点,四连杆打纬机构的往复摆动使得墙板受到较大的冲击,是机器振动的主要来源.针对墙板上曲轴孔与摇轴孔承受的支撑力,建立相应的运动学和动力学公式.通过对2个固定孔相对位置的承载力计算和分析,结果显示,2个孔各自承受的作用力在不同的主轴转角下具有不同的数值和作用方向,并且在2个孔不同的安装角度下,墙板受到的冲击载荷也是变化的,当打纬角确定时,能够计算出不同安装角度下的最大总支撑力,选取最小值进行孔位设计就能取得墙板较好的振动和寿命要求.%The loom wallboard is characterized by big size and complicated structure, and the back and forth swinging operations of the four-bar linkage beating-up mechanisms make it withstand a great impact load from which originates the major vibration of the loom. Therefore, this paper established corresponding kinematics equations and dynamics equations for the supporting forces borne by crankshaft hole and rockshaft hole of the loom wallboard. The computation of the bearing stress of the two fixed holes at relative positions indicated the bearing stress had varied values and directions at different rotating angles of the shaft; and the impact load against the wallboard varied with the installation angle of the two holes. The total maximum supporting force value could be computed when the angle of beating-up is fixed. When designing the positions of the holes, the minimum value should be taken so as to gain lower vibration and longer working life.

  2. 一汉族瘢痕疙瘩家系的易感基因定位分析研究%Preliminary linkage analysis and mapping of keloid susceptibility locus in a Chinese pedigree

    Institute of Scientific and Technical Information of China (English)

    严欣; 高建华; 陈阳; 宋玫; 刘晓军

    2007-01-01

    目的 采用连锁分析方法探讨瘢痕疙瘩(keloid)家系的疾病易感基因与15q22.31-q23及18q21.1区域的连锁关系.方法 1个中国东北地区5代keloid家系,采集家系中32名成员的外周血标本提取DNA,选择位于15q22.31-q23及18q21.1区域7个微卫星标记,应用聚合酶链式反应(PCR)得到扩增产物片断,测定PCR产物片段大小,得到每个样本的基因型,运用连锁分析软件Linkage 5.11的MLINK程序计算每个标记的LOD值,根据两点间LOD值判断连锁关系.结果 D15S108、D15S216、D15S534、D18S363、D18S846五个位点的两点LOD值在重组率为0时均小于-2,可以排除连锁关系,而D18S460、D18S467两位点在重组率θ为0.05和0.10时的两点LOD值均大于1,D18S460在θ=0时大于2,提示此家系keloid易感基因与这两个位点存在一定连锁关系.结论 此汉族keloid家系的易感基因可能位于染色体18q21.1区域内,初步确定SMAD2和PIAS2基因为可能的易感基因.

  3. Issues in identification and linkage of patient records across an integrated delivery system.

    Science.gov (United States)

    Arellano, M G; Weber, G I

    1998-01-01

    patient. One approach we have used with great success is to assign a common, sequential identification number to all linked medical record numbers for the same patient regardless of facility. The assignment of linkage identification numbers is computer-intensive and is generally accomplished with a highly iterative process. Both system memory and hard disk resources are fully tested as the number of good linkages in an overlap evaluation reaches the half-million mark or greater. Because the primary linkage analysis goal is to develop linkages on pairs of records, with confidence levels based on the comparison of information for those two records, thresholds must be set to decide which linkages should be accepted as true without any human evaluation. If the threshold is set too low, the defined linkage groups may incorrectly join the medical record numbers for different persons. But if the threshold is set too high, there will be undesired duplication of persons in the enterprise system. As in the identification of the underlying linkage pairs, the development of a confidence measure greatly facilitates the assignment of the unique identification numbers needed in the EPI implementation. PMID:10338786

  4. [MapDraw: a microsoft excel macro for drawing genetic linkage maps based on given genetic linkage data].

    Science.gov (United States)

    Liu, Ren-Hu; Meng, Jin-Ling

    2003-05-01

    MAPMAKER is one of the most widely used computer software package for constructing genetic linkage maps.However, the PC version, MAPMAKER 3.0 for PC, could not draw the genetic linkage maps that its Macintosh version, MAPMAKER 3.0 for Macintosh,was able to do. Especially in recent years, Macintosh computer is much less popular than PC. Most of the geneticists use PC to analyze their genetic linkage data. So a new computer software to draw the same genetic linkage maps on PC as the MAPMAKER for Macintosh to do on Macintosh has been crying for. Microsoft Excel,one component of Microsoft Office package, is one of the most popular software in laboratory data processing. Microsoft Visual Basic for Applications (VBA) is one of the most powerful functions of Microsoft Excel. Using this program language, we can take creative control of Excel, including genetic linkage map construction, automatic data processing and more. In this paper, a Microsoft Excel macro called MapDraw is constructed to draw genetic linkage maps on PC computer based on given genetic linkage data. Use this software,you can freely construct beautiful genetic linkage map in Excel and freely edit and copy it to Word or other application. This software is just an Excel format file. You can freely copy it from ftp://211.69.140.177 or ftp://brassica.hzau.edu.cn and the source code can be found in Excel's Visual Basic Editor. PMID:15639879

  5. A consensus linkage map of the grass carp (Ctenopharyngodon idella based on microsatellites and SNPs

    Directory of Open Access Journals (Sweden)

    Li Jiale

    2010-02-01

    Full Text Available Abstract Background Grass carp (Ctenopharyngodon idella belongs to the family Cyprinidae which includes more than 2000 fish species. It is one of the most important freshwater food fish species in world aquaculture. A linkage map is an essential framework for mapping traits of interest and is often the first step towards understanding genome evolution. The aim of this study is to construct a first generation genetic map of grass carp using microsatellites and SNPs to generate a new resource for mapping QTL for economically important traits and to conduct a comparative mapping analysis to shed new insights into the evolution of fish genomes. Results We constructed a first generation linkage map of grass carp with a mapping panel containing two F1 families including 192 progenies. Sixteen SNPs in genes and 263 microsatellite markers were mapped to twenty-four linkage groups (LGs. The number of LGs was corresponding to the haploid chromosome number of grass carp. The sex-specific map was 1149.4 and 888.8 cM long in females and males respectively whereas the sex-averaged map spanned 1176.1 cM. The average resolution of the map was 4.2 cM/locus. BLAST searches of sequences of mapped markers of grass carp against the whole genome sequence of zebrafish revealed substantial macrosynteny relationship and extensive colinearity of markers between grass carp and zebrafish. Conclusions The linkage map of grass carp presented here is the first linkage map of a food fish species based on co-dominant markers in the family Cyprinidae. This map provides a valuable resource for mapping phenotypic variations and serves as a reference to approach comparative genomics and understand the evolution of fish genomes and could be complementary to grass carp genome sequencing project.

  6. An EST-derived SNP and SSR genetic linkage map of cassava (Manihot esculenta Crantz).

    Science.gov (United States)

    Rabbi, Ismail Yusuf; Kulembeka, Heneriko Philbert; Masumba, Esther; Marri, Pradeep Reddy; Ferguson, Morag

    2012-07-01

    Cassava (Manihot esculenta Crantz) is one of the most important food security crops in the tropics and increasingly being adopted for agro-industrial processing. Genetic improvement of cassava can be enhanced through marker-assisted breeding. For this, appropriate genomic tools are required to dissect the genetic architecture of economically important traits. Here, a genome-wide SNP-based genetic map of cassava anchored in SSRs is presented. An outbreeder full-sib (F1) family was genotyped on two independent SNP assay platforms: an array of 1,536 SNPs on Illumina's GoldenGate platform was used to genotype a first batch of 60 F1. Of the 1,358 successfully converted SNPs, 600 which were polymorphic in at least one of the parents and was subsequently converted to KBiosciences' KASPar assay platform for genotyping 70 additional F1. High-precision genotyping of 163 informative SSRs using capillary electrophoresis was also carried out. Linkage analysis resulted in a final linkage map of 1,837 centi-Morgans (cM) containing 568 markers (434 SNPs and 134 SSRs) distributed across 19 linkage groups. The average distance between adjacent markers was 3.4 cM. About 94.2% of the mapped SNPs and SSRs have also been localized on scaffolds of version 4.1 assembly of the cassava draft genome sequence. This more saturated genetic linkage map of cassava that combines SSR and SNP markers should find several applications in the improvement of cassava including aligning scaffolds of the cassava genome sequence, genetic analyses of important agro-morphological traits, studying the linkage disequilibrium landscape and comparative genomics.

  7. Multipoint linkage detection in the presence of heterogeneity.

    Science.gov (United States)

    Chiu, Yen-Feng; Liang, Kung-Yee; Beaty, Terri H

    2002-06-01

    Linkage heterogeneity is common for complex diseases. It is well known that loss of statistical power for detecting linkage will result if one assumes complete homogeneity in the presence of linkage heterogeneity. To this end, Smith (1963, Annals of Human Genetics 27, 175-182) proposed an admixture model to account for linkage heterogeneity. It is well known that for this model, the conventional chi-squared approximation to the likelihood ratio test for no linkage does not apply even when the sample size is large. By dealing with nuclear families and one marker at a time for genetic diseases with simple modes of inheritance, score-based test statistics (Liang and Rathouz, 1999, Biometrics 55, 65-74) and likelihood-ratio-based test statistics (Lemdani and Pons, 1995, Biometrics 51, 1033-1041) have been proposed which have a simple large-sample distribution under the null hypothesis of linkage. In this paper, we extend their work to more practical situations that include information from multiple markers and multi-generational pedigrees while allowing for a class of general genetic models. Three different approaches are proposed to eliminate the nuisance parameters in these test statistics. We show that all three approaches lead to the same asymptotic distribution under the null hypothesis of no linkage. Simulation results show that the proposed test statistics have adequate power to detect linkage and that the performances of these two classes of test statistics are quite comparable. We have applied the proposed method to a family study of asthma (Barnes et al., 1996), in which the score-based test shows evidence of linkage with p-value <0.0001 in the region of interest on chromosome 12. Additionally, we have implemented this score-based test within the frequently used computer package GENEHUNTER.

  8. A Linkage Study in 8 Pakistani Families Segregating as Autosomal Recessive Primary Microcephaly

    Directory of Open Access Journals (Sweden)

    M. Hassanullah

    2011-07-01

    Full Text Available The current study was designed to find the most frequent MCPH phenotype in inbred Pakistani families. Primary microcephaly is marked by small brain size and is usually inherited as recessive trait. In the present study, we performed linkage analysis on 8 Pakistani families with autosomal recessive primary microcephaly (MCPH and linked 6 of them to known MCPH genes/loci like MCPH1 (Microcephalin, MCPH3 (CDK5RAP2 and MCPH5 (ASPM. Majority of the families showed linkage with MCPH5, the most common MCPH locus in Pakistan. The linked families were then subjected to mutational analysis, revealing a previously known G to A transition at nucleotide position 3978 in exon 17 of ASPM gene in three of the families. To decrease its incidence, it is indispensible to train the people of the possible devastating outcome of cousin marriages and to find the carriers through carrier screening programs.

  9. Efficiency of multiplex ligation-dependent probe amplification combined with short tandem repeat linkage analysis for the prenatal diagnosis for Duchenne muscular dystrophy%MLPA联合遗传连锁分析在假肥大型肌营养不良症产前诊断中的价值

    Institute of Scientific and Technical Information of China (English)

    李涛; 吴东; 侯巧芳; 王莉; 郭谦楠; 康冰; 刘红彦; 杨科; 丁雪冰

    2013-01-01

    Objective To investigate the efficiency of multiplex ligation-dependent probe amplification (MLPA) combined with short tandem repeat (STR) linkage analysis for the prenatal diagnosis for Duchenne muscular dystrophy (DMD).Methods Gender of the fetus was first determined by the presence of Y chromosome sex-determining gene (SRY).Subsequently,combined MLPA and STR linkage analysis were applied for the probands,pregnant women and fetuses in 45 affected families.Results Among the 45 families,31 SRY-positive fetuses were identified,among whom six were diagnosed with DMD.For 14 SRY-negative fetuses,four were diagnosed as carriers.The remainders were normal.Conclusion MLPA can detect mutations in the exons of dystrophin gene,whilst STR linkage analysis can determine whether the fetus has inherited the maternal X chromosome bearing the mutant gene.As the result,the method can therefore detect affected fetuses in which no exonic mutations are detected with MLPA.By combining the two methods,the diagnostic rate for DMD can be greatly improved.%目的 探讨多重连接依赖探针扩增技术(multiplex ligation-dependent probe amplification,MLPA)联合短串联重复序列(short tandem repeat,STR)基因连锁分析用于Duchenne型假肥大型肌营养不良症(Duchenne muscular dystrophy,DMD)产前诊断的价值.方法 通过检测Y染色体性别决定基因(Y chromosome sex-determining gene,SR Y)判断胎儿性别;MLPA检测45个DMD家系中先证者、孕妇以及胎儿Dystrophin基因突变情况,并对家系成员和胎儿进行第45、49、50内含子以及5′和3 ′端STR的连锁分析.结果 45个进行产前诊断的家系中,SRY阳性31例,其中6例为DMD患病胎儿;阴性14例,其中4例为携带者,余未见异常.结论 MLPA能检测胎儿Dystrophin基因外显子突变情况,STR连锁能分析胎儿是否继承母源性风险X染色体,因此,STR连锁分析能发现MLPA技术检测不到的外显子突变胎儿.将两种方法结合起来

  10. Chromopeptides from C-phycocyanin. Structure and linkage of a phycocyanobilin bound to the β subunit

    International Nuclear Information System (INIS)

    The smallest cyanogen bromide fragment derived from the β subunit of Synechococcus sp. 6301 C-phycocyanin, the blue heptapeptide 2, has been investigated by 360-MHz 1H NMR spectroscopy. The peptide portion, heptapeptide 3, was synthesized independently and used in comparative spectroscopic analysis. These studies have led to complete assignment of the structure of the peptide-linked phycocyanobilin and elucidation of the nature of the thioether chromophore-peptide linkage

  11. Nonparametric simulation-based statistics for detecting linkage in general pedigrees.

    OpenAIRE

    Davis, S.; Schroeder, M; Goldin, L. R.; Weeks, D E

    1996-01-01

    We present here four nonparametric statistics for linkage analysis that test whether pairs of affected relatives share marker alleles more often than expected. These statistics are based on simulating the null distribution of a given statistic conditional on the unaffecteds' marker genotypes. Each statistic uses a different measure of marker sharing: the SimAPM statistic uses the simulation-based affected-pedigree-member measure based on identity-by-state (IBS) sharing. The SimKIN (kinship) m...

  12. The Determinants of Regional Specialisation in Business Services: Agglomeration Economies, Vertical Linkages and Innovation

    OpenAIRE

    MELICIANI Valentina; Savona, Maria

    2011-01-01

    The article accounts for the determinants of sectoral specialisation in business services (BS) across the EU-27 regions as determined by: (i) agglomeration economies (ii) the region-specific structure of intermediate linkages (iii) technological innovation and knowledge intensity and (iv) the presence of these factors in neighbouring regions. The empirical analysis draws upon the REGIO panel database over the period 1999–2003. By estimating a Spatial Durbin Model, we find significant spatial ...

  13. Chromopeptides from C-phycocyanin. Structure and linkage of a phycocyanobilin bound to the. beta. subunit

    Energy Technology Data Exchange (ETDEWEB)

    Lagarias, J.C.; Glazer, A.N.; Rapoport, H.

    1979-08-15

    The smallest cyanogen bromide fragment derived from the ..beta.. subunit of Synechococcus sp. 6301 C-phycocyanin, the blue heptapeptide 2, has been investigated by 360-MHz /sup 1/H NMR spectroscopy. The peptide portion, heptapeptide 3, was synthesized independently and used in comparative spectroscopic analysis. These studies have led to complete assignment of the structure of the peptide-linked phycocyanobilin and elucidation of the nature of the thioether chromophore-peptide linkage.

  14. Impact Vectors - Construction and Linkage of CCF Data to Quantification

    International Nuclear Information System (INIS)

    This presentation will discuss the basic definition of impact vector and steps of construction. The linkage to the direct estimation of multiple failure probabilities and to the parameter estimation of CCF models is described. Despite of its central role to utilize the statistical information of potential CCF events the impact vector method is still undeveloped in many practical features. Instructions with a spectrum of example cases are being prepared in the Nordic CCF Analysis Group. A basic description of the method is presented, for example, in 'Guidelines on Modeling CCFs in PSA. Prepared by A. Mosleh, D.M. Rasmuson and F.M. Marshall for USNRC, November 1998'. Due to its importance as general tool for the estimation of multiple failure probabilities and CCF model parameters better procedures for the impact vector method needs to developed, regarding also the use of the CCF event data processed and stored in ICDE database. The needed development work is started in the Nordic CCF Analysis Group. (author)

  15. Clinical and linkage study of a large family with simple ectopia lentis linked to FBN1

    Energy Technology Data Exchange (ETDEWEB)

    Edwards, M.J.; Roberts, J.; Partington, M.W. [Newcastle and Northern New South Wales Genetics Service (Australia); Colley, P.W. [John Hunter Hospital, Newcastle (Australia); Hollway, G.E.; Kozman, H.M.; Mulley, J.C. [Adelaide Children`s Hospital, North Adelaide (Australia)

    1994-10-15

    Simple ectopia lentis (EL) was studied in a large family, by clinical examination and analysis of linkage to markers in the region of FBN1, the gene for fibrillin which causes Marfan syndrome on chromosome 15. No patient had clinical or echocardiographic evidence of Marfan syndrome, although there was a trend towards relatively longer measurements of height; lower segment; arm span; middle finger, hand, and foot length in the affected members of the family, compared with unaffected sibs of the same sex. Analysis of linkage to intragenic FBN1 markers was inconclusive because they were relatively uninformative. Construction of a multipoint background map from the CEPH reference families identified microsatellite markers linked closely to FBN1 which could demonstrate linkage of EL in this family to the FBN1 region. LINKMAP analysis detected a multipoint lod score of 5.68 at D15S119, a marker approximately 6 cM distal to FBN1, and a multipoint lod score of 5.04 at FBN1. The EL gene in this family is likely to be allelic to Marfan syndrome, and molecular characterization of the FBN1 mutation should now be possible. 25 refs., 6 figs., 2 tabs.

  16. Genotyping and Linkage Disequilibrium Analysis of 67 SNP Loci on X Chromosome%67个X-SNP位点的分型检测和连锁不平衡检验

    Institute of Scientific and Technical Information of China (English)

    李莉; 柳燕; 林源; 李成涛; 张素华; 邵伟波

    2011-01-01

    目的 筛选一组在中国汉族人群中具有法医学应用前景的X-SNP位点.方法 根据dbSNP和HapMap两个数据库提供的位点信息和频率数据从X染色体上筛选出67个候选X-SNP位点,采用多重PCR联合基质辅助激光解析电离飞行时间质谱技术检测中国汉族人群428名无关个体,获得67个候选X-SNP位点在中国汉族人群中的频率数据,通过遗传多态性分析和连锁不平衡检验按拟定标准进一步筛选获得具有法医学应用前景的X-SNP位点. 结果 成功获得了67个候选X-SNP位点在中国汉族人群中的等位基因频率数据.Hardy-Weinberg平衡检验示仅有1个位点(rs 12849634)未达到遗传平衡;有2个位点(rs1229078、rs1544545)的最小等位基因频率低于0.3;有6对位点两两存在紧密连锁,有2对位点两两存在轻度连锁.最终确定52个相互独立的、在中国汉族人群中具有法医学应用前景的X-SNP,其在三联体和二联体亲权鉴定中的累积非父排除率分别为0.999 999 999 96和0.999 9995,在女性和男性群体中的累积个人识别率分别为0.999 999 999 999 999 999 999 84和0.999 999 999 999 999 31.结论 本研究筛选出52个相互独立的X-SNP位点,能够满足当前法医遗传学鉴定应用要求,有利于解决特殊亲缘关系的鉴定难题.%Objective To screen a panel of SNP loci on X chromosome(X-SNP loci) that is informative in Chinese Han population and evaluate its potential value in forensic identification. Methods Sixty-seven candidate X-SNP loci were selected according to the information on dbSNP and HapMap. Genomic DNA extracted from blood samples of 428 unrelated Chinese Han individuals were analyzed through multiplex amplification followed by matrix assisted laser desorption/ionization time-of-flight mass spectrometry, and allele frequencies of the 67 X-SNP loci were calculated. In view of the population data and situation of linkage disequilibrium, X-SNP markers promising in

  17. Predicting sales performance: Strengthening the personality – job performance linkage

    NARCIS (Netherlands)

    T.B. Sitser (Thomas)

    2014-01-01

    markdownabstract__Abstract__ Many organizations worldwide use personality measures to select applicants for sales jobs or to assess incumbent sales employees. In the present dissertation, consisting of four independent studies, five approaches to strengthen the personality-sales performance linkage

  18. Viral linkage in HIV-1 seroconverters and their partners in an HIV-1 prevention clinical trial.

    Directory of Open Access Journals (Sweden)

    Mary S Campbell

    Full Text Available BACKGROUND: Characterization of viruses in HIV-1 transmission pairs will help identify biological determinants of infectiousness and evaluate candidate interventions to reduce transmission. Although HIV-1 sequencing is frequently used to substantiate linkage between newly HIV-1 infected individuals and their sexual partners in epidemiologic and forensic studies, viral sequencing is seldom applied in HIV-1 prevention trials. The Partners in Prevention HSV/HIV Transmission Study (ClinicalTrials.gov #NCT00194519 was a prospective randomized placebo-controlled trial that enrolled serodiscordant heterosexual couples to determine the efficacy of genital herpes suppression in reducing HIV-1 transmission; as part of the study analysis, HIV-1 sequences were examined for genetic linkage between seroconverters and their enrolled partners. METHODOLOGY/PRINCIPAL FINDINGS: We obtained partial consensus HIV-1 env and gag sequences from blood plasma for 151 transmission pairs and performed deep sequencing of env in some cases. We analyzed sequences with phylogenetic techniques and developed a Bayesian algorithm to evaluate the probability of linkage. For linkage, we required monophyletic clustering between enrolled partners' sequences and a Bayesian posterior probability of ≥ 50%. Adjudicators classified each seroconversion, finding 108 (71.5% linked, 40 (26.5% unlinked, and 3 (2.0% indeterminate transmissions, with linkage determined by consensus env sequencing in 91 (84%. Male seroconverters had a higher frequency of unlinked transmissions than female seroconverters. The likelihood of transmission from the enrolled partner was related to time on study, with increasing numbers of unlinked transmissions occurring after longer observation periods. Finally, baseline viral load was found to be significantly higher among linked transmitters. CONCLUSIONS/SIGNIFICANCE: In this first use of HIV-1 sequencing to establish endpoints in a large clinical trial, more than

  19. Identifying Nanotechnological Linkages in the Finnish Economy - An Explorative Study

    OpenAIRE

    Nikulainen, Tuomo

    2007-01-01

    Nanotechnology, as an emerging science-based technology, is seen to have great potential both in scientific as well as economic terms. In this paper the focus is on identifying the technological linkages between the Finnish nanotechnology community and the industrial incumbents. These technological link-ages are first observed at a broader level in comparison with the technological strengths of the Finnish industries, and then in greater detail at the level of companies. In addition, the abso...

  20. Skewed RAPD markers in linkage maps of Citrus

    Directory of Open Access Journals (Sweden)

    Roberto Pedroso de Oliveira

    2004-01-01

    Full Text Available The objective of this work was to analyze the effects of RAPD markers with skewed segregation on genetic linkage maps. Segregation data for 123 Citrus sinensis (L. Osbeck cv. Pêra markers and 53 C. reticulata Blanco cv. Cravo markers in F1 progeny composed of 94 hybrids were used. Genetic linkage maps of the two varieties were constructed with non-skewed markers (p < 0.05 and p < 0.01 using the program MAPMAKER 3.0 and a pseudo-testcross strategy. The maps were compared to those constructed with all markers. Alterations in the genetic distances were observed based on the location of the skewed markers within the linkage groups. Generally, the skewed markers were located at the end of the linkage groups, sometimes forming entire linkage groups, without causing significant distance modifications. However, skewed markers located between non-skewed markers caused significant distance modifications and, in some cases, altered the order of the markers. Most of the skewed markers can be included in linkage maps, but in each case the degree of distance modification caused by each marker needs to be assessed.

  1. The assembly modes of rigid 11-bar linkages

    CERN Document Server

    Emiris, Ioannis Z

    2010-01-01

    Designing an m-bar linkage with a maximal number of assembly modes is important in robot kinematics, and has further applications in structural biology and computational geometry. A related question concerns the number of assembly modes of rigid mechanisms as a function of their nodes n, which is uniquely defined given m. Rigid 11-bar linkages, where n=7, are the simplest planar linkages for which these questions were still open. It will be proven that the maximal number of assembly modes of such linkages is exactly 56. The rigidity of a linkage is captured by a polynomial system derived from distance, or Cayley-Menger, matrices. The upper bound on the number of assembly modes is obtained as the mixed volume of a 5x5 system. An 11-bar linkage admitting 56 configurations is constructed using stochastic optimisation methods. This yields a general lower bound of $\\Omega(2.3^n)$ on the number of assembly modes, slightly improving the current record of $\\Omega(2.289^n)$, while the best known upper bound is roughly...

  2. 应用突变直接检测联合SNPs家系连锁分析进行眼皮肤白化病Ⅱ型的产前基因诊断%Prenatal genetic diagnosis of oculocutaneous albinism type Ⅱ through mutation detection combined with SNPs linkage analysis

    Institute of Scientific and Technical Information of China (English)

    陈潇菲; 魏海云; 周祎; 郑辉; 方群; 蒋玮莹; 李洪义

    2014-01-01

    目的 为仅检出1个致病等位基因的两个眼皮肤白化病(oculocutaneous albinism,OCA)的核心家系进行分型并提供产前基因诊断.方法 应用DNA测序法检测先证者的TYR、P、TYRP1和SLC45A2 4个OCA基因,结合临床表型特点判定其OCA类型,在此基础上运用突变位点检测结合致病基因内单核苷酸多态位点家系连锁分析法进行产前基因诊断.结果 家系1先证者仅在P基因检出c.1255C>T杂合性致病突变,该突变来自母亲,结合临床表型特征综合分析判定先证者为OCA2患者.羊水筛查未见致病突变,家系连锁分析结果提示胎儿为OCA2携带者,出生时表型正常;家系2先证者仅在P基因检出c.1920_1949 del30bp和ins AACA杂合性致病突变,该突变来自父亲,结合临床表型特征综合分析判定先证者为OCA2患者.羊水筛查检出c.1920_1949 del30bp和ins AACA杂合突变,家系连锁分析结果提示胎儿为OCA2携带者,出生时表型正常.结论 首次成功应用突变直接检测联合单核苷酸多态位点家系连锁分析法完成只检出1个致病突变的家系的OCA产前诊断.%Objective To provide prenatal diagnosis for two families affected with oculocutaneous albinism (OCA),in both of which only 1 pathogenic allele has been identified.Methods To determine the clinical classification of OCA through DNA sequencing for TYR,P,TYRP1 and SLC45A2 genes in combination with phenotype analysis.Prenatal diagnosis was carried out by direct sequencing and intragenic SNPs family-based linkage analysis.Results In the first family,only 1 heterozygous mutation c.1255C>T was found in the proband,which was inherited from her mother.Together with its clinical phenotype,the proband was suspected to have OCA2.Screening of amniotic fluid,however,has found no mutation.With family-based linkage analysis,the fetus was deemed to be an OCA2 carrier.In the second family,again only one heterozygous mutation c.1920_1949 del30bp and ins AACA was

  3. Structural determinants of alternating (α1 → 4) and (α1 → 6) linkage specificity in reuteransucrase of Lactobacillus reuteri

    Science.gov (United States)

    Meng, Xiangfeng; Pijning, Tjaard; Dobruchowska, Justyna M.; Yin, Huifang; Gerwig, Gerrit J.; Dijkhuizen, Lubbert

    2016-01-01

    The glucansucrase GTFA of Lactobacillus reuteri 121 produces an α-glucan (reuteran) with a large amount of alternating (α1 → 4) and (α1 → 6) linkages. The mechanism of alternating linkage formation by this reuteransucrase has remained unclear. GTFO of the probiotic bacterium Lactobacillus reuteri ATCC 55730 shows a high sequence similarity (80%) with GTFA of L. reuteri 121; it also synthesizes an α-glucan with (α1 → 4) and (α1 → 6) linkages, but with a clearly different ratio compared to GTFA. In the present study, we show that residues in loop977 (970DGKGYKGA977) and helix α4 (1083VSLKGA1088) are main determinants for the linkage specificity difference between GTFO and GTFA, and hence are important for the synthesis of alternating (α1 → 4) and (α1 → 6) linkages in GTFA. More remote acceptor substrate binding sites (i.e.+3) are also involved in the determination of alternating linkage synthesis, as shown by structural analysis of the oligosaccharides produced using panose and maltotriose as acceptor substrate. Our data show that the amino acid residues at acceptor substrate binding sites (+1, +2, +3…) together form a distinct physicochemical micro-environment that determines the alternating (α1 → 4) and (α1 → 6) linkages synthesis in GTFA. PMID:27748434

  4. A genome-wide linkage and association scan reveals novel loci for hypertension and blood pressure traits.

    Directory of Open Access Journals (Sweden)

    Youling Guo

    Full Text Available Hypertension is caused by the interaction of environmental and genetic factors. The condition which is very common, with about 18% of the adult Hong Kong Chinese population and over 50% of older individuals affected, is responsible for considerable morbidity and mortality. To identify genes influencing hypertension and blood pressure, we conducted a combined linkage and association study using over 500,000 single nucleotide polymorphisms (SNPs genotyped in 328 individuals comprising 111 hypertensive probands and their siblings. Using a family-based association test, we found an association with SNPs on chromosome 5q31.1 (rs6596140; P<9 × 10(-8 for hypertension. One candidate gene, PDC, was replicated, with rs3817586 on 1q31.1 attaining P = 2.5 × 10(-4 and 2.9 × 10(-5 in the within-family tests for DBP and MAP, respectively. We also identified regions of significant linkage for systolic and diastolic blood pressure on chromosomes 2q22 and 5p13, respectively. Further family-based association analysis of the linkage peak on chromosome 5 yielded a significant association (rs1605685, P<7 × 10(-5 for DBP. This is the first combined linkage and association study of hypertension and its related quantitative traits with Chinese ancestry. The associations reported here account for the action of common variants whereas the discovery of linkage regions may point to novel targets for rare variant screening.

  5. Construction of a genetic linkage map in Lilium using a RIL mapping population based on SRAP marker

    Directory of Open Access Journals (Sweden)

    Chen Li-Jing

    2015-01-01

    Full Text Available A genetic linkage map of lily was constructed using RILs (recombinant inbred lines population of 180 individuals. This mapping population was developed by crossing Raizan No.1 (Formolongo and Gelria (Longiflomm cultivars through single-seed descent (SSD. SRAPs were generated by using restriction enzymes EcoRI in combination with either MseI. The resulting products were separated by electrophoresis on 6% denaturing polyacrylamide gel and visualized by silver staining. The segregation of each marker and linkage analysis was done using the program Mapmaker3.0. With 50 primer pairs, a total of 189 parental polymorphic bands were detected and 78 were used for mapping. The total map length was 2,135.5 cM consisted of 16 linkage groups. The number of markers in the linkage groups varied from 1 to 12. The length of linkage groups was range from 11.2 cM to 425.9 cM and mean marker interval distance range from 9.4 cM to 345.4 cM individually. The mean marker interval distance between markers was 27.4 cM. The map developed in the present study was the first sequence-related amplified polymorphism markers map of lily constructed with recombinant inbred lines, it could be used for genetic mapping and molecular marker assisted breeding and quantitative trait locus mapping of Lilium.

  6. Linkage of financial development with electricity-growth, nexus of India and Pakistan

    Directory of Open Access Journals (Sweden)

    Adnan RASHID

    2015-11-01

    Full Text Available This paper tries to identify the indirect linkage between intermediary development with energygrowth nexus for India and Pakistan. In this succession the study employ system based GMM approach along with principal component analysis for development of intermediary index. Findings of the study demonstrate the positive and significant impact of economic growth on electricity consumption of both nations. However a miscellaneous trend for urbanization and negative trend for prices with electricity consumption has also been found in this study. On the other hand, the linkage between financial development through growth on electricity consumption is positive and significant for both nations. These findings have important implications for the policy makers. They can use these Findings to ensure long term structural development to control future power constraints, which leads them towards higher level of sustainable development.

  7. Genetic linkage map of Brassica campestris L.using AFLP and RAPD markers

    Institute of Scientific and Technical Information of China (English)

    卢钢; 陈杭; 等

    2002-01-01

    A genetic linkage map comprised of 131 loci was constructed with an F2 population derived from an inter-subspecific cross between Brassica campestris L.ssp.chinensis cv.aijiaohang” and ssp.rapifera cv.,”'isihai”.The genetic map included 93 RAPD loci,36 AFLP loci and 2 morphological loci organized into 10 main linkage groups(LGs) and 2 small groups,covering 1810.9cM with average distance between adjacent markers being approximately 13.8cM.The map is suitable for identification of molecular markers linked to important agronomic traits.QTL analysis,and even for marker-assisted selection in breeding programs of Chinese cabbage and turnip.

  8. Genetic linkage studies in non-epidermolytic palmoplantar keratoderma: evidence for heterogeneity.

    Science.gov (United States)

    Kelsell, D P; Stevens, H P; Ratnavel, R; Bryant, S P; Bishop, D T; Leigh, I M; Spurr, N K

    1995-06-01

    The palmoplantar keratodermas (PPK) are a group of skin diseases characterized by thickening of the skin of the palms and soles due to abnormal keratinization. We have performed linkage analysis on families affected with three distinct forms of non-epidermolytic PPK (NEPPK): focal, diffuse and punctate. Genetic heterogeneity was demonstrated, with focal NEPPK linked to the region on chromosome 17 harbouring the type I keratin cluster, diffuse NEPPK linked to the region on chromosome 12 containing the type II keratin cluster, and in the punctate NEPPK pedigrees, linkage was excluded to both of these keratin clusters. This study provides evidence for genetic differences between these forms of NEPPK and also between NEPPK and epidermolytic PPK (EPPK) in which mutations in keratin 9 have been demonstrated.

  9. On the power for linkage detection using a test based on scan statistics.

    Science.gov (United States)

    Hernández, Sonia; Siegmund, David O; de Gunst, Mathisca

    2005-04-01

    We analyze some aspects of scan statistics, which have been proposed to help for the detection of weak signals in genetic linkage analysis. We derive approximate expressions for the power of a test based on moving averages of the identity by descent allele sharing proportions for pairs of relatives at several contiguous markers. We confirm these approximate formulae by simulation. The results show that when there is a single trait-locus on a chromosome, the test based on the scan statistic is slightly less powerful than that based on the customary allele sharing statistic. On the other hand, if two genes having a moderate effect on a trait lie close to each other on the same chromosome, scan statistics improve power to detect linkage. PMID:15772104

  10. A genome-wide scan in affected sibling pairs with idiopathic recurrent miscarriage suggests genetic linkage

    DEFF Research Database (Denmark)

    Kolte, Astrid Marie; Nielsen, H S; Moltke, Ida;

    2011-01-01

    Previously, siblings of patients with idiopathic recurrent miscarriage (IRM) have been shown to have a higher risk of miscarriage. This study comprises two parts: (i) an epidemiological part, in which we introduce data on the frequency of miscarriage among 268 siblings of 244 patients with IRM and...... (ii) a genetic part presenting data from a genome-wide linkage study of 38 affected sibling pairs with IRM. All IRM patients (probands) had experienced three or more miscarriages and affected siblings two or more miscarriages. The sibling pairs were genotyped by the Affymetrix GeneChip 50K Xba......I platform and non-parametric linkage analysis was performed via the software package Merlin. We find that siblings of IRM patients exhibit a higher frequency of miscarriage than population controls regardless of age at the time of pregnancy. We identify chromosomal regions with LOD scores between 2.5 and 3...

  11. LD-Spline: Mapping SNPs on genotyping platforms to genomic regions using patterns of linkage disequilibrium

    Directory of Open Access Journals (Sweden)

    Bush William S

    2009-12-01

    Full Text Available Abstract Background Gene-centric analysis tools for genome-wide association study data are being developed both to annotate single locus statistics and to prioritize or group single nucleotide polymorphisms (SNPs prior to analysis. These approaches require knowledge about the relationships between SNPs on a genotyping platform and genes in the human genome. SNPs in the genome can represent broader genomic regions via linkage disequilibrium (LD, and population-specific patterns of LD can be exploited to generate a data-driven map of SNPs to genes. Methods In this study, we implemented LD-Spline, a database routine that defines the genomic boundaries a particular SNP represents using linkage disequilibrium statistics from the International HapMap Project. We compared the LD-Spline haplotype block partitioning approach to that of the four gamete rule and the Gabriel et al. approach using simulated data; in addition, we processed two commonly used genome-wide association study platforms. Results We illustrate that LD-Spline performs comparably to the four-gamete rule and the Gabriel et al. approach; however as a SNP-centric approach LD-Spline has the added benefit of systematically identifying a genomic boundary for each SNP, where the global block partitioning approaches may falter due to sampling variation in LD statistics. Conclusion LD-Spline is an integrated database routine that quickly and effectively defines the genomic region marked by a SNP using linkage disequilibrium, with a SNP-centric block definition algorithm.

  12. Linkage and association of phospholipid transfer protein activity to LASS4.

    Science.gov (United States)

    Rosenthal, Elisabeth A; Ronald, James; Rothstein, Joseph; Rajagopalan, Ramakrishnan; Ranchalis, Jane; Wolfbauer, G; Albers, John J; Brunzell, John D; Motulsky, Arno G; Rieder, Mark J; Nickerson, Deborah A; Wijsman, Ellen M; Jarvik, Gail P

    2011-10-01

    Phospholipid transfer protein activity (PLTPa) is associated with insulin levels and has been implicated in atherosclerotic disease in both mice and humans. Variation at the PLTP structural locus on chromosome 20 explains some, but not all, heritable variation in PLTPa. In order to detect quantitative trait loci (QTLs) elsewhere in the genome that affect PLTPa, we performed both oligogenic and single QTL linkage analysis on four large families (n = 227 with phenotype, n = 330 with genotype, n = 462 total), ascertained for familial combined hyperlipidemia. We detected evidence of linkage between PLTPa and chromosome 19p (lod = 3.2) for a single family and chromosome 2q (lod = 2.8) for all families. Inclusion of additional marker and exome sequence data in the analysis refined the linkage signal on chromosome 19 and implicated coding variation in LASS4, a gene regulated by leptin that is involved in ceramide synthesis. Association between PLTPa and LASS4 variation was replicated in the other three families (P = 0.02), adjusting for pedigree structure. To our knowledge, this is the first example for which exome data was used in families to identify a complex QTL that is not the structural locus.

  13. Linkage disequilibrium in wild and cultured populations of Pacific oyster ( Crassostrea gigas)

    Science.gov (United States)

    Guo, Xiang; Li, Qi; Kong, Lingfeng; Yu, Hong

    2016-04-01

    Linkage disequilibrium (LD) can be applied for mapping the actual genes responsible for variation of economically important traits through association mapping. The feasibility and efficacy of association studies are strongly dependent on the extent of LD which determines the number and density of markers in the studied population, as well as the experimental design for an association analysis. In this study, we first characterized the extent of LD in a wild population and a cultured mass-selected line of Pacific oyster ( Crassostrea gigas). A total of 88 wild and 96 cultured individuals were selected to assess the level of genome-wide LD with 53 microsatellites, respectively. For syntenic marker pairs, no significant association was observed in the wild population; however, three significant associations occurred in the cultured population, and the significant LD extended up to 12.7 cM, indicating that strong artificial selection is a key force for substantial increase of genome-wide LD in cultured population. The difference of LD between wild and cultured populations showed that association studies in Pacific oyster can be achieved with reasonable marker densities at a relatively low cost by choosing an association mapping population. Furthermore, the frequent occurrence of LD between non-syntenic loci and rare alleles encourages the joint application of linkage analysis and LD mapping when mapping genes in oyster. The information on the linkage disequilibrium in the cultured population is useful for future association mapping in oyster.

  14. Linkage disequilibrium in the human insulin/insulin-like growth factor II region of human chromosome II.

    OpenAIRE

    Cox, N J; Bell, G I; Xiang, K S

    1988-01-01

    Caucasian (N = 128) and Chinese (N = 84) subjects were typed for RFLPs in the insulin (INS)/insulin-like growth factor II (IGF2) region of chromosome 11. Both the analysis of extended haplotypes and the pairwise measures of linkage disequilibrium among the RFLPs indicate that there is extensive linkage disequilibrium in the INS/IGF2 region. The disequilibrium extends across the hypervariable region (HVR) located just 5' to the INS gene and encompasses a region of at least 40 kbp. Previous stu...

  15. A Novel Non-Parametric Regression Reveals Linkage on Chromosome 4 for the Number of Externalizing Symptoms in Sib-Pairs

    OpenAIRE

    Ghosh, Saurabh; Laura J Bierut; Porjesz, Bernice; Edenberg, Howard J.; Dick, Danielle; Goate, Alison; Hesselbrock, Victor; Nurnberger, John; Foroud, Tatiana; Kramer, John; Rice, John,; Begleiter, Henri

    2008-01-01

    In this report, we present results of a genome-wide linkage scan using as a phenotype the number of externalizing symptoms associated with alcohol use disorders. Subjects were collected by the Collaborative Study on the Genetics of Alcoholism project from families in which at least three first degree relatives were affected by alcohol dependence. We use a novel non-parametric regression method based on kernel smoothing for our analysis. We report a statistically significant linkage close to t...

  16. Linkage studies in Spanish autosomal dominant polycystic kidney disease-type 2 (ADPKD-2) families

    Energy Technology Data Exchange (ETDEWEB)

    San Millan, J.L.; Viribay, M.; Perral, B. [Hospital Ramon y Cajal, Madrid (Spain)] [and others

    1994-09-01

    ADPKD results from mutations in at least two genetically distinct loci. Most of the cases (ADPKD-1) are due to mutations in the locus PKD1, on the short arm of chromosome 16. ADPKD-2 accounts for 15% of ADPKD in Spanish population. Previous linkage studies have localized the gene for ADPKD-2 (PKD2) in the chromosome region 4q13-q23, and the distance between the flanking markers, D4S231 and D4S423/D4S414, was 7 cM. We have analyzed seven unrelated families with ADPKD not linked to PKD1 by using eight microsatellite markers that map within the candidate region. All the families did show linkage to any of the markers for which they were informative. Pairwise linkage analysis revealed that loci D4S414 and D4S423 are tightly linked to the disease with lod scores of 3.12 and 6.50, respectively, at a recombination fraction of 0.00. Multilocus linkage analysis indicates that the most likely location for PKD2 is distal to D4S1542, with odds of 1000:1 over the location proximal to D4S1542. Two recombination events involving PKD2 chromosomes have been identified in our seven families. These results provide a proximal boundary for the PKD2 locus and, considering previous studies, its localization is further refined to a 3 cM interval flanked by markers D4S1542 and D4S414/D4S423.

  17. Quantitative Linkage for Autism Spectrum Disorders Symptoms in Attention-Deficit/Hyperactivity Disorder : Significant Locus on Chromosome 7q11

    NARCIS (Netherlands)

    Nijmeijer, Judith; Arias-Vasquez, Alejandro; Rommelse, Nanda N. J.; Altink, Marieke E.; Buschgens, Cathelijne J. M.; Fliers, Ellen A.; Franke, Barbara; Minderaa, Rudolf; Sergeant, Joseph A.; Buitelaar, Jan K.; Hoekstra, Pieter J.; Hartman, Catharina A.

    2014-01-01

    We studied 261 ADHD probands and 354 of their siblings to assess quantitative trait loci associated with autism spectrum disorder symptoms (as measured by the Children's Social Behavior Questionnaire (CSBQ)) using a genome-wide linkage approach, followed by locus-wide association analysis. A genome-

  18. Quantitative Linkage for Autism Spectrum Disorders Symptoms in Attention-Deficit/Hyperactivity Disorder: Significant Locus on Chromosome 7q11

    Science.gov (United States)

    Nijmeijer, Judith S.; Arias-Vásquez, Alejandro; Rommelse, Nanda N.; Altink, Marieke E.; Buschgens, Cathelijne J.; Fliers, Ellen A.; Franke, Barbara; Minderaa, Ruud B.; Sergeant, Joseph A.; Buitelaar, Jan K.; Hoekstra, Pieter J.; Hartman, Catharina A.

    2014-01-01

    We studied 261 ADHD probands and 354 of their siblings to assess quantitative trait loci associated with autism spectrum disorder symptoms (as measured by the Children's Social Behavior Questionnaire (CSBQ) using a genome-wide linkage approach, followed by locus-wide association analysis. A genome-wide significant locus for the CSBQ subscale…

  19. 地面移动Altmann连杆机构%Ground Mobile Altmann Linkage

    Institute of Scientific and Technical Information of China (English)

    刘超; 王皓; 姚燕安

    2015-01-01

    提出Altmann连杆机构的一个新用途,将其用来作为地面移动机构,以翻跟斗步态实现沿直线的行走运动,并通过自身扭动与整体反转的步态实现转向运动。提出地面移动Altmann连杆机构的设计概念和构型方案。分析地面移动Altmann连杆机构的移动原理,包括利用奇异位形来实现机构的转向运动。规划出直行和转向两种移动步态。分析两种步态的移动轨迹,并计算两种移动步态的关键参数。研究结果表明,通过对直行和转向两种步态的切换控制,可以使Altmann地面移动连杆机构以固定的步长,从平面上一个初始点移动到另一个目标点。该地面移动连杆机构基于空间单闭链六杆机构,结构简单,刚度好,同时具有良好的折叠特性,便于存储和运输。%A novel application of the Altmann linkage is presented and used as a novel ground mobile mechanism. It can move in straight by tumbling and turn by twisting and inverting. The design concept of the ground mobile Altamann linkage is proposed. The motion principle of this proposed ground mobile Altmann linkage is analyzed. By taking advantage of the singular configuration of the mechanism, the control of turning can be achieved. The gaits of the moving in straight and the turning are planned. The locomotion tracts of the two gaits are analyzed respectively, and the analysis of the key parameters is performed. The results of the research prove that the ground mobile Altmann linkage can move from an initialpoint to a target point in a plane by the switch control of the straight and the turning gaits. This ground mobile linkage has simple structure, good rigidity due to it is a spatial single-loop linkage. And it is easy to store and transport due to it has good folding ability.

  20. 基于交通通达性的关中—天水经济区县际经济联系测度及时空动态分析%The measurement of inter-county economic linkage and spatio-temporal dynamics analysis in Guanzhong-Tianshui economic region based on the traffic accessibility

    Institute of Scientific and Technical Information of China (English)

    王妙妙; 曹小曙

    2016-01-01

    'an,Xianyang,Baoji,Tongchuan,Weinan,Yangling district,Shangluo's Shangzhou district,Luonan county,Zhashui county and Danfeng county in Shaanxi province and Tianshui in Gansu province.Based on the weighted average travel time,intensity of economic linkages and membership data of city roads,railway sites,aviation airports of the 58 counties in GuanzhongTianshui economic region,this paper utilizes GIS network analysis and exploratory spatial data analysis method to make a comprehensive analysis of the spatial pattem and evolution of economic relation between counties in Guanzhong-Tianshui economic region from 1980 to 2014 from the aspects of different means of transportation including roads,railway sites and aviation airports.The results show that there is a coupling between the increase level of accessibility of different means of transportation and the gross economic linkages in counties of this economic region.The increase level of accessibility of different means of transportation has a significant spatial autocorrelation and integration,and the gross economic linkages in counties are just the opposite.Meanwhile,there is a positive correlation between city's comprehensive quality and city's gross economic relations based on different means of transportation.In the economic relations between counties based on different means of transportation,leading cities and isolate cities coexist,most of which are in the stage of selfdevelopment,thus the regional integration process is slow.Besides,the spatial pattern of multinuclear economic relations with catenulate groups has formed,which concerns Xi'anXianyang,Baoji,and Tianshui.There exists little economic linkage between these groups,and a horizontal axis of the weak economic ties has formed along the arterial traffic.

  1. RLT-S: A Web System for Record Linkage.

    Directory of Open Access Journals (Sweden)

    Abdullah-Al Mamun

    Full Text Available Record linkage integrates records across multiple related data sources identifying duplicates and accounting for possible errors. Real life applications require efficient algorithms to merge these voluminous data sources to find out all records belonging to same individuals. Our recently devised highly efficient record linkage algorithms provide best-known solutions to this challenging problem.We have developed RLT-S, a freely available web tool, which implements our single linkage clustering algorithm for record linkage. This tool requires input data sets and a small set of configuration settings about these files to work efficiently. RLT-S employs exact match clustering, blocking on a specified attribute and single linkage based hierarchical clustering among these blocks.RLT-S is an implementation package of our sequential record linkage algorithm. It outperforms previous best-known implementations by a large margin. The tool is at least two times faster for any dataset than the previous best-known tools.RLT-S tool implements our record linkage algorithm that outperforms previous best-known algorithms in this area. This website also contains necessary information such as instructions, submission history, feedback, publications and some other sections to facilitate the usage of the tool.RLT-S is integrated into http://www.rlatools.com, which is currently serving this tool only. The tool is freely available and can be used without login. All data files used in this paper have been stored in https://github.com/abdullah009/DataRLATools. For copies of the relevant programs please see https://github.com/abdullah009/RLATools.

  2. Mobility of the Myard 5R Linkage Involved in "Gogu Problem"

    Institute of Scientific and Technical Information of China (English)

    LIU Jingfang; HUANG Zhen; LI Yanwen

    2009-01-01

    Since the traditional Grübler-Kutzbach criterion fails in many overconstrained mechanisms, developing a general mobility formula is a hot topic lasting for more than 150 years in mechanisms. GOGU systematically investigated various mobility methods, and pointed that the methods were not fit for two kinds of paradoxical overconstrained mechanisms. The mobility on the two kinds of mechanisms in "Gogu problem", and has developed into a systematic mobility methodology. Myard 5R linkage is one of the single-loop mechanisms involved in "Gogu problem", its joint axes are distributed in space with special geometric conditions, which increases the difficulty of mobility analysis. The study is to calculate the global mobility of the Myard 5R linkage using the mobility methodology. Firstly, the mobility methodology based on screw theory is briefly introduced. Secondly, some homogeneous transforms are performed accnrding to the D-H parameters and the invarianee of the linkage plane symmetry is revealed, which provides an idea to judge a plane-symmetric loop. The special geometric features of the axes distribution are discussed as well. Finally, the global mobility of the more paradoxical mechanisms.

  3. A linkage between DNA markers on the X chromosome and male sexual orientation.

    Science.gov (United States)

    Hamer, D H; Hu, S; Magnuson, V L; Hu, N; Pattatucci, A M

    1993-07-16

    The role of genetics in male sexual orientation was investigated by pedigree and linkage analyses on 114 families of homosexual men. Increased rates of same-sex orientation were found in the maternal uncles and male cousins of these subjects, but not in their fathers or paternal relatives, suggesting the possibility of sex-linked transmission in a portion of the population. DNA linkage analysis of a selected group of 40 families in which there were two gay brothers and no indication of nonmaternal transmission revealed a correlation between homosexual orientation and the inheritance of polymorphic markers on the X chromosome in approximately 64 percent of the sib-pairs tested. The linkage to markers on Xq28, the subtelomeric region of the long arm of the sex chromosome, had a multipoint lod score of 4.0 (P = 10(-5), indicating a statistical confidence level of more than 99 percent that at least one subtype of male sexual orientation is genetically influenced. PMID:8332896

  4. A linkage between DNA markers on the X chromosome and male sexual orientation

    Energy Technology Data Exchange (ETDEWEB)

    Hamer, D.H.; Hu, S.; Magnuson, V.L.; Hu, N.; Pattatucci, A.M.L.

    1993-07-16

    The role of genetics in male sexual orientation was investigated by pedigree and linkage analyses on 114 families of homosexual men. Increased rates of same-sex orientation were found in the maternal uncles and male cousins of these subjects, but not in their fathers or paternal relatives, suggesting the possibility of sex-linked transmission in a portion of the population. DNA linkage analysis of a selected group of 40 families in which there were two gay brothers and no indication of nonmaternal transmission revealed a correlation between homosexual orientation and the inheritance of polymorphic markers on the X chromosome in approximately 64 percent of the sib-pairs tested. The linkage to markers on Xq28, the subtelomeric region of the long arm of the sex chromosome, had a multipoint lod score of 4.0(P = 10[sup [minus]5]), indicating a statistical confidence level of more than 99 percent that at least one subtype of male sexual orientation is genetically influenced.

  5. Optimal Monetary Policy with Durable Consumption Goods and Factor Demand Linkages

    DEFF Research Database (Denmark)

    Petrella, Ivan; Santoro, Emiliano

    This paper deals with the implications of factor demand linkages for monetary policy design. We develop a dynamic general equilibrium model with two sectors that produce durable and non-durable goods, respectively. Part of the output produced in each sector is used as an intermediate input of pro...... is crucial, as this does not only influence the user cost of durables through the conventional demand channel, but also affects in opposite directions the real marginal cost of production in either sector through the intermediate input channel.......This paper deals with the implications of factor demand linkages for monetary policy design. We develop a dynamic general equilibrium model with two sectors that produce durable and non-durable goods, respectively. Part of the output produced in each sector is used as an intermediate input......-durable spending in response to a monetary policy shock. A main result of our monetary policy analysis is that strategic complementarities generated by factor demand linkages amplify social welfare loss. As the degree of interconnection between sectors increases, the cost of misperceiving the correct production...

  6. Evidence of linkage of HDL level variation to APOC3 in two samples with different ascertainment.

    Science.gov (United States)

    Gagnon, France; Jarvik, Gail P; Motulsky, Arno G; Deeb, Samir S; Brunzell, John D; Wijsman, Ellen M

    2003-11-01

    The APOA1-C3-A4-A5 gene complex encodes genes whose products are implicated in the metabolism of HDL and/or triglycerides. Although the relationship between polymorphisms in this gene cluster and dyslipidemias was first reported more than 15 years ago, association and linkage results have remained inconclusive. This is due, in part, to the oligogenic and multivariate nature of dyslipidemic phenotypes. Therefore, we investigate evidence of linkage of APOC3 and HDL using two samples of dyslipidemic pedigrees: familial combined hyperlipidemia (FCHL) and isolated low-HDL (ILHDL). We used a strategy that deals with several difficulties inherent in the study of complex traits: by using a Bayesian Markov Chain Monte Carlo (MCMC) approach we allow for oligogenic trait models, as well as simultaneous incorporation of covariates, in the context of multipoint analysis. By using this approach on extended pedigrees we provide evidence of linkage of APOC3 and HDL level variation in two samples with different ascertainment. In addition to APOC3, we estimate that two to three genes, each with a substantial effect on total variance, are responsible for HDL variation in both data sets. We also provide evidence, using the FCHL data set, for a pleiotropic effect between HDL, HDL3 and triglycerides at the APOC3 locus.

  7. The first genetic linkage map of Eucommia ulmoides

    Indian Academy of Sciences (India)

    Dawei Wang; Yu Li; Long Li; Yongcheng Wei; Zhouqi Li

    2014-04-01

    In accordance with pseudo-testcross strategy, the first genetic linkage map of Eucommia ulmoides Oliv. was constructed by an F1 population of 122 plants using amplified fragment length polymorphism (AFLP) markers. A total of 22 AFLP primer combinations generated 363 polymorphic markers. We selected 289 markers segregating as 1:1 and used them for constructing the parent-specific linkage maps. Among the candidate markers, 127 markers were placed on the maternal map LF and 108 markers on the paternal map Q1. The maternal map LF spanned 1116.1 cM in 14 linkage groups with a mean map distance of 8.78 cM; the paternal map Q1 spanned 929.6 cM in 12 linkage groups with an average spacing of 8.61 cM. The estimated coverage of the genome through two methods was 78.5 and 73.9% for LF, and 76.8 and 71.2% for Q1, respectively. This map is the first linkage map of E. ulmoides and provides a basis for mapping quantitative-trait loci and breeding applications.

  8. Using record linkage to monitor equity and variation in screening programmes

    Directory of Open Access Journals (Sweden)

    O’Reilly Dermot

    2012-04-01

    Full Text Available Abstract Background Ecological or survey based methods to investigate screening uptake rates are fraught with many limitations which can be circumvented by record linkage between Census and health services datasets using variations in breast screening attendance as an exemplar. The aim of this current study is to identify the demographic, socio-economic factors associated with uptake of breast screening. Methods Record linkage study: combining 2001 Census data within the Northern Ireland Longitudinal Study (NILS with data relating to validated breast screening histories from the National Breast Screening System. A cohort was identified of 37,059 women aged 48-64 at the Census who were invited for routine breast screening in the three years following the Census. All cohort attributes were as recorded on the Census form. Results The record linkage methodology enabled the records of almost 40,000 of those invited for screening to be analysed at an individual level, exceeding the largest published survey by a factor of ten. This produced a more robust analysis and demonstrated (in fully adjusted models the lower uptake amongst non-married women and those in the lowest social class (OR 0.74; 95%CI 0.66, 0.82, factors that had not been reported earlier in the UK. In addition, with the availability of both individual and area information it was possible to show that the much lower screening uptake in urban areas is not due to differences in population composition suggesting unrecognised organisational problems. Conclusions Linkage of screening data to Census-based longitudinal studies is an efficient and powerful way to increase the evidence base on sources of variation in screening uptake within the UK.

  9. An integrated linkage, chromosome, and genome map for the yellow fever mosquito Aedes aegypti.

    Directory of Open Access Journals (Sweden)

    Vladimir A Timoshevskiy

    Full Text Available BACKGROUND: Aedes aegypti, the yellow fever mosquito, is an efficient vector of arboviruses and a convenient model system for laboratory research. Extensive linkage mapping of morphological and molecular markers localized a number of quantitative trait loci (QTLs related to the mosquito's ability to transmit various pathogens. However, linking the QTLs to Ae. aegypti chromosomes and genomic sequences has been challenging because of the poor quality of polytene chromosomes and the highly fragmented genome assembly for this species. METHODOLOGY/PRINCIPAL FINDINGS: Based on the approach developed in our previous study, we constructed idiograms for mitotic chromosomes of Ae. aegypti based on their banding patterns at early metaphase. These idiograms represent the first cytogenetic map developed for mitotic chromosomes of Ae. aegypti. One hundred bacterial artificial chromosome clones carrying major genetic markers were hybridized to the chromosomes using fluorescent in situ hybridization. As a result, QTLs related to the transmission of the filarioid nematode Brugia malayi, the avian malaria parasite Plasmodium gallinaceum, and the dengue virus, as well as sex determination locus and 183 Mbp of genomic sequences were anchored to the exact positions on Ae. aegypti chromosomes. A linear regression analysis demonstrated a good correlation between positions of the markers on the physical and linkage maps. As a result of the recombination rate variation along the chromosomes, 12 QTLs on the linkage map were combined into five major clusters of QTLs on the chromosome map. CONCLUSION: This study developed an integrated linkage, chromosome, and genome map-iMap-for the yellow fever mosquito. Our discovery of the localization of multiple QTLs in a few major chromosome clusters suggests a possibility that the transmission of various pathogens is controlled by the same genomic loci. Thus, the iMap will facilitate the identification of genomic determinants of

  10. Genome-wide linkage study of atopic dermatitis in West Highland White Terriers

    Directory of Open Access Journals (Sweden)

    Paps Judith S

    2011-04-01

    Full Text Available Abstract Background Canine atopic dermatitis (AD is a common, heritable, chronic allergic skin condition prevalent in the West Highland White Terrier (WHWT. In canine AD, environmental allergens trigger an inflammatory response causing visible skin lesions and chronic pruritus that can lead to secondary bacterial and yeast infections. The disorder shares many of the clinical and histopathological characteristics of human AD and represents an animal model of this disorder that could be used to further elucidate genetic causes of human AD. Microsatellite markers genotyped in families of WHWTs affected with AD were used to perform a genome-wide linkage study in order to isolate chromosomal regions associated with the disorder. Results Blood samples and health questionnaires were collected from 108 WHWTs spanning three families. A linkage simulation using these 108 dogs showed high power to detect a highly penetrant mutation. Ninety WHWTs were genotyped using markers from the Minimal Screening Set 2 (MSS-2. Two hundred and fifty six markers were informative and were used for linkage analysis. Using a LOD score of 2.7 as a significance threshold, no chromosomal regions were identified with significant linkage to AD. LOD scores greater than 1.0 were located in a 56 cM region of chromosome 7. Conclusions The study was unable to detect any chromosomal regions significantly linked to canine AD. This could be a result of factors such as environmental modification of phenotype, incorrect assignment of phenotype, a mutation of low penetrance, or incomplete genome coverage. A genome-wide SNP association study in a larger cohort of WHWTs may prove more successful by providing higher density coverage and higher statistical power.

  11. Quantitative genetics theory for non-inbred populations in linkage disequilibrium

    Directory of Open Access Journals (Sweden)

    José Marcelo Soriano Viana

    2004-01-01

    Full Text Available Although linkage disequilibrium, epistasis and inbreeding are common phenomena in genetic systems that control quantitative traits, theory development and analysis are very complex, especially when they are considered together. The objective of this study is to offer additional quantitative genetics theory to define and analyze, in relation to non-inbred cross pollinating populations, components of genotypic variance, heritabilities and predicted gains, assuming linkage disequilibrium and absence of epistasis. The genotypic variance and its components, additive and due to dominance genetic variances, are invariant over the generations only in regard to completely linked genes and to those in equilibrium. When the population is structured in half-sib families, the additive variance in the parents' generation and the genotypic variance in the population can be estimated. When the population is structured in full-sib families, none of the components of genotypic variance can be estimated. The narrow sense heritability level at plant level can be estimated from the parent-offspring or mid parent-offspring regression. When there is dominance, the narrow sense heritability estimate in the in F2 is biased due to linkage disequilibrium when estimated by the Warner method, but not when estimated by means of the plant F2-family F3 regression. The bias is proportional to the number of pairs of linked genes, without independent assortment, and to the degree of dominance, and tends to be positive when genes in the coupling phase predominate or negative and of higher value when genes in the repulsion phase predominate. Linkage disequilibrium is also cause of bias in estimates of the narrow sense heritabilities at full-sib family mean and at plant within half-sib and full-sib families levels. Generally, the magnitude of the bias is proportional to the number of pairs of genes in disequilibrium and to the frequency of recombining gametes.

  12. Systematic, genome-wide, sex-specific linkage of cardiovascular traits in French Canadians.

    Science.gov (United States)

    Seda, Ondrej; Tremblay, Johanne; Gaudet, Daniel; Brunelle, Pierre-Luc; Gurau, Alexandru; Merlo, Ettore; Pilote, Louise; Orlov, Sergei N; Boulva, Francis; Petrovich, Milan; Kotchen, Theodore A; Cowley, Allen W; Hamet, Pavel

    2008-04-01

    The sexual dimorphism of cardiovascular traits, as well as susceptibility to a variety of related diseases, has long been recognized, yet their sex-specific genomic determinants are largely unknown. We systematically assessed the sex-specific heritability and linkage of 539 hemodynamic, metabolic, anthropometric, and humoral traits in 120 French-Canadian families from the Saguenay-Lac-St-Jean region of Quebec, Canada. We performed multipoint linkage analysis using microsatellite markers followed by peak-wide linkage scan based on Affymetrix Human Mapping 50K Array Xba240 single nucleotide polymorphism genotypes in 3 settings, including the entire sample and then separately in men and women. Nearly one half of the traits were age and sex independent, one quarter were both age and sex dependent, and one eighth were exclusively age or sex dependent. Sex-specific phenotypes are most frequent in heart rate and blood pressure categories, whereas sex- and age-independent determinants are predominant among humoral and biochemical parameters. Twenty sex-specific loci passing multiple testing criteria were corroborated by 2-point single nucleotide polymorphism linkage. Several resting systolic blood pressure measurements showed significant genotype-by-sex interaction, eg, male-specific locus at chromosome 12 (male-female logarithm of odds difference: 4.16; interaction P=0.0002), which was undetectable in the entire population, even after adjustment for sex. Detailed interrogation of this locus revealed a 220-kb block overlapping parts of TAO-kinase 3 and SUDS3 genes. In summary, a large number of complex cardiovascular traits display significant sexual dimorphism, for which we have demonstrated genomic determinants at the haplotype level. Many of these would have been missed in a traditional, sex-adjusted setting.

  13. Construction of a microsatellites-based linkage map for the white grouper (Epinephelus aeneus).

    Science.gov (United States)

    Dor, Lior; Shirak, Andrey; Gorshkov, Sergei; Band, Mark R; Korol, Abraham; Ronin, Yefim; Curzon, Arie; Hulata, Gideon; Seroussi, Eyal; Ron, Micha

    2014-08-01

    The white grouper (Epinephelus aeneus) is a promising candidate for domestication and aquaculture due to its fast growth, excellent taste, and high market price. A linkage map is an essential framework for mapping quantitative trait loci for economic traits and the study of genome evolution. DNA of a single individual was deep-sequenced, and microsatellite markers were identified in 177 of the largest scaffolds of the sequence assembly. The success rate of developing polymorphic homologous markers was 94.9% compared with 63.1% of heterologous markers from other grouper species. Of the 12 adult mature fish present in the broodstock tank, two males and two females were identified as parents of the assigned offspring by parenthood analysis using 34 heterologous markers. A single full-sib family of 48 individuals was established for the construction of first-generation linkage maps based on genotyping data of 222 microsatellites. The markers were assigned to 24 linkage groups in accordance to the 24 chromosomal pairs. The female and male maps consisting of 203 and 202 markers spanned 1053 and 886 cM, with an average intermarker distance of 5.8 and 5.0 cM, respectively. Mapping of markers to linkage groups ends was enriched by using markers originating from scaffolds harboring telomeric repeat-containing RNA. Comparative mapping showed high synteny relationships among the white grouper, kelp grouper (E. bruneus), orange-spotted grouper (E. coioides), and Nile tilapia (Oreochromis niloticus). Thus, it would be useful to integrate the markers that were developed for different groupers, depending on sharing of sequence data, into a comprehensive consensus map. PMID:24902605

  14. Genome-wide linkage scan for contraction velocity characteristics of knee musculature in the Leuven Genes for Muscular Strength Study.

    Science.gov (United States)

    De Mars, Gunther; Windelinckx, An; Huygens, Wim; Peeters, Maarten W; Beunen, Gaston P; Aerssens, Jeroen; Vlietinck, Robert; Thomis, Martine A I

    2008-09-17

    The torque-velocity relationship is known to be affected by ageing, decreasing its protective role in the prevention of falls. Interindividual variability in this torque-velocity relationship is partly determined by genetic factors (h(2): 44-67%). As a first attempt, this genome-wide linkage study aimed to identify chromosomal regions linked to the torque-velocity relationship of the knee flexors and extensors. A selection of 283 informative male siblings (17-36 yr), belonging to 105 families, was used to conduct a genome-wide SNP-based (Illumina Linkage IVb panel) multipoint linkage analysis for the torque-velocity relationship of the knee flexors and extensors. The strongest evidence for linkage was found at 15q23 for the torque-velocity slope of the knee extensors (TVSE). Other interesting linkage regions with LOD scores >2 were found at 7p12.3 [logarithm of the odds ratio (LOD) = 2.03, P = 0.0011] for the torque-velocity ratio of the knee flexors (TVRF), at 2q14.3 (LOD = 2.25, P = 0.0006) for TVSE, and at 4p14 and 18q23 for the torque-velocity ratio of the knee extensors TVRE (LOD = 2.23 and 2.08; P = 0.0007 and 0.001, respectively). We conclude that many small contributing genes are involved in causing variation in the torque-velocity relationship of the knee flexor and extensor muscles. Several earlier reported candidate genes for muscle strength and muscle mass and new candidates are harbored within or in close vicinity of the linkage regions reported in the present study. PMID:18682575

  15. Fine mapping of multiple QTL using combined linkage and linkage disequilibrium mapping – A comparison of single QTL and multi QTL methods

    Directory of Open Access Journals (Sweden)

    Meuwissen Theo HE

    2007-04-01

    Full Text Available Abstract Two previously described QTL mapping methods, which combine linkage analysis (LA and linkage disequilibrium analysis (LD, were compared for their ability to detect and map multiple QTL. The methods were tested on five different simulated data sets in which the exact QTL positions were known. Every simulated data set contained two QTL, but the distances between these QTL were varied from 15 to 150 cM. The results show that the single QTL mapping method (LDLA gave good results as long as the distance between the QTL was large (> 90 cM. When the distance between the QTL was reduced, the single QTL method had problems positioning the two QTL and tended to position only one QTL, i.e. a "ghost" QTL, in between the two real QTL positions. The multi QTL mapping method (MP-LDLA gave good results for all evaluated distances between the QTL. For the large distances between the QTL (> 90 cM the single QTL method more often positioned the QTL in the correct marker bracket, but considering the broader likelihood peaks of the single point method it could be argued that the multi QTL method was more precise. Since the distances were reduced the multi QTL method was clearly more accurate than the single QTL method. The two methods combine well, and together provide a good tool to position single or multiple QTL in practical situations, where the number of QTL and their positions are unknown.

  16. 基于流域尺度的农业用地景观-水质关联分析%Analysis on linkage between farm landscape and water quality in Jiulong River watershed

    Institute of Scientific and Technical Information of China (English)

    孙芹芹; 黄金良; 洪华生; 李青生; 林杰; 冯媛

    2011-01-01

    Correlation analysis was performed to explore the relationships between CODMn, NH4+-N, TP and farm landscape in the Jiulong River watershed. Linear regressions between water quality and farm land percents were also processed in flood season, dry season and average season. The results showed that the total proportion of farm lands located in the slopes less than 15 degrees and greater than 25 degrees were positively correlated with CODMn, NH4+-N and TP concentrations in the water. Contagion index (CONTAG) of farm lands was positively correlated with TP concentrations, and Shannon Diversity Index (SHDI) of farm lands was negatively correlated with TP concentrations.The determinate coefficients were 0.565 and -0.527, respectively. Water eutrophication was susceptible to farm land pollutions in flood season and dry season. The farm lands located in the slopes less than 15 degrees took up 74.3% in the 100m-width riparian buffer. The farm lands located in the riparian buffer and in the deep slopes played a crucial role in water quality management, especially the non-point source pollution control in the Jiulong River watershed.%基于Landsat遥感影像进行九龙江流域不同坡度类型的农业用地景观与水质指标(CODMn、NH4+-N、TP)的相关性分析,并分别对丰水期、枯水期、平水期的农业用地类型百分比与各水质指标进行线性回归.结果显示,坡度小于15°和大于25°的农业用地占总农业用地的面积比例与各水质指标呈较强的正相关.景观聚集度指数(CONTAG)与水体中TP浓度呈显著正相关,决定系数为0.565;香农多样性指数(SHDI)与水体中TP浓度呈显著负相关,相关系数为-0.527.丰水期和枯水期是九龙江流域水质变化较大的时期.对河流近岸100 m范围内的农业用地类型组成进行统计发现,坡度小于15°的农业用地面积平均比例为74.3%.河岸缓冲区和陡坡农业用地的数量及分布是影响该地区水质及控制农业非点源污染的关键.

  17. Combined RAPD and RFLP molecular linkage map of asparagus.

    Science.gov (United States)

    Jiang, C; Lewis, M E; Sink, K C

    1997-02-01

    Two linkage maps of asparagus (Asparagus officinalis L.) were constructed using a double pseudotestcross mapping strategy with restriction fragment length polymorphisms (RFLPs), random amplified polymorphic DNAs (RAPDs), and allozymes as markers in a population generated from crossing MW25 x A19, two heterozygous parents. All data were inverted and combined with the natural data to detect linkages in repulsion phase. Two sets of data, one for each parent, were formed according to the inheritance patterns of the markers. The maternal MW25 map has a total of 163 marker loci placed in 13 linkage groups covering 1281 cM, with an average and a maximum distance between adjacent loci of 7.9 and 29 cM, respectively. The paternal A19 map has 183 marker loci covering 1324 cM in 9 linkage groups, with an average and a maximum distance between two adjacent loci of 7.7 and 29 cM, respectively. Six multiallelic RFLPs segregating in the pattern a/c x b/c and eight heterozygous loci (four RAPDs, and four RFLPs segregating in the pattern a/b x a/b (HZ loci)) were common to both maps. These 14 loci were used as bridges to align homologous groups between the two maps. In this case, RFLPs were more frequent and informative than RAPDs. Nine linkage groups in the MW25 map were homologous to six groups in the A19 map. In two cases, two or more bridge loci were common to a group; thus, the orientation of homologous linkage groups was also determined. In four other cases, only one locus was common to the two homologous groups and the orientation was unknown. Mdh, four RFLPs, and 14 RAPDs were assigned to chromosome L5, which also has the sex locus M. PMID:18464808

  18. Construction of an integrated high density simple sequence repeat linkage map in cultivated strawberry (Fragaria × ananassa) and its applicability.

    Science.gov (United States)

    Isobe, Sachiko N; Hirakawa, Hideki; Sato, Shusei; Maeda, Fumi; Ishikawa, Masami; Mori, Toshiki; Yamamoto, Yuko; Shirasawa, Kenta; Kimura, Mitsuhiro; Fukami, Masanobu; Hashizume, Fujio; Tsuji, Tomoko; Sasamoto, Shigemi; Kato, Midori; Nanri, Keiko; Tsuruoka, Hisano; Minami, Chiharu; Takahashi, Chika; Wada, Tsuyuko; Ono, Akiko; Kawashima, Kumiko; Nakazaki, Naomi; Kishida, Yoshie; Kohara, Mitsuyo; Nakayama, Shinobu; Yamada, Manabu; Fujishiro, Tsunakazu; Watanabe, Akiko; Tabata, Satoshi

    2013-02-01

    The cultivated strawberry (Fragaria × ananassa) is an octoploid (2n = 8x = 56) of the Rosaceae family whose genomic architecture is still controversial. Several recent studies support the AAA'A'BBB'B' model, but its complexity has hindered genetic and genomic analysis of this important crop. To overcome this difficulty and to assist genome-wide analysis of F. × ananassa, we constructed an integrated linkage map by organizing a total of 4474 of simple sequence repeat (SSR) markers collected from published Fragaria sequences, including 3746 SSR markers [Fragaria vesca expressed sequence tag (EST)-derived SSR markers] derived from F. vesca ESTs, 603 markers (F. × ananassa EST-derived SSR markers) from F. × ananassa ESTs, and 125 markers (F. × ananassa transcriptome-derived SSR markers) from F. × ananassa transcripts. Along with the previously published SSR markers, these markers were mapped onto five parent-specific linkage maps derived from three mapping populations, which were then assembled into an integrated linkage map. The constructed map consists of 1856 loci in 28 linkage groups (LGs) that total 2364.1 cM in length. Macrosynteny at the chromosome level was observed between the LGs of F. × ananassa and the genome of F. vesca. Variety distinction on 129 F. × ananassa lines was demonstrated using 45 selected SSR markers.

  19. A Sequence-Tagged Linkage Map of Brassica rapa

    OpenAIRE

    Kim, Jung Sun; Chung, Tae Young; King, Graham J; Jin, Mina; Yang, Tae-Jin; Jin, Yong-Moon; Kim, Ho-Il; Park, Beom-Seok

    2006-01-01

    A detailed genetic linkage map of Brassica rapa has been constructed containing 545 sequence-tagged loci covering 1287 cM, with an average mapping interval of 2.4 cM. The loci were identified using a combination of 520 RFLP and 25 PCR-based markers. RFLP probes were derived from 359 B. rapa EST clones and amplification products of 11 B. rapa and 26 Arabidopsis. Including 21 SSR markers provided anchors to previously published linkage maps for B. rapa and B. napus and is followed as the refere...

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

    Institute of Scientific and Technical Information of China (English)

    WANG Cheng-liang; CHEN Juan-juan

    2007-01-01

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

  1. Robust vibration control of flexible linkage mechanisms using piezoelectric films

    Science.gov (United States)

    Liao, Wen-Hwei; Chou, Jyh-Horng; Horng, Ing-Rong

    1997-08-01

    Based on the state space model of the flexible linkage mechanism equipped with piezoelectric films, a robust control methodology for suppressing elastodynamic responses of the high-speed flexible linkage mechanism with linear time-varying parameter perturbations by employing an observer-based feedback controller is presented. The instability caused by the linear time-varying parameter perturbations and the instability caused by the combined effect of control and observation spillover are investigated and carefully prevented by two robust stability criteria proposed in this paper. Numerical simulation of a slider - crank mechanism example is performed to evaluate the improvement of the elastodynamic responses.

  2. 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

  3. LD2SNPing: linkage disequilibrium plotter and RFLP enzyme mining for tag SNPs

    OpenAIRE

    Cheng Yu-Huei; Chang Yan-Jhu; Chuang Li-Yeh; Chang Hsueh-Wei; Hung Yu-Chen; Chen Hsiang-Chi; Yang Cheng-Hong

    2009-01-01

    Abstract Background Linkage disequilibrium (LD) mapping is commonly used to evaluate markers for genome-wide association studies. Most types of LD software focus strictly on LD analysis and visualization, but lack supporting services for genotyping. Results We developed a freeware called LD2SNPing, which provides a complete package of mining tools for genotyping and LD analysis environments. The software provides SNP ID- and gene-centric online retrievals for SNP information and tag SNP selec...

  4. Genome-wide linkage using the Social Responsiveness Scale in Utah autism pedigrees

    Directory of Open Access Journals (Sweden)

    Coon Hilary

    2010-04-01

    Full Text Available Abstract Background Autism Spectrum Disorders (ASD are phenotypically heterogeneous, characterized by impairments in the development of communication and social behaviour and the presence of repetitive behaviour and restricted interests. Dissecting the genetic complexity of ASD may require phenotypic data reflecting more detail than is offered by a categorical clinical diagnosis. Such data are available from the Social Responsiveness Scale (SRS which is a continuous, quantitative measure of social ability giving scores that range from significant impairment to above average ability. Methods We present genome-wide results for 64 multiplex and extended families ranging from two to nine generations. SRS scores were available from 518 genotyped pedigree subjects, including affected and unaffected relatives. Genotypes from the Illumina 6 k single nucleotide polymorphism panel were provided by the Center for Inherited Disease Research. Quantitative and qualitative analyses were done using MCLINK, a software package that uses Markov chain Monte Carlo (MCMC methods to perform multilocus linkage analysis on large extended pedigrees. Results When analysed as a qualitative trait, linkage occurred in the same locations as in our previous affected-only genome scan of these families, with findings on chromosomes 7q31.1-q32.3 [heterogeneity logarithm of the odds (HLOD = 2.91], 15q13.3 (HLOD = 3.64, and 13q12.3 (HLOD = 2.23. Additional positive qualitative results were seen on chromosomes 6 and 10 in regions that may be of interest for other neuropsychiatric disorders. When analysed as a quantitative trait, results replicated a peak found in an independent sample using quantitative SRS scores on chromosome 11p15.1-p15.4 (HLOD = 2.77. Additional positive quantitative results were seen on chromosomes 7, 9, and 19. Conclusions The SRS linkage peaks reported here substantially overlap with peaks found in our previous affected-only genome scan of clinical diagnosis

  5. Education and poverty linkage in Malawi: A district level analysis

    OpenAIRE

    Steven Henry Dunga; Mmapula Brendah Sekatane

    2013-01-01

    The need to reduce poverty in all its forms remains a priority around the world. The fact that countries with higher incidences of growth have an associated reduction in poverty levels is uncontested both in theory and in empirical findings. The channels through which growth results into poverty reduction are not clear. This study looks at education as a channel through which economic growth and poverty reduction are linked. Using data on districts in Malawi, we estimate a regression with the...

  6. Linkage analysis of circulating levels of adiponectin in hispanic children

    Science.gov (United States)

    Adiponectin, a hormone produced exclusively by adipose tissue, is inversely associated with insulin resistance and pro-inflammatory conditions. The aim of this study was to find quantitative trait loci (QTLs) that affect circulating levels of adiponectin in Hispanic children participating in the VVA...

  7. A multivalent three-point linkage analysis model of autotetraploids

    Science.gov (United States)

    A cytogenetic study was conducted on a dihaploid individual (2n'='2X'='18) of switchgrass to establish a chromosome karyotype. Size differences, condensation patterns, and arm-length ratios were used as identifying features and fluorescence in-situ hybridization (FISH) assigned 5S and 45S rDNA loci...

  8. Can University-Industry Linkages Stimulate Student Employability?

    Science.gov (United States)

    Ishengoma, Esther; Vaaland, Terje I.

    2016-01-01

    Purpose: The purpose of this paper is to identify important university-industry linkage (UIL) activities that can stimulate the likelihood of employability among students. Design/methodology/approach: A total of 404 respondents located in Tanzania, comprising students, faculty members and employees from 20 companies operating within the oil and…

  9. Linkage disequilibrium in young genetically isolated Dutch population

    NARCIS (Netherlands)

    Y.S. Aulchenko (Yurii); P. Heutink (Peter); I. Mackay (Ian); A.M. Bertoli Avella (Aida); J. Pullen (Jan); N. Vaessen (Norbert); T.A.M. Rademaker (Tessa); L.A. Sandkuijl (Lodewijk); L. Cardon (Lon); C.M. van Duijn (Cock); B.A. Oostra (Ben)

    2004-01-01

    textabstractThe design and feasibility of genetic studies of complex diseases are critically dependent on the extent and distribution of linkage disequilibrium (LD) across the genome and between different populations. We have examined genomewide and region-specific LD in a young genetically isolated

  10. Genetic linkage study of bipolar disorder and the serotonin transporter

    Energy Technology Data Exchange (ETDEWEB)

    Kelsoe, J.R.; Morison, M.; Mroczkowski-Parker, Z.; Bergesch, P.; Rapaport, M.H.; Mirow, A.L. [Univ. of California, San Diego, CA (United States)] [and others

    1996-04-09

    The serotonin transporter (HTT) is an important candidate gene for the genetic transmission of bipolar disorder. It is the site of action of many antidepressants, and plays a key role in the regulation of serotonin neurotransmission. Many studies of affectively ill patients have found abnormalities in serotonin metabolism, and dysregulation of the transporter itself. The human serotonin transporter has been recently cloned and mapped to chromosome 17. We have identified a PstI RFLP at the HTT locus, and here report our examination of this polymorphism for possible linkage to bipolar disorder. Eighteen families were examined from three populations: the Old Order Amish, Iceland, and the general North American population. In addition to HTT, three other microsatellite markers were examined, which span an interval known to contain HTT. Linkage analyses were conducted under both dominant and recessive models, as well as both narrow (bipolar only) and broad (bipolar + recurrent unipolar) diagnostic models. Linkage could be excluded to HTT under all models examined. Linkage to the interval spanned by the microsatellites was similarly excluded under the dominant models. In two individual families, maximum lod scores of 1.02 and 0.84 were obtained at D17S798 and HTT, respectively. However, these data overall do not support the presence of a susceptibility locus for bipolar disorder near the serotonin transporter. 20 refs., 2 tabs.

  11. Linkage Disequilibrium Decay and Haplotype Block Structure in the Pig

    NARCIS (Netherlands)

    Amaral, A.J.; Megens, H.J.W.C.; Crooijmans, R.P.M.A.; Heuven, H.C.M.; Groenen, M.A.M.

    2008-01-01

    Linkage disequilibrium (LD) may reveal much about domestication and breed history. Ail investigation was conducted, to analyze the extent of LD, haploblock partitioning, and haplotype diversity within haploblocks across several pig breeds from China and Europe and in European wild boar. In total, 37

  12. Mapping organizational linkages in the agricultural innovation system of Azerbaijan

    NARCIS (Netherlands)

    Temel, T.

    2004-01-01

    This study describes the evolving context and organisational linkages in the agricultural innovation system of Azerbaijan and suggests ways to promote effective organisational ties for the development, distribution and use of new or improved information and knowledge related to agriculture. Graph-th

  13. Association Between Pachytene Chromosomes and Linkage Groups in Carrot

    Science.gov (United States)

    The genome of carrot (Daucus carota L.) consists of ~ 480 Mb/1C organized in 9 chromosome pairs. The importance of carrots in human nutrition is triggering the development of genomic resources, including carrot linkage maps, a bacterial artificial chromosome (BAC) clone library and BAC end sequence...

  14. Recombination patterns reveal information about centromere location on linkage maps

    DEFF Research Database (Denmark)

    Limborg, Morten T.; McKinney, Garrett J.; Seeb, Lisa W.;

    2016-01-01

    . mykiss) characterized by low and unevenly distributed recombination – a general feature of male meiosis in many species. Further, a high frequency of double crossovers along chromosome arms in barley reduced resolution for locating centromeric regions on most linkage groups. Despite these limitations...

  15. Innovation and inter-firm linkages : new implications for policy

    NARCIS (Netherlands)

    Nooteboom, B

    1999-01-01

    This article discusses the implications for competition, innovation and learning of different forms of inter-firm linkage, ways to govern them, different 'generic systems' of innovation, and government policy. It employs a transformed theory of transactions that can deal with innovation and learning

  16. Low Cost Computer Graphics Simulation of Basic Kinematic Linkages.

    Science.gov (United States)

    Smith, Donald A.; Jacquot, Raymond G.

    1984-01-01

    Presents algorithms for the simulation and motion display of the three basic kinematic devices: (1) four bar linkages; (2) the slider crank; and (3) the inverted slider crank mechanisms. The algorithms were implemented on a Commodore-VIC 20 microcomputer system with 6500 bytes of available memory. (Author/JN)

  17. Monetary Policy with Sectoral Linkages and Durable Goods

    DEFF Research Database (Denmark)

    Petrella, Ivan; Rossi, Raffaele; Santoro, Emiliano

    We study the normative implications of a New Keynesian model featuring intersectoral trade of intermediate goods between two sectors that produce durables and non-durables. The interplay between durability and sectoral production linkages fundamentally alters the intersectoral stabilization trade...... are not properly accounted for by conventional measures of core inflation...

  18. Magnetic Topology of Coronal Hole Linkages

    CERN Document Server

    Titov, V S; Linker, J A; Lionello, R; Antiochos, S K

    2010-01-01

    In recent work, Antiochos and coworkers argued that the boundary between the open and closed field regions on the Sun can be extremely complex with narrow corridors of open flux connecting seemingly disconnected coronal holes from the main polar holes, and that these corridors may be the sources of the slow solar wind. We examine, in detail, the topology of such magnetic configurations using an analytical source surface model that allows for analysis of the field with arbitrary resolution. Our analysis reveals three important new results: First, a coronal hole boundary can join stably to the separatrix boundary of a parasitic polarity region. Second, a single parasitic polarity region can produce multiple null points in the corona and, more important, separator lines connecting these points. It is known that such topologies are extremely favorable for magnetic reconnection, because they allow this process to occur over the entire length of the separators rather than being confined to a small region around the...

  19. Discussing the inter-sectoral linkages in Ecuador, with a focus on the oil sector

    Directory of Open Access Journals (Sweden)

    Mercy ORELLANA BRAVO

    2015-12-01

    Full Text Available The oil sector represents a key-sector of the Ecuadorian economy, characterised by a high level of value added and a high weight in the national exports. This paper tries to find out whether the oil sector is able to induce positive effects for other economic sectors, and to also measure these effects in comparison with those generated by other sectors. The empirical analysis uses the income and employment multipliers, which are derived from Leontief Input-Output tables. The results indicate that the Ecuadorian oil sector is the most independent one, so that policies enhancing stronger linkages with other sectors are highly recommended.

  20. Two Methods of Whole-Genome Amplification Enable Accurate Genotyping Across a 2320-SNP Linkage Panel

    OpenAIRE

    Barker, David L.; Hansen, Mark S. T.; Faruqi, A. Fawad; Giannola, Diane; Irsula, Orlando R.; Lasken, Roger S; Latterich, Martin; Makarov, Vladimir; Oliphant, Arnold; Pinter, Jonathon H.; Shen, Richard; Sleptsova, Irina; Ziehler, William; Lai, Eric

    2004-01-01

    Comprehensive genome scans involving many thousands of SNP assays will require significant amounts of genomic DNA from each sample. We report two successful methods for amplifying whole-genomic DNA prior to SNP analysis, multiple displacement amplification, and OmniPlex technology. We determined the coverage of amplification by analyzing a SNP linkage marker set that contained 2320 SNP markers spread across the genome at an average distance of 2.5 cM. We observed a concordance of >99.8% in ge...