WorldWideScience

Sample records for previous linkage analysis

  1. 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.

  2. 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 ...

  3. An introduction to recombination and linkage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Mcpeek, M.S. [Univ. of Chicago, IL (United States)

    1996-12-31

    With a garden as his laboratory, Mendel was able to discern basic probabilistic laws of heredity. Although it first appeared as a baffling exception to one of Mendel`s principles, the phenomenon of variable linkage between characters was soon recognized to be a powerful tool in the process of chromosome mapping and location of genes of interest. In this introduction, we first describe Mendel`s work and the subsequent discovery of linkage. Next we describe the apparent cause of variable linkage, namely recombination, and we introduce linkage analysis. 33 refs., 1 fig., 2 tabs.

  4. Accommodating chromosome inversions in linkage analysis.

    Science.gov (United States)

    Chen, Gary K; Slaten, Erin; Ophoff, Roel A; Lange, Kenneth

    2006-08-01

    This work develops a population-genetics model for polymorphic chromosome inversions. The model precisely describes how an inversion changes the nature of and approach to linkage equilibrium. The work also describes algorithms and software for allele-frequency estimation and linkage analysis in the presence of an inversion. The linkage algorithms implemented in the software package Mendel estimate recombination parameters and calculate the posterior probability that each pedigree member carries the inversion. Application of Mendel to eight Centre d'Etude du Polymorphisme Humain pedigrees in a region containing a common inversion on 8p23 illustrates its potential for providing more-precise estimates of the location of an unmapped marker or trait gene. Our expanded cytogenetic analysis of these families further identifies inversion carriers and increases the evidence of linkage.

  5. Two-locus linkage analysis in multiple sclerosis (MS)

    Energy Technology Data Exchange (ETDEWEB)

    Tienari, P.J. (National Public Health Institute, Helsinki (Finland) Univ. of Helsinki (Finland)); Terwilliger, J.D.; Ott, J. (Columbia Univ., New York (United States)); Palo, J. (Univ. of Helsinki (Finland)); Peltonen, L. (National Public Health Institute, Helsinki (Finland))

    1994-01-15

    One of the major challenges in genetic linkage analyses is the study of complex diseases. The authors demonstrate here the use of two-locus linkage analysis in multiple sclerosis (MS), a multifactorial disease with a complex mode of inheritance. In a set of Finnish multiplex families, they have previously found evidence for linkage between MS susceptibility and two independent loci, the myelin basic protein gene (MBP) on chromosome 18 and the HLA complex on chromosome 6. This set of families provides a unique opportunity to perform linkage analysis conditional on two loci contributing to the disease. In the two-trait-locus/two-marker-locus analysis, the presence of another disease locus is parametrized and the analysis more appropriately treats information from the unaffected family member than single-disease-locus analysis. As exemplified here in MS, the two-locus analysis can be a powerful method for investigating susceptibility loci in complex traits, best suited for analysis of specific candidate genes, or for situations in which preliminary evidence for linkage already exists or is suggested. 41 refs., 6 tabs.

  6. 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.

  7. Haldane and the analysis of linkage

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 96; Issue 5. HALDANE AND THE ANALYSIS OF LINKAGE. J .H. Edwards. HALDANE AT 125 Volume 96 Issue 5 November 2017 pp 783-794. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/jgen/096/05/0783-0794. Abstract ...

  8. Hypothesis testing in genetic linkage analysis via Gibbs sampling ( )

    African Journals Online (AJOL)

    hope&shola

    2010-12-06

    Dec 6, 2010 ... Genetic linkage analysis involves estimating parameters in a genetic model in which a genetic trait is regressed on some factors such as ... Key words: Gibbs sampling, pedigree, linkage analysis, likelihood. INTRODUCTION ..... Pattern Analysis and Machine Intelligence, 6: 721-741. Guo SW, Thompson EA ...

  9. Linkage analysis: Inadequate for detecting susceptibility loci in complex disorders?

    Energy Technology Data Exchange (ETDEWEB)

    Field, L.L.; Nagatomi, J. [Univ. of Calgary, Alberta (Canada)

    1994-09-01

    Insulin-dependent diabetes mellitus (IDDM) may provide valuable clues about approaches to detecting susceptibility loci in other oligogenic disorders. Numerous studies have demonstrated significant association between IDDM and a VNTR in the 5{prime} flanking region of the insulin (INS) gene. Paradoxically, all attempts to demonstrate linkage of IDDM to this VNTR have failed. Lack of linkage has been attributed to insufficient marker locus information, genetic heterogeneity, or high frequency of the IDDM-predisposing allele in the general population. Tyrosine hydroxylase (TH) is located 2.7 kb from INS on the 5` side of the VNTR and shows linkage disequilibrium with INS region loci. We typed a highly polymorphic microsatellite within TH in 176 multiplex families, and performed parametric (lod score) linkage analysis using various intermediate reduced penetrance models for IDDM (including rare and common disease allele frequencies), as well as non-parametric (affected sib pair) linkage analysis. The scores significantly reject linkage for recombination values of .05 or less, excluding the entire 19 kb region containing TH, the 5{prime} VNTR, the INS gene, and IGF2 on the 3{prime} side of INS. Non-parametric linkage analysis also provided no significant evidence for linkage (mean TH allele sharing 52.5%, P=.12). These results have important implications for efforts to locate genes predisposing to complex disorders, strongly suggesting that regions which are significantly excluded by linkage methods may nevertheless contain predisposing genes readily detectable by association methods. We advocate that investigators routinely perform association analyses in addition to linkage analyses.

  10. 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

  11. Linkage analysis of alcohol dependence symptoms in the community.

    Science.gov (United States)

    Hansell, Narelle K; Agrawal, Arpana; Whitfield, John B; Morley, Katherine I; Gordon, Scott D; Lind, Penelope A; Pergadia, Michele L; Montgomery, Grant W; Madden, Pamela A F; Todd, Richard D; Heath, Andrew C; Martin, Nicholas G

    2010-01-01

    We have previously identified suggestive linkage for alcohol consumption in a community-based sample of Australian adults. In this companion paper, we explore the strength of genetic linkage signals for alcohol dependence symptoms. An alcohol dependence symptom score, based on DSM-IIIR and DSM-IV criteria, was examined. Twins and their nontwin siblings (1,654 males, 2,518 females), aged 21 to 81 years, were interviewed, with 803 individuals interviewed on 2 occasions, approximately 10 years apart. Linkage analyses were conducted on datasets compiled to maximize data collected at either the younger or the older age. In addition, linkage was compared between full samples and truncated samples that excluded the lightest drinkers (approximately 10% of the sample). Suggestive peaks on chromosome 5p (LODs >2.2) were found in a region previously identified in alcohol linkage studies using clinical populations. Linkage signal strength was found to vary between full and truncated samples and when samples differed only on the collection age for a sample subset. The results support the finding that large community samples can be informative in the study of alcohol-related traits.

  12. Mapping of yield, yield stability, yield adaptability and other traits in barley using linkage disequilibrium mapping and linkage analysis

    NARCIS (Netherlands)

    Kraakman, A.T.W.

    2005-01-01

    Plants is mostly done through linkage analysis. A segregating mapping population Identification and mappping of Quantitative Trait Loci (QTLs) in is created from a bi-parental cross and linkages between trait values and mapped markers reveal the positions ofQTLs. In

  13. Mapping of yield, yield stability, yield adaptability and other traits in barley using linkage disequilibrium mapping and linkage analysis

    OpenAIRE

    Kraakman, A.T.W.

    2005-01-01

    Plants is mostly done through linkage analysis. A segregating mapping population Identification and mappping of Quantitative Trait Loci (QTLs) in is created from a bi-parental cross and linkages between trait values and mapped markers reveal the positions ofQTLs. Inthisstudyweexploredlinkagedisequilibrium(LD)mappingof traits in a set of modernbarleycultivars. LDbetweenmolecularmarkerswasfoundup to a distance of 10 centimorgan,whichislargecomparedtootherspecies.Thelarge distancemightbeinducedb...

  14. Distribution and linkage disequilibrium analysis of polymorphisms of ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 95; Issue 1. Distribution and linkage disequilibrium analysis of polymorphisms of GH1 gene in different populations of pigs associated with body size. Yunyun Cheng Songcai Liu Dan Su Chao Lu Xin Zhang Qingyan Wu Siming Li Haoyu Fu Hao Yu Linlin Hao. Research Article ...

  15. Distribution and linkage disequilibrium analysis of polymorphisms of ...

    Indian Academy of Sciences (India)

    gene are associated with the body size of pigs providing genetic basis for pig breeding with the improved economic benefits. [Cheng Y., Liu S., Su D., Lu C., Zhang X., Wu Q., Li S., Fu H., Yu H. and Hao L. 2016 Distribution and linkage disequilibrium analysis of polymorphisms of GH1 gene in different populations of pigs ...

  16. [Analysis of linkage disequilibrium and linkage for 12 short tandem repeat loci on chromosome X].

    Science.gov (United States)

    Ye, Qiansu; Tang, Jianpin; Chen, Zucong; Li, Fagui; Yu, Xin; Wang, Ping; Lin, Hanguang; Shi, Meisen

    2014-12-01

    To analyze linkage disequilibrium of 12 short tandem repeat loci on chromosome X (X-STR) among an ethnic Han population from Guilin, Guangxi, and to study the genetic linkage and haplotype distributions of such loci in 2 linkage groups. 12 X-STR loci including DXS8378, DXS10159, DXS10162, DXS10164, DXS981, DXS6789, DXS7424, DXS101, DXS7133, GATA165B12, GATA31E08 and DXS7423 were genotyped using an AGCU X12 STR PCR Amplification kit. A total of 119 pedigrees were analyzed for linkage and linkage disequilibrium. Two mutations were found at DXS7424, and 1 mutation was found at DXS10164. A total of 93 haplotypes of DXS10159-DXS10162-DXS10164 were constructed for 261 unrelated males and females, in addition with 167 haplotypes of DXS6789-DXS7424-DXS101-DXS7133. The values of recombination fraction between DXS10159 and DXS10162, DXS10162 and DXS10164, DXS6789 and DXS7424, and DXS7424 and DXS101 were 0.0269, 0.0236, 0.0505 and 0.0438, respectively. Linkage disequilibrium of X-STR does not only depend on physical and genetic distances. There was incomplete linkage relationship between loci on DXS10159-DXS1016-DXS10164 and DXS6789-DXS7424-DXS101 linkage groups.

  17. Nance-Horan syndrome: linkage analysis in a family from The Netherlands

    NARCIS (Netherlands)

    Bergen, A. A.; ten Brink, J.; Schuurman, E. J.; Bleeker-Wagemakers, E. M.

    1994-01-01

    Linkage analysis was carried out in a Dutch family with Nance-Horan (NH) syndrome. Close linkage without recombination between NH and the Xp loci DXS207, DXS43, and DXS365 (zmax = 3.23) was observed. Multipoint linkage analysis and the analysis of recombinations in multiple informative meioses

  18. Heritability and linkage analysis of personality in bipolar disorder.

    Science.gov (United States)

    Greenwood, Tiffany A; Badner, Judith A; Byerley, William; Keck, Paul E; McElroy, Susan L; Remick, Ronald A; Dessa Sadovnick, A; Kelsoe, John R

    2013-11-01

    The many attempts that have been made to identify genes for bipolar disorder (BD) have met with limited success, which may reflect an inadequacy of diagnosis as an informative and biologically relevant phenotype for genetic studies. Here we have explored aspects of personality as quantitative phenotypes for bipolar disorder through the use of the Temperament and Character Inventory (TCI), which assesses personality in seven dimensions. Four temperament dimensions are assessed: novelty seeking (NS), harm avoidance (HA), reward dependence (RD), and persistence (PS). Three character dimensions are also included: self-directedness (SD), cooperativeness (CO), and self-transcendence (ST). We compared personality scores between diagnostic groups and assessed heritability in a sample of 101 families collected for genetic studies of BD. A genome-wide SNP linkage analysis was then performed in the subset of 51 families for which genetic data was available. Significant group differences were observed between BD subjects, their first-degree relatives, and independent controls for all but RD and PS, and all but HA and RD were found to be significantly heritable in this sample. Linkage analysis of the heritable dimensions produced several suggestive linkage peaks for NS (chromosomes 7q21 and 10p15), PS (chromosomes 6q16, 12p13, and 19p13), and SD (chromosomes 4q35, 8q24, and 18q12). The relatively small size of our linkage sample likely limited our ability to reach genome-wide significance in this study. While not genome-wide significant, these results suggest that aspects of personality may prove useful in the identification of genes underlying BD susceptibility. © 2013 Elsevier B.V. All rights reserved.

  19. Nickel-catalyzed proton-deuterium exchange (HDX) procedures for glycosidic linkage analysis of complex carbohydrates

    Science.gov (United States)

    The structural analysis of complex carbohydrates typically requires the assignment of three parameters: monosaccharide composition, the position of glycosidic linkages between monosaccharides, and the position and nature of non-carbohydrate substituents. The glycosidic linkage positions are often de...

  20. 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.

  1. 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.

  2. Meta-Analysis of Genome-Wide Linkage Scans of Attention Deficit Hyperactivity Disorder

    Science.gov (United States)

    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

    2010-01-01

    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, there has been limited replications between the various independent datasets. The current study gathered the results from all seven of the ADHD linkage scans and performed a Genome Scan Meta Analysis (GSMA) to identify the genomic region with most consistent linkage evidence across the studies. Genome-wide significant linkage (PSR=0.00034, POR=0.04) was identified on chromosome 16 between 64 and 83 Mb. In addition there are nine other genomic regions from the GSMA showing nominal or suggestive evidence of linkage. All these linkage results may be informative and focus the search for novel ADHD susceptibility genes. PMID:18988193

  3. A guide to evaluating linkage quality for the analysis of linked data.

    Science.gov (United States)

    Harron, Katie L; Doidge, James C; Knight, Hannah E; Gilbert, Ruth E; Goldstein, Harvey; Cromwell, David A; van der Meulen, Jan H

    2017-10-01

    Linked datasets are an important resource for epidemiological and clinical studies, but linkage error can lead to biased results. For data security reasons, linkage of personal identifiers is often performed by a third party, making it difficult for researchers to assess the quality of the linked dataset in the context of specific research questions. This is compounded by a lack of guidance on how to determine the potential impact of linkage error. We describe how linkage quality can be evaluated and provide widely applicable guidance for both data providers and researchers. Using an illustrative example of a linked dataset of maternal and baby hospital records, we demonstrate three approaches for evaluating linkage quality: applying the linkage algorithm to a subset of gold standard data to quantify linkage error; comparing characteristics of linked and unlinked data to identify potential sources of bias; and evaluating the sensitivity of results to changes in the linkage procedure. These approaches can inform our understanding of the potential impact of linkage error and provide an opportunity to select the most appropriate linkage procedure for a specific analysis. Evaluating linkage quality in this way will improve the quality and transparency of epidemiological and clinical research using linked data. © The Author 2017. Published by Oxford University Press on behalf of the International Epidemiological Association.

  4. 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...

  5. 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.

  6. Analysis of alcohol dependence phenotype in the COGA families using covariates to detect linkage

    Directory of Open Access Journals (Sweden)

    Tsai Hui-Ju

    2005-12-01

    Full Text Available Abstract Linkage analysis methods that incorporate etiological heterogeneity of complex diseases are likely to demonstrate greater power than traditional linkage analysis methods. Several such methods use covariates to discriminate between linked and unlinked pedigrees with respect to a certain disease locus. Here we apply several such methods including two mixture models, ordered subset analysis, and a conditional logistic model to genome scan data on the DSM-IV alcohol dependence phenotype on the Collaborative Studies on Genetics of Alcoholism families, and compare the results to traditional nonparametric linkage analysis. In general, there was little agreement among the various covariate-based linkage statistics. Linkage signals with empirical p-values less than 0.001 were detected on chromosomes 3, 4, 7, 10, and 12, with the highest peak occurring at the GABRB1 gene using the ecb21 covariate.

  7. The violent crime linkage analysis system: A test of interrater reliability

    NARCIS (Netherlands)

    Snook, B.; Luther, K.; House, J. C.; Bennell, C.; Taylor, Paul J

    2012-01-01

    The interrater reliability of an internationally renowned crime linkage system—the Violent Crime Linkage Analysis System (ViCLAS)—was tested. Police officers (N = 10) were presented with a case file and asked to complete a ViCLAS booklet. The level of occurrence agreement between each officer was

  8. Multipoint linkage analysis in X-linked ocular albinism of the Nettleship-Falls type

    NARCIS (Netherlands)

    Bergen, A. A.; Samanns, C.; Schuurman, E. J.; van Osch, L.; van Dorp, D. B.; Pinckers, A. J.; Bakker, E.; Gal, A.; van Ommen, G. J.; Bleeker-Wagemakers, E. M.

    1991-01-01

    An extensive linkage analysis was performed by studying ten Xp22 loci in ten families segregating for X-linked ocular albinism of the Nettleship-Falls type (XOA). Linkage was confirmed between the XOA locus (OA1) and both DXS16 (theta max = 0.10, zeta max = 4.09) and DXS237 (theta max = 0.12, zeta

  9. Nickel-catalyzed proton-deuterium exchange (HDX) for linkage analysis of complex carbohydrates

    Science.gov (United States)

    The structural assignment of complex carbohydrates typically requires the analysis of at least three parameters: 1. composition; 2. linkage; and 3. substituents. These are often assigned on a small scale by gas chromatography/mass spectrometry (GC/MS). Linkage positions are determined by permethylat...

  10. Linkage and candidate gene analysis of X-linked familial exudative vitreoretinopathy

    Energy Technology Data Exchange (ETDEWEB)

    Shastry, B.S.; Hartzer, M.K. [Oakland Univ., Rochester, MI (United States); Hejtmancik, J.F. [National Eye Institute, Bethesda, MD (United States)] [and others

    1995-05-20

    Familial exudative vitreoretinopathy (FEVR) is a hereditary eye disorder characterized by avascularity of the peripheral retina, retinal exudates, tractional detachment, and retinal folds. The disorder is most commonly transmitted as an autosomal dominant trait, but X-linked transmission also occurs. To initiate the process of identifying the gene responsible for the X-linked disorder, linkage analysis has been performed with three previously unreported three- or four-generation families. Two-point analysis showed linkage to MAOA (Z{sub max} = 2.1, {theta}{sub max} = 0) and DXS228 (Z{sub max} = 0.5, {theta}{sub max} = 0.11), and this was further confirmed by multipoint analysis with these same markers (Z{sub max} = 2.81 at MAOA), which both lie near the gene causing Norrie disease. Molecular genetic analysis further reveals a missense mutation (R121W) in the third exon of the Norrie`s disease gene that perfectly cosegregates with the disease through three generations in one family. This mutation was not detected in the unaffected family members and six normal unrelated controls, suggesting that it is likely to be the pathogenic mutation. Additionally, a polymorphic missense mutation (H127R) was detected in a severely affected patient. 21 refs., 3 figs., 1 tab.

  11. Linkage analysis in a family with the Opitz GBBB syndrome refines the location of the gene in Xp22 to a 4 cM region

    Energy Technology Data Exchange (ETDEWEB)

    May, M.; Schwartz, C. [J.C. Self Research Inist., Greenwood, SC (United States); Huston, S.; Schwartz, C. [Clemson Univ., SC (United States)] [and others

    1997-01-20

    The Opitz GBBB syndrome (OS) is characterized in part by widely spaced inner ocular canthi and hypospadias. Recently, linkage analysis showed that the gene for the X-linked form to be located in an 18 cM region spanning Xp22. We have now conducted linkage analysis in a family previously published as having the BBB syndrome and found tight linkage to DXS7104 (Z = 3.3, {theta} = 0.0). Our data narrows the candidate region to 4 cM and should facilitate the identification and characterization of one of the genes involved in midline development. 21 refs., 1 fig., 1 tab.

  12. Fine mapping analysis confirms and strengthens linkage of four chromosomal regions in familial hypospadias

    Science.gov (United States)

    Söderhäll, Cilla; Körberg, Izabella Baranowska; Thai, Hanh T T; Cao, Jia; Chen, Yougen; Zhang, Xufeng; Shulu, Zu; van der Zanden, Loes F M; van Rooij, Iris A L M; Frisén, Louise; Roeleveld, Nel; Markljung, Ellen; Kockum, Ingrid; Nordenskjöld, Agneta

    2015-01-01

    Hypospadias is a common male genital malformation and is regarded as a complex disease affected by multiple genetic as well as environmental factors. In a previous genome-wide scan for familial hypospadias, we reported suggestive linkage in nine chromosomal regions. We have extended this analysis by including new families and additional markers using non-parametric linkage. The fine mapping analysis displayed an increased LOD score on chromosome 8q24.1 and 10p15 in altogether 82 families. On chromosome 10p15, with the highest LOD score, we further studied AKR1C2, AKR1C3 and AKR1C4 involved in steroid metabolism, as well as KLF6 expressed in preputial tissue from hypospadias patients. Mutation analysis of the AKR1C3 gene showed a new mutation, c.643G>A (p.(Ala215Thr)), in a boy with penile hypospadias. This mutation is predicted to have an impact on protein function and structure and was not found in controls. Altogether, we homed in on four chromosomal regions likely to harbor genes for hypospadias. Future studies will aim for studying regulatory sequence variants in these regions. PMID:24986825

  13. Nance-Horan syndrome: Linkage analysis in a family from the Netherlands

    Energy Technology Data Exchange (ETDEWEB)

    Bergen, A.A.B.; Brink, J.T.; Schuurman, E.J.M.; Bleeker-Wagemakers, E.M. (Netherlands Ophthalmic Research Institute, Amsterdam (Netherlands))

    1994-05-01

    Linkage analysis was carried out in a Dutch family with Nance-Horan (NH) syndrome. Close linkage without recombination between NH and the Xp loci DXS207, DXS43, and DXS365 (z[sub max] = 3.23) was observed. Multipoint linkage analysis and the analysis of recombinations in multiple informative meioses suggest the genetic order Xcen-DMD (exon 49)-DXS451-(NH, DXS207, DXS365, DXS43)-(STS, DXF30)-Xpter. These data refine the localization of the NH locus on the distal Xp. 13 refs., 2 figs., 1 tab.

  14. Nance-Horan syndrome: linkage analysis in a family from The Netherlands.

    Science.gov (United States)

    Bergen, A A; ten Brink, J; Schuurman, E J; Bleeker-Wagemakers, E M

    1994-05-01

    Linkage analysis was carried out in a Dutch family with Nance-Horan (NH) syndrome. Close linkage without recombination between NH and the Xp loci DXS207, DXS43, and DXS365 (zmax = 3.23) was observed. Multipoint linkage analysis and the analysis of recombinations in multiple informative meioses suggest the genetic order Xcen-DMD (exon 49)-DXS451-(NH, DXS207, DXS365, DXS43)-(STS, DXF30)-Xpter. These data refine the localization of the NH locus on the distal Xp.

  15. 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.

  16. Autosomal linkage analysis for cannabis use behaviors in Australian adults.

    Science.gov (United States)

    Agrawal, Arpana; Morley, Katherine I; Hansell, Narelle K; Pergadia, Michele L; Montgomery, Grant W; Statham, Dixie J; Todd, Richard D; Madden, Pamela A F; Heath, Andrew C; Whitfield, John; Martin, Nicholas G; Lynskey, Michael T

    2008-12-01

    Cannabis is the most commonly used illicit drug in developed and in developing nations. Twin studies have highlighted the role of genetic influences on early stages of cannabis use, such as a lifetime history of use, early-onset use and frequent use, however, we are not aware of any genomic studies that have examined these phenotypes. Using data on 2314 families consisting of 5600 adult Australian offspring and their parents, all of whom were scanned using 1399 unique autosomal markers, we conducted autosomal linkage analyses for lifetime history of cannabis initiation, early-onset cannabis use and frequency of use, using a variance components approach in the linkage package MERLIN. Suggestive evidence for linkage was found on chromosome 18 (LOD 2.14 for frequency of use, LOD 1.97 for initiation, at 90-97 cM) and also on chromosome 19 (LOD 1.92 for early-onset at 17 cM). These LOD scores did not meet genome-wide significance. Further replication of these linkage regions in other samples will be required, although these initial results suggest further targeted efforts on chromosome 18 may yield interesting candidate genes for early stages of cannabis-related behaviors.

  17. Subsidiary Linkage Patterns

    DEFF Research Database (Denmark)

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

    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 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....

  18. Meta-analysis of genome-wide linkage studies of asthma and related traits

    Directory of Open Access Journals (Sweden)

    Ferreira Manuel A

    2008-04-01

    Full Text Available Abstract Background Asthma and allergy are complex multifactorial disorders, with both genetic and environmental components determining disease expression. The use of molecular genetics holds great promise for the identification of novel drug targets for the treatment of asthma and allergy. Genome-wide linkage studies have identified a number of potential disease susceptibility loci but replication remains inconsistent. The aim of the current study was to complete a meta-analysis of data from genome-wide linkage studies of asthma and related phenotypes and provide inferences about the consistency of results and to identify novel regions for future gene discovery. Methods The rank based genome-scan meta-analysis (GSMA method was used to combine linkage data for asthma and related traits; bronchial hyper-responsiveness (BHR, allergen positive skin prick test (SPT and total serum Immunoglobulin E (IgE from nine Caucasian asthma populations. Results Significant evidence for susceptibility loci was identified for quantitative traits including; BHR (989 pedigrees, n = 4,294 2p12-q22.1, 6p22.3-p21.1 and 11q24.1-qter, allergen SPT (1,093 pedigrees, n = 4,746 3p22.1-q22.1, 17p12-q24.3 and total IgE (729 pedigrees, n = 3,224 5q11.2-q14.3 and 6pter-p22.3. Analysis of the asthma phenotype (1,267 pedigrees, n = 5,832 did not identify any region showing genome-wide significance. Conclusion This study represents the first linkage meta-analysis to determine the relative contribution of chromosomal regions to the risk of developing asthma and atopy. Several significant results were obtained for quantitative traits but not for asthma confirming the increased phenotype and genetic heterogeneity in asthma. These analyses support the contribution of regions that contain previously identified asthma susceptibility genes and provide the first evidence for susceptibility loci on 5q11.2-q14.3 and 11q24.1-qter.

  19. Autosomal linkage analysis for the level of response to alcohol.

    Science.gov (United States)

    Schuckit, Marc A; Wilhelmsen, Kirk; Smith, Tom L; Feiler, Heidi S; Lind, Penelope; Lange, Leslie A; Kalmijn, Jelger

    2005-11-01

    The level of response (LR) to alcohol is a genetically-influenced phenotype related to the alcoholism risk. Usually measured by evaluating psychological and physiological changes that follow the administration of alcohol, the heritability of LR is estimated to be between 0.4 and 0.6, and efforts are being made to find genes related to this phenotype. This paper presents data from a family-based genome with linkage analysis focusing on alcohol challenge determinants of LR. The subjects were 18-to-29-year-old sibling pairs with at least one parent who was alcohol-dependent and who had experience with alcohol but were not yet alcohol-dependent themselves. Both members of the sibling pairs were given oral alcohol challenges (0.75-0.90 ml/kg of ethanol for females and males, respectively), with LR established using the Subjective High Assessment Scale (SHAS) and changes in body sway (BS) repeatedly over a 3.5-hr. period. Blood samples from siblings and at least one parent were genotyped using 811 microsatellite markers, with results evaluated using several related variance component approaches as implemented in SOLAR for continuous traits. In addition, association was tested using single nucleotide polymorphisms (SNPs) within the KCNMA1, HTR7 and SLC18A2 genes that may relate to a finding on chromosome 10. Data were generated from 238 sib-pairs representing 365 individuals (41.6% were males) from 165 families. The most consistent results across methods and samples were observed for SHAS on chromosome 10 between 120 and 140 cM (with a maximum LOD score of 2.6 at 122 cM), and a second region of possible interest at 173 cM (LOD = 1.2). Statistical analysis with the KCNMA1, HTR7 and SLC18A2 genes, which lie in the support region of interest revealed no evidence for association after correction for multiple comparisons. These evaluations from the largest known alcohol challenge-based genetic study to date highlight the potential importance of genes on chromosome 10 as

  20. 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

  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. 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

  3. 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

  4. 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.

  5. 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.

  6. An ultra-dense integrated linkage map for hexaploid chrysanthemum enables multi-allelic QTL analysis.

    Science.gov (United States)

    van Geest, Geert; Bourke, Peter M; Voorrips, Roeland E; Marasek-Ciolakowska, Agnieszka; Liao, Yanlin; Post, Aike; van Meeteren, Uulke; Visser, Richard G F; Maliepaard, Chris; Arens, Paul

    2017-12-01

    We constructed the first integrated genetic linkage map in a polysomic hexaploid. This enabled us to estimate inheritance of parental haplotypes in the offspring and detect multi-allelic QTL. Construction and use of linkage maps are challenging in hexaploids with polysomic inheritance. Full map integration requires calculations of recombination frequency between markers with complex segregation types. In addition, detection of QTL in hexaploids requires information on all six alleles at one locus for each individual. We describe a method that we used to construct a fully integrated linkage map for chrysanthemum (Chrysanthemum × morifolium, 2n = 6x = 54). A bi-parental F1 population of 406 individuals was genotyped with an 183,000 SNP genotyping array. The resulting linkage map consisted of 30,312 segregating SNP markers of all possible marker dosage types, representing nine chromosomal linkage groups and 107 out of 108 expected homologues. Synteny with lettuce (Lactuca sativa) showed local colinearity. Overall, it was high enough to number the chrysanthemum chromosomal linkage groups according to those in lettuce. We used the integrated and phased linkage map to reconstruct inheritance of parental haplotypes in the F1 population. Estimated probabilities for the parental haplotypes were used for multi-allelic QTL analyses on four traits with different underlying genetic architectures. This resulted in the identification of major QTL that were affected by multiple alleles having a differential effect on the phenotype. The presented linkage map sets a standard for future genetic mapping analyses in chrysanthemum and closely related species. Moreover, the described methods are a major step forward for linkage mapping and QTL analysis in hexaploids.

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

    Directory of Open Access Journals (Sweden)

    Weeks Daniel E

    2004-07-01

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

  8. 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

    from 4,731 participants of the Longitudinal Study of Ageing Danish Twins. Our results showed suggestive evidence of linkage to this region with a peak LOD score of 1.91 for marker D12S1634 located at 148 cM, and thus indicates that the previously identified disease locus at 12q24 is also a general...... 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...

  9. 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.

  10. [Prenatal genetic diagnosis of oculocutaneous albinism type II through mutation detection combined with SNPs linkage analysis].

    Science.gov (United States)

    Chen, Xiaofei; Wei, Haiyun; Zhou, Yi; Zheng, Hui; Fang, Qun; Jiang, Weiying; Li, Hongyi

    2014-04-01

    To provide prenatal diagnosis for two families affected with oculocutaneous albinism (OCA), in both of which only 1 pathogenic allele has been identified. 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. 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 found in the proband, which was inherited from her father. Together with its clinical phenotype, the proband was suspected to have OCA2. Screening of amniotic fluid has revealed a heterozygous mutation c.1920_1949 del30bp and ins AACA. By family-based linkage analysis, the fetus was deemed to be an OCA2 carrier. Both fetuses had a normal phenotype at birth. Prenatal genetic diagnosis has been provided for the first time for two families affected with OCA, in which only 1 pathogenic mutant allele was detected. The combined mutation detection and SNPs linkage analysis has turned out to be successful.

  11. 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 f...

  12. Proteomics Analysis Reveals Previously Uncharacterized Virulence Factors in Vibrio proteolyticus.

    Science.gov (United States)

    Ray, Ann; Kinch, Lisa N; de Souza Santos, Marcela; Grishin, Nick V; Orth, Kim; Salomon, Dor

    2016-07-26

    Members of the genus Vibrio include many pathogens of humans and marine animals that share genetic information via horizontal gene transfer. Hence, the Vibrio pan-genome carries the potential to establish new pathogenic strains by sharing virulence determinants, many of which have yet to be characterized. Here, we investigated the virulence properties of Vibrio proteolyticus, a Gram-negative marine bacterium previously identified as part of the Vibrio consortium isolated from diseased corals. We found that V. proteolyticus causes actin cytoskeleton rearrangements followed by cell lysis in HeLa cells in a contact-independent manner. In search of the responsible virulence factor involved, we determined the V. proteolyticus secretome. This proteomics approach revealed various putative virulence factors, including active type VI secretion systems and effectors with virulence toxin domains; however, these type VI secretion systems were not responsible for the observed cytotoxic effects. Further examination of the V. proteolyticus secretome led us to hypothesize and subsequently demonstrate that a secreted hemolysin, belonging to a previously uncharacterized clan of the leukocidin superfamily, was the toxin responsible for the V. proteolyticus-mediated cytotoxicity in both HeLa cells and macrophages. Clearly, there remains an armory of yet-to-be-discovered virulence factors in the Vibrio pan-genome that will undoubtedly provide a wealth of knowledge on how a pathogen can manipulate host cells. The pan-genome of the genus Vibrio is a potential reservoir of unidentified toxins that can provide insight into how members of this genus have successfully risen as emerging pathogens worldwide. We focused on Vibrio proteolyticus, a marine bacterium that was previously implicated in virulence toward marine animals, and characterized its interaction with eukaryotic cells. We found that this bacterium causes actin cytoskeleton rearrangements and leads to cell death. Using a

  13. Proteomics Analysis Reveals Previously Uncharacterized Virulence Factors in Vibrio proteolyticus

    Directory of Open Access Journals (Sweden)

    Ann Ray

    2016-07-01

    Full Text Available Members of the genus Vibrio include many pathogens of humans and marine animals that share genetic information via horizontal gene transfer. Hence, the Vibrio pan-genome carries the potential to establish new pathogenic strains by sharing virulence determinants, many of which have yet to be characterized. Here, we investigated the virulence properties of Vibrio proteolyticus, a Gram-negative marine bacterium previously identified as part of the Vibrio consortium isolated from diseased corals. We found that V. proteolyticus causes actin cytoskeleton rearrangements followed by cell lysis in HeLa cells in a contact-independent manner. In search of the responsible virulence factor involved, we determined the V. proteolyticus secretome. This proteomics approach revealed various putative virulence factors, including active type VI secretion systems and effectors with virulence toxin domains; however, these type VI secretion systems were not responsible for the observed cytotoxic effects. Further examination of the V. proteolyticus secretome led us to hypothesize and subsequently demonstrate that a secreted hemolysin, belonging to a previously uncharacterized clan of the leukocidin superfamily, was the toxin responsible for the V. proteolyticus-mediated cytotoxicity in both HeLa cells and macrophages. Clearly, there remains an armory of yet-to-be-discovered virulence factors in the Vibrio pan-genome that will undoubtedly provide a wealth of knowledge on how a pathogen can manipulate host cells.

  14. Multipoint development of the weighted pairwise correlation (WPC) linkage method for pedigrees of arbitrary size and application to the analysis of breast cancer and alcoholism familial data.

    Science.gov (United States)

    Zinn-Justin, A; Ziegler, A; Abel, L

    2001-07-01

    The weighted pairwise correlation (WPC) method is a simple and powerful model-free method of linkage analysis that has the advantages of being applicable to binary, ordered categorical, quantitative, or censored traits, and to consider all pairs of relatives in large pedigrees. The originally implemented approach was limited to the use of the identical by state (IBS) information, and we recently extended the WPC method to incorporate the identical by descent (IBD) information for two-point linkage analysis. Here, we develop a multipoint WPC method suitable for pedigrees of arbitrary size and large number of markers. The multipoint IBD estimation procedure for relative pairs is based on the efficient regression approach developed for pedigrees implemented in SOLAR. A robust and fast Monte-Carlo procedure is used to determine reliable P values. Application of the method to the 214 pedigrees from the Breast Cancer Linkage Consortium provided for the Genetic Analysis Workshop (GAW) 9 shows that multipoint WPC statistic values were not far from two-point maximum lod-score values obtained by the classical parametric linkage method and were higher than multipoint variance component analysis lod-scores obtained with SOLAR. The multipoint WPC method is also used to analyze the familial Collaborative Study of the Genetics of Alcoholism data on alcoholism released for GAW11. It allows a better specification of the linkage results previously obtained within the chromosome 4 region. Copyright 2001 Wiley-Liss, Inc.

  15. VT Wildlife Linkage Habitat

    Data.gov (United States)

    Vermont Center for Geographic Information — (Link to Metadata) The Wildlife Linkage Habitat Analysis uses landscape scale data to identify or predict the location of potentially significant wildlife linkage...

  16. The effect of genotyping error in sib-pair genomewide linkage scans depends crucially upon the method of analysis.

    Science.gov (United States)

    Walters, Kevin

    2005-01-01

    In genomewide linkage scans for complex diseases involving many loci with small genetic effects, it may be the case that no loci reach conventional statistical significance. A complementary method of evaluating linkage results, locus counting, may provide evidence for the existence of a number of genetic loci in these cases. Sib-pair study designs are often used in genomewide linkage scans, but because all genotype configurations are consistent with Mendelian inheritance, genotyping error will go largely undetected. Previous work on the effect of genotyping error has focused on a single disease locus. We considered the effect of two levels of genotyping error on genomewide evidence for linkage by using the simulated GAW 13 data. For affected sib-pair and non-parametric quantitative trait study designs, a 0.5% genotyping error rate reduced the number of independent linkage regions towards that expected under the null hypothesis of no linkage. A 2% genotyping error rate yielded less independent linkage regions than expected under the null hypothesis of no linkage. For a quantitative trait analysed using a parametric regression-based method, there was very little erosion of the linkage signal, even for error rates as high as 2%.

  17. Sacrococcygeal pilonidal disease: analysis of previously proposed risk factors

    Directory of Open Access Journals (Sweden)

    Ali Harlak

    2010-01-01

    Full Text Available PURPOSE: Sacrococcygeal pilonidal disease is a source of one of the most common surgical problems among young adults. While male gender, obesity, occupations requiring sitting, deep natal clefts, excessive body hair, poor body hygiene and excessive sweating are described as the main risk factors for this disease, most of these need to be verified with a clinical trial. The present study aimed to evaluate the value and effect of these factors on pilonidal disease. METHOD: Previously proposed main risk factors were evaluated in a prospective case control study that included 587 patients with pilonidal disease and 2,780 healthy control patients. RESULTS: Stiffness of body hair, number of baths and time spent seated per day were the three most predictive risk factors. Adjusted odds ratios were 9.23, 6.33 and 4.03, respectively (p<0.001. With an adjusted odds ratio of 1.3 (p<.001, body mass index was another risk factor. Family history was not statistically different between the groups and there was no specific occupation associated with the disease. CONCLUSIONS: Hairy people who sit down for more than six hours a day and those who take a bath two or less times per week are at a 219-fold increased risk for sacrococcygeal pilonidal disease than those without these risk factors. For people with a great deal of hair, there is a greater need for them to clean their intergluteal sulcus. People who engage in work that requires sitting in a seat for long periods of time should choose more comfortable seats and should also try to stand whenever possible.

  18. Applied Hierarchical Cluster Analysis with Average Linkage Algoritm

    Directory of Open Access Journals (Sweden)

    Cindy Cahyaning Astuti

    2017-11-01

    Full Text Available This research was conducted in Sidoarjo District where source of data used from secondary data contained in the book "Kabupaten Sidoarjo Dalam Angka 2016" .In this research the authors chose 12 variables that can represent sub-district characteristics in Sidoarjo. The variable that represents the characteristics of the sub-district consists of four sectors namely geography, education, agriculture and industry. To determine the equitable geographical conditions, education, agriculture and industry each district, it would require an analysis to classify sub-districts based on the sub-district characteristics. Hierarchical cluster analysis is the analytical techniques used to classify or categorize the object of each case into a relatively homogeneous group expressed as a cluster. The results are expected to provide information about dominant sub-district characteristics and non-dominant sub-district characteristics in four sectors based on the results of the cluster is formed.

  19. Radionuclides in Bayer process residues: previous analysis for radiological protection

    International Nuclear Information System (INIS)

    Cuccia, Valeria; Rocha, Zildete; Oliveira, Arno H. de

    2011-01-01

    Natural occurring radionuclides are present in many natural resources. Human activities may enhance concentrations of radionuclides and/or enhance potential of exposure to naturally occurring radioactive material (NORM). The industrial residues containing radionuclides have been receiving a considerable global attention, because of the large amounts of NORM containing wastes and the potential long term risks of long-lived radionuclides. Included in this global concern, this work focuses on the characterization of radioactivity in the main residues of Bayer process for alumina production: red mud and sand samples. Usually, the residues of Bayer process are named red mud, in their totality. However, in the industry where the samples were collected, there is an additional residues separation: sand and red mud. The analytical techniques used were gamma spectrometry (HPGe detector) and neutron activation analysis. The concentrations of radionuclides are higher in the red mud than in the sand. These solid residues present activities concentrations enhanced, when compared to bauxite. Further uses for the residues as building material must be more evaluated from the radiological point of view, due to its potential of radiological exposure enhancement, specially caused by radon emission. (author)

  20. Radionuclides in Bayer process residues: previous analysis for radiological protection

    Energy Technology Data Exchange (ETDEWEB)

    Cuccia, Valeria; Rocha, Zildete, E-mail: vc@cdtn.b, E-mail: rochaz@cdtn.b [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Oliveira, Arno H. de, E-mail: heeren@nuclear.ufmg.b [Universidade Federal de Minas Gerais (DEN/UFMG), Belo Horizonte, MG (Brazil). Dept. de Engenharia Nuclear

    2011-07-01

    Natural occurring radionuclides are present in many natural resources. Human activities may enhance concentrations of radionuclides and/or enhance potential of exposure to naturally occurring radioactive material (NORM). The industrial residues containing radionuclides have been receiving a considerable global attention, because of the large amounts of NORM containing wastes and the potential long term risks of long-lived radionuclides. Included in this global concern, this work focuses on the characterization of radioactivity in the main residues of Bayer process for alumina production: red mud and sand samples. Usually, the residues of Bayer process are named red mud, in their totality. However, in the industry where the samples were collected, there is an additional residues separation: sand and red mud. The analytical techniques used were gamma spectrometry (HPGe detector) and neutron activation analysis. The concentrations of radionuclides are higher in the red mud than in the sand. These solid residues present activities concentrations enhanced, when compared to bauxite. Further uses for the residues as building material must be more evaluated from the radiological point of view, due to its potential of radiological exposure enhancement, specially caused by radon emission. (author)

  1. A medical record linkage analysis of abortion underreporting.

    Science.gov (United States)

    Udry, J R; Gaughan, M; Schwingl, P J; van den Berg, B J

    1996-01-01

    Inaccuracy in women's reports of their abortion histories affects many areas of interest to reproductive health professionals and researchers. The identification of characteristics that affect the accuracy of reporting is essential for the improvement of data collection methods. A comparison of the medical records of 104 American women aged 27-30 in 1990-1991 with their self-reported abortion histories revealed that 19% of these women failed to report one or more abortions. Results of logistic regression analysis indicate that nonwhite women were 3.3 times as likely as whites to underreport. With each additional year that had elapsed since the first recorded abortion, women became somewhat more likely to underreport (odds ratio of 1.3), while each additional year of a woman's education slightly decreased the likelihood of underreporting (odds ratio of 0.7).

  2. Saturation of an intra-gene pool linkage map: towards a unified consensus linkage map for fine mapping and synteny analysis in common bean.

    Science.gov (United States)

    Galeano, Carlos H; Fernandez, Andrea C; Franco-Herrera, Natalia; Cichy, Karen A; McClean, Phillip E; Vanderleyden, Jos; Blair, Matthew W

    2011-01-01

    Map-based cloning and fine mapping to find genes of interest and marker assisted selection (MAS) requires good genetic maps with reproducible markers. In this study, we saturated the linkage map of the intra-gene pool population of common bean DOR364 × BAT477 (DB) by evaluating 2,706 molecular markers including SSR, SNP, and gene-based markers. On average the polymorphism rate was 7.7% due to the narrow genetic base between the parents. The DB linkage map consisted of 291 markers with a total map length of 1,788 cM. A consensus map was built using the core mapping populations derived from inter-gene pool crosses: DOR364 × G19833 (DG) and BAT93 × JALO EEP558 (BJ). The consensus map consisted of a total of 1,010 markers mapped, with a total map length of 2,041 cM across 11 linkage groups. On average, each linkage group on the consensus map contained 91 markers of which 83% were single copy markers. Finally, a synteny analysis was carried out using our highly saturated consensus maps compared with the soybean pseudo-chromosome assembly. A total of 772 marker sequences were compared with the soybean genome. A total of 44 syntenic blocks were identified. The linkage group Pv6 presented the most diverse pattern of synteny with seven syntenic blocks, and Pv9 showed the most consistent relations with soybean with just two syntenic blocks. Additionally, a co-linear analysis using common bean transcript map information against soybean coding sequences (CDS) revealed the relationship with 787 soybean genes. The common bean consensus map has allowed us to map a larger number of markers, to obtain a more complete coverage of the common bean genome. Our results, combined with synteny relationships provide tools to increase marker density in selected genomic regions to identify closely linked polymorphic markers for indirect selection, fine mapping or for positional cloning.

  3. 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.

  4. 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

    , body composition was determined at about two months of age (64 ± 11 days) via dual-energy xray absorptiometry (DXA) scanning. All pigs were genotyped using Illumina Porcine 60k SNP Beadchip and a combined LDLA approach was used to perform genomewide linkage and association analysis for body fat traits...... provide novel insights that may further the current understanding of the molecular mechanisms underlying human obesity....

  5. 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.

  6. Genetic mapping of the gene for Usher syndrome: Linkage analysis in a large Samaritan kindred

    Energy Technology Data Exchange (ETDEWEB)

    Bonne-Tamir, B.; Korostishevsky, M.; Kalinsky, H.; Seroussi, E.; Beker, R.; Weiss, S. (Sackler Faculty of Medicine, Ramat-Aviv (Israel)); Godel, V. (Ichilov Hospital, Tel-Aviv (Israel))

    1994-03-01

    Usher syndrome is a group of autosomal recessive disorders associated with congenital sensorineural deafness and progressive visual loss due to retinitis pigmentosa. Sixteen members of the small inbred Samaritan isolate with autosomal recessive deafness from 59 individuals including parents and affected and nonaffected sibs were typed for markers on chromosomes 1q and 11q for which linkage has recently been established for Usher syndrome types II and I. Statistically significant linkage was observed with four markers on 11q (D11S533, D11S527, OMP, and INT2) with a maximum six-point location score of 11.61 at the D11S533 locus. Analysis of haplotypes supports the notion that the mutation arose only once in an ancestral chromosome carrying a specific haplotype. The availability of markers closely linked to the disease locus allows indirect genotype analysis and identifies all carriers of the gene within the community. Furthermore, the detection of complete linkage disequilibrium between the D11S533 marker and the Usher gene suggests that these loci are either identical or adjacent and narrows the critical region to which physical mapping efforts are currently directed. 35 refs., 2 figs., 6 tabs.

  7. 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....

  8. 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.

  9. Industrial CO2 emissions in China based on the hypothetical extraction method: Linkage analysis

    International Nuclear Information System (INIS)

    Wang, Yuan; Wang, Wenqin; Mao, Guozhu; Cai, Hua; Zuo, Jian; Wang, Lili; Zhao, Peng

    2013-01-01

    Fossil fuel-related CO 2 emissions are regarded as the primary sources of global climate change. Unlike direct CO 2 emissions for each sector, CO 2 emissions associated with complex linkages among sectors are usually ignored. We integrated the input–output analysis with the hypothetical extraction method to uncover the in-depth characteristics of the inter-sectoral linkages of CO 2 emissions. Based on China's 2007 data, this paper compared the output and demand emissions of CO 2 among eight blocks. The difference between the demand and output emissions of a block indicates that CO 2 is transferred from one block to another. Among the sectors analyzed in this study, the Energy industry block has the greatest CO 2 emissions with the Technology industry, Construction and Service blocks as its emission's primary destinations. Low-carbon industries that have lower direct CO 2 emissions are deeply anchored to high-carbon ones. If no effective measures are taken to limit final demand emissions or adjust energy structure, shifting to an economy that is low-carbon industries oriented would entail a decrease in CO 2 emission intensity per unit GDP but an increase in overall CO 2 emissions in absolute terms. The results are discussed in the context of climate-change policy. - Highlights: • Quantitatively analyze the characteristics of inter-industrial CO 2 emission linkages. • Propose the linkage measuring method of CO 2 emissions based on the modified HEM. • Detect the energy industry is a key sector on the output of embodied carbon. • Conclude that low-carbon industries are deeply anchored to high-carbon industries

  10. Importance sampling method of correction for multiple testing in affected sib-pair linkage analysis

    OpenAIRE

    Klein, Alison P; Kovac, Ilija; Sorant, Alexa JM; Baffoe-Bonnie, Agnes; Doan, Betty Q; Ibay, Grace; Lockwood, Erica; Mandal, Diptasri; Santhosh, Lekshmi; Weissbecker, Karen; Woo, Jessica; Zambelli-Weiner, April; Zhang, Jie; Naiman, Daniel Q; Malley, James

    2003-01-01

    Using the Genetic Analysis Workshop 13 simulated data set, we compared the technique of importance sampling to several other methods designed to adjust p-values for multiple testing: the Bonferroni correction, the method proposed by Feingold et al., and naïve Monte Carlo simulation. We performed affected sib-pair linkage analysis for each of the 100 replicates for each of five binary traits and adjusted the derived p-values using each of the correction methods. The type I error rates for each...

  11. Genome-wide linkage analysis of heroin dependence in Han Chinese: results from Wave Two of a multi-stage study.

    Science.gov (United States)

    Glatt, Stephen J; Lasky-Su, Jessica A; Zhu, Shao C; Zhang, Ruimin; Zhang, Bo; Li, Jixiang; Yuan, Xiaobo; Li, Jianhua; Lyons, Michael J; Faraone, Stephen V; Tsuang, Ming T

    2008-11-01

    Previously we reported the results of Wave One of a genome-wide search for heroin dependence susceptibility loci in Han Chinese families from Yunnan Province, China, near Asia's "Golden Triangle". Our initial analysis of 194 independent affected sibling-pairs from 192 families identified two regions with nonparametric linkage (NPL) Z-scores greater than 2.0, which were suggestive of linkage. Presently we have supplemented our sample with additional individuals and families, bringing the total number of genotyped individuals to 1513 and the number of independent sibling-pairs to 397. Upon repeating our analyses with this larger sample, we found that the evidence for linkage at our most strongly implicated locus from Wave One (marker D17S1880; 53.4cM on 17q11.2; NPL Z=2.36; uncorrected p=0.009) was completely abolished (Z=-1.13; p=0.900). In contrast, the evidence for linkage at the second-most strongly implicated locus from Wave One (D4S1644; 143.3cM on 4q31.21; NPL Z=2.19; uncorrected p=0.014) increased in its magnitude and significance (Z=2.64; uncorrected p=0.004), becoming the most strongly implicated locus overall in our full sample. Other loci on chromosomes 1, 2, 4, 12, 16, and X also displayed nominally significant evidence for linkage (p< or =0.05). These loci appear to be entirely distinct from opioid-linked loci reported by other groups; however, meta-analyses of all available linkage data may reveal common sites of interest and promising candidate genes that can be further evaluated as risk factors for the illness.

  12. Genome-wide linkage analysis of 972 bipolar pedigrees using single-nucleotide polymorphisms.

    Science.gov (United States)

    Badner, J A; Koller, D; Foroud, T; Edenberg, H; Nurnberger, J I; Zandi, P P; Willour, V L; McMahon, F J; Potash, J B; Hamshere, M; Grozeva, D; Green, E; Kirov, G; Jones, I; Jones, L; Craddock, N; Morris, D; Segurado, R; Gill, M; Sadovnick, D; Remick, R; Keck, P; Kelsoe, J; Ayub, M; MacLean, A; Blackwood, D; Liu, C-Y; Gershon, E S; McMahon, W; Lyon, G J; Robinson, R; Ross, J; Byerley, W

    2012-07-01

    Because of the high costs associated with ascertainment of families, most linkage studies of Bipolar I disorder (BPI) have used relatively small samples. Moreover, the genetic information content reported in most studies has been less than 0.6. Although microsatellite markers spaced every 10 cM typically extract most of the genetic information content for larger multiplex families, they can be less informative for smaller pedigrees especially for affected sib pair kindreds. For these reasons we collaborated to pool family resources and carried out higher density genotyping. Approximately 1100 pedigrees of European ancestry were initially selected for study and were genotyped by the Center for Inherited Disease Research using the Illumina Linkage Panel 12 set of 6090 single-nucleotide polymorphisms. Of the ~1100 families, 972 were informative for further analyses, and mean information content was 0.86 after pruning for linkage disequilibrium. The 972 kindreds include 2284 cases of BPI disorder, 498 individuals with bipolar II disorder (BPII) and 702 subjects with recurrent major depression. Three affection status models (ASMs) were considered: ASM1 (BPI and schizoaffective disorder, BP cases (SABP) only), ASM2 (ASM1 cases plus BPII) and ASM3 (ASM2 cases plus recurrent major depression). Both parametric and non-parametric linkage methods were carried out. The strongest findings occurred at 6q21 (non-parametric pairs LOD 3.4 for rs1046943 at 119 cM) and 9q21 (non-parametric pairs logarithm of odds (LOD) 3.4 for rs722642 at 78 cM) using only BPI and schizoaffective (SA), BP cases. Both results met genome-wide significant criteria, although neither was significant after correction for multiple analyses. We also inspected parametric scores for the larger multiplex families to identify possible rare susceptibility loci. In this analysis, we observed 59 parametric LODs of 2 or greater, many of which are likely to be close to maximum possible scores. Although some linkage

  13. Subsidiary Linkage Patterns

    DEFF Research Database (Denmark)

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

    2012-01-01

    This paper investigates the pattern of subsidiaries' local vertical linkages under varying levels of competition and subsidiary capabilities. Contrary to most previous literature, we explicitly account for the double role of such linkages as conduits of learning prospects as well as potential cha...

  14. A Combined Linkage and Exome Sequencing Analysis for Electrocardiogram Parameters in the Erasmus Rucphen Family Study.

    Science.gov (United States)

    Silva, Claudia T; Zorkoltseva, Irina V; Amin, Najaf; Demirkan, Ayşe; van Leeuwen, Elisabeth M; Kors, Jan A; van den Berg, Marten; Stricker, Bruno H; Uitterlinden, André G; Kirichenko, Anatoly V; Witteman, Jacqueline C M; Willemsen, Rob; Oostra, Ben A; Axenovich, Tatiana I; van Duijn, Cornelia M; Isaacs, Aaron

    2016-01-01

    Electrocardiogram (ECG) measurements play a key role in the diagnosis and prediction of cardiac arrhythmias and sudden cardiac death. ECG parameters, such as the PR, QRS, and QT intervals, are known to be heritable and genome-wide association studies of these phenotypes have been successful in identifying common variants; however, a large proportion of the genetic variability of these traits remains to be elucidated. The aim of this study was to discover loci potentially harboring rare variants utilizing variance component linkage analysis in 1547 individuals from a large family-based study, the Erasmus Rucphen Family Study (ERF). Linked regions were further explored using exome sequencing. Five suggestive linkage peaks were identified: two for QT interval (1q24, LOD = 2.63; 2q34, LOD = 2.05), one for QRS interval (1p35, LOD = 2.52) and two for PR interval (9p22, LOD = 2.20; 14q11, LOD = 2.29). Fine-mapping using exome sequence data identified a C > G missense variant (c.713C > G, p.Ser238Cys) in the FCRL2 gene associated with QT (rs74608430; P = 2.8 × 10 -4 , minor allele frequency = 0.019). Heritability analysis demonstrated that the SNP explained 2.42% of the trait's genetic variability in ERF ( P = 0.02). Pathway analysis suggested that the gene is involved in cytosolic Ca 2+ levels ( P = 3.3 × 10 -3 ) and AMPK stimulated fatty acid oxidation in muscle ( P = 4.1 × 10 -3 ). Look-ups in bioinformatics resources showed that expression of FCRL2 is associated with ARHGAP24 and SETBP1 expression. This finding was not replicated in the Rotterdam study. Combining the bioinformatics information with the association and linkage analyses, FCRL2 emerges as a strong candidate gene for QT interval.

  15. Analysis of sulfidic linkages formed in natural rubber latex medical gloves by using X-ray absorption near edge structure

    Science.gov (United States)

    Chankrachang, M.; Limphirat, W.; Yongyingsakthavorn, P.; Nontakaew, U.; Tohsan, A.

    2017-09-01

    A study of sulfidic linkages formed in natural rubber (NR) latex medical gloves by using X-ray Absorption Near Edge Structure (XANES) is presented in this paper. The NR latex compound was prepared by using prevulcanization method, that is, it was prevulcanized at room temperature for 24 hrs before utilization. After the 24 hrs of prevulcanization, the latex film samples were obtained by dipping process. The dipped films were subjected to vulcanize at 110°C for 5 to 25 min. It was observed that after the compound was prevulcanized for 24 hrs, polysulfidic linkages were mainly formed in the sample. It was however found that after curing at 110°C for 5-25 min, the polysulfidic linkages are tended to change into disulfide linkages. Especially, in the case of 25 minutes cured sample, disulfide linkages are found to be the main linkages. In term of tensile strength, it was observed that when cure time increased from 5 - 10 min, tensile strengths were also increased. But when the cure time of the film is 25 minutes, tensile strength was slightly dropped. The dropped of tensile strength when cure time is longer than 10 minutes can be ascribed to a degradation of polysulfidic and disulfidic linkages during curing. Therefore, by using XANES analysis, it was found to be very useful to understand the cure characteristic, thus it can be very helpful to optimize cure time and tensile properties of the product.

  16. Neuropsychological endophenotype approach to genome-wide linkage analysis identifies susceptibility loci for ADHD on 2q21.1 and 13q12.11.

    NARCIS (Netherlands)

    Lambregts-Rommelse, N.N.J.; Arias Vasquez, A.; Altink, M.E.; Buschgens, C.J.M.; Fliers, E.A.; Asherson, P.; Faraone, S.V.; Buitelaar, J.K.; Sergeant, J.A.; Oosterlaan, J.; Franke, B.

    2008-01-01

    ADHD linkage findings have not all been consistently replicated, suggesting that other approaches to linkage analysis in ADHD might be necessary, such as the use of (quantitative) endophenotypes (heritable traits associated with an increased risk for ADHD). Genome-wide linkage analyses were

  17. Neuropsychological endophenotype approach to genome-wide linkage analysis identifies susceptibility loci for ADHD on 2q21.1 and 13q12.11

    NARCIS (Netherlands)

    Rommelse, N.N.J.; Vasquez, A.A.; Altink, M.E.; Buschgens, C.; Fliers, E.; Asherson, P.; Faraone, S.V.; Buitelaar, J.K.; Sergeant, J.A.; Oosterlaan, J.; Franke, B.

    2008-01-01

    ADHD linkage findings have not all been consistently replicated, suggesting that other approaches to linkage analysis in ADHD might be necessary, such as the use of (quantitative) endophenotypes (heritable traits associated with an increased risk for ADHD). Genome-wide linkage analyses were

  18. Linkage Analysis of Quantitative Trait Loci in the Presence of Heterogeneity

    DEFF Research Database (Denmark)

    Ekstrøm, Claus Thorn; Dalgaard, Peter

    2003-01-01

    EM-algorithm; Gaussian mixture; Heterogeneity; Linkage; Population admixture; Quantitative trait loci (QTL); Variance components......EM-algorithm; Gaussian mixture; Heterogeneity; Linkage; Population admixture; Quantitative trait loci (QTL); Variance components...

  19. Preimplantation genetic diagnosis of X-linked Charcot-Marie-Tooth disease by indirect linkage analysis.

    Science.gov (United States)

    Borgulová, Irena; Putzová, Martina; Soldatova, Inna; Stejskal, David

    2018-03-23

    To present methodical approach of preimplantation genetic diagnosis (PGD) as an option for an unaffected pregnancy in reproductive-age couples who have a genetic risk of the X-linked dominant peripheral neuropathy Charcot-Marie-Tooth type 1 disease. We performed PGD of X-linked Charcot-Marie-Tooth type 1 disease using haplotyping/indirect linkage analysis, when during analysis we reach to exclude embryos that carry a high-risk haplotype linked to the causal mutation p.Leu9Phe in the GJB1 gene. Within the PGD cycle, we examined 4 blastomeres biopsied from cleavage-stage embryos and recommended 3 embryos for transfer. Two embryos were implanted into the uterus; however, it resulted in a singleton pregnancy with a male descendant. Three years later, the couple returned again with spontaneous gravidity. A chorionic biopsy examination of this gravidity ascertained the female sex and a pericentric inversion of chromosome 5 in 70% of the cultivated foetal cells. Using indirect linkage analysis, PGD may help to identify genetic X-linked defects within embryos during screening, thereby circumventing the potential problems with abortion. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  20. Linkage analysis of alternative anxiety phenotypes in multiply affected panic disorder families

    Science.gov (United States)

    Fyer, Abby J.; Costa, Ramiro; Haghighi, Fatemeh; Logue, Mark W.; Knowles, James A.; Weissman, Myrna M.; Hodge, Susan E.; Hamilton, Steven P.

    2013-01-01

    Background The choice of phenotype definitions for genetic studies of panic and phobic disorders is complicated by family, twin and neurobiological data indicating both distinct and shared risk factors as well as heterogeneity within categories. We previously reported a genome scan in 120 multiplex panic disorder (PD) families using a phenotype that closely adhered to the DSM IV PD definition. Here we extend this work by conducting exploratory linkage analyses in this same pedigree set using ten additional literature- based panic and phobia-related phenotypes that take into account aspects of these hypothesized complexities. Methods Multiply affected families (> 2 individuals with PD) were recruited from clinical and non-clinical sources, evaluated by clinician administered semi-structured interview and subsequent blind consensus best estimate procedure. Each phenotype was analyzed under dominant and recessive models using parametric 2-point (homogeneity and heterogeneity), multipoint, and non-parametric methods. Empirically based permutations were used to estimate model specific and global (across all phenotypes) p-values. Results The highest score was a 2-point lod (4.27, global p phobia” under a recessive model and conditions of homogeneity. There was minimal support for linkage to any of the remaining nine phenotypes. Conclusions Though interpretation of findings is limited by sample size and the large number of phenotypes and models analyzed these data suggest a region on chromosome 13 as a potential site for further exploration in relation to risk for specific and social phobias. PMID:22525237

  1. Genome-wide linkage analysis of 1233 prostate cancer pedigrees from the International Consortium for Prostate Cancer Genetics using novel sumLINK and sumLOD analyses

    Science.gov (United States)

    Christensen, G. Bryce; Baffoe-Bonnie, Agnes B.; George, Asha; Powell, Isaac; Bailey-Wilson, Joan E.; Carpten, John D.; Giles, Graham G.; Hopper, John L.; Severi, Gianluca; English, Dallas R.; Foulkes, William D.; Maehle, Lovise; Moller, Pal; Eeles, Ros; Easton, Douglas; Badzioch, Michael D.; Whittemore, Alice S.; Oakley-Girvan, Ingrid; Hsieh, Chih-Lin; Dimitrov, Latchezar; Xu, Jianfeng; Stanford, Janet L.; Johanneson, Bo; Deutsch, Kerry; McIntosh, Laura; Ostrander, Elaine A.; Wiley, Kathleen E.; Isaacs, Sarah D.; Walsh, Patrick C.; Isaacs, William B.; Thibodeau, Stephen N.; McDonnell, Shannon K.; Hebbring, Scott; Schaid, Daniel J.; Lange, Ethan M.; Cooney, Kathleen A.; Tammela, Teuvo L.J.; Schleutker, Johanna; Paiss, Thomas; Maier, Christiane; Grönberg, Henrik; Wiklund, Fredrik; Emanuelsson, Monica; Farnham, James M.; Cannon-Albright, Lisa A.; Camp, Nicola J.

    2012-01-01

    Background Prostate cancer is generally believed to have a strong inherited component, but the search for susceptibility genes has been hindered by the effects of genetic heterogeneity. The recently developed sumLINK and sumLOD statistics are powerful tools for linkage analysis in the presence of heterogeneity. Methods We performed a secondary analysis of 1233 prostate cancer pedigrees from the International Consortium for Prostate Cancer Genetics (ICPCG) using two novel statistics, the sumLINK and sumLOD. For both statistics, dominant and recessive genetic models were considered. False discovery rate (FDR) analysis was conducted to assess the effects of multiple testing. Results Our analysis identified significant linkage evidence at chromosome 22q12, confirming previous findings by the initial conventional analyses of the same ICPCG data. Twelve other regions were identified with genomewide suggestive evidence for linkage. Seven regions (1q23, 5q11, 5q35, 6p21, 8q12, 11q13, 20p11-q11) are near loci previously identified in the initial ICPCG pooled data analysis or the subset of aggressive prostate cancer (PC) pedigrees. Three other regions (1p12, 8p23, 19q13) confirm loci reported by others, and two (2p24, 6q27) are novel susceptibility loci. FDR testing indicates that over 70% of these results are likely true positive findings. Statistical recombinant mapping narrowed regions to an average of 9 cM. Conclusions Our results represent genomic regions with the greatest consistency of positive linkage evidence across a very large collection of high-risk prostate cancer pedigrees using new statistical tests that deal powerfully with heterogeneity. These regions are excellent candidates for further study to identify prostate cancer predisposition genes. PMID:20333727

  2. Linkage Map Construction and Quantitative Trait Locus Analysis of Agronomic and Fiber Quality Traits in Cotton

    Directory of Open Access Journals (Sweden)

    Michael A. Gore

    2014-03-01

    Full Text Available The superior fiber properties of L. serve as a source of novel variation for improving fiber quality in Upland cotton ( L., but introgression from has been largely unsuccessful due to hybrid breakdown and a lack of genetic and genomic resources. In an effort to overcome these limitations, we constructed a linkage map and conducted a quantitative trait locus (QTL analysis of 10 agronomic and fiber quality traits in a recombinant inbred mapping population derived from a cross between TM-1, an Upland cotton line, and NM24016, an elite line with stabilized introgression from . The linkage map consisted of 429 simple-sequence repeat (SSR and 412 genotyping-by-sequencing (GBS-based single-nucleotide polymorphism (SNP marker loci that covered half of the tetraploid cotton genome. Notably, the 841 marker loci were unevenly distributed among the 26 chromosomes of tetraploid cotton. The 10 traits evaluated on the TM-1 × NM24016 population in a multienvironment trial were highly heritable, and most of the fiber traits showed considerable transgressive variation. Through the QTL analysis, we identified a total of 28 QTLs associated with the 10 traits. Our study provides a novel resource that can be used by breeders and geneticists for the genetic improvement of agronomic and fiber quality traits in Upland cotton.

  3. Genome Wide Linkage Analysis of 972 Bipolar Pedigrees Using Single Nucleotide Polymorphisms

    Science.gov (United States)

    Badner, Judith A; Koller, Daniel; Foroud, Tatiana; Edenberg, Howard; Nurnberger, John I; Zandi, Peter P; Willour, Virginia L.; McMahon, Francis J; Potash, James B; Hamshere, Marian; Grozeva, Detelina; Green, Elaine; Kirov, George; Jones, Ian; Jones, Lisa; Craddock, Nicholas; Morris, Derek; Segurado, Ricardo; Gill, Mike; Sadovnick, Dessa; Remick, Ronald; Keck, Paul; Kelsoe, John; Ayub, Muhammad; MacLean, Alan; Blackwood, Douglas; Liu, Chun-Yu; Gershon, Elliot S; McMahon, William; Lyon, Gholson; Robinson, Reid; Ross, Jessica; Byerley, William

    2011-01-01

    Because of the high costs associated with ascertainment of families most linkage studies of Bipolar I disorder (BPI) have used relatively small samples. Moreover, the genetic information content reported in most studies has been less than 0.6. While microsatellite markers spaced every 10 centimorgans typically extract most of the genetic information content for larger multiplex families, they can be less informative for smaller pedigrees especially for affected sib pair kindreds. For these reasons we collaborated to pool family resources and carry out higher density genotyping. Approximately 1100 pedigrees of European ancestry were initially selected for study and were genotyped by the Center for Inherited Disease Research using the Illumina Linkage Panel 12 set of 6090 SNPs. Of the ~1100 families, 972 were informative for further analyses and mean information content was 0.86 after pruning for LD. The 972 kindreds include 2284 cases of BPI disorder, 498 individuals with Bipolar II disorder (BPII) and 702 subjects with Recurrent Major Depression. Three affection status models were considered: ASM1 (BPI and schizoaffective disorder, BP cases (SABP) only), ASM2 (ASM1 cases plus BPII) and ASM3 (ASM2 cases plus Recurrent Major Depression). Both parametric and non-parametric linkage methods were carried out. The strongest findings occurred at 6q21 (Nonparametric Pairs Lod 3.4 for rs1046943 at 119 cM) and 9q21 (Nonparametric Pairs Lod 3.4 for rs722642 at 78 cM) using only BPI and SA, BP cases. Both results met genome-wide significant criteria, although neither was significant after correction for multiple analyses. We also inspected parametric scores for the larger multiplex families to identify possible rare susceptibility loci. In this analysis we observed 59 parametric lods of 2 or greater, many of which are likely to be close to maximum possible scores. While some linkage findings may be false positives the results could help prioritize the search for rare variants

  4. Linkage analysis in a Dutch population isolate shows no major gene for left-handedness or atypical language lateralization.

    Science.gov (United States)

    Somers, Metten; Ophoff, Roel A; Aukes, Maartje F; Cantor, Rita M; Boks, Marco P; Dauwan, Meenakshi; de Visser, Kees L; Kahn, René S; Sommer, Iris E

    2015-06-10

    Cerebral dominance of language function and hand preference are suggested to be heritable traits with possible shared genetic background. However, joined genetic studies of these traits have never been conducted. We performed a genetic linkage study in 37 multigenerational human pedigrees of both sexes (consisting of 355 subjects) enriched with left-handedness in which we also measured language lateralization. Hand preference was measured with the Edinburgh Handedness Inventory, and language lateralization was measured with functional transcranial Doppler during language production. The estimated heritability of left-handedness and language lateralization in these pedigrees is 0.24 and 0.31, respectively. A parametric major gene model was tested for left-handedness. Nonparametric analyses were performed for left-handedness, atypical lateralization, and degree of language lateralization. We did not observe genome-wide evidence for linkage in the parametric or nonparametric analyses for any of the phenotypes tested. However, multiple regions showed suggestive evidence of linkage. The parametric model showed suggestive linkage for left-handedness in the 22q13 region [heterogeneity logarithm of odds (HLOD) = 2.18]. Nonparametric multipoint analysis of left-handedness showed suggestive linkage in the same region [logarithm of odds (LOD) = 2.80]. Atypical language lateralization showed suggestive linkage in the 7q34 region (LODMax = 2.35). For strength of language lateralization, we observed suggestive linkage in the 6p22 (LODMax = 2.54), 7q32 (LODMax = 1.93), and 9q33 (LODMax = 2.10) regions. We did not observe any overlap of suggestive genetic signal between handedness and the extent of language lateralization. The absence of significant linkage argues against the presence of a major gene coding for both traits; rather, our results are suggestive of these traits being two independent polygenic complex traits. Copyright © 2015 the authors 0270-6474/15/358730-07$15.00/0.

  5. Construction of a genetic linkage map and QTL analysis in bambara groundnut.

    Science.gov (United States)

    Ahmad, Nariman Salih; Redjeki, Endah Sri; Ho, Wai Kuan; Aliyu, Siise; Mayes, Katie; Massawe, Festo; Kilian, Andrzej; Mayes, Sean

    2016-07-01

    Bambara groundnut (Vigna subterranea (L.) Verdc.) is an indigenous underutilized legume that has the potential to improve food security in semi-arid Africa. So far, there are a lack of reports of controlled breeding populations that could be used for variety development and genetic studies. We report here the construction of the first genetic linkage map of bambara groundnut using a F3 population derived from a "narrow" cross between two domesticated landraces (Tiga Nicuru and DipC) with marked divergence in phenotypic traits. The map consists of 238 DArT array and SSR based markers in 21 linkage groups with a total genetic distance of 608.3 cM. In addition, phenotypic traits were evaluated for a quantitative trait loci (QTL) analysis over two generations. A total of 36 significant QTLs were detected for 19 traits. The phenotypic effect explained by a single QTL ranged from 11.6% to 49.9%. Two stable QTLs were mapped for internode length and growth habit. The identified QTLs could be useful for marker-assisted selection in bambara groundnut breeding programmes.

  6. 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...

  7. [SNPs discovery and linkage disequilibrium analysis of BSG in Chinese Han population].

    Science.gov (United States)

    Zheng, Jie; Li, Mupeng; Sun, Tao; Hu, Xiaolei; Li, Yuanjian; Chen, Xiaoping

    2013-12-01

    To identify BSG single nucleotide polymorphisms (SNPs) in Chinese Han population. 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 amplified, sequenced and followed by Hardy-Weinberg equilibrium test and linkage disequilibrium (LD) analysis. A total of 19 SNPs were identified, 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. For the first time, systematic identification 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 well as pharmacogenetics study for drug response in Chinese Han population.

  8. 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.

  9. 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,

  10. Analysis Of Navy Hornet Squadron Mishap Costs With Regard To Previously Flown Flight Hours

    Science.gov (United States)

    2017-06-01

    HORNET SQUADRON MISHAP COSTS WITH REGARD TO PREVIOUSLY FLOWN FLIGHT HOURS by Jason R. Baumann June 2017 Thesis Advisor: Robert Eger Co...TYPE AND DATES COVERED Master’s thesis 4. TITLE AND SUBTITLE ANALYSIS OF NAVY HORNET SQUADRON MISHAP COSTS WITH REGARD TO PREVIOUSLY FLOWN...flown flight hours with mishap costs . It uses a macro level approach by evaluating how a squadron’s previously flown flight hours affect mishap cost and

  11. 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...

  12. Power of a Labrador Retriever-Greyhound pedigree for linkage analysis of hip dysplasia and osteoarthritis.

    Science.gov (United States)

    Todhunter, Rory J; Casella, George; Bliss, Stuart P; Lust, George; Williams, Alma Jo; Hamilton, Samuel; Dykes, Nathan L; Yeager, Amy E; Gilbert, Robert O; Burton-Wurster, Nancy I; Mellersh, Cathryn C; Acland, Gregory M

    2003-04-01

    To estimate the number of dogs required to find linkage to heritable traits of hip dysplasia in dogs from an experimental pedigree. 147 Labrador Retrievers, Greyhounds, and their crossbreed offspring. Labrador Retrievers with hip dysplasia were crossed with unaffected Greyhounds. Age at detection of femoral capital ossification, distraction index (DI), hip joint dorsolateral subluxation (DLS) score, and hip joint osteoarthritis (OA) were recorded. Power to find linkage of a single marker to a quantitative trait locus (QTL) controlling 100% of the variation in a dysplastic trait in the backcross dogs was determined. For the DI at the observed effect size, recombination fraction of 0.05, and heterozygosity of 0.75, 35 dogs in the backcross of the F1 to the Greyhound generation would yield linkage at a power of 0.8. For the DLS score, 35 dogs in the backcross to the Labrador Retriever generation would be required for linkage at the same power. For OSS, 45 dogs in the backcross to the founding Labrador Retrievers would yield linkage at the same power. Fewer dogs were projected to be necessary to find linkage to hip OA. Testing for linkage to the DLS at 4 loci simultaneously, each controlling 25% of the phenotypic variation, yielded an overall power of 0.7 CONCLUSIONS AND CLINICAL SIGNIFICANCE: Based on this conservative single-marker estimate, this pedigree has the requisite power to find microsatellites linked to susceptibility loci for hip dysplasia and hip OA by breeding a reasonable number of backcross dogs.

  13. Intensive Linkage Mapping in a Wasp (Bracon Hebetor) and a Mosquito (Aedes Aegypti) with Single-Strand Conformation Polymorphism Analysis of Random Amplified Polymorphic DNA Markers

    OpenAIRE

    Antolin, M. F.; Bosio, C. F.; Cotton, J.; Sweeney, W.; Strand, M. R.; Black-IV, W. C.

    1996-01-01

    The use of random amplified polymorphic DNA from the polymerase chain reaction (RAPD-PCR) allows efficient construction of saturated linkage maps. However, when analyzed by agarose gel electrophoresis, most RAPD-PCR markers segregate as dominant alleles, reducing the amount of linkage information obtained. We describe the use of single strand conformation polymorphism (SSCP) analysis of RAPD markers to generate linkage maps in a haplodiploid parasitic wasp Bracon (Habrobracon) hebetor and a d...

  14. Nance-Horan syndrome: localization within the region Xp21.1-Xp22.3 by linkage analysis.

    Science.gov (United States)

    Stambolian, D; Lewis, R A; Buetow, K; Bond, A; Nussbaum, R

    1990-07-01

    Nance-Horan Syndrome (NHS) or X-linked cataract-dental syndrome (MIM 302350) is a disease of unknown pathogenesis characterized by congenital cataracts and dental anomalies. We performed linkage analysis in three kindreds with NHS by using six RFLP markers between Xp11.3 and Xp22.3. Close linkage was found between NHS and polymorphic loci DXS43 (theta = 0 with lod score 2.89), DXS41 (theta = 0 with lod score 3.44), and DXS67 (theta = 0 with lod score 2.74), defined by probes pD2, p99-6, and pB24, respectively. Recombinations were found with the marker loci DXS84 (theta = .04 with lod score 4.13), DXS143 (theta = .06 with lod score 3.11) and DXS7 (theta = .09 with lod score 1.68). Multipoint linkage analysis determined the NHS locus to be linked completely to DXS41 (lod score = 7.07). Our linkage results, combined with analysis of Xp interstitial deletions, suggest that the NHS locus is located within or close to the Xp22.1-Xp22.2 region.

  15. Intelligence, previous convictions and interrogative suggestibility: a path analysis of alleged false-confession cases.

    Science.gov (United States)

    Sharrock, R; Gudjonsson, G H

    1993-05-01

    The main purpose of this study was to investigate the relationship between interrogative suggestibility and previous convictions among 108 defendants in criminal trials, using a path analysis technique. It was hypothesized that previous convictions, which may provide defendants with interrogative experiences, would correlate negatively with 'shift' as measured by the Gudjonsson Suggestibility Scale (Gudjonsson, 1984a), after intelligence and memory had been controlled for. The hypothesis was partially confirmed and the theoretical and practical implications of the findings are discussed.

  16. Linkage analysis and physical mapping near the gene for x-linked agammaglobulinemia at Xq22

    Energy Technology Data Exchange (ETDEWEB)

    Parolini, O.; Lassiter, G.L.; Henry, M.J.; Conley, M.E. (Univ. of Tennessee College of Medicine, Memphis (United States) St. Jude Children' s Research Hospital, Memphis, TN (United States)); Hejtmancik, J.F. (National Inst. of Health, Bethesda, MD (United States)); Allen, R.C.; Belmont, J.W. (Baylor College of Medicine, Houston, TX (United States)); Barker, D.F. (Univ. of Utah, Salt Lake City (United States))

    1993-02-01

    The gene for x-linked agammaglobulinemia (XLA) has been mapped to Xq22. No recombinations have been reported between the gene and the prob p212 at DXS178; however, this probe is informative in only 30-40% of women and the reported flanking markers, DXS3 and DXS94, and 10-15 cM apart. To identify additional probes that might be useful in genetic counseling, we examined 11 polymorphisms that have been mapped to the Xq21.3-q22 region in 13 families with XLA. In addition, pulsed-field gel electrophoresis and yeast artificial chromosomes (YACs) were used to further characterize the segman of DNA within which the gene for SLA must lie. The results demonstrated that DXS366 and DXS442, which share a 430-kb pulsed-field fragment, could replace DXS3 as proximal flanking markers. Probes at DXS178 and DXS265 identified the same 145-kb pulsed-field fragment, and both loci were contained within a 200-kb YAC identified with the probe p212. A highly polymorphic CA repeat (DCS178CA) was isolated from one end of this YAC and used in linkage analysis. Probes at DXS101 and DXS328 shared several pulsed-field fragments, the smallest of which was 250 kb. No recombinations were seen between XLA and the DXS178-DXS265-DXS178CA complex, DXS101, DXS328, DXS87, or the gene for proteolipid protein (PLP). Key crossovers, when combined with the linkage data from families with Alport syndrome, suggested the following order of loci: cen-DXS3-DXS366-DXS442-(PLP, DXS101, DXS328, DXS178-DXS265-DXS178CA complex, XL)-(DXS87, DXS94)-DXS327-(DXS350, DXS362)-tel. Our studies also limit the segment of DNA within which the XLA gene must lie to the 3- to 4-cM distance between DCS442 and DXS94 and they identify and orient polymorphisms that can be used in genetic counseling not only for XLA but also for Pelizaeus-Merzbacher disease (PLP deficiency), Alport syndrome (COL4A5 deficiency), and Fabry disease ([alpha]-galactosidase A difficiency). 31 refs., 5 figs., 2 tabs.

  17. 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.

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

    Science.gov (United States)

    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 system is more complicated and fundamentally different from other mammals. Using a genomewide linkage scan on a Labrador × greyhound cross segregating for black, yellow, and brindle coat colors, we demonstrate that pigment type switching is controlled by an additional gene, the K locus. Our results reveal three alleles with a dominance order of black (KB) > brindle (kbr) > yellow (ky), whose genetic map position on dog chromosome 16 is distinct from the predicted location of other pigmentation genes. Interaction studies reveal that Mc1r is epistatic to variation at Agouti or K and that the epistatic relationship between Agouti and K depends on the alleles being tested. These findings suggest a molecular model for a new component of the melanocortin signaling pathway and reveal how coat-color patterns and pigmentary diversity have been shaped by recent selection. PMID:17483404

  19. Localization of the X-linked ocular albinism gene (OA1) between DXS278/DXS237 and DXS143/DXS16 by linkage analysis

    NARCIS (Netherlands)

    Bergen, A. A.; Samanns, C.; van Dorp, D. B.; Ferguson-Smith, M. A.; Gal, A.; Bleeker-Wagemakers, E. M.

    1990-01-01

    Linkage analysis was performed in six families segregating for X-linked ocular albinism of the Nettleship-Falls type using four polymorphic DNA markers from the distal Xp. Linkage was found between the disease locus (OA1) and the loci DXS237 (theta max = 0.06, Zmax = 2.82), DXS278 (theta max = 0.03,

  20. Detection and fine-mapping of SC7 resistance genes via linkage and association analysis in soybean.

    Science.gov (United States)

    Yan, Honglang; Wang, Hui; Cheng, Hao; Hu, Zhenbin; Chu, Shanshan; Zhang, Guozheng; Yu, Deyue

    2015-08-01

    Soybean mosaic virus (SMV) disease is one of the most serious and broadly distributed soybean (Glycine max (L.) Merr.) diseases. Here, we combine the advantages of association and linkage analysis to identify and fine-map the soybean genes associated with resistance to SMV strain SC7. A set of 191 soybean accessions from different geographic origins and 184 recombinant inbred lines (RILs) derived from Kefeng No.1 (resistant) × Nannong 1138-2 (susceptible) were used in this study. The SC7 resistance genes were previously mapped to a 2.65 Mb region on chromosome 2 and a 380 kb region on chromosome 13. Among 19 single nucleotide polymorphisms (SNPs) detected via association analysis in the study, the SNP BARC-021625-04157 was located in the 2.65 Mb region, and the SNP BARC-041671-08065 was located near the 380 kb region; three genes harboring the SNPs were probably related to SC7 resistance. The resistance gene associated with BARC-021625-04157 was then fine-mapped to a region of approximately 158 kb on chromosome 2 using 184 RILs. Among the 15 genes within this region, one NBS-LRR type gene, one HSP40 gene and one serine carboxypeptidase-type gene might be candidate SC7 resistance genes. These results will be useful for map-based cloning and marker-assisted selection in soybean breeding programs. © 2014 Institute of Botany, Chinese Academy of Sciences.

  1. 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.

  2. Upon Further Review: V. An Examination of Previous Lightcurve Analysis from the Palmer Divide Observatory

    Science.gov (United States)

    Warner, Brian D.

    2011-01-01

    Updated results are given for nine asteroids previously reported from the Palmer Divide Observatory (PDO). The original images were re-measured to obtain new data sets using the latest version of MPO Canopus photometry software, analysis tools, and revised techniques for linking multiple observing runs covering several days to several weeks. Results that were previously not reported or were moderately different were found for 1659 Punkajarju, 1719 Jens, 1987 Kaplan, 2105 Gudy, 2961 Katsurahama, 3285 Ruth Wolfe, 3447 Burckhalter, 7816 Hanoi, and (34817) 2000 SE116. This is one in a series of papers that will examine results obtained during the initial years of the asteroid lightcurve program at PDO.

  3. Use of deterministic sampling for exploring likelihoods in linkage analysis for quantitative traits.

    NARCIS (Netherlands)

    Mackinnon, M.J.; Beek, van der S.; Kinghorn, B.P.

    1996-01-01

    Deterministic sampling was used to numerically evaluate the expected log-likelihood surfaces of QTL-marker linkage models in large pedigrees with simple structures. By calculating the expected values of likelihoods, questions of power of experimental designs, bias in parameter estimates, approximate

  4. Genetic linkage analysis in 26 families with Bardet-Biedl syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Wright, A.F.; Bruford, E.A.; Mansfield, D.C. [Western General Hospital, Edinburgh (United Kingdom)] [and others

    1994-09-01

    Bardet-Biedl syndrome is an autosomal recessive disorder characterized by polydactyly, obesity, hypogonadism, retinitis pigmentosa, renal anomalies and mental retardation. Clinical heterogeneity is quite marked both within and between families. Linkage has been reported between Bardet-Biedl syndrome and the D16408 marker in chromosomal region 16q21 in an extended Bedouin kindred and, more recently, in a subset of 17 out of 31 families using the PYGM/D11S913 markers in chromosomal region 11q13. We have analyzed linkage to the 16q21 and 11q13 regions and used markers covering chromosomes 2, 3, 17 and 18 in a set of 26 Bardet-Biedl families, each containing at least two affected individuals, with a total of 57 affected members. Evidence of linkage to the D11S527 locus has been identified assuming linkage homogeneity with a lod score of 2.72 at a recombination fraction of 0.11 (95% limits 0.03-0.25).

  5. Nance-Horan syndrome: linkage analysis in 4 families refines localization in Xp22.31-p22.13 region.

    Science.gov (United States)

    Toutain, A; Ronce, N; Dessay, B; Robb, L; Francannet, C; Le Merrer, M; Briard, M L; Kaplan, J; Moraine, C

    1997-02-01

    Nance-Horan syndrome (NHS) is an X-linked disease characterized by severe congenital cataract with microcornea, distinctive dental findings, evocative facial features and mental impairment in some cases. Previous linkage studies have placed the NHS gene in a large region from DXS143 (Xp22.31) to DXS451 (Xp22.13). To refine this localization further, we have performed linkage analysis in four families. As the maximum expected Lod score is reached in each family for several markers in the Xp22.31-p22.13 region and linkage to the rest of the X chromosome can be excluded, our study shows that NHS is a genetically homogeneous condition. An overall maximum two-point Lod score of 9.36 (theta = 0.00) is obtained with two closely linked markers taken together. DXS207 and DXS1053 in Xp22.2. Recombinant haplotypes indicate that the NHS gene lies between DXS85 and DXS1226. Multipoint analysis yield a maximum Lod score of 9.45 with the support interval spanning a 15-cM region that includes DXS16 and DXS1229/365. The deletion map of the Xp22.3-Xp21.3 region suggests that the phenotypic variability of NHS is not related to gross rearrangement of sequences of varying size but rather to allelic mutations in a single gene, presumably located proximal to DXS16 and distal to DXS1226. Comparison with the map position of the mouse Xcat mutation supports the location of the NHS gene between the GRPR and PDHA1 genes in Xp22.2.

  6. Do emotional intelligence and previous caring experience influence student nurse performance? A comparative analysis.

    Science.gov (United States)

    Stenhouse, Rosie; Snowden, Austyn; Young, Jenny; Carver, Fiona; Carver, Hannah; Brown, Norrie

    2016-08-01

    Reports of poor nursing care have focused attention on values based selection of candidates onto nursing programmes. Values based selection lacks clarity and valid measures. Previous caring experience might lead to better care. Emotional intelligence (EI) might be associated with performance, is conceptualised and measurable. To examine the impact of 1) previous caring experience, 2) emotional intelligence 3) social connection scores on performance and retention in a cohort of first year nursing and midwifery students in Scotland. A longitudinal, quasi experimental design. Adult and mental health nursing, and midwifery programmes in a Scottish University. Adult, mental health and midwifery students (n=598) completed the Trait Emotional Intelligence Questionnaire-short form and Schutte's Emotional Intelligence Scale on entry to their programmes at a Scottish University, alongside demographic and previous caring experience data. Social connection was calculated from a subset of questions identified within the TEIQue-SF in a prior factor and Rasch analysis. Student performance was calculated as the mean mark across the year. Withdrawal data were gathered. 598 students completed baseline measures. 315 students declared previous caring experience, 277 not. An independent-samples t-test identified that those without previous caring experience scored higher on performance (57.33±11.38) than those with previous caring experience (54.87±11.19), a statistically significant difference of 2.47 (95% CI, 0.54 to 4.38), t(533)=2.52, p=.012. Emotional intelligence scores were not associated with performance. Social connection scores for those withdrawing (mean rank=249) and those remaining (mean rank=304.75) were statistically significantly different, U=15,300, z=-2.61, p$_amp_$lt;0.009. Previous caring experience led to worse performance in this cohort. Emotional intelligence was not a useful indicator of performance. Lower scores on the social connection factor were associated

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

    Directory of Open Access Journals (Sweden)

    Brady Tang

    2011-04-01

    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.

  8. Genetic Linkage Analysis of the DFNB21 Locus in Autosomal Recessive Hearing Loss in Large Families from Khuzestan Province

    Directory of Open Access Journals (Sweden)

    Mahtab Khosrofar

    2017-06-01

    Full Text Available Abstract Background: Hearing loss (HL is the most common congenital defect in humans. One or two in thousand newborn babies have prelingual hearing loss. Autosomal recessive non-syndromic hearing loss (ARNSHL is the most common form of hereditary deafness. Hearing loss is more common in the developing countries which is due to genetic and environmental (cultural -health factors reasons. HL has a wide range of clinical demonstrations including: congenital or late onset, conductive or sensory-neural, syndromic or non-syndromic hearing loss. The goal of this project is to determine the portion of the DFNB21 (TECTA in ARNSHL in families with negative GJB2 gene in Khuzestan province. Materials and Methods: We studied 21 families with ARNSHL with at least 4 patients and negative for GJB2 mutations from Khuzestan province. Genetic linkage analysis was performed using STR markers linked to DFNB21 locus. Results: Following genetic linkage analysis and haplotyping, out of 21 families with ARNSHL, one family showed linkage to the DFNB21 (TECTA locus. Conclusion: The results of this project confirm other studies in Iran and give insight into the most common loci causing ARNSHL in Iran which could be helpful in research and clinic.

  9. A Hierarchical Generalized Linear Model in Combination with Dispersion Modeling to Improve Sib-Pair Linkage Analysis.

    Science.gov (United States)

    Lee, Woojoo; Kim, Jeonghwan; Lee, Youngjo; Park, Taesung; Suh, Young Ju

    2015-01-01

    We explored a hierarchical generalized linear model (HGLM) in combination with dispersion modeling to improve the sib-pair linkage analysis based on the revised Haseman-Elston regression model for a quantitative trait. A dispersion modeling technique was investigated for sib-pair linkage analysis using simulation studies and real data applications. We considered 4 heterogeneous dispersion settings according to a signal-to-noise ratio (SNR) in the various statistical models based on the Haseman-Elston regression model. Our numerical studies demonstrated that susceptibility loci could be detected well by modeling the dispersion parameter appropriately. In particular, the HGLM had better performance than the linear regression model and the ordinary linear mixed model when the SNR is low, i.e., when substantial noise was present in the data. The study shows that the HGLM in combination with dispersion modeling can be utilized to identify multiple markers showing linkage to familial complex traits accurately. Appropriate dispersion modeling might be more powerful to identify markers closest to the major genes which determine a quantitative trait. © 2015 S. Karger AG, Basel.

  10. Analysis of Product Buying Decision on Lazada E-commerce based on Previous Buyers’ Comments

    OpenAIRE

    Neil Aldrin

    2017-01-01

    The aims of the present research are: 1) to know that product buying decision possibly occurs, 2) to know how product buying decision occurs on Lazada e-commerce’s customers, 3) how previous buyers’ comments can increase product buying decision on Lazada e-commerce. This research utilizes qualitative research method. Qualitative research is a research that investigates other researches and makes assumption or discussion result so that other analysis results can be made in order to widen idea ...

  11. Linkage mechanisms in the vertebrate skull: Structure and function of three-dimensional, parallel transmission systems.

    Science.gov (United States)

    Olsen, Aaron M; Westneat, Mark W

    2016-12-01

    Many musculoskeletal systems, including the skulls of birds, fishes, and some lizards consist of interconnected chains of mobile skeletal elements, analogous to linkage mechanisms used in engineering. Biomechanical studies have applied linkage models to a diversity of musculoskeletal systems, with previous applications primarily focusing on two-dimensional linkage geometries, bilaterally symmetrical pairs of planar linkages, or single four-bar linkages. Here, we present new, three-dimensional (3D), parallel linkage models of the skulls of birds and fishes and use these models (available as free kinematic simulation software), to investigate structure-function relationships in these systems. This new computational framework provides an accessible and integrated workflow for exploring the evolution of structure and function in complex musculoskeletal systems. Linkage simulations show that kinematic transmission, although a suitable functional metric for linkages with single rotating input and output links, can give misleading results when applied to linkages with substantial translational components or multiple output links. To take into account both linear and rotational displacement we define force mechanical advantage for a linkage (analogous to lever mechanical advantage) and apply this metric to measure transmission efficiency in the bird cranial mechanism. For linkages with multiple, expanding output points we propose a new functional metric, expansion advantage, to measure expansion amplification and apply this metric to the buccal expansion mechanism in fishes. Using the bird cranial linkage model, we quantify the inaccuracies that result from simplifying a 3D geometry into two dimensions. We also show that by combining single-chain linkages into parallel linkages, more links can be simulated while decreasing or maintaining the same number of input parameters. This generalized framework for linkage simulation and analysis can accommodate linkages of differing

  12. Genome-wide linkage analysis of QTL for growth and body composition employing the PorcineSNP60 BeadChip

    Directory of Open Access Journals (Sweden)

    Fernández Ana I

    2012-05-01

    Full Text Available Abstract Background The traditional strategy to map QTL is to use linkage analysis employing a limited number of markers. These analyses report wide QTL confidence intervals, making very difficult to identify the gene and polymorphisms underlying the QTL effects. The arrival of genome-wide panels of SNPs makes available thousands of markers increasing the information content and therefore the likelihood of detecting and fine mapping QTL regions. The aims of the current study are to confirm previous QTL regions for growth and body composition traits in different generations of an Iberian x Landrace intercross (IBMAP and especially identify new ones with narrow confidence intervals by employing the PorcineSNP60 BeadChip in linkage analyses. Results Three generations (F3, Backcross 1 and Backcross 2 of the IBMAP and their related animals were genotyped with PorcineSNP60 BeadChip. A total of 8,417 SNPs equidistantly distributed across autosomes were selected after filtering by quality, position and frequency to perform the QTL scan. The joint and separate analyses of the different IBMAP generations allowed confirming QTL regions previously identified in chromosomes 4 and 6 as well as new ones mainly for backfat thickness in chromosomes 4, 5, 11, 14 and 17 and shoulder weight in chromosomes 1, 2, 9 and 13; and many other to the chromosome-wide signification level. In addition, most of the detected QTLs displayed narrow confidence intervals, making easier the selection of positional candidate genes. Conclusions The use of higher density of markers has allowed to confirm results obtained in previous QTL scans carried out with microsatellites. Moreover several new QTL regions have been now identified in regions probably not covered by markers in previous scans, most of these QTLs displayed narrow confidence intervals. Finally, prominent putative biological and positional candidate genes underlying those QTL effects are listed based on recent porcine

  13. Exploring a Nonmodel Teleost Genome Through RAD Sequencing—Linkage Mapping in Common Pandora, Pagellus erythrinus and Comparative Genomic Analysis

    Directory of Open Access Journals (Sweden)

    Tereza Manousaki

    2016-03-01

    Full Text Available Common pandora (Pagellus erythrinus is a benthopelagic marine fish belonging to the teleost family Sparidae, and a newly recruited species in Mediterranean aquaculture. The paucity of genetic information relating to sparids, despite their growing economic value for aquaculture, provides the impetus for exploring the genomics of this fish group. Genomic tool development, such as genetic linkage maps provision, lays the groundwork for linking genotype to phenotype, allowing fine-mapping of loci responsible for beneficial traits. In this study, we applied ddRAD methodology to identify polymorphic markers in a full-sib family of common pandora. Employing the Illumina MiSeq platform, we sampled and sequenced a size-selected genomic fraction of 99 individuals, which led to the identification of 920 polymorphic loci. Downstream mapping analysis resulted in the construction of 24 robust linkage groups, corresponding to the karyotype of the species. The common pandora linkage map showed varying degrees of conserved synteny with four other teleost genomes, namely the European seabass (Dicentrarchus labrax, Nile tilapia (Oreochromis niloticus, stickleback (Gasterosteus aculeatus, and medaka (Oryzias latipes, suggesting a conserved genomic evolution in Sparidae. Our work exploits the possibilities of genotyping by sequencing to gain novel insights into genome structure and evolution. Such information will boost the study of cultured species and will set the foundation for a deeper understanding of the complex evolutionary history of teleosts.

  14. Linkage analysis of schizophrenia with five dopamine receptor genes in nine pedigrees

    Energy Technology Data Exchange (ETDEWEB)

    Coon, H.; Byerley, W.; Holik, J.; Hoff, M.; Myles-Worsley, M.; Plaetke, R. (Univ. of Utah, Salt Lake City (United States)); Lannfelt, L. (Karolinska Inst., Stockholm (Sweden)); Sokoloff, P.; Schwartz, J.C. (Unite de Neurobiologie et de Pharmacologie de l' INSERM, Paris (France)); Waldo, M.; Freedman, R. (Univ. of Colorado, Denver (United States))

    1993-02-01

    Alterations in dopamine neurotransmission have been strongly implicated in the pathogenesis of schizophrenia for nearly 2 decades. Recently, the genes for five dopamine receptors have been cloned and characterized, and genetic and physical map information has become available. Using these five loci as candidate genes, the authors have tested for genetic linkage to schizophrenia in nine multigenerational families which include multiple affected individuals. In addition to testing conservative disease models, the have used a neurophysiological indicator variable, the P50 auditory evoked response. Deficits in gating of the P50 response have been shown to segregate with schizophrenia in this sample and may identify carriers of gene(s) predisposing for schizophrenia. Linkage results were consistently negative, indicating that a defect at any of the actual receptor sites is unlikely to be a major contributor to schizophrenia in the nine families studied. 47 refs., 1 fig., 4 tabs.

  15. 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

  16. Inter- and intraindustrial Job-to-Job Flows. A Linkage Analysis of Regional Vacancy Chains in Austria

    OpenAIRE

    Christine M. Aumayr

    2010-01-01

    Nine Austrian NUTS 2 inter- and intraindustrial job-to-job worker flows for 33 indus- tries are analysed by means of input-output techniques, with these job-to-job flows being an intermediate input in the production of filled vacancies. A new dataset on individual labour market episodes allows for the tracing of individual careers. A linkage analysis of the Leontief multiplier shows that business services, wholesale&retail and the metal- industry are 'key' industries in for- and backwarding e...

  17. Budget impact analysis of empagliflozin in T2D patients with a previous cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Sergio Iannazzo

    2017-06-01

    Full Text Available Budget impact analysis of empagliflozin in T2D patients with a previous cardiovascular diseaseIntroductionThe EMPA-REG OUTCOME study demonstrated that empagliflozin is effective in reducing cardiovascular morbidity and mortality in T2D patients with high risk linked to a previous cardiovascular condition. The objective of this study is the budget impact analysis of the use of empagliflozin in this population in Italy.MethodsThe analysis was conducted from the cost perspective of the Italian NHS with a 3-year time horizon. The target population, defined as T2D patients with a known cardiovascular disease, was estimated based on epidemiologic and market data. An uptake of empagliflozin growing from 10% to 30% was considered to add up or substitute combinations of metformin, insulin, glitazones and DPP-4. The uptake of 80-100% was considered to substitute sulfonylureas and repaglinide. Costs, including drugs, glycaemia monitoring, management of severe hypoglycaemia events, and cardiovascular and renal events, were estimated based on published literature and current tariffs.ResultsThe target population was estimated in 243,693 in the first year. The incremental cost for drugs (17.6 million Euro is entirely offset by the savings in glycaemia monitoring (8.1 million Euro, cardiovascular and renal events (8.8 million Euro and severe hypoglycaemic events (3.1 million Euro, with a net saving of 2.3 million Euro, approximately corresponding to -0.7% of the total expenditure. The cumulative budget impact in the 3 years was 4.9 million Euro (-0.5%.ConclusionsThe progressive adoption of empagliflozin to treat T2D patients with known cardiovascular disease in Italy, would provide significant clinical benefit without entailing additional expense for the Italian NHS.

  18. Linkage and association analysis of CACNG3 in childhood absence epilepsy

    DEFF Research Database (Denmark)

    Everett, Kate V; Chioza, Barry; Aicardi, Jean

    2007-01-01

    Childhood absence epilepsy (CAE) is an idiopathic generalised epilepsy characterised by absence seizures manifested by transitory loss of awareness with 2.5-4 Hz spike-wave complexes on ictal EEG. A genetic component to aetiology is established but the mechanism of inheritance and the genes...... did not identify any putative causal variants. A linkage disequilibrium (LD) map of CACNG3 was constructed using 23 single nucleotide polymorphisms (SNPs). Transmission disequilibrium was sought using individual SNPs and SNP-based haplotypes with the pedigree disequilibrium test in 217 CAE trios...

  19. 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.

  20. 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.

  1. Analysis of Product Buying Decision on Lazada E-commerce based on Previous Buyers’ Comments

    Directory of Open Access Journals (Sweden)

    Neil Aldrin

    2017-06-01

    Full Text Available The aims of the present research are: 1 to know that product buying decision possibly occurs, 2 to know how product buying decision occurs on Lazada e-commerce’s customers, 3 how previous buyers’ comments can increase product buying decision on Lazada e-commerce. This research utilizes qualitative research method. Qualitative research is a research that investigates other researches and makes assumption or discussion result so that other analysis results can be made in order to widen idea and opinion. Research result shows that product which has many ratings and reviews will trigger other buyers to purchase or get that product. The conclusion is that product buying decision may occur because there are some processes before making decision which are: looking for recognition and searching for problems, knowing the needs, collecting information, evaluating alternative, evaluating after buying. In those stages, buying decision on Lazada e-commerce is supported by price, promotion, service, and brand.

  2. Service for victims of crime VDS info and victims’ support: Analysis of the previous work

    Directory of Open Access Journals (Sweden)

    Ćopić Sanja M.

    2004-01-01

    Full Text Available The first victim support service in our country VDS info and victims’ support started with its work in April 2003 within the Victimology Society of Serbia. This service is aimed at victims of crime (women and men, primarily at victims of violent crime, but also of some forms of property crime (such as burglary. The aim of the Service is to offer victims of crime information on their rights and the ways of how to realize them, emotional support, as well as to refer them to other institutions/organizations depending on the certain victim’s needs. Coordinators and volunteers, who passed the appropriate training, are responsible for that. Bearing that in mind, this paper will give the brief glens on the Service itself, its organization and the way of work, followed by the analysis of the results of previous work.

  3. Multivariate analysis of anxiety disorders yields further evidence of linkage to chromosomes 4q21 and 7p in panic disorder families.

    Science.gov (United States)

    Logue, Mark W; Bauver, Sarah R; Knowles, James A; Gameroff, Marc J; Weissman, Myrna M; Crowe, Raymond R; Fyer, Abby J; Hamilton, Steven P

    2012-04-01

    Replication has been difficult to achieve in linkage studies of psychiatric disease. Linkage studies of panic disorder have indicated regions of interest on chromosomes 1q, 2p, 2q, 3, 7, 9, 11, 12q13, 12q23, and 15. Few regions have been implicated in more than one study. We examine two samples, the Iowa (IA) and the Columba panic disorder families. We use the fuzzy-clustering method presented by Kaabi et al. [Kaabi et al. (2006); Am J Hum Genet 78: 543-553] to summarize liability to panic disorder, agoraphobia, simple phobia, and social phobia. Kaabi et al. applied this method to the Yale panic disorder linkage families and found evidence of linkage to chromosomes 4q21, 4q32, 7p, and 8. When we apply the same method to the IA families, we obtain overlapping evidence of linkage to chromosomes 4q21 and 7p. Additionally, we find evidence of linkage on chromosomes 1, 5, 6, 16, and 22. The Columbia (CO) data does not indicate linkage to any of the Kaabi et al. peaks, instead implicating chromosomes 2 and 22q11 (2 Mb from COMT). There is some evidence of overlapping linkage between the IA and CO datasets on chromosomes 1 and 14. While use of fuzzy clustering has not produced complete concordance across datasets, it has produced more than previously seen in analyses of panic disorder proper. We conclude that chromosomes 4q21 and 7p should be considered strong candidate regions for panic and fear-associated anxiety disorder loci. More generally, this suggests that analyses including multiple aspects of psychopathology may lead to greater consistency across datasets. Copyright © 2012 Wiley Periodicals, Inc.

  4. 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.

  5. 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

  6. USH1G with unique retinal findings caused by a novel truncating mutation identified by genome-wide linkage analysis

    Science.gov (United States)

    Taibah, Khalid; Bin-Khamis, Ghada; Kennedy, Shelley; Hemidan, Amal; Al-Qahtani, Faisal; Tabbara, Khalid; Mubarak, Bashayer Al; Ramzan, Khushnooda; Meyer, Brian F.; Al-Owain, Mohammed

    2012-01-01

    Purpose Usher syndrome (USH) is an autosomal recessive disorder divided into three distinct clinical subtypes based on the severity of the hearing loss, manifestation of vestibular dysfunction, and the age of onset of retinitis pigmentosa and visual symptoms. To date, mutations in seven different genes have been reported to cause USH type 1 (USH1), the most severe form. Patients diagnosed with USH1 are known to be ideal candidates to benefit from cochlear implantation. Methods Genome-wide linkage analysis using Affymetrix GeneChip Human Mapping 10K arrays were performed in three cochlear implanted Saudi siblings born from a consanguineous marriage, clinically diagnosed with USH1 by comprehensive clinical, audiological, and ophthalmological examinations. From the linkage results, the USH1G gene was screened for mutations by direct sequencing of the coding exons. Results We report the identification of a novel p.S243X truncating mutation in USH1G that segregated with the disease phenotype and was not present in 300 ethnically matched normal controls. We also report on the novel retinal findings and the outcome of cochlear implantation in the affected individuals. Conclusions In addition to reporting a novel truncating mutation, this report expands the retinal phenotype in USH1G and presents the first report of successful cochlear implants in this disease. PMID:22876113

  7. Linkage Map Construction and QTL Analysis of Fruit Traits in Melon (Cucumis melo L.) Based on CAPS Markers

    International Nuclear Information System (INIS)

    Baloch, A. M.; Liu, S.; Wang, X.; Luan, F.; Baloch, A. W.; Baloch, M. J.

    2016-01-01

    In the current experiment, the quantitative trait loci (QTL) analysis was done by composite interval mapping method to detect QTLs in edge, central parts and fruit shape of melon. In this context, 235 F/sub 2/ populations along with their parents were evaluated for fruit size, shape and color under replicated trail at Horticulture Experimental Station of Northeast Agricultural University, Harbin, China, during the growing year 2014. Moreover, 96 pairs of CAPS markers were used to construct a linkage map using F/sub 2/ population that was derived from the cross between two contrasting parents (MR-1 and Topmark). The total length of linkage map was found to be 4984.1cM with an average of 51.9177 cM between the markers. In a total, we detected ten QTLs, in which one was major, while others were minor. Five QTLs were detected in the edge part of melon fruit and three QTLs were detected in central parts of melon and all were considered as Brix content. Two QTLs were related with fruit shape. Our present genetic and QTLs mapping would be proved useful in plant breeding programs for the improvement of economically important horticultural traits. (author)

  8. Haplotyping, linkage mapping and expression analysis of barley genes regulated by terminal drought stress influencing seed quality

    Directory of Open Access Journals (Sweden)

    Wobus Ulrich

    2011-01-01

    Full Text Available Abstract Background The increasingly narrow genetic background characteristic of modern crop germplasm presents a challenge for the breeding of cultivars that require adaptation to the anticipated change in climate. Thus, high priority research aims at the identification of relevant allelic variation present both in the crop itself as well as in its progenitors. This study is based on the characterization of genetic variation in barley, with a view to enhancing its response to terminal drought stress. Results The expression patterns of drought regulated genes were monitored during plant ontogeny, mapped and the location of these genes was incorporated into a comprehensive barley SNP linkage map. Haplotypes within a set of 17 starch biosynthesis/degradation genes were defined, and a particularly high level of haplotype variation was uncovered in the genes encoding sucrose synthase (types I and II and starch synthase. The ability of a panel of 50 barley accessions to maintain grain starch content under terminal drought conditions was explored. Conclusion The linkage/expression map is an informative resource in the context of characterizing the response of barley to drought stress. The high level of haplotype variation among starch biosynthesis/degradation genes in the progenitors of cultivated barley shows that domestication and breeding have greatly eroded their allelic diversity in current elite cultivars. Prospective association analysis based on core drought-regulated genes may simplify the process of identifying favourable alleles, and help to understand the genetic basis of the response to terminal drought.

  9. The investigation into CYP2E1 in relation to the level of response to alcohol through a combination of linkage and association analysis.

    Science.gov (United States)

    Webb, Amy; Lind, Penelope A; Kalmijn, Jelger; Feiler, Heidi S; Smith, Tom L; Schuckit, Marc A; Wilhelmsen, Kirk

    2011-01-01

    A low level of response to alcohol during an individual's early experience with alcohol is associated with an increase risk of alcoholism. A family-based genome-wide linkage analysis using sibling pairs that underwent an alcohol challenge where the level of response to alcohol was measured with the Subjective High Assessment Scale (SHAS) implicated the 10q terminal (10qter) region. CYP2E1, a gene known for its involvement with ethanol metabolism, maps to this region. Variance component multipoint linkage analysis was performed on a combined map of single-nucleotide polymorphism (SNP) and microsatellite data. To account for the heterogeneity evident in the dataset, a calculation assuming locus heterogeneity was made using the Heterogeneity Log of Odds (HLOD) score. Association between SNP marker allele counts and copy number and SHAS scores were evaluated using a logistic regression model. Linkage analysis detected significant linkage to CYP2E1, which was diminished because of apparent locus heterogeneity traced to a single family with extreme phenotypes. In retrospect, circumstances recorded during testing for this family suggest that their phenotype data are likely to be unreliable. Significant allelic associations were detected for several CYP2E1 polymorphisms and the SHAS score. DNA sequencing from families that contributed the greatest evidence for linkage did not detect any changes directly affecting the primary amino acid sequence. With the removal of a single family, combined evidence from microsatellites and SNPs offers significant linkage between the level of response to alcohol and the region on the end of chromosome 10. Combined linkage and association indicate that sequence changes in or near CYP2E1 affect the level of response to alcohol providing a predictor of risk of alcoholism. The absence of coding sequence changes indicates that regulatory sequences are responsible. Implicating CYP2E1 in the level of response to alcohol allows inferences to be

  10. The investigation of CYP2E1 in relation to the level of response to alcohol through a combination of linkage and association analysis

    Science.gov (United States)

    Webb, Amy; Lind, Penelope A.; Kalmijn, Jelger; Feiler, Heidi S.; Smith, Tom L.; Schuckit, Marc A.; Wilhelmsen, Kirk

    2010-01-01

    Background A low level of response to alcohol during an individual’s early experience with alcohol is associated with an increase risk for alcoholism. A family-based genome-wide linkage analysis using sibling pairs that underwent an alcohol challenge where the level of response to alcohol was measured with the Subjective High Assessment Scale (SHAS) implicated the 10q terminal region. CYP2E1, a gene known for its involvement with ethanol metabolism, maps to this region. Methods Variance component multipoint linkage analysis was performed on a combined map of single nucleotide polymorphism (SNP) and microsatellite data. To account for the heterogeneity evident in the dataset, a calculation assuming locus heterogeneity was made using the HLOD (heterogeneity LOD) score. Association between SNP marker allele counts and copy number and SHAS scores were evaluated using a logistic regression model. Results Linkage analysis detected significant linkage to CYP2E1 which was diminished due to apparent locus heterogeneity traced to a single family with extreme phenotypes. In retrospect, circumstances recorded during testing for this family suggest that their phenotype data are likely to be unreliable. Significant allelic associations were detected for several CYP2E1 polymorphisms and the SHAS score. DNA sequencing from families that contributed the greatest evidence for linkage did not detect any changes directly affecting the primary amino acid sequence. With the removal of a single family, combined evidence from microsatellites and SNPs offer significant linkage between the level of response to alcohol and the region on the end of chromosome 10. Conclusion Combined linkage and association indicate that sequence changes in or near CYP2E1 affect the level of response to alcohol providing a predictor of risk for alcoholism. The absence of coding sequence changes indicates that regulatory sequences are responsible. Implicating CYP2E1 in the level of response to alcohol allows

  11. Sectoral linkage analysis of three main air pollutants in China's industry: Comparing 2010 with 2002.

    Science.gov (United States)

    He, Weiwei; Wang, Yuan; Zuo, Jian; Luo, Yincheng

    2017-11-01

    To investigate the driving forces of air pollution in China, the changes in linkages amongst inter-industrial air pollutant emissions were analyzed by hypothetical extraction method under the input-output framework. Results showed that the emissions of SO 2 , soot and dust from industrial sources increased by 56.46%, 36.95% and 11.69% respectively in 2010, compared with 2002. As major contributors to emissions, the power and gas sectors were responsible for the growing SO 2 emissions, the nonmetal products sector for soot emissions, and the metals mining, smelting and pressing sectors for dust emissions. The increasing volume of emissions was mainly driven by the growing demand in the transport equipment and electrical equipment sectors. In addition, the expansion in the metals mining, smelting and pressing sectors could result in even more severe air pollution. Therefore, potential effective strategies to control air pollution in China are: (1) reducing the demand of major import sectors in the equipment manufacturing industry; (2) promoting R&D in low-emissions-production technologies to the power and gas sectors, the metals mining, smelting and pressing sectors, and the nonmetal products sector, and (3) auditing the considerable industrial scale expansion in the metals mining, smelting and pressing sectors and optimizing the industrial structure. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Three genome-wide association studies and a linkage analysis identify HERC2 as a human iris color gene.

    Science.gov (United States)

    Kayser, Manfred; Liu, Fan; Janssens, A Cecile J W; Rivadeneira, Fernando; Lao, Oscar; van Duijn, Kate; Vermeulen, Mark; Arp, Pascal; Jhamai, Mila M; van Ijcken, Wilfred F J; den Dunnen, Johan T; Heath, Simon; Zelenika, Diana; Despriet, Dominiek D G; Klaver, Caroline C W; Vingerling, Johannes R; de Jong, Paulus T V M; Hofman, Albert; Aulchenko, Yurii S; Uitterlinden, Andre G; Oostra, Ben A; van Duijn, Cornelia M

    2008-02-01

    Human iris color was one of the first traits for which Mendelian segregation was established. To date, the genetics of iris color is still not fully understood and is of interest, particularly in view of forensic applications. In three independent genome-wide association (GWA) studies of a total of 1406 persons and a genome-wide linkage study of 1292 relatives, all from the Netherlands, we found that the 15q13.1 region is the predominant region involved in human iris color. There were no other regions showing consistent genome-wide evidence for association and linkage to iris color. Single nucleotide polymorphisms (SNPs) in the HERC2 gene and, to a lesser extent, in the neighboring OCA2 gene were independently associated to iris color variation. OCA2 has been implicated in iris color previously. A replication study within two populations confirmed that the HERC2 gene is a new and significant determinant of human iris color variation, in addition to OCA2. Furthermore, HERC2 rs916977 showed a clinal allele distribution across 23 European populations, which was significantly correlated to iris color variation. We suggest that genetic variants regulating expression of the OCA2 gene exist in the HERC2 gene or, alternatively, within the 11.7 kb of sequence between OCA2 and HERC2, and that most iris color variation in Europeans is explained by those two genes. Testing markers in the HERC2-OCA2 region may be useful in forensic applications to predict eye color phenotypes of unknown persons of European genetic origin.

  13. Genetic Characterization of a Novel HIV-1 Circulating Recombinant Form (CRF74_01B) Identified among Intravenous Drug Users in Malaysia: Recombination History and Phylogenetic Linkage with Previously Defined Recombinant Lineages.

    Science.gov (United States)

    Cheong, Hui Ting; Chow, Wei Zhen; Takebe, Yutaka; Chook, Jack Bee; Chan, Kok Gan; Al-Darraji, Haider Abdulrazzaq Abed; Koh, Clayton; Kamarulzaman, Adeeba; Tee, Kok Keng

    2015-01-01

    In many parts of Southeast Asia, the HIV-1 epidemic has been driven by the sharing of needles and equipment among intravenous drug users (IDUs). Over the last few decades, many studies have proven time and again that the diversity of HIV-1 epidemics can often be linked to the route of infection transmission. That said, the diversity and complexity of HIV-1 molecular epidemics in the region have been increasing at an alarming rate, due in part to the high tendency of the viral RNA to recombine. This scenario was exemplified by the discovery of numerous circulating recombinant forms (CRFs), especially in Thailand and Malaysia. In this study, we characterized a novel CRF designated CRF74_01B, which was identified in six epidemiologically unlinked IDUs in Kuala Lumpur, Malaysia. The near-full length genomes were composed of CRF01_AE and subtype B', with eight breakpoints dispersed in the gag-pol and nef regions. Remarkably, this CRF shared four and two recombination hotspots with the previously described CRF33_01B and the less prevalent CRF53_01B, respectively. Genealogy-based Bayesian phylogenetic analysis of CRF74_01B genomic regions showed that it is closely related to both CRF33_01B and CRF53_01B. This observation suggests that CRF74_01B was probably a direct descendent from specific lineages of CRF33_01B, CRF53_01B and subtype B' that could have emerged in the mid-1990s. Additionally, it illustrated the active recombination processes between prevalent HIV-1 subtypes and recombinants in Malaysia. In summary, we report a novel HIV-1 genotype designated CRF74_01B among IDUs in Kuala Lumpur, Malaysia. The characterization of the novel CRF74_01B is of considerable significance towards the understanding of the genetic diversity and population dynamics of HIV-1 circulating in the region.

  14. 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.

  15. Meta-Analysis of Reciprocal Linkages between Temperate Seagrasses and Waterfowl with Implications for Conservation

    Directory of Open Access Journals (Sweden)

    Nicole M. Kollars

    2017-12-01

    Full Text Available Multi-trophic conservation and management strategies may be necessary if reciprocal linkages between primary producers and their consumers are strong. While herbivory on aquatic plants is well-studied, direct top-down control of seagrass populations has received comparatively little attention, particularly in temperate regions. Herein, we used qualitative and meta-analytic approaches to assess the scope and consequences of avian (primarily waterfowl herbivory on temperate seagrasses of the genus Zostera. Meta-analyses revealed widespread evidence of spatio-temporal correlations between Zostera and waterfowl abundances as well as strong top-down effects of grazing on Zostera. We also documented the identity and diversity of avian species reported to consume Zostera and qualitatively assessed their potential to exert top-down control. Our results demonstrate that Zostera and their avian herbivores are ecologically linked and we suggest that bird herbivory may influence the spatial structure, composition, and functioning of the seagrass ecosystem. Therefore, the consequences of avian herbivory should be considered in the management of seagrass populations. Of particular concern are instances of seagrass overgrazing by waterfowl which result in long-term reductions in seagrass biomass or coverage, with subsequent impacts on local populations of waterfowl and other seagrass-affiliated species. While our results showed that bird density and type may affect the magnitude of the top-down effects of avian herbivory, empirical research on the strength, context-dependency, and indirect effects of waterfowl–Zostera interactions remains limited. For example, increased efforts that explicitly measure the effects of different functional groups of birds on seagrass abundance and/or document how climate change-driven shifts in waterfowl migratory patterns impact seagrass phenology and population structure will advance research programs for both ecologists and

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

    Science.gov (United States)

    Leu, Costin; de Kovel, Carolien G F; Zara, Federico; Striano, Pasquale; Pezzella, Marianna; Robbiano, Angela; Bianchi, Amedeo; Bisulli, Francesca; Coppola, Antonietta; Giallonardo, Anna Teresa; Beccaria, Francesca; Trenité, Dorothée Kasteleijn-Nolst; Lindhout, Dick; Gaus, Verena; Schmitz, Bettina; Janz, Dieter; Weber, Yvonne G; Becker, Felicitas; Lerche, Holger; Kleefuss-Lie, Ailing A; Hallman, Kerstin; Kunz, Wolfram S; Elger, Christian E; Muhle, Hiltrud; Stephani, Ulrich; Møller, Rikke S; Hjalgrim, Helle; Mullen, Saul; Scheffer, Ingrid E; Berkovic, Samuel F; Everett, Kate V; Gardiner, Mark R; Marini, Carla; Guerrini, Renzo; Lehesjoki, Anna-Elina; Siren, Auli; Nabbout, Rima; Baulac, Stephanie; Leguern, Eric; Serratosa, Jose M; Rosenow, Felix; Feucht, Martha; Unterberger, Iris; Covanis, Athanasios; Suls, Arvid; Weckhuysen, Sarah; Kaneva, Radka; Caglayan, Hande; Turkdogan, Dilsad; Baykan, Betul; Bebek, Nerses; Ozbek, Ugur; Hempelmann, Anne; Schulz, Herbert; Rüschendorf, Franz; Trucks, Holger; Nürnberg, Peter; Avanzini, Giuliano; Koeleman, Bobby P C; Sander, Thomas

    2012-02-01

    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) susceptibility loci shared by a broad spectrum of GGEs, and (2) seizure type-related genetic factors preferentially predisposing to either typical absence or myoclonic seizures, respectively. Meta-analysis of three genome-wide linkage datasets was carried out in 379 GGE-multiplex families of European 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 and seizure type-related susceptibility loci, both nonparametric loci (NPL) and parametric linkage analyses were performed for a broad trait model (GGEs) in the entire set of GGE-multiplex families and a narrow trait model (typical absence or myoclonic seizures) in the subgroups of JME and GAE families. For the entire set of 379 GGE-multiplex families, linkage analysis revealed six loci achieving suggestive evidence for linkage at 1p36.22, 3p14.2, 5q34, 13q12.12, 13q31.3, and 19q13.42. The linkage finding at 5q34 was consistently supported by both NPL and parametric linkage results across all three family groups. A genome-wide significant nonparametric logarithm of odds score of 3.43 was obtained at 2q34 in 118 JME families. Significant parametric linkage to 13q31.3 was found in 235 GAE families assuming recessive inheritance (heterogeneity logarithm of odds = 5.02). Our linkage results support an oligogenic predisposition of familial GGE syndromes. The genetic risk factor at 5q34 confers risk to a broad spectrum of familial GGE syndromes, whereas susceptibility loci at 2q34 and 13q31

  17. Analysis of previous perceptual and motor experience in breaststroke kick learning

    Directory of Open Access Journals (Sweden)

    Ried Bettina

    2015-12-01

    Full Text Available One of the variables that influence motor learning is the learner’s previous experience, which may provide perceptual and motor elements to be transferred to a novel motor skill. For swimming skills, several motor experiences may prove effective. Purpose. The aim was to analyse the influence of previous experience in playing in water, swimming lessons, and music or dance lessons on learning the breaststroke kick. Methods. The study involved 39 Physical Education students possessing basic swimming skills, but not the breaststroke, who performed 400 acquisition trials followed by 50 retention and 50 transfer trials, during which stroke index as well as rhythmic and spatial configuration indices were mapped, and answered a yes/no questionnaire regarding previous experience. Data were analysed by ANOVA (p = 0.05 and the effect size (Cohen’s d ≥0.8 indicating large effect size. Results. The whole sample improved their stroke index and spatial configuration index, but not their rhythmic configuration index. Although differences between groups were not significant, two types of experience showed large practical effects on learning: childhood water playing experience only showed major practically relevant positive effects, and no experience in any of the three fields hampered the learning process. Conclusions. The results point towards diverse impact of previous experience regarding rhythmic activities, swimming lessons, and especially with playing in water during childhood, on learning the breaststroke kick.

  18. Linkage Maps of a Mediterranean × Continental Tall Fescue Population and their Comparative Analysis with Other Poaceae Species

    Directory of Open Access Journals (Sweden)

    Ryan Dierking

    2015-03-01

    Full Text Available Temperate grasses belonging to the complex are important throughout the world in pasture and grassland agriculture. Tall fescue ( Schreb. is the predominant species in the United States, covering approximately 15 million ha. Tall fescue has distinctive morphotypes, two of which are Continental (summer active and Mediterranean (summer semidormant. This is the first report of a linkage map created for Mediterranean tall fescue, while updating the Continental map with additional simple sequence repeat and sequence-tagged site markers. Additionally, this is the first time that diversity arrays technology (DArT markers were used in the construction of a tall fescue map. The male parent (Continental, R43-64, map consisted of 594 markers arranged in 22 linkage groups (LGs and covered a total of 1577 cM. The female parent (Mediterranean, 103-2, map was shorter (1258 cM and consisted of only 208 markers arranged in 29 LGs. Marker densities for R43-64 and 103-2 were 2.65 and 6.08 cM per marker, respectively. When compared with the other Poaceae species, meadow fescue ( Huds., annual ryegrass ( Lam., perennial ryegrass ( L., (L. Beauv., and barley ( L., a total of 171 and 98 orthologous or homologous sequences, identified by DArT analysis, were identified in R43-64 and 103-2, respectively. By using genomic in situ hybridization, we aimed to identify potential progenitors of both morphotypes. However, no clear conclusion on genomic constitution was reached. These maps will aid in the search for quantitative trait loci of various traits as well as help define and distinguish genetic differences between the two morphotypes.

  19. Post-transplant outcomes in pediatric ventricular assist device patients: A PediMACS-Pediatric Heart Transplant Study linkage analysis.

    Science.gov (United States)

    Sutcliffe, David L; Pruitt, Elizabeth; Cantor, Ryan S; Godown, Justin; Lane, John; Turrentine, Mark W; Law, Sabrina P; Lantz, Jodie L; Kirklin, James K; Bernstein, Daniel; Blume, Elizabeth D

    2017-12-13

    Pediatric ventricular assist device (VAD) support as bridge to transplant has improved waitlist survival, but the effects of pre-implant status and VAD-related events on post-transplant outcomes have not been assessed. This study is a linkage analysis between the PediMACS and Pediatric Heart Transplant Study databases to determine the effects of VAD course on post-transplant outcomes. Database linkage between October 1, 2012 and December 31, 2015 identified 147 transplanted VAD patients, the primary study group. The comparison cohort was composed of 630 PHTS patients without pre-transplant VAD support. The primary outcome was post-transplant survival, with secondary outcomes of post-transplant length of stay, freedom from infection and freedom from rejection. At implant, the VAD cohort was INTERMACS Profile 1 in 33 (23%), Profile 2 in 89 (63%) and Profile 3 in 14 (10%) patients. The VAD cohort was older, larger, and less likely to have congenital heart disease (p < 0.0001). However, they had greater requirements for inotrope and ventilator support and increased liver and renal dysfunction (p < 0.0001), both of which normalized at transplant after device support. Importantly, there were no differences in 1-year post-transplant survival (96% vs 93%, p = 0.3), freedom from infection (81% vs 79%, p = 0.9) or freedom from rejection (71% vs 74%, p = 0.87) between cohorts. Pediatric VAD patients have post-transplant outcomes equal to that of medically supported patients, despite greater pre-implant illness severity. Post-transplant survival, hospital length of stay, infection and rejection were not affected by patient acuity at VAD implantation or VAD-related complications. Therefore, VAD as bridge to transplant mitigates severity of illness in children. Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  20. Retrospective analysis on malignant calcification previously misdiagnosed as benign on screening mammography

    Energy Technology Data Exchange (ETDEWEB)

    Ha, Su Min [Dept. of Radiology, Research Institute of Radiology, Chung Ang University Hospital, Seoul(Korea, Republic of); Cha, Joo Hee; Kim, Hak Hee; Shin, Hee Jung; Chae, Eun Young; Choi, Woo Jung [Dept. of Radiology, Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2017-04-15

    The purpose of our study was to investigate the morphology and distribution of calcifications initially interpreted as benign or probably benign, but proven to be malignant by subsequent stereotactic biopsy, and to identify the reason for misinterpretation or underestimation at the initial diagnosis. Out of 567 women who underwent stereotactic biopsy for calcifications at our hospital between January 2012 and December 2014, 167 women were diagnosed with malignancy. Forty-six of these 167 women had previous mammography assessed as benign or probably benign which was changed to suspicious malignancy on follow-up mammography. Of these 46 women, three women with biopsy-proven benign calcifications at the site of subsequent cancer were excluded, and 43 patients were finally included. The calcifications (morphology, distribution, extent, associated findings) in the previous and follow-up mammography examinations were analyzed according to the Breast Imaging Reporting and Data System (BI-RADS) lexicon and assessment category. We classified the patients into two groups: 1) group A patients who were still retrospectively re-categorized as less than or equal to BI-RADS 3 and 2) group B patients who were re-categorized as equal to or higher than BI-RADS 4a and whose results should have prompted previous diagnostic assessment. In the follow-up mammography examinations, change in calcification morphology (n = 27, 63%) was the most frequent cause of assessment change. The most frequent previous mammographic findings of malignant calcification were amorphous morphology (n = 26, 60%) and grouped distribution (n = 36, 84%). The most frequent calcification findings at reassessment were amorphous morphology (n = 4, 9%), fine pleomorphic calcification (n = 30, 70%), grouped distribution (n = 23, 53%), and segmental calcification (n = 12, 28%). There were 33 (77%) patients in group A, and 10 patients (23%) in group B. Amorphous morphology and grouped distribution were the most frequent

  1. 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....

  2. 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) ...

  3. Construction of a genetic linkage map and analysis of quantitative trait loci associated with the agronomically important traits of Pleurotus eryngii

    Science.gov (United States)

    Chak Han Im; Young-Hoon Park; Kenneth E. Hammel; Bokyung Park; Soon Wook Kwon; Hojin Ryu; Jae-San Ryu

    2016-01-01

    Breeding new strains with improved traits is a long-standing goal of mushroom breeders that can be expedited by marker-assisted selection (MAS). We constructed a genetic linkage map of Pleurotus eryngii based on segregation analysis of markers in postmeiotic monokaryons from KNR2312. In total, 256 loci comprising 226 simple sequence-repeat (SSR) markers, 2 mating-type...

  4. Linkage analysis of bipolar illness with X-chromosome DNA markers: A susceptibility gene in Xq27-q28 cannot be excluded

    Energy Technology Data Exchange (ETDEWEB)

    De bruyn, A.; Raeymaekers, P.; Raes, G. [Univ. of Antwerp (Belgium)] [and others

    1994-12-15

    Transmission studies have supported the presence of a susceptibility gene for bipolar (BP) illness on the X-chromosome. Initial linkage studies with color blindness (CB), glucose-6-phosphate dehydrogenase (G6PD) deficiency, and the blood coagulation factor IX (F9) have suggested that a gene for BP illness is located in the Xq27-q28 region. We tested linkage with several DNA markers located in Xq27-q28 in 2 families, MAD3 and MAD4, that previously were linked to F9, and 7 newly ascertained families of BP probands. Linkage was also examined with the gene encoding the {alpha}3 subunit of the gamma-amino butyric acid receptor (GABRA3), a candidate gene for BP illness located in this region. The genetic data were analyzed with the LOD score method using age-dependent penetrance of an autosomal dominant disease gene and narrow and broad clinical models. In MAD3 and MAD4 the multipoint LOD score data suggested a localization of a BPI gene again near F9. In the 7 new families the overall linkage data excluded the Xq27-q28 region. However, if the families were grouped according to their proband`s phenotype BPI or BPII, a susceptibility gene for BPI disorder at the DXS52-F8 cluster could not be excluded. 48 refs., 2 figs., 3 tabs.

  5. Kidney transplantation after previous liver transplantation: analysis of the organ procurement transplant network database.

    Science.gov (United States)

    Gonwa, Thomas A; McBride, Maureen A; Mai, Martin L; Wadei, Hani M

    2011-07-15

    Patients after liver transplant have a high incidence of chronic kidney disease and end-stage renal disease (ESRD). We investigated kidney transplantation after liver transplantation using the Organ Procurement Transplant Network database. The Organ Procurement Transplant Network database was queried for patients who received kidney transplantation after previous liver transplantation. These patients were compared with patients who received primary kidney transplantation alone during the same time period. Between 1997 and 2008, 157,086 primary kidney transplants were performed. Of these, 680 deceased donor kidney transplants and 410 living donor kidney transplants were performed in previous recipients of liver transplants. The number of kidney after liver transplants performed each year has increased from 37 per year to 124 per year in 2008. The time from liver transplant to kidney transplant increased from 8.2 to 9.0 years for living donor transplants and from 5.4 to 9.6 years for deceased donor. The 1, 3, and 5 year actuarial graft survival in both living donor kidney after liver transplant and deceased donor kidney after liver transplant are less than the kidney transplant alone patients. However, the death-censored graft survivals are equal. The patient survival is also less but is similar to what would be expected in liver transplant recipients who did not have ESRD. In 2008, kidney after liver transplantation represented 0.9% of the total kidney alone transplants performed in the United States. Kidney transplantation is an appropriate therapy for selected patients who develop ESRD after liver transplantation.

  6. Rhabdomyosarcoma Arising in a Previously Irradiated Field: An Analysis of 43 Patients

    Energy Technology Data Exchange (ETDEWEB)

    Dang, Nguyen D. [Department of Radiation Oncology, Baylor College of Medicine, Houston, Texas (United States); Teh, Bin S. [Department of Radiation Oncology, The Methodist Hospital and Methodist Hospital Research Institute, Houston, Texas (United States); Paulino, Arnold C., E-mail: apaulino@tmhs.org [Department of Radiation Oncology, The Methodist Hospital and Methodist Hospital Research Institute, Houston, Texas (United States)

    2013-03-01

    Patients with soft tissue sarcomas that arise from previously irradiated fields have traditionally been reported to have a poor prognosis. In this report, we examined the characteristics and outcomes of patients who developed a rhabdomyosarcoma in a previously irradiated field (RMS-RIF); we hypothesize that these patients should have a better outcome compared to other postradiation soft tissue sarcomas as these tumors are chemosensitive and radiosensitive. A PubMed search of the literature from 1961-2010 yielded 33 studies with data for patients with RMS-RIF. The study included 43 patients with a median age of 6.5 years at the time of radiation therapy (RT) for the initial tumor. The median RT dose was 48 Gy. The median latency period, the time from RT to development of RMS-RIF, was 8 years. The 3-year overall survival for RMS-RIF was 42%. The 3-year overall survival was 66% for patients receiving chemotherapy and local treatment (surgery and/or RT) compared to 29% for those who had systemic treatment only or local treatment only (P=.049). Other factors associated with increased 3-year overall survival included retinoblastoma initial diagnosis (P<.001), age ≤18 years at diagnosis of RMS-RIF (P=.003), favorable site (P=.008), and stage 1 disease (P=.002). Age at time of RMS-RIF, retinoblastoma initial tumor, favorable site, stage 1 disease, and use of both systemic and local treatment were found to be favorable prognostic factors for 3-year overall survival.

  7. Linkage Technologies Which Enhance the Utility of Task-Based Occupational Analysis

    National Research Council Canada - National Science Library

    Phalen, William

    1999-01-01

    .... It is alleged that traditional task-based occupational analysis is too labor intensive, too costly, too cumbersome, and too static to meet the emerging and rapidly changing needs of a business...

  8. Planning and environment linkages program : a guide to measuring progress in linking transportation planning and environmental analysis

    Science.gov (United States)

    2009-12-01

    Transportation agencies use a variety of metrics to document progress toward achieving specific goals and objectives. This guide, developed by Federal Highway Administration (FHWA) Planning and Environmental Linkages (PEL) program, is intended to hel...

  9. Analysis on Population Level Reveals Trappability of Wild Rodents Is Determined by Previous Trap Occupant.

    Directory of Open Access Journals (Sweden)

    Marc J Brouard

    Full Text Available Live trapping is central to the study of small mammals. Thus, any bias needs to be understood and accounted for in subsequent analyses to ensure accurate population estimates. One rarely considered bias is the behavioural response of individuals to the trap, in particular the olfactory cues left behind by previous occupants (PO. We used a data set of 8,115 trap nights spanning 17 separate trapping sessions between August 2002 and November 2013 in Wytham Woods, Oxfordshire, UK to examine if the decision to enter a trap was affected by the PO, if this was detectable in traditional Capture-Mark-Recapture trapping data (i.e., individuals not uniquely marked, and if it was possible for this effect to bias the population estimates obtained. Data were collected on Apodemus sylvaticus, Myodes glareolus, and Microtus agrestis. Three Generalised Linear Models revealed a significant tendency for the three species to enter traps with same-species PO. With, for example, A. sylvaticus 9.1 times more likely to enter a same species PO trap compared to one that contained a M. agrestis in the grassland during the nocturnal period. Simulation highlighted that, when all other factors are equal, the species with the highest PO effect will have the highest capture rate and therefore return more accurate population estimates. Despite the large dataset, certain species-, sex-, and/ or age-combinations were under-represented, and thus no effects of any additional individual-specific characteristics could be evaluated. Uniquely marking individuals would allow for the PO effect to be disentangled from other biases such as trap-shyness and spatial heterogeneity, but may not be possible in all cases and will depend on the aims of the study and the resources available.

  10. Linkages between biodiversity loss and human health: a global indicator analysis

    NARCIS (Netherlands)

    Huynen, M.M.T.E.; Martens, P.; Groot, de R.S.

    2004-01-01

    The association between health and biodiversity loss was explored by means of regression analysis on a global scale, with control for confounding by socio-economic developments. For this we selected indicators of human health (life expectancy, disability adjusted life expectancy, infant mortality

  11. Possible Detection of Perchlorates by the Sample Analysis at Mars (SAM) Instrument: Comparison with Previous Missions

    Science.gov (United States)

    Navarro-Gonzalex, Rafael; Sutter, Brad; Archer, Doug; Ming, Doug; Eigenbrode, Jennifer; Franz, Heather; Glavin, Daniel; McAdam, Amy; Stern, Jennifer; McKay, Christopher; hide

    2013-01-01

    The first chemical analysis of soluble salts in the soil was carried out by the Phoenix Lander in the Martian Arctic [1]. Surprisingly, chlorine was present as magnesium or calcium perchlorate at 0.4 to 0.6 percent. Additional support for the identification of perchlorate came from the evolved gas analysis which detected the release of molecular oxygen at 350-550C [1]. When Mars-like soils from the Atacama Desert were spiked with magnesium perchlorate (1 percent) and heated using the Viking GC-MS protocol, nearly all the organics were combusted but a small amount was chlorinated, forming chloromethane and dichloromethane [2]. These chlorohydrocarbons were detected by the Viking GC-MS experiments when the Martian soil was analyzed but they were considered to be terrestrial contaminants [3]. Reinterpretation of the Viking results suggests detected compounds (CH3Cl and CH2Cl2) were carried from Earth [4]. Recently the Sample Analysis at Mars (SAM) instrument on board the Mars Science Laboratory (MSL) ran four samples from an aeolian bedform named Rocknest. The samples analyzed were portioned from the fifth scoop at this location. The samples were heated to 835C at 35C/min with a He flow. The SAM QMS detected a major oxygen release (300-500C) [5], coupled with the release of chlorinated hydrocarbons (chloromethane, dichloromethane, trichloromethane, and chloromethylpropene) detected both by SAM QMS and GC-MS derived from known Earth organic contaminants in the instrument [6]. Calcium perchlorate appears to be the best candidate for evolved O2 in the Rocknest samples at this time but other Cl species (e.g., chlorates) are possible and must be evaluated. The potential detection of perchlorates in Rocknest material adds weight to the argument that both Viking Landers measured signatures of perchlorates. Even if the source of the organic carbon detected is still unknown, the chlorine source was likely Martian. Two mechanisms have been hypothesized for the formation of soil

  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. Automatic spike sorting for extracellular electrophysiological recording using unsupervised single linkage clustering based on grey relational analysis

    Science.gov (United States)

    Lai, Hsin-Yi; Chen, You-Yin; Lin, Sheng-Huang; Lo, Yu-Chun; Tsang, Siny; Chen, Shin-Yuan; Zhao, Wan-Ting; Chao, Wen-Hung; Chang, Yao-Chuan; Wu, Robby; Shih, Yen-Yu I.; Tsai, Sheng-Tsung; Jaw, Fu-Shan

    2011-06-01

    Automatic spike sorting is a prerequisite for neuroscience research on multichannel extracellular recordings of neuronal activity. A novel spike sorting framework, combining efficient feature extraction and an unsupervised clustering method, is described here. Wavelet transform (WT) is adopted to extract features from each detected spike, and the Kolmogorov-Smirnov test (KS test) is utilized to select discriminative wavelet coefficients from the extracted features. Next, an unsupervised single linkage clustering method based on grey relational analysis (GSLC) is applied for spike clustering. The GSLC uses the grey relational grade as the similarity measure, instead of the Euclidean distance for distance calculation; the number of clusters is automatically determined by the elbow criterion in the threshold-cumulative distribution. Four simulated data sets with four noise levels and electrophysiological data recorded from the subthalamic nucleus of eight patients with Parkinson's disease during deep brain stimulation surgery are used to evaluate the performance of GSLC. Feature extraction results from the use of WT with the KS test indicate a reduced number of feature coefficients, as well as good noise rejection, despite similar spike waveforms. Accordingly, the use of GSLC for spike sorting achieves high classification accuracy in all simulated data sets. Moreover, J-measure results in the electrophysiological data indicating that the quality of spike sorting is adequate with the use of GSLC.

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

    Science.gov (United States)

    Li, Shuxian; Chen, Ying; Gao, Handong; Yin, Tongming

    2010-02-25

    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. 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. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Segmental hair analysis after a single dose of zolpidem: comparison with a previous study.

    Science.gov (United States)

    Cui, Xiaopei; Xiang, Ping; Zhang, Jingshuo; Shi, Yan; Shen, Baohua; Shen, Min

    2013-01-01

    Hair is a useful aid and sometimes even the only matrix in the analytical strategy in drug-facilitated crime (DFC) investigations. In this novel study, segmental hair analysis was performed after a single 10 mg dose of zolpidem was given to 20 Chinese volunteers. Hair was collected 1 month after administration and was analyzed using ultra-high-pressure liquid chromatography/electrospray ionization tandem mass spectrometry. Zolpidem concentrations were found to be in the range of 135.0-554.6 pg/mg in the proximal 0-2 cm segments. These results were markedly different from those reported by Villain et al., who used volunteers administered equal doses of zolpidem. The analytical method used, as well as the volunteers' hair color, inter-individual variations such as metabolic capacity, hair growth rate, drug incorporation rates, physical state of the hair, age, gender, body weight, etc. and diffusion from sweat or other secretions are all factors that should be considered when interpreting the DFC results.

  19. Proteomics analysis in frozen horse mackerel previously high-pressure processed.

    Science.gov (United States)

    Pazos, Manuel; Méndez, Lucía; Vázquez, Manuel; Aubourg, Santiago P

    2015-10-15

    The effect of high-pressure processing (HPP) (150, 300 and 450 MPa for 0, 2.5 and 5 min) on total sodium dodecyl sulphate (SDS)-soluble and sarcoplasmic proteins in frozen (-10 °C for 3 months) horse mackerel (Trachurus trachurus) was evaluated. Proteomics tools based on image analysis of SDS-PAGE protein gels and protein identification by tandem mass spectrometry (MS/MS) were applied. Although total SDS-soluble fraction indicated no important changes induced by HPP, this processing modified the 1-D SDS-PAGE sarcoplasmic patterns in a direct-dependent manner and exerted a selective effect on particular proteins depending on processing conditions. Thus, application of the highest pressure (450 MPa) provoked a significant degradation of phosphoglycerate mutase 2, glycogen phosphorylase muscle form, pyruvate kinase muscle isozyme, beta-enolase and triosephosphate isomerase and phosphoglucomutase-1. Conversely, protein bands assigned to tropomyosin alpha-1 chain, fast myotomal muscle troponin T and parvalbumin beta 2 increased their intensity after applying a 450-MPa processing. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Fate of manuscripts previously rejected by the American Journal of Neuroradiology: a follow-up analysis.

    Science.gov (United States)

    McDonald, R J; Cloft, H J; Kallmes, D F

    2009-02-01

    This is a follow-up article to "Fate of Submitted Manuscripts Rejected from the American Journal of Neuroradiology: Outcomes and Commentary." The purpose of this study was to quantify differences in citation frequency between manuscripts published in the American Journal of Neuroradiology (AJNR) and those published after AJNR rejection and to understand citation frequency differences among rejected manuscripts. In this study, a MEDLINE search identified all manuscripts published in AJNR in 2005 and those initially rejected by AJNR in 2004 but subsequently published elsewhere. Once identified, the citation frequencies of both groups were determined by using SCOPUS. Citation data were used in comparative studies between AJNR rejected and accepted articles and in studies comparing citation frequency differences among rejected manuscripts as a function of journal and/or publication classifications. Among 315 subsequently published rejections from AJNR in 2004, 696 citations accumulated between 2005 and 2007 (2.4 citations/journal year), whereas 441 AJNR articles published in 2005 accumulated 2490 citations between 2005 and 2007 (6.4 citations/journal year, P journals classified as either neuroradiology or general radiology had significantly higher citation frequencies than other submission types and journal classifications. Nonparametric analysis of citation frequency showed significant correlations with impact factors of respective publishing journals (rho = 0.444). Results from this study suggest that publications initially rejected from AJNR have a significantly lower citation frequency than those accepted by AJNR. Among rejected manuscripts, citations frequencies were highest in technical reports and among journals close to the neuroradiologic discipline.

  1. 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.

  2. Enhanced understanding of ectoparasite: host trophic linkages on coral reefs through stable isotope analysis

    Science.gov (United States)

    Demopoulos, Amanda W. J.; Sikkel, Paul C.

    2015-01-01

    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 in13C 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.

  3. Improving configuration management of thermalhydraulic analysis by automating the linkage between pipe geometry and plant idealization

    International Nuclear Information System (INIS)

    Gibb, R.; Girard, R.; Thompson, W.

    1997-01-01

    All safety analysis codes require some representation of actual plant data as a part of their input. Such representations, referred to at Point Lepreau Generating Station (PLGS) as plant idealizations, may include piping layout, orifice, pump or valve opening characteristics, boundary conditions of various sorts, reactor physics parameters, etc. As computing power increases, the numerical capabilities of thermalhydraulic analysis tools become more sophisticated, requiring more detailed assessments, and consequently more complex and complicated idealizations of the system models. Thus, a need has emerged to create a precise plant model layout in electronic form which ensures a realistic representation of the plant systems, and form which analytical approximations of any chosen degree of accuracy may be created. The benefits of this process are twofold. Firstly, the job of developing a plant idealization is made simpler, and therefore is cheaper for the utility. More important however, are the improvements in documentation and reproducibility that this process imparts to the resultant idealization. Just as the software that performs the numerical operations on the input data must be subject to verification/validation, equally robust measures must be taken to ensure that these software operations are being applied to valid idealizations, that are formally documented. Since the CATHENA Code is one of the most important thermalhydraulic code used for safety analysis at PLGS the main effort was directed towards the systems plant models for this code. This paper reports the results of the work carried on at PLGS and ANSL to link the existing piping data base to the actual CATHENA plant idealization. An introduction to the concept is given first, followed by a description of the databases, and the supervisory tool which manages the data, and associated software. An intermediate code, which applied some thermalhydraulic rules to the data, and translated the resultant data

  4. A Molecular Genetic Linkage Map of Eucommia ulmoides and Quantitative Trait Loci (QTL Analysis for Growth Traits

    Directory of Open Access Journals (Sweden)

    Yu Li

    2014-01-01

    Full Text Available Eucommia ulmoides is an economically important tree species for both herbal medicine and organic chemical industry. Effort to breed varieties with improved yield and quality is limited by the lack of knowledge on the genetic basis of the traits. A genetic linkage map of E. ulmoides was constructed from a full-sib family using sequence-related amplified polymorphism, amplified fragment length polymorphism, inter-simple sequence repeat and simple sequence repeat markers. In total, 706 markers were mapped in 25 linkage groups covering 2133 cM. The genetic linkage map covered approximately 89% of the estimated E. ulmoides genome with an average of 3.1 cM between adjacent markers. The present genetic linkage map was used to identify quantitative trait loci (QTL affecting growth-related traits. Eighteen QTLs were found to explain 12.4%–33.3% of the phenotypic variance. This genetic linkage map provides a tool for marker-assisted selection and for studies of genome in E. ulmoides.

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

    Directory of Open Access Journals (Sweden)

    Delphine Fradin

    2010-09-01

    Full Text Available 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.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.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.

  6. Impact analysis of coal-electricity pricing linkage scheme in China based on stochastic frontier cost function

    International Nuclear Information System (INIS)

    Li, Hong-Zhou; Tian, Xian-Liang; Zou, Tao

    2015-01-01

    Highlights: • This study evaluates the coal-electricity pricing linkage policy in China. • Six stochastic frontier cost models are used to estimate efficiency measures. • The coal-electricity pricing linkage scheme is a double-edged sword. • We suggest the threshold value of 5% or group specific. - Abstract: This study evaluates the feasibility and fairness of 2012 amendment to coal-electricity pricing linkage policy in China. Our empirical design is based on several stochastic frontier cost functions and the results show that the amended pricing linkage scheme is a double-edged sword as follows. On the one hand, it provides incentives for less-efficient (with efficiency less than 90%) power plants to increase their efficiency. One the other hand, it imposes a penalty to highly-efficient power plants (with efficiency more than 90%). And even worse, the higher the efficiency is, the bigger the penalty will be. To make the current coal-electricity pricing linkage scheme more feasible, we suggest the threshold value of 5 instead of 10%, and a group specific threshold value instead of the current one-size-for-all practice

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

    Science.gov (United States)

    Fradin, Delphine; Cheslack-Postava, Keely; Ladd-Acosta, Christine; Newschaffer, Craig; Chakravarti, Aravinda; Arking, Dan E; Feinberg, Andrew; Fallin, M Daniele

    2010-09-02

    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. 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). 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.

  8. UGT1A1 gene linkage analysis: application of polymorphic markers rs4148326/rs4124874 in the Iranian population

    Directory of Open Access Journals (Sweden)

    Zakiye Nadeali

    2017-08-01

    Full Text Available Objective(s: Mutations in the UGT1A1 gene are responsible for hyperbilirubinemia syndromes including Crigler-Najjar type 1 and 2 and Gilbert syndrome. In view of the genetic heterogeneity and involvement of large numbers of the disease causing mutations, the application of polymorphic markers in the UGTA1 gene could be useful in molecular diagnosis of the disease. Materials and Methods: In the present study, two polymorphic markers including rs4148326 and rs4124874 in the UGT1A1 gene region were characterized. The markers were selected using bioinformatics analysis of the UGT1A1 gene region and genotyped in 212 unrelated healthy individuals and 13 family trios in the Iranian population using Tetra-Primer ARMS PCR technique. The allele frequency and population status of the alleles were estimated using GENEPOP, FBAT, PowerMarker and Arlequin software. Results: The results indicated that in the case of rs4148326 marker, allele frequency for T and C allele was 66.04% and 33.96%, respectively. For rs4124874 marker, allele frequency for G and T alleles was 39.4% and 60.6%, respectively. The values of heterozygosity index for the markers examined were 64.1 for rs4148326 and 72.1 for rs4124874, respectively. The haplotype estimation analysis of the markers resulted in three informative haplotypes with frequencies ≥0.05. Moreover, the results suggested the presence of linkage disequilibrium between two markers. Conclusion: Altogether, the data suggested that rs4148326 and rs4124874 could be introduced as informative markers for molecular diagnosis of Crigler-Najjar type 1 and 2 and Gilbert syndrome in the Iranian population.

  9. 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. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.

  10. Identification of Single Nucleotide Polymorphisms and analysis of Linkage Disequilibrium in sunflower elite inbred lines using the candidate gene approach

    Directory of Open Access Journals (Sweden)

    Heinz Ruth A

    2008-01-01

    Full Text Available Abstract Background Association analysis is a powerful tool to identify gene loci that may contribute to phenotypic variation. This includes the estimation of nucleotide diversity, the assessment of linkage disequilibrium structure (LD and the evaluation of selection processes. Trait mapping by allele association requires a high-density map, which could be obtained by the addition of Single Nucleotide Polymorphisms (SNPs and short insertion and/or deletions (indels to SSR and AFLP genetic maps. Nucleotide diversity analysis of randomly selected candidate regions is a promising approach for the success of association analysis and fine mapping in the sunflower genome. Moreover, knowledge of the distance over which LD persists, in agronomically meaningful sunflower accessions, is important to establish the density of markers and the experimental design for association analysis. Results A set of 28 candidate genes related to biotic and abiotic stresses were studied in 19 sunflower inbred lines. A total of 14,348 bp of sequence alignment was analyzed per individual. In average, 1 SNP was found per 69 nucleotides and 38 indels were identified in the complete data set. The mean nucleotide polymorphism was moderate (θ = 0.0056, as expected for inbred materials. The number of haplotypes per region ranged from 1 to 9 (mean = 3.54 ± 1.88. Model-based population structure analysis allowed detection of admixed individuals within the set of accessions examined. Two putative gene pools were identified (G1 and G2, with a large proportion of the inbred lines being assigned to one of them (G1. Consistent with the absence of population sub-structuring, LD for G1 decayed more rapidly (r2 = 0.48 at 643 bp; trend line, pooled data than the LD trend line for the entire set of 19 individuals (r2 = 0.64 for the same distance. Conclusion Knowledge about the patterns of diversity and the genetic relationships between breeding materials could be an invaluable aid in crop

  11. Genetic analysis of autoimmune gld mice. I. Identification of a restriction fragment length polymorphism closely linked to the gld mutation within a conserved linkage group

    Science.gov (United States)

    1988-01-01

    A linkage map of distal mouse chromosome 1 was generated using restriction fragment length polymorphism (RFLP) analysis of DNA prepared from 95 [C3H-gld/gld X Mus spretus)F1 X C3H-gld/gld] backcross mice. The gene order was: (centromere) C4bp, Ren-1,2, Ly-5, [At-3/gld], Apoa-2/Ly-17, Spna-1 (telomere). All mice expressing the phenotype of gld homozygotes were homozygous for the At-3 RFLP characteristic of C3H mice and none of the mice heterozygous for At-3 RFLPs had characteristics of gld homozygotes, demonstrating close linkage between these genes. The identification of an RFLP closely linked to the gld gene provides a starting point for the identification of a genetic defect that results in abnormal T cells and autoimmune disease. PMID:2894402

  12. Challenges in administrative data linkage for research

    Directory of Open Access Journals (Sweden)

    Katie Harron

    2017-12-01

    Full Text Available Linkage of population-based administrative data is a valuable tool for combining detailed individual-level information from different sources for research. While not a substitute for classical studies based on primary data collection, analyses of linked administrative data can answer questions that require large sample sizes or detailed data on hard-to-reach populations, and generate evidence with a high level of external validity and applicability for policy making. There are unique challenges in the appropriate research use of linked administrative data, for example with respect to bias from linkage errors where records cannot be linked or are linked together incorrectly. For confidentiality and other reasons, the separation of data linkage processes and analysis of linked data is generally regarded as best practice. However, the ‘black box’ of data linkage can make it difficult for researchers to judge the reliability of the resulting linked data for their required purposes. This article aims to provide an overview of challenges in linking administrative data for research. We aim to increase understanding of the implications of (i the data linkage environment and privacy preservation; (ii the linkage process itself (including data preparation, and deterministic and probabilistic linkage methods and (iii linkage quality and potential bias in linked data. We draw on examples from a number of countries to illustrate a range of approaches for data linkage in different contexts.

  13. Analysis of Mendelian inheritance and genetic linkage in microsatellite loci of Eucalyptus urophylla S.T. Blake.

    Science.gov (United States)

    Pupin, S; Rosse, L N; Souza, I C G; Cambuim, J; Marino, C L; Moraes, M L T; Sebbenn, A M

    2017-08-17

    Eucalyptus urophylla is an important species in the Brazilian forest sector due to its rapid growth rates and resistance to disease. The aim of this study was to verify Mendelian inheritance, genetic linkage, and genotypic disequilibrium for 15 microsatellite loci, with the goal of producing a robust set of genetic markers. Mendelian inheritance and genetic linkage analyses were carried out using genotypes from maternal trees, and their open-pollinated seeds and genotypic disequilibrium were assessed using adult trees. By comparing heterozygous maternal genotypes and their seeds, we found no significant deviations from the expected 1:1 Mendelian segregation and the expected 1:1:1:1 segregation hypothesis for pairwise loci. For adult trees, we did not find strong evidence of genotypic imbalance for pairwise loci. Our results indicated that the analyzed set of microsatellite loci could be used to carry out analyses of genetic diversity, mating system, and parentage in E. urophylla.

  14. JamesWattandhisLinkages

    Indian Academy of Sciences (India)

    Admin

    sometimes called) for a straight line. e gene ate a circle with ... See Figu e. A(1). Such an assembly is a linkage. In particular, it is a fou -ba linkage. A linkage can consist of any number of bodies and connections as well as a ... written to his friend and business partner Matthew Boulton: “I have got a glimpse of a method.

  15. The suitability of XRF analysis for compositional classification of archaeological ceramic fabric: A comparison with a previous NAA study

    Energy Technology Data Exchange (ETDEWEB)

    Padilla, R. [Centro de Aplicaciones Tecnologicas y Desarrollo Nuclear (CEADEN), Laboratorio de Analisis Quimico, Calle 30 no. 502, Playa, Ciudad Habana (Cuba)]. E-mail: roman.padilla@infomed.sld.cu; Espen, P. van [University of Antwerp (Belgium); Torres, P.P. Godo [Centro de Antropologia, Havana (Cuba)

    2006-02-03

    The main drawbacks of EDXRF techniques, restricting its more frequent use for the specific purpose of compositional analysis of archaeological ceramic fabric, have been the insufficient sensitivity to determine some important elements (like Cr, REE, among others), a somewhat worse precision and the inability to perform standard-less quantitative procedures in the absence of suitable certified reference materials (CRM) for ceramic fabric. This paper presents the advantages of combining two energy dispersive X-ray fluorescence methods for fast and non-destructive analysis of ceramic fabric with increased sensitivity. Selective polarized excitation using secondary targets (EDPXRF) and radioisotope excitation (R-XRF) using a {sup 241}Am source. The analytical performance of the methods was evaluated by analyzing several CRM of sediment type, and the fitness for the purpose of compositional classification was compared with that obtained by using Instrumental Neutron Activation Analysis in a previous study of Cuban aborigine pottery.

  16. An Enhanced Linkage Map of the Sheep Genome Comprising More Than 1000 Loci

    Science.gov (United States)

    Maddox, Jillian F.; Davies, Kizanne P.; Crawford, Allan M.; Hulme, Dennis J.; Vaiman, Daniel; Cribiu, Edmond P.; Freking, Bradley A.; Beh, Ken J.; Cockett, Noelle E.; Kang, Nina; Riffkin, Christopher D.; Drinkwater, Roger; Moore, Stephen S.; Dodds, Ken G.; Lumsden, Joanne M.; van Stijn, Tracey C.; Phua, Sin H.; Adelson, David L.; Burkin, Heather R.; Broom, Judith E.; Buitkamp, Johannes; Cambridge, Lisa; Cushwa, William T.; Gerard, Emily; Galloway, Susan M.; Harrison, Blair; Hawken, Rachel J.; Hiendleder, Stefan; Henry, Hannah M.; Medrano, Juan F.; Paterson, Korena A.; Schibler, Laurent; Stone, Roger T.; van Hest, Beryl

    2001-01-01

    A medium-density linkage map of the ovine genome has been developed. Marker data for 550 new loci were generated and merged with the previous sheep linkage map. The new map comprises 1093 markers representing 1062 unique loci (941 anonymous loci, 121 genes) and spans 3500 cM (sex-averaged) for the autosomes and 132 cM (female) on the X chromosome. There is an average spacing of 3.4 cM between autosomal loci and 8.3 cM between highly polymorphic [polymorphic information content (PIC) ≥ 0.7] autosomal loci. The largest gap between markers is 32.5 cM, and the number of gaps of >20 cM between loci, or regions where loci are missing from chromosome ends, has been reduced from 40 in the previous map to 6. Five hundred and seventy-three of the loci can be ordered on a framework map with odds of >1000 : 1. The sheep linkage map contains strong links to both the cattle and goat maps. Five hundred and seventy-two of the loci positioned on the sheep linkage map have also been mapped by linkage analysis in cattle, and 209 of the loci mapped on the sheep linkage map have also been placed on the goat linkage map. Inspection of ruminant linkage maps indicates that the genomic coverage by the current sheep linkage map is comparable to that of the available cattle maps. The sheep map provides a valuable resource to the international sheep, cattle, and goat gene mapping community. PMID:11435411

  17. Probabilistic record linkage.

    Science.gov (United States)

    Sayers, Adrian; Ben-Shlomo, Yoav; Blom, Ashley W; Steele, Fiona

    2016-06-01

    Studies involving the use of probabilistic record linkage are becoming increasingly common. However, the methods underpinning probabilistic record linkage are not widely taught or understood, and therefore these studies can appear to be a 'black box' research tool. In this article, we aim to describe the process of probabilistic record linkage through a simple exemplar. We first introduce the concept of deterministic linkage and contrast this with probabilistic linkage. We illustrate each step of the process using a simple exemplar and describe the data structure required to perform a probabilistic linkage. We describe the process of calculating and interpreting matched weights and how to convert matched weights into posterior probabilities of a match using Bayes theorem. We conclude this article with a brief discussion of some of the computational demands of record linkage, how you might assess the quality of your linkage algorithm, and how epidemiologists can maximize the value of their record-linked research using robust record linkage methods. © The Author 2015; Published by Oxford University Press on behalf of the International Epidemiological Association.

  18. 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.

  19. Efficient Record Linkage Algorithms Using Complete Linkage Clustering

    Science.gov (United States)

    Mamun, Abdullah-Al; Aseltine, Robert; Rajasekaran, Sanguthevar

    2016-01-01

    Data from different agencies share data of the same individuals. Linking these datasets to identify all the records belonging to the same individuals is a crucial and challenging problem, especially given the large volumes of data. A large number of available algorithms for record linkage are prone to either time inefficiency or low-accuracy in finding matches and non-matches among the records. In this paper we propose efficient as well as reliable sequential and parallel algorithms for the record linkage problem employing hierarchical clustering methods. We employ complete linkage hierarchical clustering algorithms to address this problem. In addition to hierarchical clustering, we also use two other techniques: elimination of duplicate records and blocking. Our algorithms use sorting as a sub-routine to identify identical copies of records. We have tested our algorithms on datasets with millions of synthetic records. Experimental results show that our algorithms achieve nearly 100% accuracy. Parallel implementations achieve almost linear speedups. Time complexities of these algorithms do not exceed those of previous best-known algorithms. Our proposed algorithms outperform previous best-known algorithms in terms of accuracy consuming reasonable run times. PMID:27124604

  20. Efficient Record Linkage Algorithms Using Complete Linkage Clustering.

    Science.gov (United States)

    Mamun, Abdullah-Al; Aseltine, Robert; Rajasekaran, Sanguthevar

    2016-01-01

    Data from different agencies share data of the same individuals. Linking these datasets to identify all the records belonging to the same individuals is a crucial and challenging problem, especially given the large volumes of data. A large number of available algorithms for record linkage are prone to either time inefficiency or low-accuracy in finding matches and non-matches among the records. In this paper we propose efficient as well as reliable sequential and parallel algorithms for the record linkage problem employing hierarchical clustering methods. We employ complete linkage hierarchical clustering algorithms to address this problem. In addition to hierarchical clustering, we also use two other techniques: elimination of duplicate records and blocking. Our algorithms use sorting as a sub-routine to identify identical copies of records. We have tested our algorithms on datasets with millions of synthetic records. Experimental results show that our algorithms achieve nearly 100% accuracy. Parallel implementations achieve almost linear speedups. Time complexities of these algorithms do not exceed those of previous best-known algorithms. Our proposed algorithms outperform previous best-known algorithms in terms of accuracy consuming reasonable run times.

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

    Science.gov (United States)

    Li, Li; Guo, Ximing; Zhang, Guofan

    2009-02-01

    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.

  2. At what price? A cost-effectiveness analysis comparing trial of labour after previous caesarean versus elective repeat caesarean delivery.

    Directory of Open Access Journals (Sweden)

    Christopher G Fawsitt

    Full Text Available BACKGROUND: Elective repeat caesarean delivery (ERCD rates have been increasing worldwide, thus prompting obstetric discourse on the risks and benefits for the mother and infant. Yet, these increasing rates also have major economic implications for the health care system. Given the dearth of information on the cost-effectiveness related to mode of delivery, the aim of this paper was to perform an economic evaluation on the costs and short-term maternal health consequences associated with a trial of labour after one previous caesarean delivery compared with ERCD for low risk women in Ireland. METHODS: Using a decision analytic model, a cost-effectiveness analysis (CEA was performed where the measure of health gain was quality-adjusted life years (QALYs over a six-week time horizon. A review of international literature was conducted to derive representative estimates of adverse maternal health outcomes following a trial of labour after caesarean (TOLAC and ERCD. Delivery/procedure costs derived from primary data collection and combined both "bottom-up" and "top-down" costing estimations. RESULTS: Maternal morbidities emerged in twice as many cases in the TOLAC group than the ERCD group. However, a TOLAC was found to be the most-effective method of delivery because it was substantially less expensive than ERCD (€ 1,835.06 versus € 4,039.87 per women, respectively, and QALYs were modestly higher (0.84 versus 0.70. Our findings were supported by probabilistic sensitivity analysis. CONCLUSIONS: Clinicians need to be well informed of the benefits and risks of TOLAC among low risk women. Ideally, clinician-patient discourse would address differences in length of hospital stay and postpartum recovery time. While it is premature advocate a policy of TOLAC across maternity units, the results of the study prompt further analysis and repeat iterations, encouraging future studies to synthesis previous research and new and relevant evidence under a single

  3. Genome-wide linkage analysis of heroin dependence in Han Chinese: results from wave one of a multi-stage study.

    Science.gov (United States)

    Glatt, Stephen J; Su, Jessica A; Zhu, Shao C; Zhang, Ruimin; Zhang, Bo; Li, Jixiang; Yuan, Xiaobo; Li, Jianhua; Lyons, Michael J; Faraone, Stephen V; Tsuang, Ming T

    2006-09-05

    The contribution of genes to the etiology of heroin dependence is greater than for any other illicit drug. The specific genes mediating this effect remain unknown, despite several candidate gene association studies of the condition. Here we report the results of a genome-wide search for heroin dependence susceptibility loci using multipoint linkage analysis. In phase I, we ascertained 207 independent affected sibling pairs from 202 Han Chinese families from Yunnan Province, China (near Asia's "Golden Triangle"). After data-cleaning, 194 fully independent sibling pairs (i.e., with no overlapping individuals) from 192 families were genotyped on 404 short tandem-repeat markers spaced at an average inter-marker distance of 9 cM. Although none of our findings achieved genome-wide significance, we found two regions with non-parametric linkage (NPL) Z-scores greater than 2.0. An NPL Z-score of 2.19 (uncorrected P-value = 0.014) was observed at D4S1644, located at 143.3 cM on chromosomal region 4q31.21. The highest NPL Z-score of 2.36 (uncorrected P-value = 0.009) was observed at 53.4 cM on chromosomal region 17q11.2 at marker D17S1880. This is among the first published reports of a genome-wide linkage analysis of heroin dependence. Forthcoming results from other groups and from two additional waves of ascertainment (one planned, one currently ongoing) for our own study should be able to support or refute the putative susceptibility loci we have identified, after which positional candidate genes can be further evaluated as risk factors for the illness.

  4. Genetic Linkage Analysis of DFNB2 Locus with Autosomal Recessive Hearing Loss in Families Negative for GJB2 Mutations in Khuzestan Province

    Directory of Open Access Journals (Sweden)

    Parisa Tahmasebi

    2016-09-01

    Full Text Available Abstract Background: Hearing loss is a common sensory impairment in humans which half of its causes are genetic reasons. Genetic hearing loss can be divided into the two types of syndromic and non-syndromic, which 80% of non-syndromic cases is Autosomal Recessive Non-Syndromic Hearing Loss. The aim of the present research is to determine the contribution of DFNB2 locus (MYO7A gene in causing an autosomal recessive hearing loss in the one group of the deaf families of Khuzestan province. Materials and Methods: This study was conducted on 26 families with autosomal recessive hearing loss (with 4 patients and negative for GJB2 mutations in Khuzestan province. 22 families suffered from ARNSHL and 4 families suffered from Usher syndrome. Linkage analysis was performed by using STR (Short Tandem Repeat markers related to DFNB2 locus. Each family’s genotype was determined by PCR-PAGE method. Furthermore, haplotypes drawing and LOD score calculations were performed. Results: From 26 families with hearing loss participating in this research, following genetic linkage analysis and haplotypes drawing, two families (7.7% of the families showed linkage to DFNB2 locus. One family (4.5% suffered from ARNSHL and another family suffered from Usher syndrome. Conclusion: The results of the present research show that the contribution of DFNB2 locus in causing hearing loss in the population of Khuzestan province was similar to other studies conducted in Iran and this locus with other important loci should be considered to check in the hearing loss panel.

  5. [Suicide and suicide attempts by exogenous poisoning in Rio de Janeiro, Brazil: information analysis through probabilistic linkage].

    Science.gov (United States)

    Santos, Simone Agadir; Legay, Letícia Fortes; Aguiar, Fernanda Pinheiro; Lovisi, Giovanni Marcos; Abelha, Lucia; Oliveira, Sergio Pacheco de

    2014-05-01

    Poisoning is one of the three main means used in suicide and suicides attempts. In order to improve the quality of such information, a cross-sectional descriptive study was conducted on case records in the State of Rio de Janeiro, Brazil, from 2006 to 2008, in the databases of the Information System on Diseases of Notification (SINAN), the Mortality Information System (SIM), and the Poison Control Center in Niterói (CCIn-Niterói). Probabilistic linkage was used to develop a model for monitoring suicides and suicide attempts by poisoning. Although 68.8% of the 948 records at CCIn had been reported by health professionals, only 2.6% were included in the other databases. Linking CCIn and SIM showed 61.3% underreporting. Information is important for surveillance, public policy-making, and decision-making. Probabilistic linkage allowed identifying problems in each system and provided better data quality and a more accurate diagnosis of the real situation in a complex and serious problem like suicidal behavior.

  6. A pantograph linkage

    International Nuclear Information System (INIS)

    Cole, G.V.

    1982-01-01

    A pantograph linkage is actuated by two linear actuators, pivotally connected together at the linkage. The displacement of the actuators is monitored by rectilinear potentiometers to provide feedback signals to a microprocessor which also receives input signals related to a required movement of a slave end of the linkage. In response to these signals, the microprocessor provides signals to control the displacement of the linear actuators to effect the required movement of the slave end. The movement of the slave end might be straightline in a substantially horizontal or vertical direction. (author)

  7. Effects of cooking on the cell walls (dietary fiber) of 'Scarlet Warren' winter squash ( Cucurbita maxima ) studied by polysaccharide linkage analysis and solid-state (13)C NMR.

    Science.gov (United States)

    Ratnayake, R M Sunil; Sims, Ian M; Newman, Roger H; Melton, Laurence D

    2011-07-13

    Cell wall polysaccharides of 'Scarlet Warren' winter squash ( Cucurbita maxima ) were investigated before and after thermal processing. Linkage analysis of polysaccharides was done by gas chromatography coupled to mass spectrometry (GC-MS). The linkage analysis showed the cell wall polysaccharide compositions of raw and cooked squash were similar. The total pectic polysaccharides (galacturonan, rhamnogalacturonan, arabinan, and arabinogalactan) contents of the cell walls of both raw and cooked squash were 39 mol %. The amounts of pectic polysaccharides and xyloglucan in the cell walls of squash showed little alteration on heating. The cellulose content of the raw and cooked cell walls was relatively high at 47 mol %, whereas the xyloglucan content was low at 4 mol %. Solid-state (13)C nuclear magnetic resonance (NMR) spectroscopy techniques were used to examine the molecular motion of the polysaccharides in the cell walls. The mobility of highly flexible galactan depends on the water content of the sample, but no difference was seen between raw and cooked samples. Likewise, the mobility of semimobile pectic polysaccharides was apparently unaltered by cooking. No change was detected in the rigid cellulose microfibrils on cooking.

  8. 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.

  9. 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.

  10. 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)

    Hashim, R.; Ahmad, S.; Sattar, A.; Khan, F.A.

    2011-01-01

    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

  11. Multiobjective optimization of a steering linkage

    International Nuclear Information System (INIS)

    Sleesonsom, S.; Bureerat, S.

    2016-01-01

    In this paper, multi-objective optimization of a rack-and-pinion steering linkage is proposed. This steering linkage is a common mechanism used in small cars with three advantages as it is simple to construct, economical to manufacture, and compact and easy to operate. In the previous works, many researchers tried to minimize a steering error but minimization of a turning radius is somewhat ignored. As a result, a multi-objective optimization problem is assigned to simultaneously minimize a steering error and a turning radius. The design variables are linkage dimensions. The design problem is solved by the hybrid of multi-objective population-based incremental learning and differential evolution with various constraint handling schemes. The new design strategy leads to effective design of rack-and-pinion steering linkages satisfying both steering error and turning radius criteria

  12. Multiobjective optimization of a steering linkage

    Energy Technology Data Exchange (ETDEWEB)

    Sleesonsom, S.; Bureerat, S. [Sustainable and Infrastructure Research and Development Center, Dept. of Mechanical Engineering, Faculty of Engineering, Khon Kaen University, Khon Kaen (Thailand)

    2016-08-15

    In this paper, multi-objective optimization of a rack-and-pinion steering linkage is proposed. This steering linkage is a common mechanism used in small cars with three advantages as it is simple to construct, economical to manufacture, and compact and easy to operate. In the previous works, many researchers tried to minimize a steering error but minimization of a turning radius is somewhat ignored. As a result, a multi-objective optimization problem is assigned to simultaneously minimize a steering error and a turning radius. The design variables are linkage dimensions. The design problem is solved by the hybrid of multi-objective population-based incremental learning and differential evolution with various constraint handling schemes. The new design strategy leads to effective design of rack-and-pinion steering linkages satisfying both steering error and turning radius criteria.

  13. NMR-based phytochemical analysis of Vitis vinifera cv Falanghina leaves. Characterization of a previously undescribed biflavonoid with antiproliferative activity.

    Science.gov (United States)

    Tartaglione, Luciana; Gambuti, Angelita; De Cicco, Paola; Ercolano, Giuseppe; Ianaro, Angela; Taglialatela-Scafati, Orazio; Moio, Luigi; Forino, Martino

    2018-03-01

    Vitis vinifera cv Falanghina is an ancient grape variety of Southern Italy. A thorough phytochemical analysis of the Falanghina leaves was conducted to investigate its specialised metabolite content. Along with already known molecules, such as caftaric acid, quercetin-3-O-β-d-glucopyranoside, quercetin-3-O-β-d-glucuronide, kaempferol-3-O-β-d-glucopyranoside and kaempferol-3-O-β-d-glucuronide, a previously undescribed biflavonoid was identified. For this last compound, a moderate bioactivity against metastatic melanoma cells proliferation was discovered. This datum can be of some interest to researchers studying human melanoma. The high content in antioxidant glycosylated flavonoids supports the exploitation of grape vine leaves as an inexpensive source of natural products for the food industry and for both pharmaceutical and nutraceutical companies. Additionally, this study offers important insights into the plant physiology, thus prompting possible technological researches of genetic selection based on the vine adaptation to specific pedo-climatic environments. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Social Media Interventions to Promote HIV Testing, Linkage, Adherence, and Retention: Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Cao, Bolin; Gupta, Somya; Wang, Jiangtao; Hightow-Weidman, Lisa B; Muessig, Kathryn E; Tang, Weiming; Pan, Stephen; Pendse, Razia; Tucker, Joseph D

    2017-11-24

    Social media is increasingly used to deliver HIV interventions for key populations worldwide. However, little is known about the specific uses and effects of social media on human immunodeficiency virus (HIV) interventions. This systematic review examines the effectiveness of social media interventions to promote HIV testing, linkage, adherence, and retention among key populations. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and Cochrane guidelines for this review and registered it on the International Prospective Register of Systematic Reviews, PROSPERO. We systematically searched six databases and three conference websites using search terms related to HIV, social media, and key populations. We included studies where (1) the intervention was created or implemented on social media platforms, (2) study population included men who have sex with men (MSM), transgender individuals, people who inject drugs (PWID), and/or sex workers, and (3) outcomes included promoting HIV testing, linkage, adherence, and/or retention. Meta-analyses were conducted by Review Manager, version 5.3. Pooled relative risk (RR) and 95% confidence intervals were calculated by random-effects models. Among 981 manuscripts identified, 26 studies met the inclusion criteria. We found 18 studies from high-income countries, 8 in middle-income countries, and 0 in low-income countries. Eight were randomized controlled trials, and 18 were observational studies. All studies (n=26) included MSM; five studies also included transgender individuals. The focus of 21 studies was HIV testing, four on HIV testing and linkage to care, and one on antiretroviral therapy adherence. Social media interventions were used to do the following: build online interactive communities to encourage HIV testing/adherence (10 studies), provide HIV testing services (9 studies), disseminate HIV information (9 studies), and develop intervention materials (1 study). Of the

  15. Social Media Interventions to Promote HIV Testing, Linkage, Adherence, and Retention: Systematic Review and Meta-Analysis

    Science.gov (United States)

    Gupta, Somya; Wang, Jiangtao; Hightow-Weidman, Lisa B; Muessig, Kathryn E; Tang, Weiming; Pan, Stephen; Pendse, Razia; Tucker, Joseph D

    2017-01-01

    Background Social media is increasingly used to deliver HIV interventions for key populations worldwide. However, little is known about the specific uses and effects of social media on human immunodeficiency virus (HIV) interventions. Objective This systematic review examines the effectiveness of social media interventions to promote HIV testing, linkage, adherence, and retention among key populations. Methods We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and Cochrane guidelines for this review and registered it on the International Prospective Register of Systematic Reviews, PROSPERO. We systematically searched six databases and three conference websites using search terms related to HIV, social media, and key populations. We included studies where (1) the intervention was created or implemented on social media platforms, (2) study population included men who have sex with men (MSM), transgender individuals, people who inject drugs (PWID), and/or sex workers, and (3) outcomes included promoting HIV testing, linkage, adherence, and/or retention. Meta-analyses were conducted by Review Manager, version 5.3. Pooled relative risk (RR) and 95% confidence intervals were calculated by random-effects models. Results Among 981 manuscripts identified, 26 studies met the inclusion criteria. We found 18 studies from high-income countries, 8 in middle-income countries, and 0 in low-income countries. Eight were randomized controlled trials, and 18 were observational studies. All studies (n=26) included MSM; five studies also included transgender individuals. The focus of 21 studies was HIV testing, four on HIV testing and linkage to care, and one on antiretroviral therapy adherence. Social media interventions were used to do the following: build online interactive communities to encourage HIV testing/adherence (10 studies), provide HIV testing services (9 studies), disseminate HIV information (9 studies), and develop

  16. Heterozygosity analysis of polycystic kidney disease 1 gene microsatellite markers for linkage analysis of autosomal dominant polycystic kidney disease type 1 in the iranian population

    Directory of Open Access Journals (Sweden)

    Razieh Fatehi

    2017-01-01

    Full Text Available Background: Autosomal dominant polycystic kidney disease (ADPKD is the most common genetic cause of end-stage renal disease. Although imaging techniques are a means of accurate diagnosis when the cysts appear in the third or fourth decades of the patient's life, they are of little value for early diagnosis. Genetic tests are required for preimplantation genetic diagnosis, decision-making for kidney donation to an affected relative. Although mutation of the polycystic kidney disease (PKD1 gene is solely responsible for the most cases of ADPKD, direct genetic testing is limited by the large size of this gene and the presence of many mutations without hot spots. Therefore, indirect diagnosis with linkage analysis using informative microsatellite markers has been suggested. Materials and Methods: In this study, we assessed the informativeness of the PKD1 gene markers D16S475, D16S291, and D16S3252 in Iranian population. Using specific primers, fluorescent polymerase chain reaction (PCR was performed on genomic DNA extracted from fifty unrelated individuals. PCR products were analyzed by the ALFexpress DNA sequencer system, and the number and frequency of alleles were determined to calculate the heterozygosity (HET and polymorphism information content (PIC values. Results: We found that the HET and PIC values for the D16S475 marker are 0.92 and 0.91, respectively. These two values are 0.82 and 0.80 for D16S291 and 0.50 and 0.47 for D16S3252, respectively. Conclusion: Based on this data, D16S475 and D16S291 are highly and D16S3252 is moderately informative for indirect genetic diagnosis of PKD1 mutations in this population.

  17. Confirmation of protoplast fusion-derived linkages in Staphylococcus aureus by transformation with protoplast DNA.

    Science.gov (United States)

    Stahl, M L; Pattee, P A

    1983-01-01

    Transformation provided definitive evidence for linkage between tyrB282::Tn551 ermB321 and omega (Chr::Tn551)34, and thus between the separate large linkage groups containing these markers, in Staphylococcus aureus NCTC 8325. Transformation also defined the chromosomal loci for the purC193::Tn551 and omega (Chr::Tn551)42 markers and the linkage of a tetracycline resistance marker (tet-3490) with a fusidic acid resistance marker (fus-149). The use of DNA isolated from protoplasts under conditions that reduced hydrodynamic shear greatly facilitated the demonstration of most of these linkages. These results provide direct evidence confirming several of the linkages predicted by a microcomputer-assisted protoplast fusion analysis in a previous study (M. L. Stahl and P. A. Pattee, J. Bacteriol. 154:395-405, 1983); those markers whose predicted linkages were not confirmed by transformation are probably separated by chromosomal distances that exceed the limits of detection by transformation, even with protoplast DNA. PMID:6572625

  18. Effects of Worldwide Population Subdivision on ALDH2 Linkage Disequilibrium

    OpenAIRE

    Peterson, Raymond J.; Goldman, David; Long, Jeffrey C.

    1999-01-01

    The effect of human population subdivision on linkage disequilibrium has previously been studied for unlinked genes. However, no study has focused on closely linked polymorphisms or formally partitioned linkage disequilibrium within and among worldwide populations. With an emphasis on population subdivision, the goal of this paper is to investigate the causes of linkage disequilibrium in ALDH2, the gene that encodes aldehyde dehydrogenase 2. Haplotypes for 756 people from 17 populations acros...

  19. Linkage analysis and comparative mapping of canine progressive rod–cone degeneration (prcd) establishes potential locus homology with retinitis pigmentosa (RP17) in humans

    Science.gov (United States)

    Acland, Gregory M.; Ray, Kunal; Mellersh, Cathryn S.; Gu, Weikuan; Langston, Amelia A.; Rine, Jasper; Ostrander, Elaine A.; Aguirre, Gustavo D.

    1998-01-01

    Progressive rod–cone degeneration (prcd) is the most widespread hereditary retinal disease leading to blindness in dogs and phenotypically is the canine counterpart of retinitis pigmentosa (RP) in humans. In previous efforts to identify the genetic locus for prcd, the canine homologs for many of the genes causally associated with RP in humans, such as RHO, PDE6B, and RDS/peripherin, have been excluded. In parallel with a recent undertaking to establish a framework map of the canine genome, multiple prcd-informative pedigrees have been typed with a panel of more than 100 anchor loci and microsatellite-based markers. Identification of a linkage group flanking prcd ([TK1, GALK1, prcd]–[MYL4, C09.173, C09.2263]–RARA–C09.250–C09.474–NF1) localizes prcd close to the centromeric end of canine chromosome 9 (CFA9), and excludes RARA as a candidate gene. The conserved synteny of this region of CFA9 and distal human chromosome 17q establishes the potential locus homology of prcd in the dog with RP17, a human retinitis pigmentosa locus for which no gene has yet been identified. Assignment of the prcd disease locus to an identified canine autosome represents a powerful application of the developing canine linkage map in medical genetics. The usefulness of this approach is further demonstrated by identification of the correspondence of the prcd interval to homologous human and mouse chromosomal regions. The rapid progress that is now occurring in the field of canine genetics will expedite the identification of the genes underlying many of the inherited traits and diseases that make the dog a unique asset for the study of mammalian traits. PMID:9501213

  20. A possible mechanism behind autoimmune disorders discovered by genome-wide linkage and association analysis in celiac disease.

    Directory of Open Access Journals (Sweden)

    Malin Östensson

    Full Text Available Celiac disease is a common autoimmune disorder characterized by an intestinal inflammation triggered by gluten, a storage protein found in wheat, rye and barley. Similar to other autoimmune diseases such as type 1 diabetes, psoriasis and rheumatoid arthritis, celiac disease is the result of an immune response to self-antigens leading to tissue destruction and production of autoantibodies. Common diseases like celiac disease have a complex pattern of inheritance with inputs from both environmental as well as additive and non-additive genetic factors. In the past few years, Genome Wide Association Studies (GWAS have been successful in finding genetic risk variants behind many common diseases and traits. To complement and add to the previous findings, we performed a GWAS including 206 trios from 97 nuclear Swedish and Norwegian families affected with celiac disease. By stratifying for HLA-DQ, we identified a new genome-wide significant risk locus covering the DUSP10 gene. To further investigate the associations from the GWAS we performed pathway analyses and two-locus interaction analyses. These analyses showed an over-representation of genes involved in type 2 diabetes and identified a set of candidate mechanisms and genes of which some were selected for mRNA expression analysis using small intestinal biopsies from 98 patients. Several genes were expressed differently in the small intestinal mucosa from patients with celiac autoimmunity compared to intestinal mucosa from control patients. From top-scoring regions we identified susceptibility genes in several categories: 1 polarity and epithelial cell functionality; 2 intestinal smooth muscle; 3 growth and energy homeostasis, including proline and glutamine metabolism; and finally 4 innate and adaptive immune system. These genes and pathways, including specific functions of DUSP10, together reveal a new potential biological mechanism that could influence the genesis of celiac disease, and possibly

  1. Thermally actuated linkage arrangement

    International Nuclear Information System (INIS)

    Anderson, P.M.

    1981-01-01

    A reusable thermally actuated linkage arrangement includes a first link member having a longitudinal bore therein adapted to receive at least a portion of a second link member therein, the first and second members being sized to effect an interference fit preventing relative movement there-between at a temperature below a predetermined temperature. The link members have different coefficients of thermal expansion so that when the linkage is selectively heated by heating element to a temperature above the predetermined temperature, relative longitudinal and/or rotational movement between the first and second link members is enabled. Two embodiments of a thermally activated linkage are disclosed which find particular application in actuators for a grapple head positioning arm in a nuclear reactor fuel handling mechanism to facilitate back-up safety retraction of the grapple head independently from the primary fuel handling mechanism drive system. (author)

  2. 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.

  3. Genomewide linkage scan for diabetic renal failure and albuminuria: the FIND study.

    Science.gov (United States)

    Igo, Robert P; Iyengar, Sudha K; Nicholas, Susanne B; Goddard, Katrina A B; Langefeld, Carl D; Hanson, Robert L; Duggirala, Ravindranath; Divers, Jasmin; Abboud, Hanna; Adler, Sharon G; Arar, Nedal H; Horvath, Amanda; Elston, Robert C; Bowden, Donald W; Guo, Xiuqing; Ipp, Eli; Kao, W H Linda; Kimmel, Paul L; Knowler, William C; Meoni, Lucy A; Molineros, Julio; Nelson, Robert G; Pahl, Madeline V; Parekh, Rulan S; Rasooly, Rebekah S; Schelling, Jeffrey R; Shah, Vallabh O; Smith, Michael W; Winkler, Cheryl A; Zager, Philip G; Sedor, John R; Freedman, Barry I

    2011-01-01

    Diabetic nephropathy (DN) is a leading cause of mortality and morbidity in patients with type 1 and type 2 diabetes. The multicenter FIND consortium aims to identify genes for DN and its associated quantitative traits, e.g. the urine albumin:creatinine ratio (ACR). Herein, the results of whole-genome linkage analysis and a sparse association scan for ACR and a dichotomous DN phenotype are reported in diabetic individuals. A genomewide scan comprising more than 5,500 autosomal single nucleotide polymorphism markers (average spacing of 0.6 cM) was performed on 1,235 nuclear and extended pedigrees (3,972 diabetic participants) ascertained for DN from African-American (AA), American-Indian (AI), European-American (EA) and Mexican-American (MA) populations. Strong evidence for linkage to DN was detected on chromosome 6p (p = 8.0 × 10(-5), LOD = 3.09) in EA families as well as suggestive evidence for linkage to chromosome 7p in AI families. Regions on chromosomes 3p in AA, 7q in EA, 16q in AA and 22q in MA displayed suggestive evidence of linkage for urine ACR. The linkage peak on chromosome 22q overlaps the MYH9/APOL1 gene region, previously implicated in AA diabetic and nondiabetic nephropathies. These results strengthen the evidence for previously identified genomic regions and implicate several novel loci potentially involved in the pathogenesis of DN. Copyright © 2011 S. Karger AG, Basel.

  4. Analysis of 60 706 Exomes Questions the Role of De Novo Variants Previously Implicated in Cardiac Disease

    DEFF Research Database (Denmark)

    Paludan-Müller, Christian; Ahlberg, Gustav; Ghouse, Jonas

    2017-01-01

    sought to evaluate the pathogenicity of de novo variants previously associated with cardiac disease based on a large population-representative exome database. METHODS AND RESULTS: We performed a literature search for previous publications on de novo variants associated with severe arrhythmias...... and structural heart diseases and investigated whether these variants were present in the Exome Aggregation Consortium (ExAC) database (n=60 706). We identified monogenic variants in single case reports and smaller studies (≤200 subjects) and variants considered to increase susceptibility of disease in 3 larger...

  5. Analysis of over 10,000 Cases finds no association between previously reported candidate polymorphisms and ovarian cancer outcome

    DEFF Research Database (Denmark)

    White, Kristin L; Vierkant, Robert A; Fogarty, Zachary C

    2013-01-01

    Ovarian cancer is a leading cause of cancer-related death among women. In an effort to understand contributors to disease outcome, we evaluated single-nucleotide polymorphisms (SNP) previously associated with ovarian cancer recurrence or survival, specifically in angiogenesis, inflammation, mitosis...

  6. The relationship between emotional intelligence, previous caring experience and mindfulness in student nurses and midwives: a cross sectional analysis.

    Science.gov (United States)

    Snowden, Austyn; Stenhouse, Rosie; Young, Jenny; Carver, Hannah; Carver, Fiona; Brown, Norrie

    2015-01-01

    Emotional Intelligence (EI), previous caring experience and mindfulness training may have a positive impact on nurse education. More evidence is needed to support the use of these variables in nurse recruitment and retention. To explore the relationship between EI, gender, age, programme of study, previous caring experience and mindfulness training. Cross sectional element of longitudinal study. 938year one nursing, midwifery and computing students at two Scottish Higher Education Institutes (HEIs) who entered their programme in September 2013. Participants completed a measure of 'trait' EI: Trait Emotional Intelligence Questionnaire Short Form (TEIQue-SF); and 'ability' EI: Schutte's et al. (1998) Emotional Intelligence Scale (SEIS). Demographics, previous caring experience and previous training in mindfulness were recorded. Relationships between variables were tested using non-parametric tests. Emotional intelligence increased with age on both measures of EI [TEIQ-SF H(5)=15.157 p=0.001; SEIS H(5)=11.388, p=0.044]. Females (n=786) scored higher than males (n=149) on both measures [TEIQ-SF, U=44,931, z=-4.509, pintelligence. Mindfulness training was associated with higher 'ability' emotional intelligence. Implications for recruitment, retention and further research are explored. Copyright © 2014. Published by Elsevier Ltd.

  7. Change detection using Landsat images and an analysis of the linkages between the change and property tax values in the Istanbul Province of Turkey.

    Science.gov (United States)

    Canaz, Sibel; Aliefendioğlu, Yeşim; Tanrıvermiş, Harun

    2017-09-15

    In this study, the Istanbul Province was monitored using Landsat 5 TM, MSS, Landsat 7 ETM+, and Landsat 8 OLI imagery from the years 1986, 2000, 2009, 2011, 2013, and 2015 in order to assess land cover changes in the province. The aim of the study was to classify manmade structures, land, green, and water areas, and to observe the changes in the province using satellite images. After classification, the images were compared in selected years to observe land cover. Moreover, these changes were correlated with the property tax values of Istanbul by years. The findings of the study showed that manmade structure areas increased while vegetation areas decreased due to rapid population growth, urbanization, and industrial and commercial development in Istanbul. These changes also explain the transformation of land from rural and natural areas to residential use, and serve as a tool with which to assess land value increments. Land value capturing is critical for the analysis of the linkages between the changes in land cover, and for assessing land transformation and urban growth. Due to inadequate market data, real estate tax values were used to analyze the linkages between detection changes, land cover, and taxation. In fact, the declared tax values of land owners are generally lower than the actual market values and therefore it is not possible to transfer the value increasing of land in urban areas by using property taxation from the owner to local and central governments. The research results also show that the integration of remote sensing results with real estate market data give us to determine the tax base values of real estate more realistically. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Genetic linkage analysis supports the presence of two susceptibility loci for alcoholism and heavy drinking on chromosome 1p22.1-11.2 and 1q21.3-24.2

    Directory of Open Access Journals (Sweden)

    Curtis David

    2005-03-01

    Full Text Available Abstract Background In order to confirm a previous finding of linkage to alcoholism on chromosome 1 we have carried out a genetic linkage study. Methods DNA from eighteen families, densely affected by alcoholism, was used to genotype a set of polymorphic microsatellite markers at loci approximately 10 centimorgans apart spanning the short arm and part of the long arm of chromosome 1. Linkage analyses were performed using the classical lod score and a model-free method. Three different definitions of affection status were defined, these were 1. Heavy Drinking (HD where affected subjects drank more than the Royal College of Psychiatrists recommended weekly amount. 2. The Research Diagnostic Criteria for alcoholism (RDCA 3. Alcohol Dependence Syndrome (ADS as defined by Edwards and Gross (1976 and now incorporated into ICD10 and DSMIV. Results Linkage analyses with the markers D1S1588, D1S2134, D1S1675 covering the cytogenetic region 1p22.1-11.2 all gave positive two point and multipoint lods with a maximum lod of 1.8 at D1S1588 (1p22.1 for the RDCA definition of alcoholism. Another lod of 1.8 was found with D1S1653 in the region 1q21.3-24.2 using the HD affection model. Conclusion These results both support the presence of linkage in the 1p22.1-11.2 region which was previously implicated by the USA Collaborative Study of the Genetics of Alcoholism (COGA study and also suggest the presence of another susceptibility locus at 1q21.3-24.2.

  9. At what price? A cost-effectiveness analysis comparing trial of labour after previous Caesarean versus elective repeat Caesarean delivery.

    LENUS (Irish Health Repository)

    Fawsitt, Christopher G

    2013-01-01

    Elective repeat caesarean delivery (ERCD) rates have been increasing worldwide, thus prompting obstetric discourse on the risks and benefits for the mother and infant. Yet, these increasing rates also have major economic implications for the health care system. Given the dearth of information on the cost-effectiveness related to mode of delivery, the aim of this paper was to perform an economic evaluation on the costs and short-term maternal health consequences associated with a trial of labour after one previous caesarean delivery compared with ERCD for low risk women in Ireland.

  10. 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......: wst5 (white streaks), necl (necrotic leaf spots), Ml-nn (powdery mildew resistance), and Pa4 (leaf rust resistance). Further, the two sections of the map are united, and the precision of the map is improved. A system for designating the positions of the loci on the linkage map is proposed. A 0......-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...

  11. Analysis of Over 10,000 Cases Finds No Association between Previously-Reported Candidate Polymorphisms and Ovarian Cancer Outcome

    Science.gov (United States)

    White, Kristin L.; Vierkant, Robert A.; Fogarty, Zachary C.; Charbonneau, Bridget; Block, Matthew S.; Pharoah, Paul D.P.; Chenevix-Trench, Georgia; Rossing, Mary Anne; Cramer, Daniel W.; Pearce, C. Leigh; Schildkraut, Joellen M.; Menon, Usha; Kjaer, Susanne Kruger; Levine, Douglas A.; Gronwald, Jacek; Culver, Hoda Anton; Whittemore, Alice S.; Karlan, Beth Y.; Lambrechts, Diether; Wentzensen, Nicolas; Kupryjanczyk, Jolanta; Chang-Claude, Jenny; Bandera, Elisa V.; Hogdall, Estrid; Heitz, Florian; Kaye, Stanley B.; Fasching, Peter A.; Campbell, Ian; Goodman, Marc T.; Pejovic, Tanja; Bean, Yukie; Lurie, Galina; Eccles, Diana; Hein, Alexander; Beckmann, Matthias W.; Ekici, Arif B.; Paul, James; Brown, Robert; Flanagan, James; Harter, Philipp; du Bois, Andreas; Schwaab, Ira; Hogdall, Claus K.; Lundvall, Lene; Olson, Sara H.; Orlow, Irene; Paddock, Lisa E.; Rudolph, Anja; Eilber, Ursula; Dansonka-Mieszkowska, Agnieszka; Rzepecka, Iwona K.; Ziolkowska-Seta, Izabela; Brinton, Louise; Yang, Hannah; Garcia-Closas, Montserrat; Despierre, Evelyn; Lambrechts, Sandrina; Vergote, Ignace; Walsh, Christine; Lester, Jenny; Sieh, Weiva; McGuire, Valerie; Rothstein, Joseph H.; Ziogas, Argyrios; Lubiński, Jan; Cybulski, Cezary; Menkiszak, Janusz; Jensen, Allan; Gayther, Simon A.; Ramus, Susan J.; Gentry-Maharaj, Aleksandra; Berchuck, Andrew; Wu, Anna H.; Pike, Malcolm C.; Van Den Berg, David; Terry, Kathryn L.; Vitonis, Allison F.; Doherty, Jennifer A.; Johnatty, Sharon; deFazio, Anna; Song, Honglin; Tyrer, Jonathan; Sellers, Thomas A.; Phelan, Catherine M.; Kalli, Kimberly R.; Cunningham, Julie M.; Fridley, Brooke L.; Goode, Ellen L.

    2013-01-01

    Background Ovarian cancer is a leading cause of cancer-related death among women. In an effort to understand contributors to disease outcome, we evaluated single-nucleotide polymorphisms (SNPs) previously associated with ovarian cancer recurrence or survival, specifically in angiogenesis, inflammation, mitosis, and drug disposition genes. Methods Twenty-seven SNPs in VHL, HGF, IL18, PRKACB, ABCB1, CYP2C8, ERCC2, and ERCC1 previously associated with ovarian cancer outcome were genotyped in 10,084 invasive cases from 28 studies from the Ovarian Cancer Association Consortium with over 37,000 observed person-years and 4,478 deaths. Cox proportional hazards models were used to examine the association between candidate SNPs and ovarian cancer recurrence or survival with and without adjustment for key covariates. Results We observed no association between genotype and ovarian cancer recurrence or survival for any of the SNPs examined. Conclusions These results refute prior associations between these SNPs and ovarian cancer outcome and underscore the importance of maximally powered genetic association studies. Impact These variants should not be used in prognostic models. Alternate approaches to uncovering inherited prognostic factors, if they exist, are needed. PMID:23513043

  12. Analysis of over 10,000 Cases finds no association between previously reported candidate polymorphisms and ovarian cancer outcome.

    Science.gov (United States)

    White, Kristin L; Vierkant, Robert A; Fogarty, Zachary C; Charbonneau, Bridget; Block, Matthew S; Pharoah, Paul D P; Chenevix-Trench, Georgia; Rossing, Mary Anne; Cramer, Daniel W; Pearce, Celeste Leigh; Schildkraut, Joellen M; Menon, Usha; Kjaer, Susanne Kruger; Levine, Douglas A; Gronwald, Jacek; Culver, Hoda Anton; Whittemore, Alice S; Karlan, Beth Y; Lambrechts, Diether; Wentzensen, Nicolas; Kupryjanczyk, Jolanta; Chang-Claude, Jenny; Bandera, Elisa V; Hogdall, Estrid; Heitz, Florian; Kaye, Stanley B; Fasching, Peter A; Campbell, Ian; Goodman, Marc T; Pejovic, Tanja; Bean, Yukie; Lurie, Galina; Eccles, Diana; Hein, Alexander; Beckmann, Matthias W; Ekici, Arif B; Paul, James; Brown, Robert; Flanagan, James M; Harter, Philipp; du Bois, Andreas; Schwaab, Ira; Hogdall, Claus K; Lundvall, Lene; Olson, Sara H; Orlow, Irene; Paddock, Lisa E; Rudolph, Anja; Eilber, Ursula; Dansonka-Mieszkowska, Agnieszka; Rzepecka, Iwona K; Ziolkowska-Seta, Izabela; Brinton, Louise; Yang, Hannah; Garcia-Closas, Montserrat; Despierre, Evelyn; Lambrechts, Sandrina; Vergote, Ignace; Walsh, Christine; Lester, Jenny; Sieh, Weiva; McGuire, Valerie; Rothstein, Joseph H; Ziogas, Argyrios; Lubinski, Jan; Cybulski, Cezary; Menkiszak, Janusz; Jensen, Allan; Gayther, Simon A; Ramus, Susan J; Gentry-Maharaj, Aleksandra; Berchuck, Andrew; Wu, Anna H; Pike, Malcolm C; Van Denberg, David; Terry, Kathryn L; Vitonis, Allison F; Doherty, Jennifer A; Johnatty, Sharon E; Defazio, Anna; Song, Honglin; Tyrer, Jonathan; Sellers, Thomas A; Phelan, Catherine M; Kalli, Kimberly R; Cunningham, Julie M; Fridley, Brooke L; Goode, Ellen L

    2013-05-01

    Ovarian cancer is a leading cause of cancer-related death among women. In an effort to understand contributors to disease outcome, we evaluated single-nucleotide polymorphisms (SNP) previously associated with ovarian cancer recurrence or survival, specifically in angiogenesis, inflammation, mitosis, and drug disposition genes. Twenty-seven SNPs in VHL, HGF, IL18, PRKACB, ABCB1, CYP2C8, ERCC2, and ERCC1 previously associated with ovarian cancer outcome were genotyped in 10,084 invasive cases from 28 studies from the Ovarian Cancer Association Consortium with over 37,000-observed person-years and 4,478 deaths. Cox proportional hazards models were used to examine the association between candidate SNPs and ovarian cancer recurrence or survival with and without adjustment for key covariates. We observed no association between genotype and ovarian cancer recurrence or survival for any of the SNPs examined. These results refute prior associations between these SNPs and ovarian cancer outcome and underscore the importance of maximally powered genetic association studies. These variants should not be used in prognostic models. Alternate approaches to uncovering inherited prognostic factors, if they exist, are needed.

  13. 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.

  14. Empirical characteristics of family-based linkage to a complex trait: the ADIPOQ region and adiponectin levels.

    Science.gov (United States)

    Hellwege, Jacklyn N; Palmer, Nicholette D; Mark Brown, W; Brown, Mark W; Ziegler, Julie T; Sandy An, S; An, Sandy S; Guo, Xiuqing; Ida Chen, Y-D; Chen, Ida Y-D; Taylor, Kent; Hawkins, Gregory A; Ng, Maggie C Y; Speliotes, Elizabeth K; Lorenzo, Carlos; Norris, Jill M; Rotter, Jerome I; Wagenknecht, Lynne E; Langefeld, Carl D; Bowden, Donald W

    2015-02-01

    We previously identified a low-frequency (1.1 %) coding variant (G45R; rs200573126) in the adiponectin gene (ADIPOQ) which was the basis for a multipoint microsatellite linkage signal (LOD = 8.2) for plasma adiponectin levels in Hispanic families. We have empirically evaluated the ability of data from targeted common variants, exome chip genotyping, and genome-wide association study data to detect linkage and association to adiponectin protein levels at this locus. Simple two-point linkage and association analyses were performed in 88 Hispanic families (1,150 individuals) using 10,958 SNPs on chromosome 3. Approaches were compared for their ability to map the functional variant, G45R, which was strongly linked (two-point LOD = 20.98) and powerfully associated (p value = 8.1 × 10(-50)). Over 450 SNPs within a broad 61 Mb interval around rs200573126 showed nominal evidence of linkage (LOD > 3) but only four other SNPs in this region were associated with p values family-based linkage analysis using a moderately dense SNP dataset, including both common and low-frequency variants, resulted in stronger evidence for an adiponectin locus than association data alone. Thus, linkage analysis can be a useful tool to facilitate identification of high-impact genetic variants.

  15. [Use of coronary angioplasty in acute myocardial infarction without previous use of thrombolytic agents. Analysis of 201 patients].

    Science.gov (United States)

    Mattos, L A; Cano, M N; Maldonado, G; Feres, F; Pinto, I M; Tanajura, L F; Piegas, L S; Barbosa, M; Timerman, A; Paulista, P P

    1990-11-01

    To evaluate the experience with the use of primary PTCA in the set of acute myocardial infarction (AMI) without the previous administration of thrombolytic agents. Two hundred and one patients with AMI, aged 35 to 86 years (mean = 57.2). There were 83.5% men. Twenty patients were older than 70 years and 48.2% had an anterior AMI. PTCA was performed early in the AMI, with a delay no longer than 12 hours. In 95%, it was done solely to the infarct related artery. Seventy percent patients were in Killip class I, 21% in class II, and 8% in classes III and IV (more than 50% of this subset of patients were in cardiogenic shock). Primary success was achieved in 84.5%. In hospital mortality was 5.9%, and there were 7% reinfarctions. Among the 84 patients who underwent a late cinecoronariography study, there were 19% restenosis and 8.3% reocclusions. In the long term follow up 75% were asymptomatic. Repeat PTCA was required in 10.2% of the cases, late coronary surgery was performed on 10.8% of the patients, and post-hospital cardiac mortality was 8.8% during an average follow up of 28 months (range 2-72 months). Primary PTCA is a effective way of reperfusion in the AMI, with a high primary success, low complications rate and without any major contraindications.

  16. 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

    adulthood, asthma is frequently associated also with quantitative measures of atopy. Genome wide quantitative multipoint linkage analysis was conducted for serum IgE levels and percentage of positive skin prick test (SPT(per)) using three large groups of families originally ascertained for asthma....... In this report, 438 and 429 asthma families were informative for linkage using IgE and SPT(per) which represents 690 independent families. Suggestive linkage (LOD >/= 2) was found on chromosomes 1, 3, and 8q with maximum LODs of 2.34 (IgE), 2.03 (SPT(per)), and 2.25 (IgE) near markers D1S1653, D3S2322-D3S1764......, and D8S2324, respectively. The results from chromosomes 1 and 3 replicate previous reports of linkage. We also replicate linkage to 5q with peak LODs of 1.96 (SPT(per)) and 1.77 (IgE) at or near marker D5S1480. Our results provide further evidence implicating chromosomes 1, 3, and 5q. The current report...

  17. PKD2 mutation in an Iranian autosomal dominant polycystic kidney disease family with misleading linkage analysis data

    Directory of Open Access Journals (Sweden)

    Mona Entezam

    2016-06-01

    Conclusion: Although analysis of additive informative polymorphic markers can overcome the misleading haplotype data, it is limited because of the lack of other highly polymorphic microsatellite markers closer to the gene. Direct mutation screening can identify the causative mutation in the apparently unlinked pedigree; moreover, it is the only approach to achieve the confirmed diagnosis in individuals with equivocal imaging results.

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

    DEFF Research Database (Denmark)

    Inskeep, William P; Jay, Zackary J; Herrgard, Markus

    2013-01-01

    /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...

  19. Transcriptomic analysis in a Drosophila model identifies previously implicated and novel pathways in the therapeutic mechanism in neuropsychiatric disorders

    Directory of Open Access Journals (Sweden)

    Priyanka eSingh

    2011-03-01

    Full Text Available We have taken advantage of a newly described Drosophila model to gain insights into the potential mechanism of antiepileptic drugs (AEDs, a group of drugs that are widely used in the treatment of several neurological and psychiatric conditions besides epilepsy. In the recently described Drosophila model that is inspired by pentylenetetrazole (PTZ induced kindling epileptogenesis in rodents, chronic PTZ treatment for seven days causes a decreased climbing speed and an altered CNS transcriptome, with the latter mimicking gene expression alterations reported in epileptogenesis. In the model, an increased climbing speed is further observed seven days after withdrawal from chronic PTZ. We used this post-PTZ withdrawal regime to identify potential AED mechanism. In this regime, treatment with each of the five AEDs tested, namely, ethosuximide (ETH, gabapentin (GBP, vigabatrin (VGB, sodium valproate (NaVP and levetiracetam (LEV, resulted in rescuing of the altered climbing behavior. The AEDs also normalized PTZ withdrawal induced transcriptomic perturbation in fly heads; whereas AED untreated flies showed a large number of up- and down-regulated genes which were enriched in several processes including gene expression and cell communication, the AED treated flies showed differential expression of only a small number of genes that did not enrich gene expression and cell communication processes. Gene expression and cell communication related upregulated genes in AED untreated flies overrepresented several pathways - spliceosome, RNA degradation, and ribosome in the former category, and inositol phosphate metabolism, phosphatidylinositol signaling, endocytosis and hedgehog signaling in the latter. Transcriptome remodeling effect of AEDs was overall confirmed by microarray clustering that clearly separated the profiles of AED treated and untreated flies. Besides being consistent with previously implicated pathways, our results provide evidence for a role of

  20. Analysis of guest binary mixtures by tert-butylcalix[6]arene using host memory of previously bound guests.

    Science.gov (United States)

    Safina, Goulnaz D; Ziganshin, Marat A; Gubaidullin, Aidar T; Gorbatchuk, Valery V

    2013-02-28

    A new principle of quantitative and qualitative analysis of binary organic mixtures is offered, which is based on an ability of calixarene receptor for specific polymorphic transitions related to the composition of the analyzed guest mixture. The ability of tert-butylcalix[6]arene to remember selectively some guests bound from headspace both of pure liquids and their binary mixtures is used. The image of guest mixture remains written in metastable polymorphs of host after partial or complete guest elimination from clathrates. The memory was read using differential scanning calorimetry as the enthalpy of exothermic polymorphic transition of host collapse. This enthalpy monotonously changes with the variation of guests' ratio in mixture, unlike the enthalpies of endothermic pseudopolymorphic transitions of guest release. So, the composition of volatile binary mixture can be estimated using only one receptor and only one its parameter even in absence of preferential binding from a binary mixture of guests. This is an example of a genuine molecular recognition.

  1. Identification of Linkages between EDCs in Personal Care Products and Breast Cancer through Data Integration Combined with Gene Network Analysis.

    Science.gov (United States)

    Jeong, Hyeri; Kim, Jongwoon; Kim, Youngjun

    2017-09-30

    Approximately 1000 chemicals have been reported to possibly have endocrine disrupting effects, some of which are used in consumer products, such as personal care products (PCPs) and cosmetics. We conducted data integration combined with gene network analysis to: (i) identify causal molecular mechanisms between endocrine disrupting chemicals (EDCs) used in PCPs and breast cancer; and (ii) screen candidate EDCs associated with breast cancer. Among EDCs used in PCPs, four EDCs having correlation with breast cancer were selected, and we curated 27 common interacting genes between those EDCs and breast cancer to perform the gene network analysis. Based on the gene network analysis, ESR1, TP53, NCOA1, AKT1, and BCL6 were found to be key genes to demonstrate the molecular mechanisms of EDCs in the development of breast cancer. Using GeneMANIA, we additionally predicted 20 genes which could interact with the 27 common genes. In total, 47 genes combining the common and predicted genes were functionally grouped with the gene ontology and KEGG pathway terms. With those genes, we finally screened candidate EDCs for their potential to increase breast cancer risk. This study highlights that our approach can provide insights to understand mechanisms of breast cancer and identify potential EDCs which are in association with breast cancer.

  2. 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.

  3. Expression, SNV identification, linkage disequilibrium, and combined genotype association analysis of the muscle-specific gene CSRP3 in Chinese cattle.

    Science.gov (United States)

    He, Hua; Zhang, Hui-Lin; Li, Zhi-Xiong; Liu, Yu; Liu, Xiao-Lin

    2014-02-01

    The cysteine and glycine-rich protein 3 (CSRP3) plays an important role in the myofiber differentiation. Here, we identified five SNVs in all exon and intron regions of the CSRP3 gene using DNA sequencing, PCR-RFLP and forced-PCR-RFLP methods in 554 cattle. Four of the five SNVs were significantly associated with growth performance and carcass traits of the cattle. In addition, we evaluated haplotype frequency and linkage disequilibrium coefficient of five sequence variants. The result of haplotype analysis demonstrated 28 haplotypes present in Qinchuan and two haplotypes in Chinese Holstein. Only haplotypes 1 and 8 were being shared by two populations, haplotype 14 had the highest haplotype frequency in Qinchuan (17.4%) and haplotype 8 had the highest haplotype frequency in Chinese Holstein (94.4%). Statistical analyses of combined genotypes indicated that some combined genotypes were significantly or highly significantly associated with growth and carcass traits in the Qinchuan cattle population. qPCR analyses also showed that bovine CSRP3 gene was exclusively expressed in longissimus dorsi muscle and heart tissues. The data support the high potential of the CSRP3 as a marker gene for the improvement of growth performance and carcass traits in selection programs. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. 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.

  5. 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.

  6. 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.

  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. Analysis of linkage effects among industry sectors in China's stock market before and after the financial crisis

    Science.gov (United States)

    Yang, Rui; Li, Xiangyang; Zhang, Tong

    2014-10-01

    This paper uses two physics-derived techniques, the minimum spanning tree and the hierarchical tree, to investigate the networks formed by CITIC (China International Trust and Investment Corporation) industry indices in three periods from 2006 to 2013. The study demonstrates that obvious industry clustering effects exist in the networks, and Durable Consumer Goods, Industrial Products, Information Technology, Frequently Consumption and Financial Industry are the core nodes in the networks. We also use the rolling window technique to investigate the dynamic evolution of the networks' stability, by calculating the mean correlations and mean distances, as well as the variance of correlations and the distances of these indices. China's stock market is still immature and subject to administrative interventions. Therefore, through this analysis, regulators can focus on monitoring the core nodes to ensure the overall stability of the entire market, while investors can enhance their portfolio allocations or investment decision-making.

  9. 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...

  10. Social network analysis of multi-level linkages: a Swedish case study on Northern Forest-Based sectors.

    Science.gov (United States)

    Keskitalo, E Carina H; Baird, Julia; Laszlo Ambjörnsson, Emmeline; Plummer, Ryan

    2014-10-01

    Forest use in Northern Sweden is being influenced both by global trends and local situations. This results in interactions between numerous groups that may impact local forest governance. Social network analysis can here provide insight into the total pattern of positive, negative, and cross-level interactions within user group community structure (within and among groups). This study analyses interactions within selected renewable resource sectors in two northern Swedish municipalities, both with regard to whether they are positive, neutral, or negative, as well as with regard to how local actors relate to actors across levels, e.g., with regional, national, and international actors. The study illustrates that many interactions both within and outside a given sector are seen as neutral or positive, and that considerable interaction and impact are defined as national and in some cases even international. It also indicates that the impact of Sweden's only existing Model Forest may to some extent constitute a bridge between different sectors and levels, in comparison with the interactions between sectors in a municipality where such a cooperation mechanism does not exist.

  11. 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

  12. Analysis by the reductive-cleavage method of linkage positions in a polysaccharide containing 4-linked D-glucopyranosyluronic residues.

    Science.gov (United States)

    Vodonik, S A; Gray, G R

    1988-04-01

    The fate of 4-linked D-glucopyranosyluronic residues under reductive-cleavage conditions was investigated by using the Klebsiella aerogenes type 54 strain A3 capsular polysaccharide. Treatment of the fully methylated polysaccharide with triethylsilane and trimethylsilyl trifluoromethanesulfonate in dichloromethane, followed by in situ acetylation, yielded 1,5-anhydro-2,3,4,6-tetra-O-methyl-D-glucitol, 3,4-di-O-acetyl-1,5-anhydro-2,6-di-O-methyl-D-glucitol, and 3-O-acetyl-1,5-anhydro-2,4-di-O-methyl-L-fucitol, as expected, but the expected product of reductive cleavage of the 4-linked D-glucopyranosyluronic residue, namely, methyl 3-O-acetyl-2,6-anhydro-4,5-di-O-methyl-L-gulonate, was not observed. Instead, methyl 2-O-acetyl-3,6-anhydro-4,5-di-O-methyl-L-gulonate (6) was identified as the sole product of reductive cleavage of the 4-linked D-glucopyranosyluronic residue. That compound 6 arose as a result of rearrangement during reductive cleavage rather than by reductive cleavage of a 5-linked D-glucofuranosyluronic residue, was established by reductive cleavage of the fully methylated polysaccharide following reduction of its ester groups with either lithium aluminum hydride or lithium aluminum deuteride. The products of the latter reductive cleavage were the same as before, except for the absence of 6 and the presence of 4,6-di-O-acetyl-1,5-anhydro-2,3-di-O-methyl-D-glucitol, or its 6,6-dideuterio isomer. Although the reductive-cleavage technique is suitable for the direct analysis of polysaccharides containing 4-linked D-glucopyranosyluronic residues, it does not establish whether the uronic residue is a 4-linked pyranoside or a 5-linked furanoside. The expected product is, however, derived from the 4-linked D-glucopyranosyluronic residue after sequential methylation, reduction of its ester group and reductive cleavage.

  13. Design of special planar linkages

    CERN Document Server

    Zhao, Jing-Shan; Ma, Ning; Chu, Fulei

    2013-01-01

    Planar linkages play a very important role in mechanical engineering. As the simplest closed chain mechanisms, planar four-bar linkages are widely used in mechanical engineering, civil engineering and aerospace engineering.Design of Special Planar Linkages proposes a uniform design theory for planar four-bar linkages. The merit of the method proposed in this book is that it allows engineers to directly obtain accurate results when there are such solutions for the specified n precise positions; otherwise, the best approximate solutions will be found. This book discusses the kinematics and reach

  14. Biological process linkage networks.

    Directory of Open Access Journals (Sweden)

    Dikla Dotan-Cohen

    Full Text Available The traditional approach to studying complex biological networks is based on the identification of interactions between internal components of signaling or metabolic pathways. By comparison, little is known about interactions between higher order biological systems, such as biological pathways and processes. We propose a methodology for gleaning patterns of interactions between biological processes by analyzing protein-protein interactions, transcriptional co-expression and genetic interactions. At the heart of the methodology are the concept of Linked Processes and the resultant network of biological processes, the Process Linkage Network (PLN.We construct, catalogue, and analyze different types of PLNs derived from different data sources and different species. When applied to the Gene Ontology, many of the resulting links connect processes that are distant from each other in the hierarchy, even though the connection makes eminent sense biologically. Some others, however, carry an element of surprise and may reflect mechanisms that are unique to the organism under investigation. In this aspect our method complements the link structure between processes inherent in the Gene Ontology, which by its very nature is species-independent. As a practical application of the linkage of processes we demonstrate that it can be effectively used in protein function prediction, having the power to increase both the coverage and the accuracy of predictions, when carefully integrated into prediction methods.Our approach constitutes a promising new direction towards understanding the higher levels of organization of the cell as a system which should help current efforts to re-engineer ontologies and improve our ability to predict which proteins are involved in specific biological processes.

  15. Construction of a Genetic Linkage Map and QTL Analysis of Fruit-related Traits in an F1 Red Fuji x Hongrou Apple Hybrid

    Directory of Open Access Journals (Sweden)

    Liu Zunchun

    2016-01-01

    Full Text Available A genetic linkage map of the apple, composed of 175 SSR and 105 SRAP markers, has been constructed using 110 F1 individuals obtained from a cross between the ‘Red Fuji’ Malus domestica and ‘Hongrou’ Malus sieversii cultivars, which have relatively high levels of DNA marker polymorphism and differ remarkably in fruit-related traits. The linkage map comprised 17 linkage groups, covering 1299.67 cM with an average marker distance of 4.6 cM between adjacent markers, or approximately 91% of Malus genome. Linkage groups were well populated and, although marker density ranged from 2.1 to 9.5 cM, just 10 gaps of more than 15 cM were observed. Moreover, just 12.5% of markers displayed segregation distortion. The present genetic linkage map was used to identify quantitative trait loci (QTLs affecting fruit-related traits. 23 QTLs for ten fruit traits were detected by multiple interval mapping: 3 QTLs for Vc content, One QTL for single fruit weight, 2 QTLs for peel-phenols content, 2 QTLs for flesh-hardness, 2 QTLs for diameter, 6 QTLs for acid content, 1 QTL for sugar content, 2 QTLs for soluble solids content, 2 QTLs for flesh-phenols and 2 QTLs for brittleness. These QTLs were located on linkage groups C1, C2, C3, C5, C6, C7, C9, C10, C14 and C17, respectively. The phenotypic variations exhibited by each QTL ranged from 2% to 72%, and their LOD values varied from 2.03 to 8.93, of which five QTLs were major effect genes (R2 ≥ 10%. The tight linkage markers (*me2em7-460f, *MS01a03-180m, *me1em6-307m, *CH05c06-102f, *me1em8-423f would be helpful to elucidate the molecular mechanisms of apple domestication and breeding in the future.

  16. North-South Business Linkages

    DEFF Research Database (Denmark)

    Sørensen, Olav Jull; Kuada, John

    2006-01-01

    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....

  17. Genome-wide linkage and association scans for pulse pressure in Chinese twins

    DEFF Research Database (Denmark)

    Zhang, Dongfeng; Pang, Zengchang; Li, Shuxia

    2012-01-01

    report the results of our gene mapping studies conducted in the Chinese population in mainland China. The genome-wide linkage and association scans were carried out on 63 middle-aged dizygotic twin pairs using high-density markers. The linkage analysis identified three significant linkage peaks (all...

  18. A meta-analysis of drug resistant tuberculosis in Sub-Saharan Africa: how strongly associated with previous treatment and HIV co-infection?

    Science.gov (United States)

    Berhan, Asres; Berhan, Yifru; Yizengaw, Desalegn

    2013-11-01

    In Sub-Saharan Africa, the fight against tuberculosis (TB) has encountered a great challenge because of the emergence of drug resistant TB strains and the high prevalence of HIV infection. The aim of this meta-analysis was to determine the association of drug-resistant TB with anti-TB drug treatment history and HIV co-infection. After electronic based literature search in the databases of Medline, HINARI, EMBASE and the Cochrane library, article selection and data extraction were carried out. HIV co-infection and previous history of TB treatment were used as predictors for the occurrence of any anti-TB drug resistant or multiple drug resistant TB (MDR-TB). The risk ratios for each included study and for the pooled sample were computed using the random-effects model. Heterogeneity test, sensitivity analyses and funnel plots were also done. The pooled analysis showed that the risk of developing drug-resistant TB to at least one anti-TB drug was about 3 times higher in individuals who had a previous history of anti-TB treatment than new TB cases. The risk of having MDR-TB in previously anti-TB treated TB cases was more than 5-fold higher than that of new TB cases. Resistance to Ethambutol and Rifampicin was more than fivefold higher among the previously treated with anti-TB drugs. However, HIV infection was not associated with drug-resistant TB. There was a strong association of previous anti-TB treatment with MDR-TB. Primary treatment warrants special emphasis, and screening for anti-TB drugs sensitivity has to be strengthened.

  19. PREVIOUS SECOND TRIMESTER ABORTION

    African Journals Online (AJOL)

    PNLC

    PREVIOUS SECOND TRIMESTER ABORTION: A risk factor for third trimester uterine rupture in three ... for accurate diagnosis of uterine rupture. KEY WORDS: Induced second trimester abortion - Previous uterine surgery - Uterine rupture. ..... scarred uterus during second trimester misoprostol- induced labour for a missed ...

  20. First-generation linkage map for the common frog Rana temporaria reveals sex-linkage group

    Science.gov (United States)

    Cano, J M; Li, M-H; Laurila, A; Vilkki, J; Merilä, J

    2011-01-01

    The common frog (Rana temporaria) has become a model species in the fields of ecology and evolutionary biology. However, lack of genomic resources has been limiting utility of this species for detailed evolutionary genetic studies. Using a set of 107 informative microsatellite markers genotyped in a large full-sib family (800 F1 offspring), we created the first linkage map for this species. This partial map—distributed over 15 linkage groups—has a total length of 1698.8 cM. In line with the fact that males are the heterogametic sex in this species and a reduction of recombination is expected, we observed a lower recombination rate in the males (map length: 1371.5 cM) as compared with females (2089.8 cM). Furthermore, three loci previously documented to be sex-linked (that is, carrying male-specific alleles) in adults from the wild mapped to the same linkage group. The linkage map described in this study is one of the densest ones available for amphibians. The discovery of a sex linkage group in Rana temporaria, as well as other regions with strongly reduced male recombination rates, should help to uncover the genetic underpinnings of the sex-determination system in this species. As the number of linkage groups found (n=15) is quite close to the actual number of chromosomes (n=13), the map should provide a useful resource for further evolutionary, ecological and conservation genetic work in this and other closely related species. PMID:21587305

  1. Impact of the Four-Hour Rule in Western Australian hospitals: Trend analysis of a large record linkage study 2002-2013

    Science.gov (United States)

    Ngo, Hanh; Forero, Roberto; Mountain, David; Fatovich, Daniel; Man, Wing Nicola; Sprivulis, Peter; Mohsin, Mohammed; Toloo, Sam; Celenza, Antonio; Fitzgerald, Gerard; McCarthy, Sally; Hillman, Ken

    2018-01-01

    Background In 2009, the Western Australian (WA) Government introduced the Four-Hour Rule (FHR) program. The policy stated that most patients presenting to Emergency Departments (EDs) were to be seen and either admitted, transferred, or discharged within 4 hours. This study utilised de-identified data from five participating hospitals, before and after FHR implementation, to assess the impact of the FHR on several areas of ED functioning. Methods A state (WA) population-based intervention study design, using longitudinal data obtained from administrative health databases via record linkage methodology, and interrupted time series analysis technique. Findings There were 3,214,802 ED presentations, corresponding to 1,203,513 ED patients. After the FHR implementation, access block for patients admitted through ED for all five sites showed a significant reduction of up to 13.2% (Rate Ratio 0.868, 95%CI 0.814, 0.925) per quarter. Rate of ED attendances for most hospitals continued to rise throughout the entire study period and were unaffected by the FHR, except for one hospital. Pattern of change in ED re-attendance rate post-FHR was similar to pre-FHR, but the trend reduced for two hospitals. ED occupancy was reduced by 6.2% per quarter post-FHR for the most ‘crowded’ ED. ED length of stay and ED efficiency improved in four hospitals and deteriorated in one hospital. Time to being seen by ED clinician and Did-Not-Wait rate improved for some hospitals. Admission rates in post-FHR increased, by up to 1% per quarter, for two hospitals where the pre-FHR trend was decreasing. Conclusions The FHR had a consistent effect on ‘flow’ measures: significantly reducing ED overcrowding and access block and enhancing ED efficiency. Time-based outcome measures mostly improved with the FHR. There is some evidence of increased ED attendance, but no evidence of increased ED re-attendance. Effects on patient disposition status were mixed. Overall, this reflects the value of

  2. 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

  3. Care Cascade for targeted tuberculosis testing and linkage to Care in Homeless Populations in the United States: a meta-analysis.

    Science.gov (United States)

    Parriott, Andrea; Malekinejad, Mohsen; Miller, Amanda P; Marks, Suzanne M; Horvath, Hacsi; Kahn, James G

    2018-04-12

    Homelessness increases the risk of tuberculosis (TB) disease and latent TB infection (LTBI), but persons experiencing homelessness often lack access to testing and treatment. We assessed the yield of TB testing and linkage to care for programs targeting homeless populations in the United States. We conducted a comprehensive search of peer-reviewed and grey literature, adapting Cochrane systematic review methods. Two reviewers independently assessed study eligibility and abstracted key data on the testing to care cascade: number of persons reached, recruited for testing, tested for LTBI, with valid test results, referred to follow-up care, and initiating care. We used random effects to calculate pooled proportions and 95% confidence intervals (CI) of persons retained in each step via inverse-variance weighted meta-analysis, and cumulative proportions as products of adjacent step proportions. We identified 23 studies published between 1986 and 2014, conducted in 12 states and 15 cities. Among studies using tuberculin skin tests (TST) we found that 93.7% (CI 72.4-100%) of persons reached were recruited, 97.9% (89.3-100%) of those recruited had tests placed, 85.5% (78.6-91.3%) of those with tests placed returned for reading, 99.9% (99.6-100%) of those with tests read had valid results, and 24.7% (21.0-28.5%) with valid results tested positive. All persons testing positive were referred to follow-up care, and 99.8% attended at least one session of follow-up care. Heterogeneity was high for most pooled proportions. For a hypothetical cohort of 1000 persons experiencing homelessness reached by a targeted testing program using TST, an estimated 917 were tested, 194 were positive, and all of these initiated follow-up care. Targeted TB testing of persons experiencing homelessness appears effective in detecting LTBI and connecting persons to care and potential treatment. Future evaluations should assess diagnostic use of interferon gamma release assays and completion of

  4. Skill Training Analysis--Phase II: The Linkage of Unit Level Skill Training and Maintenance Productivity in Air Force F-16 Units.

    Science.gov (United States)

    1984-04-13

    sod IIN)OW a’ Manangement Consulting & Research, Inc. (MCR) had the task of developing a linkage between training received at installation-level...and parts availability can change the results achieved. However, intuitively, training must have an effect on maintenance productivity and, if a large...1980. 11-2 - -: . .’., .:. Jb . I.-_ . .. ...... NE- 16. a 19 1 -11- information is recorded each time there is a change in any of the ,-. columns A

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

    OpenAIRE

    Brenna-Hansen Silje; Li Jieying; Kent Matthew P; Boulding Elizabeth G; Dominik Sonja; Davidson William S; Lien Sigbjørn

    2012-01-01

    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 Nort...

  6. Differences between the radiation hybrid and genetic linkage maps of bovine chromosome 5 resolved with a quasi-phylogenetic method of analysis.

    Science.gov (United States)

    Barendse, W; Armitage, S M; Aleyasin, A; Womack, J E

    2000-05-01

    Two major differences were detected in gene order between the radiation hybrid map and the genetic linkage map of bovine Chromosome (Chr) 5, and these were resolved by analyzing the raw radiation hybrid data by a quasi-phylogenetic method. Seventeen loci were typed on the new cattle whole genome radiation hybrid panel. Most of these loci are framework loci and include AGLA293, BM315, BM6026, BP1, BZRP, CD9, CSSM22, CSSM34, CYP2D@, ETH2, ETH10, ETH152, IGF1, LALBA, SLC2A3, SYT1, and TPI1. BP1 was found to be closer to the centromere than either BM6026 or SYT1 with two standard computer software packages for analyzing radiation hybrid panel data. This is inconsistent with any of the genetic linkage maps as well as their consensus. CYP2D@ was placed between ETH2 and BZRP, and this is also inconsistent with the genetic linkage maps, since CYP2D@ should be the most telomeric of the loci tested in this study. Resolution was reached by analyzing the raw radiation hybrid data for clones that bind some but not all of the loci, and the binding pattern was more consistent with the linkage maps and less consistent with the software-generated radiation hybrid map. The comparative mapping data confirm the relative inversion of gene order of SYT1 compared with humans and mice. A non-polymorphic fragment for CD9 indicates the conservation of gene order for three loci located on human Chr 12p. The genes of bovine Chr 5 conserved on human Chr 12p are located separately from the genes conserved on human Chr 12q. It is recommended that the raw data for radiation hybrid maps be made publicly available so that conflicts in gene order can be evaluated explicity.

  7. Analysis of current research addressing complementary use of life-cycle assessment and risk assessment for engineered nanomaterials: have lessons been learned from previous experience with chemicals?

    DEFF Research Database (Denmark)

    Grieger, Khara Deanne; Laurent, Alexis; Miseljic, Mirko

    2012-01-01

    While it is generally agreed that successful strategies to address the health and environmental impacts of engineered nanomaterials (NM) should consider the well-established frameworks for conducting life-cycle assessment (LCA) and risk assessment (RA), scientific research, and specific guidance...... on how to practically apply these methods are still very much under development. This paper evaluates how research efforts have applied LCA and RA together for NM, particularly reflecting on previous experiences with applying these methods to chemicals. Through a literature review and a separate analysis...... of research focused on applying LCA and RA together for NM, it appears that current research efforts have taken into account some key ‘‘lessons learned’’ from previous experience with chemicals while many key challenges remain for practically applying these methods to NM. We identified two main approaches...

  8. 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.

  9. 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...

  10. Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial.

    Science.gov (United States)

    Easton, J Donald; Lopes, Renato D; Bahit, M Cecilia; Wojdyla, Daniel M; Granger, Christopher B; Wallentin, Lars; Alings, Marco; Goto, Shinya; Lewis, Basil S; Rosenqvist, Mårten; Hanna, Michael; Mohan, Puneet; Alexander, John H; Diener, Hans-Christoph

    2012-06-01

    In the ARISTOTLE trial, the rate of stroke or systemic embolism was reduced by apixaban compared with warfarin in patients with atrial fibrillation (AF). Patients with AF and previous stroke or transient ischaemic attack (TIA) have a high risk of stroke. We therefore aimed to assess the efficacy and safety of apixaban compared with warfarin in prespecified subgroups of patients with and without previous stroke or TIA. Between Dec 19, 2006, and April 2, 2010, patients were enrolled in the ARISTOTLE trial at 1034 clinical sites in 39 countries. 18,201 patients with AF or atrial flutter were randomly assigned to receive apixaban 5 mg twice daily or warfarin (target international normalised ratio 2·0-3·0). The median duration of follow-up was 1·8 years (IQR 1·4-2·3). The primary efficacy outcome was stroke or systemic embolism, analysed by intention to treat. The primary safety outcome was major bleeding in the on-treatment population. All participants, investigators, and sponsors were masked to treatment assignments. In this subgroup analysis, we estimated event rates and used Cox models to compare outcomes in patients with and without previous stroke or TIA. The ARISTOTLE trial is registered with ClinicalTrials.gov, number NTC00412984. Of the trial population, 3436 (19%) had a previous stroke or TIA. In the subgroup of patients with previous stroke or TIA, the rate of stroke or systemic embolism was 2·46 per 100 patient-years of follow-up in the apixaban group and 3·24 in the warfarin group (hazard ratio [HR] 0·76, 95% CI 0·56 to 1·03); in the subgroup of patients without previous stroke or TIA, the rate of stroke or systemic embolism was 1·01 per 100 patient-years of follow-up with apixaban and 1·23 with warfarin (HR 0·82, 95% CI 0·65 to 1·03; p for interaction=0·71). The absolute reduction in the rate of stroke and systemic embolism with apixaban versus warfarin was 0·77 per 100 patient-years of follow-up (95% CI -0·08 to 1·63) in patients with

  11. Examination of genetic linkage of chromosome 15 to schizophrenia in a large Veterans Affairs Cooperative Study sample.

    Science.gov (United States)

    Tsuang, D W; Skol, A D; Faraone, S V; Bingham, S; Young, K A; Prabhudesai, S; Haverstock, S L; Mena, F; Menon, A S; Bisset, D; Pepple, J; Sauter, F; Baldwin, C; Weiss, D; Collins, J; Boehnke, M; Schellenberg, G D; Tsuang, M T

    2001-12-08

    Previous studies have reported genetic linkage evidence for a schizophrenia gene on chromosome 15q. Here, chromosome 15 was examined by genetic linkage analysis using 166 schizophrenia families, each with two or more affected subjects. The families, assembled from multiple centers by the Department of Veterans Affairs Cooperative Study Program, consisted of 392 sampled affected subjects and 216 affected sibling pairs. By DSM-III-R criteria, 360 subjects (91.8%) had a diagnosis of schizophrenia and 32 (8.2%) were classified as schizo-affective disorder, depressed. Participating families had diverse ethnic backgrounds. The largest single group were northern European American families (n = 62, 37%), but a substantial proportion was African American kindreds (n = 60, 36%). The chromosome 15 markers tested were spaced at intervals of approximately 10 cM over the entire chromosome and 2-5 cM for the region surrounding the alpha-7 nicotinic cholinergic receptor subunit gene (CHRNA7). These markers were genotyped and the data analyzed using semiparametric affecteds-only linkage analysis. In the European American families, there was a maximum Z-score of 1.65 between markers D15S165 and D15S1010. These markers are within 1 cM from CHRNA-7, the site previously implicated in schizophrenia. However, there was no evidence for linkage to this region in the African America kindreds. Copyright 2001 Wiley-Liss, Inc.

  12. An SSR-based linkage map of yardlong bean (Vigna unguiculata (L.) Walp. subsp. unguiculata Sesquipedalis Group) and QTL analysis of pod length.

    Science.gov (United States)

    Kongjaimun, Alisa; Kaga, Akito; Tomooka, Norihiko; Somta, Prakit; Shimizu, Takehiko; Shu, Yujian; Isemura, Takehisa; Vaughan, Duncan A; Srinives, Peerasak

    2012-02-01

    Yardlong bean (Vigna unguiculata (L.) Walp. subsp. unguiculata Sesquipedalis Group) (2n = 2x = 22) is one of the most important vegetable legumes of Asia. The objectives of this study were to develop a genetic linkage map of yardlong bean using SSR makers from related Vigna species and to identify QTLs for pod length. The map was constructed from 226 simple sequence repeat (SSR) markers from cowpea (Vigna unguiculata (L.) Walp. subsp. unguiculata Unguiculata Group), azuki bean (Vigna angularis (Willd.) Ohwi & Ohashi), and mungbean (Vigna radiata (L.) Wilczek) in a BC(1)F(1) ((JP81610 × TVnu457) × JP81610) population derived from the cross between yardlong bean accession JP81610 and wild cowpea (Vigna unguiculata subsp. unguiculata var. spontanea) accession TVnu457. The markers were clustered into 11 linkage groups (LGs) spanning 852.4 cM in total length with a mean distance between adjacent markers of 3.96 cM. All markers on LG11 showed segregation distortion towards the homozygous yardlong bean JP81610 genotype. The markers on LG11 were also distorted in the rice bean (Vigna umbellata (Thunb.) Ohwi & Ohashi) map, suggesting the presence of common segregation distortion factors in Vigna species on this LG. One major and six minor QTLs were identified for pod length variation between yardlong bean and wild cowpea. Using flanking markers, six of the seven QTLs were confirmed in an F(2) population of JP81610 × TVnu457. The molecular linkage map developed and markers linked to pod length QTLs would be potentially useful for yardlong bean and cowpea breeding.

  13. Molecular analysis of clinical isolates previously diagnosed as Mycobacterium intracellulare reveals incidental findings of "Mycobacterium indicus pranii" genotypes in human lung infection.

    Science.gov (United States)

    Kim, Su-Young; Park, Hye Yun; Jeong, Byeong-Ho; Jeon, Kyeongman; Huh, Hee Jae; Ki, Chang-Seok; Lee, Nam Yong; Han, Seung-Jung; Shin, Sung Jae; Koh, Won-Jung

    2015-09-30

    Mycobacterium intracellulare is a major cause of Mycobacterium avium complex lung disease in many countries. Molecular studies have revealed several new Mycobacteria species that are closely related to M. intracellulare. The aim of this study was to re-identify and characterize clinical isolates from patients previously diagnosed with M. intracellulare lung disease at the molecular level. Mycobacterial isolates from 77 patients, initially diagnosed with M. intracellulare lung disease were re-analyzed by multi-locus sequencing and pattern of insertion sequences. Among the 77 isolates, 74 (96 %) isolates were designated as M. intracellulare based on multigene sequence-based analysis. Interestingly, the three remaining strains (4 %) were re-identified as "Mycobacterium indicus pranii" according to distinct molecular phylogenetic positions in rpoB and hsp65 sequence-based typing. In hsp65 sequevar analysis, code 13 was found in the majority of cases and three unreported codes were identified. In 16S-23S rRNA internal transcribed spacer (ITS) sequevar analysis, all isolates of both species were classified within the Min-A ITS sequevar. Interestingly, four of the M. intracellulare isolates harbored IS1311, a M. avium-specific element. Two of three patients infected with "M. indicus pranii" had persistent positive sputum cultures after antibiotic therapy, indicating the clinical relevance of this study. This analysis highlights the importance of precise identification of clinical isolates genetically close to Mycobacterium species, and suggests that greater attention should be paid to nontuberculous mycobacteria lung disease caused by "M. indicus pranii".

  14. Genomic characterization of DArT markers based on high-density linkage analysis and physical mapping to the Eucalyptus genome.

    Directory of Open Access Journals (Sweden)

    César D Petroli

    Full Text Available Diversity Arrays Technology (DArT provides a robust, high throughput, cost-effective method to query thousands of sequence polymorphisms in a single assay. Despite the extensive use of this genotyping platform for numerous plant species, little is known regarding the sequence attributes and genome-wide distribution of DArT markers. We investigated the genomic properties of the 7,680 DArT marker probes of a Eucalyptus array, by sequencing them, constructing a high density linkage map and carrying out detailed physical mapping analyses to the Eucalyptus grandis reference genome. A consensus linkage map with 2,274 DArT markers anchored to 210 microsatellites and a framework map, with improved support for ordering, displayed extensive collinearity with the genome sequence. Only 1.4 Mbp of the 75 Mbp of still unplaced scaffold sequence was captured by 45 linkage mapped but physically unaligned markers to the 11 main Eucalyptus pseudochromosomes, providing compelling evidence for the quality and completeness of the current Eucalyptus genome assembly. A highly significant correspondence was found between the locations of DArT markers and predicted gene models, while most of the 89 DArT probes unaligned to the genome correspond to sequences likely absent in E. grandis, consistent with the pan-genomic feature of this multi-Eucalyptus species DArT array. These comprehensive linkage-to-physical mapping analyses provide novel data regarding the genomic attributes of DArT markers in plant genomes in general and for Eucalyptus in particular. DArT markers preferentially target the gene space and display a largely homogeneous distribution across the genome, thereby providing superb coverage for mapping and genome-wide applications in breeding and diversity studies. Data reported on these ubiquitous properties of DArT markers will be particularly valuable to researchers working on less-studied crop species who already count on DArT genotyping arrays but for

  15. Risk of stillbirth, preterm delivery, and fetal growth restriction following exposure in a previous birth: systematic review and meta-analysis.

    Science.gov (United States)

    Malacova, E; Regan, A; Nassar, N; Raynes-Greenow, C; Leonard, H; Srinivasjois, R; W Shand, A; Lavin, T; Pereira, G

    2018-01-01

    Little is known about the risk of non-recurrent adverse birth outcomes. To evaluate the risk of stillbirth, preterm birth (PTB), and small for gestational age (SGA) as a proxy for fetal growth restriction (FGR) following exposure to one or more of these factors in a previous birth. We searched MEDLINE, EMBASE, Maternity and Infant Care, and Global Health from inception to 30 November 2016. Studies were included if they investigated the association between stillbirth, PTB, or SGA (as a proxy for FGR) in two subsequent births. Meta-analysis and pooled association presented as odds ratios (ORs) and adjusted odds ratios (aORs). Of the 3399 studies identified, 17 met the inclusion criteria. A PTB or SGA (as a proxy for FGR) infant increased the risk of subsequent stillbirth ((pooled OR 1.70; 95% confidence interval, 95% CI, 1.34-2.16) and (pooled OR 1.98; 95% CI 1.70-2.31), respectively). A combination of exposures, such as a preterm SGA (as a proxy for FGR) birth, doubled the risk of subsequent stillbirth (pooled OR 4.47; 95% CI 2.58-7.76). The risk of stillbirth also varied with prematurity, increasing three-fold following PTB preterm SGA (as a proxy for FGR) preterm (preterm or small for gestational age can increase the chance of long-term health problems. The effect of having a stillbirth, preterm birth, or small-for-gestational-age infant in a previous pregnancy on future pregnancy health has not been summarised. We identified 3399 studies of outcomes of previous pregnancies, and 17 were summarised by our study. What were the main findings? The outcome of the previous pregnancy influenced the risk of poor outcomes in the next pregnancy. Babies born to mothers who had a previous preterm birth or small-for-gestational-age birth were more likely to be stillborn. The smaller and the more preterm the previous baby, the higher the risk of stillbirth in the following pregnancy. The risk of stillbirth in the following pregnancy was doubled if the previous baby was born

  16. Laparoscopy After Previous Laparotomy

    Directory of Open Access Journals (Sweden)

    Zulfo Godinjak

    2006-11-01

    Full Text Available Following the abdominal surgery, extensive adhesions often occur and they can cause difficulties during laparoscopic operations. However, previous laparotomy is not considered to be a contraindication for laparoscopy. The aim of this study is to present that an insertion of Veres needle in the region of umbilicus is a safe method for creating a pneumoperitoneum for laparoscopic operations after previous laparotomy. In the last three years, we have performed 144 laparoscopic operations in patients that previously underwent one or two laparotomies. Pathology of digestive system, genital organs, Cesarean Section or abdominal war injuries were the most common causes of previouslaparotomy. During those operations or during entering into abdominal cavity we have not experienced any complications, while in 7 patients we performed conversion to laparotomy following the diagnostic laparoscopy. In all patients an insertion of Veres needle and trocar insertion in the umbilical region was performed, namely a technique of closed laparoscopy. Not even in one patient adhesions in the region of umbilicus were found, and no abdominal organs were injured.

  17. 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.

  18. Nonsyndromic cleft lip and palate: No evidence of linkage to HLA or factor 13A

    Energy Technology Data Exchange (ETDEWEB)

    Hecht, J.T.; Yaping Wang; Connor, B.; Daiger, S.P. (Univ. of Texas, Houston (United States)); Blanton, S.H. (Univ. of Texas, Houston (United States) Univ. of Virginia, Charlottesville (United States))

    1993-06-01

    Nonsyndromic cleft lip with or without cleft palate (CLP) is a common craniofacial anomaly, the etiology of which is not known. Population studies have shown that a large proportion of cases occur sporadically. Recently, segregation analyses applied to CLP families have demonstrated that an autosomal dominant/codominant gene(s) may cause clefting in cases. Associations of autosomal dominant CLP and nonsyndromic cleft palate (CP) with HLA and F13A genes on chromosome 6p have been suggested previously. Linkage to these two areas on chromosome 6p were tested in 12 autosomal dominant families with CLP. With a LOD score of [minus]2 or less for exclusion, no evidence of linkage was found to four chromosome 6p markers. Multipoint analysis showed no evidence of a clefting locus in this region spanning 54 cM on chromosome 6p in these CLP families. 30 refs., 2 figs., 1 tab.

  19. Comparing single-nucleotide polymorphism marker-based and microsatellite marker-based linkage analyses.

    OpenAIRE

    Ulgen, Ayse; Li, Wentian

    2005-01-01

    Abstract We compared linkage analysis results for an alcoholism trait, ALDX1 (DSM-III-R and Feigner criteria) using a nonparametric linkage analysis method, which takes into account allele sharing among several affected persons, for both microsatellite and single-nucleotide polymorphism (SNP) markers (Affymetrix and Illumina) in the Collaborative Study on the Genetics of Alcoholism (COGA) dataset provided to participants at the Genetic Analysis Workshop 14 (GAW14). The two sets of linkage res...

  20. Analysis of current research addressing complementary use of life-cycle assessment and risk assessment for engineered nanomaterials: have lessons been learned from previous experience with chemicals?

    International Nuclear Information System (INIS)

    Grieger, Khara D.; Laurent, Alexis; Miseljic, Mirko; Christensen, Frans; Baun, Anders; Olsen, Stig I.

    2012-01-01

    While it is generally agreed that successful strategies to address the health and environmental impacts of engineered nanomaterials (NM) should consider the well-established frameworks for conducting life-cycle assessment (LCA) and risk assessment (RA), scientific research, and specific guidance on how to practically apply these methods are still very much under development. This paper evaluates how research efforts have applied LCA and RA together for NM, particularly reflecting on previous experiences with applying these methods to chemicals. Through a literature review and a separate analysis of research focused on applying LCA and RA together for NM, it appears that current research efforts have taken into account some key “lessons learned” from previous experience with chemicals while many key challenges remain for practically applying these methods to NM. We identified two main approaches for using these methods together for NM: “LC-based RA” (traditional RA applied in a life-cycle perspective) and “RA-complemented LCA” (conventional LCA supplemented by RA in specific life-cycle steps). Hence, the latter is the only identified approach which genuinely combines LC- and RA-based methods for NM-risk research efforts to date as the former is rather a continuation of normal RA according to standard assessment procedures (e.g., REACH). Both these approaches along with recommendations for using LCA and RA together for NM are similar to those made previously for chemicals, and thus, there does not appear to be much progress made specific for NM. We have identified one issue in particular that may be specific for NM when applying LCA and RA at this time: the need to establish proper dose metrics within both methods.

  1. Potential protective effect of lactation against incidence of type 2 diabetes mellitus in women with previous gestational diabetes mellitus: A systematic review and meta-analysis.

    Science.gov (United States)

    Tanase-Nakao, Kanako; Arata, Naoko; Kawasaki, Maki; Yasuhi, Ichiro; Sone, Hirohito; Mori, Rintaro; Ota, Erika

    2017-05-01

    Lactation may protect women with previous gestational diabetes mellitus (GDM) from developing type 2 diabetes mellitus, but the results of existing studies are inconsistent, ranging from null to beneficial. We aimed to conduct a systematic review to gather available evidence. Databases MEDLINE, CINAHL, PubMed, and EMBASE were searched on December 15, 2015, without restriction of language or publication year. A manual search was also conducted. We included observational studies (cross-sectional, case-control, and cohort study) with information on lactation and type 2 diabetes mellitus incidence among women with previous GDM. We excluded case studies without control data. Data synthesis was conducted by random-effect meta-analysis. Fourteen reports of 9 studies were included. Overall risk of bias using RoBANS ranged from low to unclear. Longer lactation for more than 4 to 12 weeks postpartum had risk reduction of type 2 diabetes mellitus compared with shorter lactation (OR 0.77, 95% CI 0.01-55.86; OR 0.56, 95% CI 0.35-0.89; OR 0.22, 95% CI 0.13-0.36; type 2 diabetes mellitus evaluation time 2 y, 2-5 y, and >5 y, respectively). Exclusive lactation for more than 6 to 9 weeks postpartum also had lower risk of type 2 diabetes mellitus compared with exclusive formula (OR 0.42, 95% CI 0.22-0.81). The findings support the evidence that longer and exclusive lactation may be beneficial for type 2 diabetes mellitus prevention in women with previous GDM. However, the evidence relies only on observational studies. Therefore, further studies are required to address the true causal effect. © 2017 The Authors. Diabetes/Metabolism Research and Reviews Published by John Wiley & Sons Ltd.

  2. Ameloblastic fibroma: a stage in the development of a hamartomatous odontoma or a true neoplasm? Critical analysis of 162 previously reported cases plus 10 new cases.

    Science.gov (United States)

    Buchner, Amos; Vered, Marilena

    2013-11-01

    To analyze neoplastic and hamartomatous variants of ameloblastic fibromas (AFs). Analysis of 172 cases (162 previously reported, 10 new). AF emerged as a lesion primarily of children and adolescents (mean age, 14.9 years), with about 80% diagnosed when odontogenesis is completed (age, 22 years are considered true neoplasms, while those in younger patients may be either true neoplasms or odontomas in early stages of development. Although the histopathology of hamartomatous and neoplastic variants of AF are indistinguishable, clinical and radiologic features can be of some help to distinguish between them. Asymptomatic small unilocular lesions with no or minimal bone expansion in young individuals are likely to be developing odontomas, and large, expansile lesions with extensive bone destruction are neoplasms. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. 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.

  4. Accuracy of Probabilistic Linkage Using the Enhanced Matching System for Public Health and Epidemiological Studies.

    Science.gov (United States)

    Aldridge, Robert W; Shaji, Kunju; Hayward, Andrew C; Abubakar, Ibrahim

    2015-01-01

    The Enhanced Matching System (EMS) is a probabilistic record linkage program developed by the tuberculosis section at Public Health England to match data for individuals across two datasets. This paper outlines how EMS works and investigates its accuracy for linkage across public health datasets. EMS is a configurable Microsoft SQL Server database program. To examine the accuracy of EMS, two public health databases were matched using National Health Service (NHS) numbers as a gold standard unique identifier. Probabilistic linkage was then performed on the same two datasets without inclusion of NHS number. Sensitivity analyses were carried out to examine the effect of varying matching process parameters. Exact matching using NHS number between two datasets (containing 5931 and 1759 records) identified 1071 matched pairs. EMS probabilistic linkage identified 1068 record pairs. The sensitivity of probabilistic linkage was calculated as 99.5% (95%CI: 98.9, 99.8), specificity 100.0% (95%CI: 99.9, 100.0), positive predictive value 99.8% (95%CI: 99.3, 100.0), and negative predictive value 99.9% (95%CI: 99.8, 100.0). Probabilistic matching was most accurate when including address variables and using the automatically generated threshold for determining links with manual review. With the establishment of national electronic datasets across health and social care, EMS enables previously unanswerable research questions to be tackled with confidence in the accuracy of the linkage process. In scenarios where a small sample is being matched into a very large database (such as national records of hospital attendance) then, compared to results presented in this analysis, the positive predictive value or sensitivity may drop according to the prevalence of matches between databases. Despite this possible limitation, probabilistic linkage has great potential to be used where exact matching using a common identifier is not possible, including in low-income settings, and for vulnerable

  5. Accuracy of Probabilistic Linkage Using the Enhanced Matching System for Public Health and Epidemiological Studies.

    Directory of Open Access Journals (Sweden)

    Robert W Aldridge

    Full Text Available The Enhanced Matching System (EMS is a probabilistic record linkage program developed by the tuberculosis section at Public Health England to match data for individuals across two datasets. This paper outlines how EMS works and investigates its accuracy for linkage across public health datasets.EMS is a configurable Microsoft SQL Server database program. To examine the accuracy of EMS, two public health databases were matched using National Health Service (NHS numbers as a gold standard unique identifier. Probabilistic linkage was then performed on the same two datasets without inclusion of NHS number. Sensitivity analyses were carried out to examine the effect of varying matching process parameters.Exact matching using NHS number between two datasets (containing 5931 and 1759 records identified 1071 matched pairs. EMS probabilistic linkage identified 1068 record pairs. The sensitivity of probabilistic linkage was calculated as 99.5% (95%CI: 98.9, 99.8, specificity 100.0% (95%CI: 99.9, 100.0, positive predictive value 99.8% (95%CI: 99.3, 100.0, and negative predictive value 99.9% (95%CI: 99.8, 100.0. Probabilistic matching was most accurate when including address variables and using the automatically generated threshold for determining links with manual review.With the establishment of national electronic datasets across health and social care, EMS enables previously unanswerable research questions to be tackled with confidence in the accuracy of the linkage process. In scenarios where a small sample is being matched into a very large database (such as national records of hospital attendance then, compared to results presented in this analysis, the positive predictive value or sensitivity may drop according to the prevalence of matches between databases. Despite this possible limitation, probabilistic linkage has great potential to be used where exact matching using a common identifier is not possible, including in low-income settings, and for

  6. Artificial oocyte activation to improve reproductive outcomes in women with previous fertilization failure: a systematic review and meta-analysis of RCTs.

    Science.gov (United States)

    Sfontouris, Ioannis A; Nastri, Carolina O; Lima, Maria L S; Tahmasbpourmarzouni, Eisa; Raine-Fenning, Nick; Martins, Wellington P

    2015-08-01

    In couples with previous fertilization failure, are reproductive outcomes improved using ICSI followed by artificial oocyte activation (ICSI-AOA) compared with conventional ICSI? There is insufficient evidence available from RCTs to judge the efficacy and safety of ICSI-AOA for couples with previous fertilization failure. In cases with previous low fertilization rates or total fertilization failure using ICSI due to sperm-related, oocyte activation deficiency, several methods of AOA have been described, which employ mechanical, electrical or chemical stimuli. Reported fertilization and pregnancy rates appear to be improved after ICSI-AOA compared with conventional ICSI; however, the small studies performed to date make it difficult to assess the clinical efficacy or safety of AOA. The present systematic review and meta-analysis identified RCTs that compared ICSI-AOA and conventional ICSI. The last electronic search was conducted in August 2014 and there was no limitation regarding language, publication date, or publication status. We included studies that randomized either oocytes or women and included them in two different parts of this review: a women-based review and an oocyte-based review. For the women-based review, the primary outcome of effectiveness was live birth per randomized woman and the primary outcome for safety was congenital anomalies per clinical pregnancy. For the oocyte-based review, the primary outcome was embryo formation per oocyte randomized. Record screening and data extraction were performed independently by two authors and risk of bias was assessed by three authors. The effects of ICSI-AOA compared with conventional ICSI were summarized as risk ratio (RR) and the precision of the estimates was evaluated by the 95% confidence interval (CI). A total of 14 articles were assessed for eligibility and 9 included in the meta-analysis: 2 studies comprised the woman-based review (n = 168 women) and 7 studies the oocyte-based review (n = 4234

  7. Genome-wide Linkage and Association Analyses to Identify Genes Influencing Adiponectin Levels: The GEMS Study

    Science.gov (United States)

    Ling, Hua; Waterworth, Dawn M.; Stirnadel, Heide A.; Pollin, Toni I.; Barter, Philip J.; Kesäniemi, Y. Antero; Mahley, Robert W.; McPherson, Ruth; Waeber, Gérard; Bersot, Thomas P.; Cohen, Jonathan C.; Grundy, Scott M.; Mooser, Vincent E.; Mitchell, Braxton D.

    2014-01-01

    Adiponectin has a variety of metabolic effects on obesity, insulin sensitivity, and atherosclerosis. To identify genes influencing variation in plasma adiponectin levels, we performed genome-wide linkage and association scans of adiponectin in two cohorts of subjects recruited in the Genetic Epidemiology of Metabolic Syndrome Study. The genome-wide linkage scan was conducted in families of Turkish and southern European (TSE, n = 789) and Northern and Western European (NWE, N = 2,280) origin. A whole genome association (WGA) analysis (500K Affymetrix platform) was carried out in a set of unrelated NWE subjects consisting of approximately 1,000 subjects with dyslipidemia and 1,000 overweight subjects with normal lipids. Peak evidence for linkage occurred at chromosome 8p23 in NWE subjects (lod = 3.10) and at chromosome 3q28 near ADIPOQ, the adiponectin structural gene, in TSE subjects (lod = 1.70). In the WGA analysis, the single-nucleotide polymorphisms (SNPs) most strongly associated with adiponectin were rs3774261 and rs6773957 (P < 10−7). These two SNPs were in high linkage disequilibrium (r2 = 0.98) and located within ADIPOQ. Interestingly, our fourth strongest region of association (P < 2 × 10−5) was to an SNP within CDH13, whose protein product is a newly identified receptor for high-molecular-weight species of adiponectin. Through WGA analysis, we confirmed previous studies showing SNPs within ADIPOQ to be strongly associated with variation in adiponectin levels and further observed these to have the strongest effects on adiponectin levels throughout the genome. We additionally identified a second gene (CDH13) possibly influencing variation in adiponectin levels. The impact of these SNPs on health and disease has yet to be determined. PMID:19165155

  8. Linkage study of nonsyndromic cleft lip with or without cleft palate using candidate genes and mapped polymorphic markers

    Energy Technology Data Exchange (ETDEWEB)

    Stein, J.D.; Nelson, L.D.; Conner, B.J. [Univ. of Texas, Houston (United States)] [and others

    1994-09-01

    Nonsyndromic cleft lip with or without cleft palate (CL(P)) involves fusion or growth failure of facial primordia during development. Complex segregation analysis of clefting populations suggest that an autosomal dominant gene may play a role in this common craniofacial disorder. We have ascertained 16 multigenerational families with CL(P) and tested linkage to 29 candidate genes and 139 mapped short tandem repeat markers. The candidate genes were selected based on their expression in craniofacial development or were identified through murine models. These include: TGF{alpha}, TGF{beta}1, TGF{beta}2, TGF{beta}3, EGF, EGFR, GRAS, cMyc, FGFR, Jun, JunB, PDFG{alpha}, PDGF{beta}, IGF2R, GCR Hox7, Hox8, Hox2B, twirler, 5 collagen and 3 extracellular matrix genes. Linkage was tested assuming an autosomal dominant model with sex-specific decreased penetrance. Linkage to all of the candidate loci was excluded in 11 families. RARA was tested and was not informative. However, haplotype analysis of markers flanking RARA on 17q allowed exclusion of this candidate locus. We have previously excluded linkage to 61 STR markers in 11 families. Seventy-eight mapped short tandem repeat markers have recently been tested in 16 families and 30 have been excluded. The remaining are being analyzed and an exclusion map is being developed based on the entire study results.

  9. 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.

  10. 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

  11. STAKEHOLDER LINKAGES FOR SUSTAINABLE LAND ...

    African Journals Online (AJOL)

    Osondu

    This paper presents stakeholder types involved in sustainable land management (SLM), their interests and ... (DAs), and Rural Kebele Administration (RKA) offices were major stakeholders involved in SLM activities in the ... Key words: Stakeholders; farmer-expert linkages; resource management; Ethiopia. Introduction.

  12. Evolutionary Analysis Predicts Sensitive Positions of MMP20 and Validates Newly- and Previously-Identified MMP20 Mutations Causing Amelogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Barbara Gasse

    2017-06-01

    Full Text Available Amelogenesis imperfecta (AI designates a group of genetic diseases characterized by a large range of enamel disorders causing important social and health problems. These defects can result from mutations in enamel matrix proteins or protease encoding genes. A range of mutations in the enamel cleavage enzyme matrix metalloproteinase-20 gene (MMP20 produce enamel defects of varying severity. To address how various alterations produce a range of AI phenotypes, we performed a targeted analysis to find MMP20 mutations in French patients diagnosed with non-syndromic AI. Genomic DNA was isolated from saliva and MMP20 exons and exon-intron boundaries sequenced. We identified several homozygous or heterozygous mutations, putatively involved in the AI phenotypes. To validate missense mutations and predict sensitive positions in the MMP20 sequence, we evolutionarily compared 75 sequences extracted from the public databases using the Datamonkey webserver. These sequences were representative of mammalian lineages, covering more than 150 million years of evolution. This analysis allowed us to find 324 sensitive positions (out of the 483 MMP20 residues, pinpoint functionally important domains, and build an evolutionary chart of important conserved MMP20 regions. This is an efficient tool to identify new- and previously-identified mutations. We thus identified six functional MMP20 mutations in unrelated families, finding two novel mutated sites. The genotypes and phenotypes of these six mutations are described and compared. To date, 13 MMP20 mutations causing AI have been reported, making these genotypes and associated hypomature enamel phenotypes the most frequent in AI.

  13. 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

  14. Nucleotide sequence of the goat embryonic alpha globin gene (zeta) and linkage and evolutionary analysis of the complete alpha globin cluster.

    Science.gov (United States)

    Wernke, S M; Lingrel, J B

    1986-12-05

    In previous studies we identified and sequenced clones containing two adult alpha globin genes of the goat. Additional studies have revealed the presence of an embryonic alpha globin gene termed zeta. Sequence analysis of the gene shows that it is the largest mammalian or avian globin gene cloned to date. Its unusual size is mainly due to a 14 base-pair tandem repeat sequence in its first intron. A similar sequence is also found in the first intron of the human zeta gene. The goat zeta coding sequence differs greatly from that of the adult alpha, particularly at amino acid position 38, where it codes for the amino acid replacement of Gln for Thr. This change may confer a higher intrinsic O2 affinity on the zeta globin protein, ensuring a sufficient O2 supply for the developing goat embryo. The cloning and sequencing of this gene completes the alpha globin locus of the goat, composed of three genes in the following order 5'-zeta-I alpha-II alpha-3'. Evolutionary comparisons of the goat alpha locus with other amphibian, avian and mammalian loci reveal several interesting features. Statistical analysis confirms the hypothesis that the embryonic alpha gene is much older (400 million years) than the embryonic beta gene (200 million years), and that it is descended from a primordial gene, whose present-day counterpart is the Xenopus larval alpha globin gene. Our results also suggest that after the divergence of the avian line, the alpha A gene converted the alpha D gene during the evolution of the pre-mammalian line. The alpha D globin gene remains unconverted in the avian line, potentially because of insertion/deletion sequences that may prevent any gene conversion event. The divergence rates of specific globin genes have been analyzed and found to form an essentially straight line, in agreement with the neutralist view of evolution.

  15. Evidence for linkage disequilibrium in chromosome 13-linked Duchenne-like muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Othmane, K.B.; Speer, M.C.; Stauffer, J. [Duke Univ. Medical Center, Durham, NC (United States)] [and others

    1995-09-01

    Duchenne-like muscular dystrophy (DLMD) is an autosomal recessive Limb Girdle muscular dystrophy (LGMD2C) characterized by late age of onset, proximal muscle weakness leading to disability, high creatine kinase values, normal intelligence and normal dystrophin in muscle biopsy. We have shown previously that three DLMD families from Tunisia are linked to chromosome 13q12. To further localize the LGMD2C gene, we have investigated seven additional families (119 individuals). Both genotyping and two-point linkage analysis were performed as described elsewhere. 7 refs., 1 fig., 1 tab.

  16. The Importance of Geographical Proximity for New Product Development Activities within Inter-firm Linkages

    DEFF Research Database (Denmark)

    Dahlgren, Johan Henrich

    important as a resource and where collaboration partners are important. Hypotheses are tested by means of a quantitative analysis of a data set containing information about 4842 domestic and international inter-firm linkages of Danish firms in manufacturing industries. The findings in this analysis exhibit...... for international linkages. It is further suggested closer geographical distance for inter-firm linkages with medium and high level of interaction, suppliers or customers accounting for more than one third of total purchases or sales, and for linkages lasting for at least 10 years.Key words: capabilities, economics...

  17. Safety and tolerability of frovatriptan in the acute treatment of migraine and prevention of menstrual migraine: Results of a new analysis of data from five previously published studies.

    Science.gov (United States)

    MacGregor, E Anne; Pawsey, Stephen P; Campbell, John C; Hu, Xiaojun

    2010-04-01

    Triptans are a recommended first-line treatment for moderate to severe migraine. Using clinical trial data, we evaluated the safety and tolerability of frovatriptan as acute treatment (AT) and as short-term preventive (STP) therapy for menstrual migraine (MM). Data from 2 Phase III AT trials (AT1: randomized, placebo controlled, 1 attack; AT2: 12-months, noncomparative, open label) and 3 Phase IIIb STP trials in MM (MMP1 and MMP2: randomized, placebo controlled, double blind, 3 perimenstrual periods; MMP3: open label, noncomparative, 12 perimenstrual periods) were analyzed. In AT1, patients treated each attack with frovatriptan 2.5 mg, sumatriptan 100 mg, or placebo. In AT2, they used frovatriptan 2.5 mg. In MMP1 and MMP2, women administered frovatriptan 2.5 mg for 6 days during the perimenstrual period, taking a loading dose of 2 or 4 tablets on day 1, followed by once-daily or BID frovatriptan 2.5 mg, respectively; in MMP3, they used BID frovatriptan 2.5 mg. In AT1, which was previously published in part, group differences in adverse events (AEs) were analyzed using the Fisher exact test, and response rates were compared using logistic regression. Post hoc analyses of sustained pain-free status with no AEs (SNAE) and sustained pain response with no AEs (SPRNAE) were performed using a 2-sample test for equality of proportions without continuity correction. For AT2 and the STP studies, data were summarized using descriptive statistics. Results of individual safety analyses for the STP studies were previously reported; the present report includes new results from a pooled analysis of MMP1 and MMP2 and a new analysis of MMP3 in which AEs were coded using Medical Dictionary for Regulatory Activities version 8.0. AT1 included 1206 patients in the safety group; AT2 included 496. In the STP studies, safety data were collected for 1487 women. In AT1 and AT2, 85.6% and 88.3%, respectively, of enrolled patients were women. Overall, AEs were generally mild to moderate (AT

  18. Common standards in facial esthetics: craniofacial analysis of most attractive black and white subjects according to People magazine during previous 10 years.

    Science.gov (United States)

    Iglesias-Linares, Alejandro; Yáñez-Vico, Rosa-María; Moreno-Manteca, Blanca; Moreno-Fernández, Ana María; Mendoza-Mendoza, Asunción; Solano-Reina, Enrique

    2011-06-01

    The aim of the present case-control study was to determine--using the 10 most recent annual listings of the most beautiful black and white people--whether any common, measurable esthetic parameter could be extracted from both groups. A total of 80 women (40 white and 40 black), who had been included in the list of People magazine's 100 most beautiful people during the previous 10 years, were selected. Lateral photographs of all 80 subjects were obtained from Internet databases, oriented, and sized. A modified photogrammetric analysis was performed on the lateral view of each subject to obtain the angle and proportion measurements. Differences between the 2 groups were compared with 95% significance using the Student t test for independent samples. Facial similarities in the 2 ethnic groups were observed for the angle of the inferior facial third, labiomental angle, angle of facial convexity, and cervicomental angle. These results point to a similar conformation of the lower part of the face in relation to the neck that was shared by both groups of beautiful women. Additionally, both groups showed similar results for the lower lip projection. Likewise, similar proportional measurements were found for the upper lip proportion, notwithstanding differences in protrusion. Modern society is changing the classic concept of facial beauty because of globalization and the prevalence of multiethnic communities in the developed world. Independently of ethnic origin, beautiful women tend to have similar facial features that are a mixture of both black and white features. Copyright © 2011 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  19. Genomewide Linkage Screen for Waldenström Macroglobulinemia Susceptibility Loci in High-Risk Families

    Science.gov (United States)

    McMaster, Mary L.; Goldin, Lynn R.; Bai, Yan; Ter-Minassian, Monica; Boehringer, Stefan; Giambarresi, Therese R.; Vasquez, Linda G.; Tucker, Margaret A.

    2006-01-01

    Waldenström macroglobulinemia (WM), a distinctive subtype of non-Hodgkin lymphoma that features overproduction of immunoglobulin M (IgM), clearly has a familial component; however, no susceptibility genes have yet been identified. We performed a genomewide linkage analysis in 11 high-risk families with WM that were informative for linkage, for a total of 122 individuals with DNA samples, including 34 patients with WM and 10 patients with IgM monoclonal gammopathy of undetermined significance (IgM MGUS). We genotyped 1,058 microsatellite markers (average spacing 3.5 cM), performed both nonparametric and parametric linkage analysis, and computed both two-point and multipoint linkage statistics. The strongest evidence of linkage was found on chromosomes 1q and 4q when patients with WM and with IgM MGUS were both considered affected; nonparametric linkage scores were 2.5 (P=.0089) and 3.1 (P=.004), respectively. Other locations suggestive of linkage were found on chromosomes 3 and 6. Results of two-locus linkage analysis were consistent with independent effects. The findings from this first linkage analysis of families at high risk for WM represent important progress toward identifying gene(s) that modulate susceptibility to WM and toward understanding its complex etiology. PMID:16960805

  20. Landscape linkages and biodiversity in European landscapes

    NARCIS (Netherlands)

    Jongman, R.H.G.

    2004-01-01

    Linear features are structuring landscape elements. We change our landscapes and rebuild them into new linkages, and landscapes are even constructed around these linkages. Landscape linkages are important for species migration and dispersal on a large scale and a small scale: storks, bats and

  1. Familial dyslexia in a large Swedish family: a whole genome linkage scan.

    Science.gov (United States)

    Svensson, Idor; Nilsson, Staffan; Wahlström, Jan; Jernås, Margareta; Carlsson, Lena M; Hjelmquist, Erland

    2011-01-01

    There is a compelling body of evidence that developmental dyslexia runs in families and seems to be highly inheritable. Several investigations during the last two decades have shown possible locations of genes that might be involved in dyslexia, including regions of chromosomes 1, 2, 3, 6, 11, 13, 15 and 18. In addition, six candidate genes (KIAA0319, DYX1C1, DCDC2, ROBO1, MRPL19 and C2ORF3) seem to be related to dyslexia. The present study carried out a whole genome scan in a six-generation pedigree. In addition to literacy skills the assessment included cognitive skills and records concerning the history of reading and writing ability. Thirty-five percent were regarded as dyslexic in the family. A linkage analysis using both a quantitative and a qualitative approach has been performed. No evidence was obtained to support the hypothesis that the transmission of dyslexia in this pedigree is due to a highly penetrant major gene, and previous linkage findings were not replicated; however, power in this small study was not adequate to confirm linkage of genes with small to moderate effects. The results were discussed in relation to diagnostic procedures and sample characteristics.

  2. 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.......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....

  3. Fault linkage and continental breakup

    Science.gov (United States)

    Cresswell, Derren; Lymer, Gaël; Reston, Tim; Stevenson, Carl; Bull, Jonathan; Sawyer, Dale; Morgan, Julia

    2017-04-01

    The magma-poor rifted margin off the west coast of Galicia (NW Spain) has provided some of the key observations in the development of models describing the final stages of rifting and continental breakup. In 2013, we collected a 68 x 20 km 3D seismic survey across the Galicia margin, NE Atlantic. Processing through to 3D Pre-stack Time Migration (12.5 m bin-size) and 3D depth conversion reveals the key structures, including an underlying detachment fault (the S detachment), and the intra-block and inter-block faults. These data reveal multiple phases of faulting, which overlap spatially and temporally, have thinned the crust to between zero and a few km thickness, producing 'basement windows' where crustal basement has been completely pulled apart and sediments lie directly on the mantle. Two approximately N-S trending fault systems are observed: 1) a margin proximal system of two linked faults that are the upward extension (breakaway faults) of the S; in the south they form one surface that splays northward to form two faults with an intervening fault block. These faults were thus demonstrably active at one time rather than sequentially. 2) An oceanward relay structure that shows clear along strike linkage. Faults within the relay trend NE-SW and heavily dissect the basement. The main block bounding faults can be traced from the S detachment through the basement into, and heavily deforming, the syn-rift sediments where they die out, suggesting that the faults propagated up from the S detachment surface. Analysis of the fault heaves and associated maps at different structural levels show complementary fault systems. The pattern of faulting suggests a variation in main tectonic transport direction moving oceanward. This might be interpreted as a temporal change during sequential faulting, however the transfer of extension between faults and the lateral variability of fault blocks suggests that many of the faults across the 3D volume were active at least in part

  4. 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....... At the same time, local African enterprises are eager to, and increasingly capable of, linking up to the foreign investors in order to expand their activities and acquire technology, skills and market access. The changing strategies of MNCs and the improving capabilities of African enterprises offer new...... opportunities for governments and donors to mobilize extractive FDI for development goals. This paper seeks to take stock of what we know about the state of and driving forces of linkage formation in South Sahel Africa extractives based on a review of the extant literature. The paper argues that while MNCs...

  5. Previous Adverse Infant Outcomes as Predictors of Preconception Care Use: An Analysis of the 2010 and 2012 Los Angeles Mommy and Baby (LAMB) Surveys.

    Science.gov (United States)

    Batra, Priya; Higgins, Chandra; Chao, Shin M

    2016-06-01

    Objectives This study aimed to understand the impact of a previous adverse infant outcome (AIO) on use of preconception care prior to a subsequent pregnancy. Methods Responses from the 2010 and 2012 Los Angeles Mommy and Baby Surveys were analyzed. Weighted multivariate logistic regression was employed to identify significant associations between having had a previous AIO (preterm delivery, low birth weight infant, stillbirth, or major birth defect) and receipt of preconception care prior to the most recent pregnancy. Select patient-level covariates were included: chronic disease, age, education level, race/ethnicity, country of birth, insurance status prior to pregnancy and pregnancy intent. Adjustment for missing responses was performed using multiple chained imputation. Results After controlling for covariates, having had a previous AIO was associated with an increased odds of having utilized preconception care in the most recent pregnancy (OR 1.237, p = 0.040). Per the final regression model, a woman reporting a previous AIO and an intended subsequent pregnancy had a 42.4 % likelihood of having used preconception care. Of these women, only 28.8 % reported doing so because of concern regarding a previous birth complication. Discussion Women reporting a previous AIO were more likely to have used preconception care in a subsequent pregnancy. The prevalence of preconception care utilization remained low overall. Pregnancy intent emerged as a strong secondary predictor; any concerted strategy to improve access to preconception care must include initiatives to help ensure that pregnancies are planned.

  6. Clinical evaluation of recombinant factor VIII preparation (Kogenate) in previously treated patients with hemophilia A: descriptive meta-analysis of post-marketing study data.

    Science.gov (United States)

    Yoshioka, A; Fukutake, K; Takamatsu, J; Shirahata, A

    2006-08-01

    The safety and efficacy of Kogenate, a recombinant factor VIII (rFVIII) preparation for the treatment of bleeding episodes, were studied in a 123-patient meta-analysis population of previously treated patients (PTPs), including 15 enrolled in the registration Phase III trial (PTP-I group), 93 from the post-marketing special investigation (PTP-II group), and 15 from short-term special investigations in surgery or tooth extraction (SI group). These patients (82 severe, 31 moderate, 9 mild, and 1 unknown), aged 11 months to 72 years, were enrolled in 28 centers in Japan. Blood samples taken at the baseline and at 3, 6, 9, 12, 18, and 24 months after the introduction of Kogenate were evaluated for FVIII inhibitor antibodies, antibodies formed against trace proteins derived from the rFVIII production process, and for general changes in laboratory test results. Mean exposure to Kogenate was 1103 days in PTP-I, 86 days in PTP-II, 27 days in patients in surgery, and 2 days in patients with tooth extraction. Assessment of FVIII inhibitor activity was conducted in 115 of the 123 patients by means of the Bethesda assay. Twelve patients were found to have a low titer of FVIII inhibitor (0.5-3.0 BU/mL) prior to any administration of Kogenate, and 103 were inhibitor-negative at the baseline. Among this latter group, 3 patients (2.9%) tested inhibitor-positive, with titers ranging from 1.2 to 2.1 BU/mL, with 4 patients below 1.0 BU/mL. One patient in the 11 PTPs investigated (PTP-I) developed antibodies against baby hamster kidney protein and mouse immunoglobulin G, but these findings were transient and asymptomatic. Hemostasis was achieved (markedly effective or effective) in 3666 of the 3855 bleeding episodes (95.1%) observed in 108 patients. Only 1 infusion was necessary in 3790 (98.3%) of these episodes. These data indicate that Kogenate is safe and very effective for the treatment of bleeding in PTPs with hemophilia A.

  7. Autosomal dominant distal myopathy: Linkage to chromosome 14

    Energy Technology Data Exchange (ETDEWEB)

    Laing, N.G.; Laing, B.A.; Wilton, S.D.; Dorosz, S.; Mastaglia, F.L.; Kakulas, B.A. [Australian Neuromuscular Research Institute, Perth (Australia); Robbins, P.; Meredith, C.; Honeyman, K.; Kozman, H.

    1995-02-01

    We have studied a family segregating a form of autosomal dominant distal myopathy (MIM 160500) and containing nine living affected individuals. The myopathy in this family is closest in clinical phenotype to that first described by Gowers in 1902. A search for linkage was conducted using microsatellite, VNTR, and RFLP markers. In total, 92 markers on all 22 autosomes were run. Positive linkage was obtained with 14 of 15 markers tested on chromosome 14, with little indication of linkage elsewhere in the genome. Maximum two-point LOD scores of 2.60 at recombination fraction .00 were obtained for the markers MYH7 and D14S64 - the family structure precludes a two-point LOD score {ge} 3. Recombinations with D14S72 and D14S49 indicate that this distal myopathy locus, MPD1, should lie between these markers. A multipoint analysis assuming 100% penetrance and using the markers D14S72, D14S50, MYH7, D14S64, D14S54, and D14S49 gave a LOD score of exactly 3 at MYH7. Analysis at a penetrance of 80% gave a LOD score of 2.8 at this marker. This probable localization of a gene for distal myopathy, MPD1, on chromosome 14 should allow other investigators studying distal myopathy families to test this region for linkage in other types of the disease, to confirm linkage or to demonstrate the likely genetic heterogeneity. 24 refs., 3 figs., 1 tab.

  8. Linkage of PRA models. Phase 1, Results

    Energy Technology Data Exchange (ETDEWEB)

    Smith, C.L.; Knudsen, J.K.; Kelly, D.L.

    1995-12-01

    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.

  9. An analysis of 97 previously diagnosed de novo adult acute erythroid leukemia patients following the 2016 revision to World Health Organization classification.

    Science.gov (United States)

    Qiu, Shaowei; Jiang, Erlie; Wei, Hui; Lin, Dong; Zhang, Guangji; Wei, Shuning; Zhou, Chunlin; Liu, Kaiqi; Wang, Ying; Liu, Bingcheng; Liu, Yuntao; Gong, Benfa; Gong, Xiaoyuan; Feng, Sizhou; Mi, Yingchang; Han, Mingzhe; Wang, Jianxiang

    2017-08-09

    The incidence of acute erythroid leukemia subtype (AEL) is rare, accounting for 5% of cases of acute myeloid leukemia (AML), and the outcome is dismal. However, in 2016 revision to the WHO classification, the subcategory of AEL has been removed. Myeloblasts are redefined as the percentage of total marrow cells, not non-erythroid cells. Therefore, the previously diagnosed AEL cases are currently diagnosed as AML or myelodyspalstic syndrome (MDS) according to new criteria. We respectively reviewed cases of 97 de novo previously diagnosed AEL and all the patients were diagnosed as AML or MDS according to the new classification scheme, and then the clinical characteristics of these two subtypes were compared. Statistical analyses were performed by SPSS software version 18.0. The median age was 37 years-old, the two-thirds of previous AEL cases were diagnosed as MDS, and there was no obvious difference between two subtypes except for male/female ratio and age. Cytogenetic, rather than MDS/AML subtypes, can better represent the prognostic factor of previously diagnosed AEL patients. When the cytogenetic risk of patients belonged to MRC intermediate category and age were below 40 years-old in previous AEL cases, the patients who received induction chemotherapy without transplantation had a similar survival compared with the patients who underwent transplantation (3-year OS: 67.2% vs 68.5%). Cytogenetic, rather than MDS/AML subtypes, can better represent the prognostic factor of previously diagnosed AEL patients. Transplantation was a better choice for those whose cytogenetic category was unfavorable.

  10. Privacy preserving interactive record linkage (PPIRL).

    Science.gov (United States)

    Kum, Hye-Chung; Krishnamurthy, Ashok; Machanavajjhala, Ashwin; Reiter, Michael K; Ahalt, Stanley

    2014-01-01

    Record linkage to integrate uncoordinated databases is critical in biomedical research using Big Data. Balancing privacy protection against the need for high quality record linkage requires a human-machine hybrid system to safely manage uncertainty in the ever changing streams of chaotic Big Data. In the computer science literature, private record linkage is the most published area. It investigates how to apply a known linkage function safely when linking two tables. However, in practice, the linkage function is rarely known. Thus, there are many data linkage centers whose main role is to be the trusted third party to determine the linkage function manually and link data for research via a master population list for a designated region. Recently, a more flexible computerized third-party linkage platform, Secure Decoupled Linkage (SDLink), has been proposed based on: (1) decoupling data via encryption, (2) obfuscation via chaffing (adding fake data) and universe manipulation; and (3) minimum information disclosure via recoding. We synthesize this literature to formalize a new framework for privacy preserving interactive record linkage (PPIRL) with tractable privacy and utility properties and then analyze the literature using this framework. Human-based third-party linkage centers for privacy preserving record linkage are the accepted norm internationally. We find that a computer-based third-party platform that can precisely control the information disclosed at the micro level and allow frequent human interaction during the linkage process, is an effective human-machine hybrid system that significantly improves on the linkage center model both in terms of privacy and utility.

  11. When to conduct probabilistic linkage vs. deterministic linkage? A simulation study.

    Science.gov (United States)

    Zhu, Ying; Matsuyama, Yutaka; Ohashi, Yasuo; Setoguchi, Soko

    2015-08-01

    When unique identifiers are unavailable, successful record linkage depends greatly on data quality and types of variables available. While probabilistic linkage theoretically captures more true matches than deterministic linkage by allowing imperfection in identifiers, studies have shown inconclusive results likely due to variations in data quality, implementation of linkage methodology and validation method. The simulation study aimed to understand data characteristics that affect the performance of probabilistic vs. deterministic linkage. We created ninety-six scenarios that represent real-life situations using non-unique identifiers. We systematically introduced a range of discriminative power, rate of missing and error, and file size to increase linkage patterns and difficulties. We assessed the performance difference of linkage methods using standard validity measures and computation time. Across scenarios, deterministic linkage showed advantage in PPV while probabilistic linkage showed advantage in sensitivity. Probabilistic linkage uniformly outperformed deterministic linkage as the former generated linkages with better trade-off between sensitivity and PPV regardless of data quality. However, with low rate of missing and error in data, deterministic linkage performed not significantly worse. The implementation of deterministic linkage in SAS took less than 1min, and probabilistic linkage took 2min to 2h depending on file size. Our simulation study demonstrated that the intrinsic rate of missing and error of linkage variables was key to choosing between linkage methods. In general, probabilistic linkage was a better choice, but for exceptionally good quality data (<5% error), deterministic linkage was a more resource efficient choice. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Sonographic Measurement of Lower Uterine Segment Thickness to Predict Uterine Rupture During a Trial of Labor in Women With Previous Cesarean Section: A Meta-analysis

    NARCIS (Netherlands)

    Kok, N.; Wiersma, I. C.; Opmeer, B. C.; de Graaf, I. M.; Mol, B. W.; Pajkrt, E.

    2014-01-01

    Along with the increasing rate of cesarean section (CS) births has been a concomitant decrease in the rate of vaginal birth after cesarean (VBAC), mostly due to concerns about uterine rupture during a trial of labor (TOL). The risk of uterine rupture in laboring women with a previous CS must be

  13. Metal loading in Soda Butte Creek upstream of Yellowstone National Park, Montana and Wyoming; a retrospective analysis of previous research; and quantification of metal loading, August 1999

    Science.gov (United States)

    Boughton, G.K.

    2001-01-01

    Acid drainage from historic mining activities has affected the water quality and aquatic biota of Soda Butte Creek upstream of Yellowstone National Park. Numerous investigations focusing on metals contamination have been conducted in the Soda Butte Creek basin, but interpretations of how metals contamination is currently impacting Soda Butte Creek differ greatly. A retrospective analysis of previous research on metal loading in Soda Butte Creek was completed to provide summaries of studies pertinent to metal loading in Soda Butte Creek and to identify data gaps warranting further investigation. Identification and quantification of the sources of metal loading to Soda Butte Creek was recognized as a significant data gap. The McLaren Mine tailings impoundment and mill site has long been identified as a source of metals but its contribution relative to the total metal load entering Yellowstone National Park was unknown. A tracer-injection and synoptic-sampling study was designed to determine metal loads upstream of Yellowstone National Park.A tracer-injection and synoptic-sampling study was conducted on an 8,511-meter reach of Soda Butte Creek from upstream of the McLaren Mine tailings impoundment and mill site downstream to the Yellowstone National Park boundary in August 1999. Synoptic-sampling sites were selected to divide the creek into discrete segments. A lithium bromide tracer was injected continuously into Soda Butte Creek for 24.5 hours. Downstream dilution of the tracer and current-meter measurements were used to calculate the stream discharge. Stream discharge values, combined with constituent concentrations obtained by synoptic sampling, were used to quantify constituent loading in each segment of Soda Butte Creek.Loads were calculated for dissolved calcium, silica, and sulfate, as well as for dissolved and total-recoverable iron, aluminum, and manganese. Loads were not calculated for cadmium, copper, lead, and zinc because these elements were infrequently

  14. Strike-slip tectonics during rift linkage

    Science.gov (United States)

    Pagli, C.; Yun, S. H.; Ebinger, C.; Keir, D.; Wang, H.

    2017-12-01

    The kinematics of triple junction linkage and the initiation of transforms in magmatic rifts remain debated. Strain patterns from the Afar triple junction provide tests of current models of how rifts grow to link in area of incipient oceanic spreading. Here we present a combined analysis of seismicity, InSAR and GPS derived strain rate maps to reveal that the plate boundary deformation in Afar is accommodated primarily by extensional tectonics in the Red Sea and Gulf of Aden rifts, and does not require large rotations about vertical axes (bookshelf faulting). Additionally, models of stress changes and seismicity induced by recent dykes in one sector of the Afar triple junction provide poor fit to the observed strike-slip earthquakes. Instead we explain these patterns as rift-perpendicular shearing at the tips of spreading rifts where extensional strains terminate against less stretched lithosphere. Our results demonstrate that rift-perpendicular strike-slip faulting between rift segments achieves plate boundary linkage during incipient seafloor spreading.

  15. Preliminary genetic linkage map of the abalone Haliotis diversicolor Reeve

    Science.gov (United States)

    Shi, Yaohua; Guo, Ximing; Gu, Zhifeng; Wang, Aimin; Wang, Yan

    2010-05-01

    Haliotis diversicolor Reeve is one of the most important mollusks cultured in South China. Preliminary genetic linkage maps were constructed with amplified fragment length polymorphism (AFLP) markers. A total of 2 596 AFLP markers were obtained from 28 primer combinations in two parents and 78 offsprings. Among them, 412 markers (15.9%) were polymorphic and segregated in the mapping family. Chi-square tests showed that 151 (84.4%) markers segregated according to the expected 1:1 Mendelian ratio ( P<0.05) in the female parent, and 200 (85.8%) in the male parent. For the female map, 179 markers were used for linkage analysis and 90 markers were assigned to 17 linkage groups with an average interval length of 25.7 cm. For the male map, 233 markers were used and 94 were mapped into 18 linkage groups, with an average interval of 25.0 cm. The estimated genome length was 2 773.0 cm for the female and 2 817.1 cm for the male map. The observed length of the linkage map was 1 875.2 cm and 1 896.5 cm for the female and male maps, respectively. When doublets were considered, the map length increased to 2 152.8 cm for the female and 2 032.7 cm for the male map, corresponding to genome coverage of 77.6% and 72.2%, respectively.

  16. Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF.

    Science.gov (United States)

    Hankey, Graeme J; Patel, Manesh R; Stevens, Susanna R; Becker, Richard C; Breithardt, Günter; Carolei, Antonio; Diener, Hans-Christoph; Donnan, Geoffrey A; Halperin, Jonathan L; Mahaffey, Kenneth W; Mas, Jean-Louis; Massaro, Ayrton; Norrving, Bo; Nessel, Christopher C; Paolini, John F; Roine, Risto O; Singer, Daniel E; Wong, Lawrence; Califf, Robert M; Fox, Keith A A; Hacke, Werner

    2012-04-01

    In ROCKET AF, rivaroxaban was non-inferior to adjusted-dose warfarin in preventing stroke or systemic embolism among patients with atrial fibrillation (AF). We aimed to investigate whether the efficacy and safety of rivaroxaban compared with warfarin is consistent among the subgroups of patients with and without previous stroke or transient ischaemic attack (TIA). In ROCKET AF, patients with AF who were at increased risk of stroke were randomly assigned (1:1) in a double-blind manner to rivaroxaban 20 mg daily or adjusted dose warfarin (international normalised ratio 2·0-3·0). Patients and investigators were masked to treatment allocation. Between Dec 18, 2006, and June 17, 2009, 14 264 patients from 1178 centres in 45 countries were randomly assigned. The primary endpoint was the composite of stroke or non-CNS systemic embolism. In this substudy we assessed the interaction of the treatment effects of rivaroxaban and warfarin among patients with and without previous stroke or TIA. Efficacy analyses were by intention to treat and safety analyses were done in the on-treatment population. ROCKET AF is registered with ClinicalTrials.gov, number NCT00403767. 7468 (52%) patients had a previous stroke (n=4907) or TIA (n=2561) and 6796 (48%) had no previous stroke or TIA. The number of events per 100 person-years for the primary endpoint in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (2·79% rivaroxaban vs 2·96% warfarin; hazard ratio [HR] 0·94, 95% CI 0·77-1·16) and those without (1·44%vs 1·88%; 0·77, 0·58-1·01; interaction p=0·23). The number of major and non-major clinically relevant bleeding events per 100 person-years in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (13·31% rivaroxaban vs 13·87% warfarin; HR 0·96, 95% CI 0·87-1·07) and those without (16·69%vs 15·19%; 1·10, 0·99-1·21; interaction p=0·08

  17. 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.

  18. LINKAGE MAPPING OF THE SPINAL MUSCULAR-ATROPHY GENE

    NARCIS (Netherlands)

    BURGHES, AHM; INGRAHAM, SE; KOTEJARAI, Z; ROSENFELD, S; HERTA, N; NADKARNI, N; DIDONATO, CJ; CARPTEN, J; HURKO, O; FLORENCE, J; MOXLEY, RT; COBBEN, JM; MENDELL, [No Value

    Spinal muscular atrophy (SMA) is a common autosomal recessive disorder resulting in loss of motor neurons. We have performed linkage analysis on a panel of families using nine markers that are closely linked to the SMA gene. The highest lod score was obtained with the marker D5S351 (Z(max) = 10.04

  19. International Environmental Problems, Issue Linkage and the European Union

    NARCIS (Netherlands)

    Kroeze-Gil, J.

    2003-01-01

    This thesis explores the circumstances under which issue linkage can be applied to achieve cooperation on international environmental problems in general and on environmental problems in the European Union in particular. A major topic in this thesis is the development and analysis of cooperative and

  20. Improving linkage with substance abuse treatment using brief case management and motivational interviewing.

    Science.gov (United States)

    Rapp, Richard C; Otto, Amy L; Lane, D Timothy; Redko, Cristina; McGatha, Sue; Carlson, Robert G

    2008-04-01

    Poor linkage with substance abuse treatment remains a problem, negating the benefits that can accrue to both substance abusers and the larger society. Numerous behavioral interventions have been tested to determine their potential role in improving linkage. A randomized clinical trial of 678 substance abusers compared the linkage effect of two brief interventions with the referral standard of care (SOC) at a centralized intake unit (CIU). Interventions included five sessions of strengths-based case management (SBCM) or one session of motivational interviewing (MI). A priori hypotheses predicted that both interventions would be better than the standard of care in predicting linkage and that SBCM would be more effective than MI. We analyzed the effect of the two interventions on overall treatment linkage rates and by treatment modality. Logistic regression analysis examined predictors of treatment linkage for the sample and each group. Two hypotheses were confirmed in that SBCM (n=222) was effective in improving linkage compared to the SOC (n=230), 55.0% vs. 38.7% (pMotivational interviewing (n=226) was not significantly more effective in improving linkage than the standard of care (44.7% vs. 38.7%; p>.05). The three trial groups differed only slightly on the client characteristics that predicted linkage with treatment. The results of this study confirm a body of literature that supports the effectiveness of case management in improving linkage with treatment. The role of motivational interviewing in improving linkage was not supported. Results are discussed in the context of other case management and motivational interviewing linkage studies.

  1. Confirmatory linkage study of hypochondroplasia

    Energy Technology Data Exchange (ETDEWEB)

    Hecht, J.T.; Herrera, C.; Greenhaw, G.A. [Univ. of Texas Medical School, Houston, TX (United States)] [and others

    1994-09-01

    Hypochondroplasia is an autosomal dominant form of disproportionate short stature disorder that has clinical and radiographic findings similar to but milder than achondroplasia. Based on these findings it has been suggested that achondroplasia and hypochondroplasia are allelic conditions. We and others have mapped the achondroplasia locus to telomeric region of chromosome 4. Tested linkage to 4p markers in 6 hypochondroplasia families and a maximum LOD score of 1.7 at {theta} = 0 was found for IUDA. Here we report the results of a linkage study in 4 multigenerational families with hypochondroplasia using 7 short tandem repeat markers (D4S127, D4S412, D4S43, D4S115, IUDA, D4S227, D4S169) from the short arm of chromosome 4. These families have been well characterized and show the typical clinical and radiographic features of hypochondroplasia. One family was Afro-American, one Hispanic and two were Caucasian. We found a maximum multipoint LOD score of 2.9 at D4S115. The results of this study provide confirmatory evidence that achondroplasia and hypochondroplasia map to the same chromosomal location and suggests that they are indeed allelic conditions.

  2. A Narrow and Highly Significant Linkage Signal for Severe Bipolar Disorder in the Chromosome 5q33 Region in Latin American Pedigrees

    Science.gov (United States)

    Jasinska, A.J.; Service, S.; Jawaheer, D.; DeYoung, J.; Levinson, M.; Zhang, Z.; Kremeyer, B.; Muller, H.; Aldana, I.; Garcia, J.; Restrepo, G.; Lopez, C.; Palacio, C.; Duque, C.; Parra, M.; Vega, J.; Ortiz, D.; Bedoya, G.; Mathews, C.; Davanzo, P.; Fournier, E.; Bejarano, J.; Ramirez, M.; Ortiz, C. Araya; Araya, X.; Molina, J.; Sabatti, C.; Reus, V.; Ospina, J.; Macaya, G.; Ruiz-Linares, A.; Freimer, N.B.

    2016-01-01

    We previously reported linkage of bipolar disorder to 5q33-q34 in families from two closely related population isolates, the Central Valley of Costa Rica (CVCR) and Antioquia, Colombia (CO). Here we present follow up results from fine-scale mapping in large CVCR and CO families segregating severe bipolar disorder, BP-I, and in 343 population trios/duos from CVCR and CO. Employing densely spaced SNPs to fine map the prior linkage peak region increases linkage evidence and clarifies the position of the putative BP-I locus. We performed two-point linkage analysis with 1134 SNPs in an approximately 9 Mb region between markers D5S410 and D5S422. Combining pedigrees from CVCR and CO yields a LOD score of 4.9 at SNP rs10035961. Two other SNPs (rs7721142 and rs1422795) within the same 94 kb region also displayed LOD scores greater than 4. This linkage peak coincides with our prior microsatellite results and suggests a narrowed BP-I susceptibility regions in these families. To investigate if the locus implicated in the familial form of BP-I also contributes to disease risk in the population, we followed up the family results with association analysis in duo and trio samples, obtaining signals within 2 Mb of the peak linkage signal in the pedigrees; rs12523547 and rs267015 (P = 0.00004 and 0.00016, respectively) in the CO sample and rs244960 in the CVCR sample and the combined sample, with P = 0.00032 and 0.00016, respectively. It remains unclear whether these association results reflect the same locus contributing to BP susceptibility within the extended pedigrees. PMID:19319892

  3. Discrimination of candidate subgenome-specific loci by linkage map construction with an S1population of octoploid strawberry (Fragaria × ananassa).

    Science.gov (United States)

    Nagano, Soichiro; Shirasawa, Kenta; Hirakawa, Hideki; Maeda, Fumi; Ishikawa, Masami; Isobe, Sachiko N

    2017-05-12

    The strawberry, Fragaria × ananassa, is an allo-octoploid (2n = 8x = 56) and outcrossing species. Although it is the most widely consumed berry crop in the world, its complex genome structure has hindered its genetic and genomic analysis, and thus discrimination of subgenome-specific loci among the homoeologous chromosomes is needed. In the present study, we identified candidate subgenome-specific single nucleotide polymorphism (SNP) and simple sequence repeat (SSR) loci, and constructed a linkage map using an S 1 mapping population of the cultivar 'Reikou' with an IStraw90 Axiom® SNP array and previously published SSR markers. The 'Reikou' linkage map consisted of 11,574 loci (11,002 SNPs and 572 SSR loci) spanning 2816.5 cM of 31 linkage groups. The 11,574 loci were located on 4738 unique positions (bin) on the linkage map. Of the mapped loci, 8999 (8588 SNPs and 411 SSR loci) showed a 1:2:1 segregation ratio of AA:AB:BB allele, which suggested the possibility of deriving loci from candidate subgenome-specific sequences. In addition, 2575 loci (2414 SNPs and 161 SSR loci) showed a 3:1 segregation of AB:BB allele, indicating they were derived from homoeologous genomic sequences. Comparative analysis of the homoeologous linkage groups revealed differences in genome structure among the subgenomes. Our results suggest that candidate subgenome-specific loci are randomly located across the genomes, and that there are small- to large-scale structural variations among the subgenomes. The mapped SNPs and SSR loci on the linkage map are expected to be seed points for the construction of pseudomolecules in the octoploid strawberry.

  4. Identification of a previously undetected metabolic defect in the Complex II Caenorhabditis elegans mev-1 mutant strain using respiratory control analysis.

    Science.gov (United States)

    Fong, Sheng; Ng, Li Fang; Ng, Li Theng; Moore, Philip K; Halliwell, Barry; Gruber, Jan

    2017-04-01

    Hypometabolism may play an important role in the pathogenesis of ageing and ageing-related diseases. The nematode Caenorhabditis elegans offers the opportunity to study "living mitochondria" in a small (~1 mm) animal replete with a highly stereotypical, yet complex, anatomy and physiology. Basal oxygen consumption rate is often employed as a proxy for energy metabolism in this context. This parameter is traditionally measured using single-chamber Clark electrodes without the addition of metabolic modulators. Recently, multi-well oxygen electrodes, facilitating addition of metabolic modulators and hence study of respiratory control during different mitochondrial respiration states, have been developed. However, only limited official protocols exist for C. elegans, and key limitations of these techniques are therefore unclear. Following modification and testing of some of the existing protocols, we used these methods to explore mitochondrial bioenergetics in live nematodes of an electron transfer chain Complex II mutant strain, mev-1, and identified a previously undetected metabolic defect. We find that mev-1 mutants cannot respond adequately to increased energy demands, suggesting that oxidative phosphorylation is more severely impaired in these animals than has previously been appreciated.

  5. A Genome Wide Linkage Search for Breast Cancer Susceptibility Genes

    Science.gov (United States)

    Smith, Paula; McGuffog, Lesley; Easton, Douglas F.; Mann, Graham J.; Pupo, Gulietta M.; Newman, Beth; Chenevix-Trench, Georgia; Szabo, Csilla; Southey, Melissa; Renard, Hélène; Odefrey, Fabrice; Lynch, Henry; Stoppa-Lyonnet, Dominique; Couch, Fergus; Hopper, John L.; Giles, Graham G.; McCredie, Margaret R. E.; Buys, Saundra; Andrulis, Irene; Senie, Ruby; Goldgar, David E.; Oldenburg, Rogier; Kroeze-Jansema, Karin; Kraan, Jaennelle; Meijers-Heijboer, Hanne; Klijn, Jan G. M.; van Asperen, Christi; van Leeuwen, Inge; Vasen, Hans F. A.; Cornelisse, Cees J.; Devilee, Peter; Baskcomb, Linda; Seal, Sheila; Barfoot, Rita; Mangion, Jon; Hall, Anita; Edkins, Sarah; Rapley, Elizabeth; Wooster, Richard; Chang-Claude, Jenny; Eccles, Diana; Evans, D. Gareth; Futreal, P. Andrew; Nathanson, Katherine L.; Weber, Barbara L.; Rahman, Nazneen; Stratton, Michael R.

    2009-01-01

    Mutations in known breast cancer susceptibility genes account for a minority of the familial aggregation of the disease. To search for further breast cancer susceptibility genes, we performed a combined analysis of four genome-wide linkage screens, which included a total of 149 multiple case breast cancer families. All families included at least three cases of breast cancer diagnosed below age 60 years, at least one of whom had been tested and found not to carry a BRCA1 or BRCA2 mutation. Evidence for linkage was assessed using parametric linkage analysis, assuming both a dominant and a recessive mode of inheritance, and using nonparametric methods. The highest LOD score obtained in any analysis of the combined data was 1.80 under the dominant model, in a region on chromosome 4 close to marker D4S392. Three further LOD scores over 1 were identified in the parametric analyses and two in the nonparametric analyses. A maximum LOD score of 2.40 was found on chromosome arm 2p in families with four or more cases of breast cancer diagnosed below age 50 years. The number of linkage peaks did not differ from the number expected by chance. These results suggest regions that may harbor novel breast cancer susceptibility genes. They also indicate that no single gene is likely to account for a large fraction of the familial aggregation of breast cancer that is not due to mutations in BRCA1 or BRCA2. PMID:16575876

  6. 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....

  7. Diversity Arrays Technology (DArT) Marker Platforms for Diversity Analysis and Linkage Mapping in a Complex Crop, the Octoploid Cultivated Strawberry (Fragaria × ananassa).

    OpenAIRE

    Sánchez-Sevilla, José F; Horvath, Aniko; Botella, Miguel A; Gaston, Amélia; Folta, Kevin; Kilian, Andrzej; Denoyes, Beatrice; Amaya, Iraida

    2015-01-01

    Cultivated strawberry (Fragaria ? ananassa) is a genetically complex allo-octoploid crop with 28 pairs of chromosomes (2n = 8x = 56) for which a genome sequence is not yet available. The diploid Fragaria vesca is considered the donor species of one of the octoploid sub-genomes and its available genome sequence can be used as a reference for genomic studies. A wide number of strawberry cultivars are stored in ex situ germplasm collections world-wide but a number of previous studies have addres...

  8. Assignment of the murine protein kinase gene DLK to chromosome 15 in the vicinity of the bt/Koa locus by genetic linkage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Toshio; Yanagisawa, Masahiro; Matsubara, Nobumichi [Tokyo Univ. (Japan)] [and others

    1997-03-01

    We have cloned protein kinase genes from murine primordial germ cell-derived EG cells by a PCR-based strategy using degenerate primers corresponding to the conserved sequences in the catalytic domain of protein kinases. One of these clones, designated Gek2 (germ cell kinase 2), was used as a probe for screening of a mouse brain cDNA library and obtained clones contained an entire coding sequence. Comparison of the sequence of Gek2 with those in databases revealed that it was identical to a previously reported protein kinase gene, DLK. 8 refs., 1 fig.

  9. Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials

    DEFF Research Database (Denmark)

    Fayers, Peter M; Palumbo, Antonio; Hulin, Cyrille

    2011-01-01

    The role of thalidomide for previously untreated elderly patients with multiple myeloma remains unclear. Six randomized controlled trials, launched in or after 2000, compared melphalan and prednisone alone (MP) and with thalidomide (MPT). The effect on overall survival (OS) varied across trials. We...... interval 0.73-0.94, P = .004), representing increased median OS time of 6.6 months, from 32.7 months (MP) to 39.3 months (MPT). The thalidomide regimen was also associated with superior PFS (hazard ratio = 0.68, 95% confidence interval 0.61-0.76, P ... or better was 59% on MPT and 37% on MP). Although the trials differed in terms of patient baseline characteristics and thalidomide regimens, there was no evidence that treatment affected OS differently according to levels of the prognostic factors. We conclude that thalidomide added to MP improves OS...

  10. Detection of QTL for Carcass Quality on Chromosome 6 by Exploiting Linkage and Linkage Disequilibrium in Hanwoo

    Directory of Open Access Journals (Sweden)

    J.-H. Lee

    2012-01-01

    Full Text Available The purpose of this study was to improve mapping power and resolution for the QTL influencing carcass quality in Hanwoo, which was previously detected on the bovine chromosome (BTA 6. A sample of 427 steers were chosen, which were the progeny from 45 Korean proven sires in the Hanwoo Improvement Center, Seosan, Korea. The samples were genotyped with the set of 2,535 SNPs on BTA6 that were imbedded in the Illumina bovine 50 k chip. A linkage disequilibrium variance component mapping (LDVCM method, which exploited both linkage between sires and their steers and population-wide linkage disequilibrium, was applied to detect QTL for four carcass quality traits. Fifteen QTL were detected at 0.1% comparison-wise level, for which five, three, five, and two QTL were associated with carcass weight (CWT, backfat thickness (BFT, longissimus dorsi muscle area (LMA, and marbling score (Marb, respectively. The number of QTL was greater compared with our previous results, in which twelve QTL for carcass quality were detected on the BTA6 in the same population by applying other linkage disequilibrium mapping approaches. One QTL for LMA was detected on the distal region (110,285,672 to 110,633,096 bp with the most significant evidence for linkage (p<10−5. Another QTL that was detected on the proximal region (33,596,515 to 33,897,434 bp was pleiotrophic, i.e. influencing CWT, BFT, and LMA. Our results suggest that the LDVCM is a good alternative method for QTL fine-mapping in detection and characterization of QTL.

  11. Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials

    DEFF Research Database (Denmark)

    Fayers, Peter M; Palumbo, Antonio; Hulin, Cyrille

    2011-01-01

    carried out a meta-analysis of the 1685 individual patients in these trials. The primary endpoint was OS, and progression-free survival (PFS) and 1-year response rates were secondary endpoints. There was a highly significant benefit to OS from adding thalidomide to MP (hazard ratio = 0.83; 95% confidence...

  12. Prevalence of high-risk human papillomavirus and cervical intraepithelial neoplasias in a previously unscreened population--a pooled analysis from three studies.

    Science.gov (United States)

    Basu, Partha; Mittal, Srabani; Bhaumik, Suchismita; Mandal, Shyam Sunder; Samaddar, Anusree; Ray, Chinmayi; Siddiqi, Maqsood; Biswas, Jaydip; Sankaranarayanan, Rengaswamy

    2013-04-01

    Population prevalence of human papillomavirus (HPV) and cervical intraepithelial neoplasias (CIN) is an important indicator to judge the disease burden in the community, to monitor the performance of cervical cancer screening program and to assess the impact of HPV vaccination program. India being a country without any cervical cancer screening program has no published data on the population prevalence of CIN and only a few large community-based studies to report the high-risk HPV prevalence. The objective of our study was to study HPV and CIN prevalence in a previously unscreened population. We pooled together the results of three research studies originally designed to assess the performance of visual inspection after acetic acid application and Hybrid Capture 2 (HC 2). Nearly 60% of the screened women had colposcopy irrespective of their screening test results. The diagnosis and grading of cervical neoplasias were based on histology. The age standardized prevalence of HPV by HC 2 test was 6.0%. Age-adjusted prevalence of CIN1 and CIN2 was 2.3% and 0.5%, respectively. The age-adjusted prevalence of CIN3 was 0.4% and that of invasive cancer was 0.2%. The prevalence of high-risk HPV was relatively low in the population we studied, which is reflected in the low prevalence of high-grade CIN. The prevalence of CIN3 remained constant across age groups due to absence of screening. Copyright © 2012 UICC.

  13. Diversity Arrays Technology (DArT Marker Platforms for Diversity Analysis and Linkage Mapping in a Complex Crop, the Octoploid Cultivated Strawberry (Fragaria × ananassa.

    Directory of Open Access Journals (Sweden)

    José F Sánchez-Sevilla

    Full Text Available Cultivated strawberry (Fragaria × ananassa is a genetically complex allo-octoploid crop with 28 pairs of chromosomes (2n = 8x = 56 for which a genome sequence is not yet available. The diploid Fragaria vesca is considered the donor species of one of the octoploid sub-genomes and its available genome sequence can be used as a reference for genomic studies. A wide number of strawberry cultivars are stored in ex situ germplasm collections world-wide but a number of previous studies have addressed the genetic diversity present within a limited number of these collections. Here, we report the development and application of two platforms based on the implementation of Diversity Array Technology (DArT markers for high-throughput genotyping in strawberry. The first DArT microarray was used to evaluate the genetic diversity of 62 strawberry cultivars that represent a wide range of variation based on phenotype, geographical and temporal origin and pedigrees. A total of 603 DArT markers were used to evaluate the diversity and structure of the population and their cluster analyses revealed that these markers were highly efficient in classifying the accessions in groups based on historical, geographical and pedigree-based cues. The second DArTseq platform took benefit of the complexity reduction method optimized for strawberry and the development of next generation sequencing technologies. The strawberry DArTseq was used to generate a total of 9,386 SNP markers in the previously developed '232' × '1392' mapping population, of which, 4,242 high quality markers were further selected to saturate this map after several filtering steps. The high-throughput platforms here developed for genotyping strawberry will facilitate genome-wide characterizations of large accessions sets and complement other available options.

  14. Diversity Arrays Technology (DArT) Marker Platforms for Diversity Analysis and Linkage Mapping in a Complex Crop, the Octoploid Cultivated Strawberry (Fragaria × ananassa).

    Science.gov (United States)

    Sánchez-Sevilla, José F; Horvath, Aniko; Botella, Miguel A; Gaston, Amèlia; Folta, Kevin; Kilian, Andrzej; Denoyes, Beatrice; Amaya, Iraida

    2015-01-01

    Cultivated strawberry (Fragaria × ananassa) is a genetically complex allo-octoploid crop with 28 pairs of chromosomes (2n = 8x = 56) for which a genome sequence is not yet available. The diploid Fragaria vesca is considered the donor species of one of the octoploid sub-genomes and its available genome sequence can be used as a reference for genomic studies. A wide number of strawberry cultivars are stored in ex situ germplasm collections world-wide but a number of previous studies have addressed the genetic diversity present within a limited number of these collections. Here, we report the development and application of two platforms based on the implementation of Diversity Array Technology (DArT) markers for high-throughput genotyping in strawberry. The first DArT microarray was used to evaluate the genetic diversity of 62 strawberry cultivars that represent a wide range of variation based on phenotype, geographical and temporal origin and pedigrees. A total of 603 DArT markers were used to evaluate the diversity and structure of the population and their cluster analyses revealed that these markers were highly efficient in classifying the accessions in groups based on historical, geographical and pedigree-based cues. The second DArTseq platform took benefit of the complexity reduction method optimized for strawberry and the development of next generation sequencing technologies. The strawberry DArTseq was used to generate a total of 9,386 SNP markers in the previously developed '232' × '1392' mapping population, of which, 4,242 high quality markers were further selected to saturate this map after several filtering steps. The high-throughput platforms here developed for genotyping strawberry will facilitate genome-wide characterizations of large accessions sets and complement other available options.

  15. Genome-wide linkage and association scans for pulse pressure in Chinese twins.

    Science.gov (United States)

    Zhang, Dongfeng; Pang, Zengchang; Li, Shuxia; Jiang, Wenjie; Wang, Shaojie; Thomassen, Mads; Hjelmborg, Jacob V B; Kruse, Torben A; Ohm Kyvik, Kirsten; Christensen, Kaare; Zhu, Gu; Tan, Qihua

    2012-11-01

    Elevated pulse pressure (PP) is associated with cardiovascular disorders and mortality in various populations. The genetic influence on PP has been confirmed by heritability estimates using related individuals. Recently, efforts have been made by mapping genes that are linked to the phenotype. We report the results of our gene mapping studies conducted in the Chinese population in mainland China. The genome-wide linkage and association scans were carried out on 63 middle-aged dizygotic twin pairs using high-density markers. The linkage analysis identified three significant linkage peaks (all with a single point Ppeaks closely overlapping with linkage peaks reported by two American studies. Multiple regions with suggestive linkages were identified, with many of the peaks overlapping with published linkage regions. The genome-wide association analysis detected a suggestive association on chromosome 4 (rs17031508, P<8.34e(-08)) located within a wide region of suggestive linkage. Our results provide some evidence for genetic linkages and associations with PP in the Chinese population. Further investigation is warranted to replicate the findings and to explore the susceptibility loci or genes for PP.

  16. Single Nucleotide Polymorphism Identification, Characterization, and Linkage Mapping in Quinoa

    Directory of Open Access Journals (Sweden)

    P. J. Maughan

    2012-11-01

    Full Text Available Quinoa ( Willd. is an important seed crop throughout the Andean region of South America. It is important as a regional food security crop for millions of impoverished rural inhabitants of the Andean Altiplano (high plains. Efforts to improve the crop have led to an increased focus on genetic research. We report the identification of 14,178 putative single nucleotide polymorphisms (SNPs using a genomic reduction protocol as well as the development of 511 functional SNP assays. The SNP assays are based on KASPar genotyping chemistry and were detected using the Fluidigm dynamic array platform. A diversity screen of 113 quinoa accessions showed that the minor allele frequency (MAF of the SNPs ranged from 0.02 to 0.50, with an average MAF of 0.28. Structure analysis of the quinoa diversity panel uncovered the two major subgroups corresponding to the Andean and coastal quinoa ecotypes. Linkage mapping of the SNPs in two recombinant inbred line populations produced an integrated linkage map consisting of 29 linkage groups with 20 large linkage groups, spanning 1404 cM with a marker density of 3.1 cM per SNP marker. The SNPs identified here represent important genomic tools needed in emerging plant breeding programs for advanced genetic analysis of agronomic traits in quinoa.

  17. Buprenorphine Initiation and Linkage to Outpatient Buprenorphine do not Reduce Frequency of Injection Opiate Use Following Hospitalization.

    Science.gov (United States)

    Cushman, Phoebe A; Liebschutz, Jane M; Anderson, Bradley J; Moreau, Merredith R; Stein, Michael D

    2016-09-01

    Buprenorphine has established effectiveness for outpatient treatment of opioid use disorder. Our previously published STOP (Suboxone Transition to Opiate Program) trial showed that buprenorphine induction, stabilization, and linkage to outpatient treatment in opioid-dependent inpatients (injection and non-injection drug users) decreased illicit opioid use over 6months. The present study was a planned subgroup analysis of injection opiate users from STOP. To determine if inpatient buprenorphine initiation and linkage to outpatient buprenorphine reduce injection opiate users' frequency of injection opiate use (IOU). Inpatient injection opiate users at a safety-net hospital were randomized to buprenorphine linkage (induction, stabilization, bridge prescription, and facilitated referral to outpatient treatment) or detoxification (5-day inpatient buprenorphine taper). Conditional fixed-effects Poisson regression was used to estimate the effects of intervention on 30-day (self-report) at 1, 3, and 6months, measured using 30-day timeline follow-back. The secondary outcome was linkage effectiveness, measured as % presenting to initial outpatient buprenorphine visits after hospital discharge. Analysis was limited to persons (n=62 randomized to detoxification and n=51 to linkage) with baseline IOU. There were no significant differences in age, ethnicity, or baseline IOU frequency. At follow-up, linkage patients (70.6%) were significantly more likely (pbuprenorphine visits than detoxification patients (9.7%). However, there was no significant between group difference in the rate of IOU at 1- (IRR=0.73, p=0.32), 3- (IRR=1.20, p=0.54), or 6-month (IRR=0.73, p=0.23) follow-ups. Using person-day analysis, participants self-reported IOU on 5.8% of follow-up days in which they used prescription buprenorphine and 37.5% of non-buprenorphine days. Using a generalized estimating equation, the estimated odds of IOU was 4.57 times higher (pbuprenorphine days. Despite STOP's success in

  18. Structural analysis of eight novel and 112 previously reported missense mutations in the interactive FXI mutation database reveals new insight on FXI deficiency.

    Science.gov (United States)

    Saunders, Rebecca E; Shiltagh, Nuha; Gomez, Keith; Mellars, Gillian; Cooper, Carolyn; Perry, David J; Tuddenham, Edward G; Perkins, Stephen J

    2009-08-01

    Factor XI (FXI) functions in blood coagulation. FXI is composed of four apple (Ap) domains and a serine protease (SP) domain. Deficiency of FXI leads to an injury-related bleeding disorder, which is remarkable for the lack of correlation between bleeding symptoms and FXI coagulant activity (FXI:C). The number of mutations previously reported in our interactive web database (http://www.FactorXI.org) is now significantly increased to 183 through our new patient studies and from literature surveys. Eight novel missense mutations give a total of 120 throughout the FXI gene (F11). The most abundant defects in FXI are revealed to be those from low-protein plasma levels (Type I: CRM-) that originate from protein misfolding, rather than from functional defects (Type II: CRM+). A total of 70 Ap missense mutations were analysed using a consensus Ap domain structure generated from the FXI dimer crystal structure. This showed that all parts of the Ap domain were affected. The 47 SP missense mutations were also distributed throughout the SP domain structure. The periphery of the Ap beta-sheet structure is sensitive to structural perturbation caused by residue changes throughout the Ap domain, yet this beta-sheet is crucial for FXI dimer formation. Residues located at the Ap4:Ap4 interface in the dimer are much less directly involved. We conclude that the abundance of Type I defects in FXI results from the sensitivity of the Ap domain folding to residue changes within this, and discuss how structural knowledge of the mutations improves our understanding of FXI deficiencies.

  19. An analysis of discrepancies between United Kingdom cancer research funding and societal burden and a comparison to previous and United States values.

    Science.gov (United States)

    Carter, Ashley J R; Delarosa, Beverly; Hur, Hannah

    2015-11-02

    Ideally, the allocation of research funding for each specific type of cancer should be proportional to its societal burden. This burden can be estimated with the metric 'years of life lost' (YLL), which combines overall mortality and age at death. Using United Kingdom data from 2010, we compared research funding from the National Cancer Research Institute to this YLL burden metric for 26 types of cancers in order to identify the discrepancies between cancer research funding allocation and societal burden. We also compared these values to United States data from 2010 and United Kingdom data published in 2005. Our study revealed a number of discrepancies between cancer research funding and burden. Some cancers are funded at levels far higher than their relative burden suggests (testicular, leukaemia, Hodgkin's lymphoma, breast, cervical, ovarian, prostate) while other cancers appear under-funded (gallbladder, lung, nasopharyngeal, intestine, stomach, pancreatic, thyroid, oesophageal, liver, kidney, bladder, and brain/central nervous system). United Kingdom funding patterns over the past decade have generally moved to increase funding to previously under-funded cancers with one notable exception showing a converse trend (breast cancer). The broad relationship between United Kingdom and United States funding patterns is similar with a few exceptions (e.g. leukaemia, Hodgkin's lymphoma, prostate, testicular cancer). There are discrepancies between cancer research funding allocation and societal burden in the United Kingdom. These discrepancies are broadly similar in both the United Kingdom and the United States and, while they appear to be improving, this is not consistent across all types of cancer.

  20. The dopamine transporter protein gene (SLC6A3): Primary linage mapping and linkage studies in Tourette syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Gelernter, J.; Kruger, S.D.; Pakstis, A.J. [Yale Univ., New Haven, CT (United States)]|[West Haven Veterans Affairs Medical Center, CT (United States)] [and others

    1995-12-10

    The dopamine transporter, the molecule responsible for presynaptic reuptake of dopamine and a major site of action of psychostimulant drugs, including cocaine, is encoded by locus SLC6A3 (alias DAT1). The protein`s actions and DAT`s specific localization to dopaminergic neurons make it a candidate gene for several psychiatric illnesses. SLC6A3 has been mapped to distal chromosome 5p, using physical methods. Genetic linkage methods were used to place SLC6A3 in the genetic linkage map. Four extended pedigrees (one of which overlaps with CEPH) were typed. Linkage with Tourette syndrome (TS) was also examined. SLC6A3 showed close linkage with several markers previously mapped to distal chromosome 5p, including D5S11 (Z{sub max} = 16.0, {theta}{sub M} = {theta}{sub F} = 0.03, results from four families) and D5S678 (Z{sub max} = 7.84, {theta}{sub M} = {theta}{sub F} = 0, results from two families). Observed crossovers established that SLC6A3 is a distal marker close to D5S10 and D5S678, but these three distal markers could not be ordered. Linkage between TS and SLC6A3 could be excluded independently in two branches of a large kindred segregating TS; the lod score in a third family was also negative, but not significant. Cumulative results show a lod score of -6.2 at {theta} = 0 and of -3.9 at {theta} = 0.05 (dominant model, narrow disease definition). SLC6A3 thus maps to distal chromosome 5p by linkage analysis, in agreement with previous physical mapping data. A mutation at SLC6A3 is not causative for TS in the two large families that generated significant negative lod scores (if the parameters of our analyses were correct) and is unlikely to be causative in the family that generated a negative lod score that did not reach significance. These results do not exclude a role for the dopamine transporter in influencing risk for TS in combination with other loci. 23 refs., 1 fig., 2 tabs.

  1. 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

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

    Science.gov (United States)

    Amoroso, Cheryl; Proudfoot, Judith; Bubner, Tanya; Jayasinghe, Upali W; Holton, Christine; Winstanley, Julie; Beilby, Justin; Harris, Mark F

    2007-12-03

    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. 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. 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. 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 exploring the impact, outcomes, and facilitators of high

  3. [Lower uterine segment thickness measurement in pregnant women with previous caesarean section: intra- and interobserver reliability analysis using bi- and tridimensional ultrasonography].

    Science.gov (United States)

    Barra, Daniela de Abreu; Martins, Wellington de Paula; Gallarretta, Francisco Maximilliano; Nastri, Carolina Oliveira; Nicolau, Luis Guilherme; Mauad Filho, Francisco

    2008-03-01

    to compare the intra and interobserver reproducibility of the total thickness measurement of the inferior uterine segment (IUS), through the abdominal route, and of the muscle layer measurement, through the vaginal route, using bi and tridimensional ultrasonography. the IUS thickness measurement of 30 women, between the 36th and 39th weeks of gestation with previous caesarean section, done by two observers, was studied. Abdominal ultrasonography with the patient in both supine and lithotomy position was performed. In the sagittal section, the IUS was identified and four bidimensional images and two tridimensional blocks of the total thickness were collected through the abdominal route, and the same for the muscle layer, through the vaginal route. Tridimensional acquisitions were manipulated in the multiplanar mode. The time was measured with a chronometer. Reproducibility was evaluated by the computation of the absolute difference between measurements, the ratio of differences smaller than 1 mm, the intraclass coefficient (ICC), and the Bland and Altman's concordance limits. the average bidimensional measurement of IUS thickness was 7.4 mm through the abdominal and 2.7 mm through the vaginal route, and the tridimensional measurement was 6.9 mm through the abdominal and 5.1 mm through the vaginal route. Intra- and interobserver reproducibility of vaginal versus abdominal route: smaller absolute difference (0.2-0.4 mm versus 0.8-1.5 mm), greater ratio of differences (85.8-97.8% versus 48.7-72,8%), with p0.05[A1] and similar lower concordance limits (-38 to 3.4 versus -3.6 to 4 mm) for tridimensional ultrasonography and ICC (0.6-0.9 versus 0.7-0.9). from the above, we came to the conclusion that the measurement of the IUS muscle layer, through the vaginal route using tridimensional ultrasonography is more reproducible. Nevertheless, our results do not indicate that this measurement shows any clinical evidence to predict uterine tear, as that was not the aim of this

  4. Building linkages and bargaining power between smallholder ...

    African Journals Online (AJOL)

    Mo

    This paper emphasizes the importance of facilitating the process of linkages between smallholder farmers and service providers as ... have used the same principles to form linkages with fertiliser suppliers to access other inputs such as manures, ... however, be used for other innovation systems in community development.

  5. Linkage activities amongst researchers, extension agents, farmers ...

    African Journals Online (AJOL)

    This paper examined the research- extension- farmer- input dealer and marketer linkage activities in the North West Province of South Africa. A simple random sampling technique was used to select researchers, extension agents, farmers, agricultural input dealers and marketers. Their responses in linkage activities were ...

  6. Anthropological analysis of differences in psychomotor skills area high school students and their linkages with the formal representation of kinesiological education classes in the curriculum

    Directory of Open Access Journals (Sweden)

    Bešović Milica

    2012-01-01

    Full Text Available In order to determine differences in anthropological space psychomotor skills and their connection with the formal representation of kinesiological education classes in the curriculum of secondary school students, conducted the study in part on a simple random sample of 200 female high school population of entities, which are described with 7 sets of primary psychomotor indicators. According to the criterion of formal representation of kinesiological education classes in the curriculum, the sample was stratified on the subsample with two or four hours a week. To determine the difference discriminant analysis was applied. According to the actual parameters, confirmed the initial assumption that the system of psychomotor variables and criterion variables no statistically significant association, then it was concluded that the results do not contradict current scientific knowledge indicated the need and transition model curriculum in favor of the treated population biopsihosocijalnog integrity of its entities.

  7. Conformational differences in protein disulfide linkages between normal hair and hair from subjects with trichothiodystrophy: a quantitative analysis by Raman microspectroscopy.

    Science.gov (United States)

    Schlücker, S; Liang, C; Strehle, K R; DiGiovanna, J J; Kraemer, K H; Levin, I W

    2006-08-15

    Raman spectra of normal hair shafts and hair shafts from patients exhibiting trichothiodystrophy (TTD) were obtained using line focus laser illumination. Because hair from TTD patients has a significant decrease in the content of the sulfur-containing amino acids in comparison to normal hair, the 550-500 cm(-1) disulfide stretching mode region of the Raman spectrum was examined in detail. A quantitative spectral analysis demonstrates significant increases in the two energetically less favored gauche-gauche-trans (g-g-t) and trans-gauche-trans (t-g-t) forms. These observations suggest that the increased amounts of these less stable disulfide conformers are contributing factors to or associated with the hair brittleness observed for this congenital disorder. Structure-spectra correlations for the three dominant disulfide conformers are confirmed by quantum chemical calculations using modern density functional theory (DFT). Copyright 2006 Wiley Periodicals, Inc.

  8. Wagner vitreoretinal degeneration with genetic linkage refinement on chromosome 5q13-q14.

    Science.gov (United States)

    Zech, J C; Morlé, L; Vincent, P; Alloisio, N; Bozon, M; Gonnet, C; Milazzo, S; Grange, J D; Trepsat, C; Godet, J; Plauchu, H

    1999-05-01

    It has been previously described that Wagner disease is linked to chromosome 5q13-q14. This study was carried out to describe the ophthalmological aspects and report the results of genetic linkage analysis in a large pedigree affected by Wagner disease. Fourty members of one same family agreed to be examined. Twenty patients presented vitreoretinal degeneration in both eyes without any extra-ocular abnormalities. In young patients, visual acuity was usually normal after correction of frequent mild myopia. Presenile cataracts progressed by the third decade and required removal for visual rehabilitation. The primary disorder involved an abnormal vitreous. A few avascular vitreous bands were usually the only optical feature in the mostly empty vitreous cavity. A circumferential vitreous condensation formed in contact with the retina on many spots. Less common retinal findings included retinal detachment, abnormal retinal pigmentation, progressive atrophy of the RPE simulating choroideremia and lattice degeneration. Genetic analysis revealed a highly significant linkage (lod score >5.0) between the disease and 10 markers of the chromosome 5q13-q14 region. Two recombination events allowed us to refine the linked interval to 20 cM between the D5S650 and D5S618 markers. Ophthalmological aspects of Wagner's disease appear to progress with age. Regular ophthalmological examination is important for detecting retinal abnormalities. The gene involved in Wagner's disease lies in a 20 cM interval on chromosome 5q13-q14.

  9. The Fibromyalgia Family Study: A Genome-Scan Linkage Study

    Science.gov (United States)

    Arnold, Lesley M.; Fan, Jinbo; Russell, I. Jon; Yunus, Muhammad B.; Khan, Muhammad Asim; Kushner, Irving; Olson, Jane M.; Iyengar, Sudha K.

    2013-01-01

    Objective Familial aggregation of fibromyalgia has been increasingly recognized. The goal of the current study was to conduct a genome wide linkage scan to identify susceptibility loci for fibromyalgia. Methods We genotyped members of 116 families from the Fibromyalgia Family Study and performed a model-free genome-wide linkage analysis of fibromyalgia with 341 microsatellite markers, using the Haseman-Elston regression approach. Results The estimated sibling recurrence risk ratio (λs) for fibromyalgia was 13.6 (95% CI: 10.0–18.5), based on a reported population prevalence of 2%. Genome-wide suggestive evidence of linkage was found at marker D17S2196 (Empirical P =0.00030) and D17S1294 (Empirical P =0.00035) on chromosome 17p11.2-q11.2. Conclusion The estimated sibling recurrence risk ratio suggests a strong genetic component of fibromyalgia. This is the first study to report genome-wide suggestive linkage of fibromyalgia to the chromosome 17p11.2-q11.2 region. Further investigation of these multi-case families from the Fibromyalgia Family Study is warranted to identify potential causal risk variants for fibromyalgia. PMID:23280346

  10. Confirmation of linkage of Best`s macular dystrophy to 11q13, and evidence for genetic heterogeneity

    Energy Technology Data Exchange (ETDEWEB)

    Mansergh, F.C.; Kenna, P.F.; Farrar, G.J. [Trinity College, Dublin (United Kingdom)] [and others

    1994-09-01

    Best`s macular dystrophy, also known as vitelliform macular degeneration, is an autosomal dominant, early onset form of macular degeneration. The disease is characterized by a roughly circular deposit of lipofuscin beneath the pigment epithelium of the retinal macula. Linkage studies were performed in two families, one Irish and one German, segregating typical Best`s macular dystrophy. In the Irish family (BTMD1), linkage analysis mapped the disease causing gene to chromosome 11q13, in a 10 cM region between the microsatellite markers PYGM and D11S871. Both markers showed different recombinants with the disease phenotype. This is a region that has previously shown linkage in families affected with Best`s macular dystrophy. Lod scores of 9.63, 9.12, 6.92, and 6.83 at zero recombination, were obtained with markers D11S1344, D11S1361, D11S1357 and D11S903, respectively. This data places the disease locus definitvely within the region between PYGM and D11S871. Linkage has been significantly excluded in this region in the German family (FamE), thereby providing evidence for genetic heterogeneity in this disease. The retinal specific gene, rod outer membrane protein 1 (ROM1), which maps to this region, has been screened for mutations in family BTMD1 by SSCPE analysis and by direct sequencing. Some of the promoter region, the three exons, and both introns have been sequenced; however, no mutations were found. It is likely that a gene other than ROM1 within this region may be responsible for causing the disease phenotype.

  11. Linkage experiment at Mt. Chacaltaya

    International Nuclear Information System (INIS)

    Honda, Ken

    1983-01-01

    At Mt. Chakaltaya, AS-EC linkage experiments have been made to study the hadrons and the high energy gamma-ray at the center of air showers. Thirty-five particle detectors for air showers were distributed in an area of radius 50 m. At the center, X-ray films were inserted at intervals of 2 c.u. in lead stack. Under this detector, there was a burst detector. The correspondence of the data of an emulsion chamber (EC) and those of an air shower was determined. The correspondence of high energy events was found easily, but it became hard in case of the events with energy less than 10 TeV. The age distribution of burst data was obtained. The air showers with large burst size had, on an average, young age. The lateral distribution of burst size was obtained. The results suggested that the age was an important parameter of the development of air showers. In the case of large burst size, the energy was large. (Kato, T.)

  12. Using Linkage Maps as a Tool To Determine Patterns of Chromosome Synteny in the Genus Salvelinus

    Directory of Open Access Journals (Sweden)

    Matthew C. Hale

    2017-11-01

    Full Text Available Next generation sequencing techniques have revolutionized the collection of genome and transcriptome data from nonmodel organisms. This manuscript details the application of restriction site-associated DNA sequencing (RADseq to generate a marker-dense genetic map for Brook Trout (Salvelinus fontinalis. The consensus map was constructed from three full-sib families totaling 176 F1 individuals. The map consisted of 42 linkage groups with a total female map size of 2502.5 cM, and a total male map size of 1863.8 cM. Synteny was confirmed with Atlantic Salmon for 38 linkage groups, with Rainbow Trout for 37 linkage groups, Arctic Char for 36 linkage groups, and with a previously published Brook Trout linkage map for 39 linkage groups. Comparative mapping confirmed the presence of 8 metacentric and 34 acrocentric chromosomes in Brook Trout. Six metacentric chromosomes seem to be conserved with Arctic Char suggesting there have been at least two species-specific fusion and fission events within the genus Salvelinus. In addition, the sex marker (sdY; sexually dimorphic on the Y chromosome was mapped to Brook Trout BC35, which is homologous with Atlantic Salmon Ssa09qa, Rainbow Trout Omy25, and Arctic Char AC04q. Ultimately, this linkage map will be a useful resource for studies on the genome organization of Salvelinus, and facilitates comparisons of the Salvelinus genome with Salmo and Oncorhynchus.

  13. A high-density linkage map and QTL mapping of fruit-related traits in pumpkin (Cucurbita moschata Duch.).

    Science.gov (United States)

    Zhong, Yu-Juan; Zhou, Yang-Yang; Li, Jun-Xing; Yu, Ting; Wu, Ting-Quan; Luo, Jian-Ning; Luo, Shao-Bo; Huang, He-Xun

    2017-10-06

    Pumpkin (Cucurbita moschata) is an economically worldwide crop. Few quantitative trait loci (QTLs) were reported previously due to the lack of genomic and genetic resources. In this study, a high-density linkage map of C. moschata was structured by double-digest restriction site-associated DNA sequencing, using 200 F2 individuals of CMO-1 × CMO-97. By filtering 74,899 SNPs, a total of 3,470 high quality SNP markers were assigned to the map spanning a total genetic distance of 3087.03 cM on 20 linkage groups (LGs) with an average genetic distance of 0.89 cM. Based on this map, both pericarp color and strip were fined mapped to a novel single locus on LG8 in the same region of 0.31 cM with phenotypic variance explained (PVE) of 93.6% and 90.2%, respectively. QTL analysis was also performed on carotenoids, sugars, tuberculate fruit, fruit diameter, thickness and chamber width with a total of 12 traits. 29 QTLs distributed in 9 LGs were detected with PVE from 9.6% to 28.6%. It was the first high-density linkage SNP map for C. moschata which was proved to be a valuable tool for gene or QTL mapping. This information will serve as significant basis for map-based gene cloning, draft genome assembling and molecular breeding.

  14. A Consensus Genetic Map for Pinus taeda and Pinus elliottii and Extent of Linkage Disequilibrium in Two Genotype-Phenotype Discovery Populations of Pinus taeda.

    Science.gov (United States)

    Westbrook, Jared W; Chhatre, Vikram E; Wu, Le-Shin; Chamala, Srikar; Neves, Leandro Gomide; Muñoz, Patricio; Martínez-García, Pedro J; Neale, David B; Kirst, Matias; Mockaitis, Keithanne; Nelson, C Dana; Peter, Gary F; Davis, John M; Echt, Craig S

    2015-06-11

    A consensus genetic map for Pinus taeda (loblolly pine) and Pinus elliottii (slash pine) was constructed by merging three previously published P. taeda maps with a map from a pseudo-backcross between P. elliottii and P. taeda. The consensus map positioned 3856 markers via genotyping of 1251 individuals from four pedigrees. It is the densest linkage map for a conifer to date. Average marker spacing was 0.6 cM and total map length was 2305 cM. Functional predictions of mapped genes were improved by aligning expressed sequence tags used for marker discovery to full-length P. taeda transcripts. Alignments to the P. taeda genome mapped 3305 scaffold sequences onto 12 linkage groups. The consensus genetic map was used to compare the genome-wide linkage disequilibrium in a population of distantly related P. taeda individuals (ADEPT2) used for association genetic studies and a multiple-family pedigree used for genomic selection (CCLONES). The prevalence and extent of LD was greater in CCLONES as compared to ADEPT2; however, extended LD with LGs or between LGs was rare in both populations. The average squared correlations, r(2), between SNP alleles less than 1 cM apart were less than 0.05 in both populations and r(2) did not decay substantially with genetic distance. The consensus map and analysis of linkage disequilibrium establish a foundation for comparative association mapping and genomic selection in P. taeda and P. elliottii. Copyright © 2015 Westbrook et al.

  15. A genome-wide scan for autoimmune thyroiditis in the Old Order Amish: replication of genetic linkage on chromosome 5q11.2-q14.3.

    Science.gov (United States)

    Allen, Elsie M; Hsueh, Wen-Chi; Sabra, Mona M; Pollin, Toni I; Ladenson, Paul W; Silver, Kristi D; Mitchell, Braxton D; Shuldiner, Alan R

    2003-03-01

    Autoimmune thyroiditis (AITD) is a common disorder characterized by circulating antibodies to epitopes of thyroid tissue and hypothyroidism (Hashimoto's thyroiditis or AITD-hypothyroidism), although many subjects with AITD are euthyroid. Current evidence suggests that AITD is familial and polygenic. We studied AITD in a homogeneous founder Caucasian population, the Old Order Amish of Lancaster County, Pennsylvania. We found autoimmune thyroiditis, defined by the presence of circulating antimicrosomal antibodies, to be relatively common in the Amish, with a prevalence of 22.7%. The prevalence of AITD-hypothyroidism was 9.2%. We performed a genome-wide linkage analysis with 373 short tandem repeat markers in 445 subjects from 29 families. We observed suggestive evidence of linkage of AITD to a locus on chromosome 5q11.2-q14.3 (LOD, 2.30; P = 0.0006 at 94 cM; closest marker, D5S428), a region that was previously reported to be linked to AITD-hypothyroidism in a Japanese study. AITD-hypothyroidism showed a more modest linkage peak to the same region (LOD, 1.46; P = 0.005). Possible linkage (nominal P Amish.

  16. Heritability and genome-wide linkage scan of subjective happiness.

    Science.gov (United States)

    Bartels, Meike; Saviouk, Viatcheslav; de Moor, Marleen H M; Willemsen, Gonneke; van Beijsterveldt, Toos C E M; Hottenga, Jouke-Jan; de Geus, Eco J C; Boomsma, Dorret I

    2010-04-01

    Causes of individual differences in happiness, as assessed with the Subjective Happiness Scale, are investigated in a large of sample twins and siblings from the Netherlands Twin Register. Over 12,000 twins and siblings, average age 24.7 years (range 12 to 88), took part in the study. A genetic model with an age by sex design was fitted to the data with structural equation modeling in Mx. The heritability of happiness was estimated at 22% for males and 41% in females. No effect of age was observed. To identify the genomic regions contributing to this heritability, a genome-wide linkage study for happiness was conducted in sibling pairs. A subsample of 1157 offspring from 441 families was genotyped with an average of 371 micro-satellite markers per individual. Phenotype and genotype data were analyzed in MERLIN with multipoint variance component linkage analysis and age and sex as covariates. A linkage signal (logarithm of odds score 2.73, empirical p value 0.095) was obtained at the end of the long arm of chromosome 19 for marker D19S254 at 110 cM. A second suggestive linkage peak was found at the short arm of chromosome 1 (LOD of 2.37) at 153 cM, marker D1S534 (empirical p value of .209). These two regions of interest are not overlapping with the regions found for contrasting phenotypes (such as depression, which is negatively associated with happiness). Further linkage and future association studies are warranted.

  17. 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.

  18. Effect of B vitamins and lowering homocysteine on cognitive impairment in patients with previous stroke or transient ischemic attack: a prespecified secondary analysis of a randomized, placebo-controlled trial and meta-analysis.

    Science.gov (United States)

    Hankey, Graeme J; Ford, Andrew H; Yi, Qilong; Eikelboom, John W; Lees, Kennedy R; Chen, Christopher; Xavier, Denis; Navarro, Jose C; Ranawaka, Udaya K; Uddin, Wasim; Ricci, Stefano; Gommans, John; Schmidt, Reinhold; Almeida, Osvaldo P; van Bockxmeer, Frank M

    2013-08-01

    High plasma total homocysteine (tHcy) has been associated with cognitive impairment but lowering tHcy with B-vitamins has produced equivocal results. We aimed to determine whether B-vitamin supplementation would reduce tHcy and the incidence of new cognitive impairment among individuals with stroke or transient ischemic attack≥6 months previously. A total of 8164 patients with stroke or transient ischemic attack were randomly allocated to double-blind treatment with one tablet daily of B-vitamins (folic acid, 2 mg; vitamin B6, 25 mg; vitamin B12, 500 μg) or placebo and followed up for 3.4 years (median) in the VITAmins TO Prevent Stroke (VITATOPS) trial. For this prespecified secondary analysis of VITATOPS, the primary outcome was a new diagnosis of cognitive impairment, defined as a Mini-Mental State Examination (MMSE) score6 months after the qualifying stroke; 2608 participants were cognitively unimpaired (MMSE≥24), of whom 2214 participants (1110 B-vitamins versus 1104 placebo) had follow-up MMSEs during 2.8 years (median). At final follow-up, allocation to B-vitamins, compared with placebo, was associated with a reduction in mean tHcy (10.2 μmol/L versus 14.2 μmol/L; Pvitamin B6, and vitamin B12 to a self-selected clinical trial cohort of cognitively unimpaired patients with previous stroke or transient ischemic attack lowered mean tHcy but had no effect on the incidence of cognitive impairment or cognitive decline, as measured by the MMSE, during a median of 2.8 years. URL: http://www.controlled-trials.com. Unique identifier: ISRCTN74743444; URL: http://www.clinicaltrials.gov. Unique identifier: NCT00097669.

  19. A genetic linkage map for the saltwater crocodile (Crocodylus porosus

    Directory of Open Access Journals (Sweden)

    Lance Stacey L

    2009-07-01

    Full Text Available Abstract Background Genome elucidation is now in high gear for many organisms, and whilst genetic maps have been developed for a broad array of species, surprisingly, no such maps exist for a crocodilian, or indeed any other non-avian member of the Class Reptilia. Genetic linkage maps are essential tools for the mapping and dissection of complex quantitative trait loci (QTL, and in order to permit systematic genome scans for the identification of genes affecting economically important traits in farmed crocodilians, a comprehensive genetic linage map will be necessary. Results A first-generation genetic linkage map for the saltwater crocodile (Crocodylus porosus was constructed using 203 microsatellite markers amplified across a two-generation pedigree comprising ten full-sib families from a commercial population at Darwin Crocodile Farm, Northern Territory, Australia. Linkage analyses identified fourteen linkage groups comprising a total of 180 loci, with 23 loci remaining unlinked. Markers were ordered within linkage groups employing a heuristic approach using CRIMAP v3.0 software. The estimated female and male recombination map lengths were 1824.1 and 319.0 centimorgans (cM respectively, revealing an uncommonly large disparity in recombination map lengths between sexes (ratio of 5.7:1. Conclusion We have generated the first genetic linkage map for a crocodilian, or indeed any other non-avian reptile. The uncommonly large disparity in recombination map lengths confirms previous preliminary evidence of major differences in sex-specific recombination rates in a species that exhibits temperature-dependent sex determination (TSD. However, at this point the reason for this disparity in saltwater crocodiles remains unclear. This map will be a valuable resource for crocodilian researchers, facilitating the systematic genome scans necessary for identifying genes affecting complex traits of economic importance in the crocodile industry. In addition

  20. Linkage disequilibrium and population structure in Fragaria chiloensis revealed by SSR markers transferred from commercial strawberry

    Directory of Open Access Journals (Sweden)

    Felipe Alberto Oñate

    2017-11-01

    Full Text Available The Chilean strawberry [Fragaria chiloensis (L. Mill.] is the maternal progenitor of the commercial strawberry (Fragaria ´ ananassa Duch., which is characterized by fruits with high organoleptic quality and is well-suited to areas where drought and salinity represent a constraint on crop growth and productivity. We examined the patterns of linkage disequilibrium, genetic diversity and population structure among 54 accessions of F. chiloensis to understand the genetic basis of this species. We used a core microsatellite marker set (n = 95 from a consensus linkage map of strawberry. A transferability rate of 82.1% (78/95 was found, and 38 markers were selected for this study. The SSR primers produced a total of 259 alleles, which varied between 112 and 342 bp. Lower genetic diversity at the species level (HE = 0.17, Shannon’s index = 0.28 was found compared to previous studies of this species. No climatic region pattern for SSR diversity was observed. Structure analysis suggests that the accessions are grouped into three significantly differentiated clusters. Pairwise estimates of φST indicated a low degree of differentiation between the three genetic groups (φST = 0.023 to 0.06. These groups are in concordance with potential glacial refugia in the region, with many accessions being an admixture of them.

  1. A new genetic linkage map of the zygomycete fungus Phycomyces blakesleeanus.

    Directory of Open Access Journals (Sweden)

    Suman Chaudhary

    Full Text Available Phycomyces blakesleeanus is a member of the subphylum Mucoromycotina. A genetic map was constructed from 121 progeny of a cross between two wild type isolates of P. blakesleeanus with 134 markers. The markers were mostly PCR-RFLPs. Markers were located on 46 scaffolds of the genome sequence, covering more than 97% of the genome. Analysis of the alleles in the progeny revealed nine or 12 linkage groups, depending on the log of the odds (LOD score, across 1583.4 cM at LOD 5. The linkage groups were overlaid on previous mapping data from crosses between mutants, aided by new identification of the mutations in primary metabolism mutant strains. The molecular marker map, the phenotype map and the genome sequence are overall congruent, with some exceptions. The new genetic map provides a genome-wide estimate for recombination, with the average of 33.2 kb per cM. This frequency is one piece of evidence for meiosis during zygospore development in Mucoromycotina species. At the same time as meiosis, transmission of non-recombinant chromosomes is also evident in the mating process in Phycomyces. The new map provides scaffold ordering for the genome sequence and a platform upon which to identify the genes in mutants that are affected in traits of interest, such as carotene biosynthesis, phototropism or gravitropism, using positional cloning.

  2. Missing Linkages in California's Landscape [ds420

    Data.gov (United States)

    California Department of Resources — The critical need for conserving landscape linkages first came to the forefront of conservation thinking in California in November 2000, when a statewide interagency...

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    The genetic loci affecting the commonly used BMI have been intensively investigated using linkage approaches in multiple populations. This study aims at performing the first genome-wide linkage scan on BMI in the Chinese population in mainland China with hypothesis that heterogeneity in genetic...... 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...... in western countries. Multiple loci showing suggestive linkage were found on chromosome 1 (lod score 2.38 at 242 cM), chromosome 8 (2.48 at 95 cM), and chromosome 14 (2.2 at 89.4 cM). The strong linkage identified in the Chinese subjects that is consistent with that found in populations of European origin...

  4. Covalent Linkage of HIV-1 Trimers to Synthetic Liposomes Elicits Improved B Cell and Antibody Responses.

    Science.gov (United States)

    Bale, Shridhar; Goebrecht, Geraldine; Stano, Armando; Wilson, Richard; Ota, Takayuki; Tran, Karen; Ingale, Jidnyasa; Zwick, Michael B; Wyatt, Richard T

    2017-08-15

    We have demonstrated that a liposomal array of well-ordered trimers enhances B cell activation, germinal center formation, and the elicitation of tier-2 autologous neutralizing antibodies. Previously, we coupled well-ordered cleavage-independent NFL trimers via their C-terminal polyhistidine tails to nickel lipids integrated into the lipid bilayer. Despite favorable in vivo effects, concern remained over the potentially longer-term in vivo instability of noncovalent linkage of the trimers to the liposomes. Accordingly, we tested both cobalt coupling and covalent linkage of the trimers to the liposomes by reengineering the polyhistidine tail to include a free cysteine on each protomer of model BG505 NFL trimers to allow covalent linkage. Both cobalt and cysteine coupling resulted in a high-density array of NFL trimers that was stable in both 20% mouse serum and 100 mM EDTA, whereas the nickel-conjugated trimers were not stable under these conditions. Binding analysis and calcium flux with anti-Env-specific B cells confirmed that the trimers maintained conformational integrity following coupling. Following immunization of mice, serologic analysis demonstrated that the covalently coupled trimers elicited Env-directed antibodies in a manner statistically significantly improved compared to soluble trimers and nickel-conjugated trimers. Importantly, the covalent coupling not only enhanced gp120-directed responses compared to soluble trimers, it also completely eliminated antibodies directed to the C-terminal His tag located at the "bottom" of the spike. In contrast, soluble and noncovalent formats efficiently elicited anti-His tag antibodies. These data indicate that covalent linkage of well-ordered trimers to liposomes in high-density array displays multiple advantages in vitro and in vivo IMPORTANCE Enveloped viruses typically encode a surface-bound glycoprotein that mediates viral entry into host cells and is a primary target for vaccine design. Liposomes with

  5. Annotated genetic linkage maps of Pinus pinaster Ait. from a Central Spain population using microsatellite and gene based markers

    Directory of Open Access Journals (Sweden)

    de Miguel Marina

    2012-10-01

    Full Text Available Abstract Background Pinus pinaster Ait. is a major resin producing species in Spain. Genetic linkage mapping can facilitate marker-assisted selection (MAS through the identification of Quantitative Trait Loci and selection of allelic variants of interest in breeding populations. In this study, we report annotated genetic linkage maps for two individuals (C14 and C15 belonging to a breeding program aiming to increase resin production. We use different types of DNA markers, including last-generation molecular markers. Results We obtained 13 and 14 linkage groups for C14 and C15 maps, respectively. A total of 211 and 215 markers were positioned on each map and estimated genome length was between 1,870 and 2,166 cM respectively, which represents near 65% of genome coverage. Comparative mapping with previously developed genetic linkage maps for P. pinaster based on about 60 common markers enabled aligning linkage groups to this reference map. The comparison of our annotated linkage maps and linkage maps reporting QTL information revealed 11 annotated SNPs in candidate genes that co-localized with previously reported QTLs for wood properties and water use efficiency. Conclusions This study provides genetic linkage maps from a Spanish population that shows high levels of genetic divergence with French populations from which segregating progenies have been previously mapped. These genetic maps will be of interest to construct a reliable consensus linkage map for the species. The importance of developing functional genetic linkage maps is highlighted, especially when working with breeding populations for its future application in MAS for traits of interest.

  6. Linkages at Tourism Destinations: Challenges in Zanzibar

    Directory of Open Access Journals (Sweden)

    Wineaster Anderson

    2011-06-01

    Full Text Available This study explores challenges facing the linkages between the tourism industry and local suppliers at the destinations. During 2010 surveys involving hotel and restaurant operators, local suppliers and tourists were conducted in Zanzibar. Qualitative analysis of the perspectives of the respondents reveals the multitude of constraints. From operators, the main constraints include poor quality of the locally supplied products, business informalities, high transaction costs and violation of agreements by local suppliers. Low production levels, low prices offered by hotels and restaurants coupled with late payments for the products delivered were the most serious problems cited by local suppliers. There is also a certain degree of mistrust between the local suppliers and the operators. However, the source of the tourism products consumed in the hotels or restaurants was not a point of concern, at least from the tourists’ perspective. Strategies to bridge the demandsupply gaps in order to maximize the benefits of tourism, among the tools for fighting the rampant poverty, have been recommended.

  7. Confirmatory linkage of hypochondroplasia to chromosome arm 4p

    Energy Technology Data Exchange (ETDEWEB)

    Hectht, J.T.; Herrera, C.A.; Greenhaw, G.A. [Univ. of Texas Medical School, Houston, TX (United States)] [and others

    1995-07-03

    Hypochondroplasia is an inherited chondrodystrophy that is characterized by disproportionate short stature. A recent linkage study by LeMerrer et al. suggested that hypochondroplasia and achondroplasia are allelic conditions. Three groups have now mapped the achondroplasia locus to the telomeric region of chromosome 4. Recently, two mutations in fibroblast growth factor receptor 3 (FGFR3) at nucleotide 1138, in the transmembrane domain, were identified in 169 of 170 unrelated individuals with achondroplasia. Here, we report the results of a linkage study in 4 multigenerational families with hypochondroplasia and mutational analysis of nucleotide 1138 in one individual from each of these families, two nonfamilial hypochondroplasia individuals and sequencing of the transmembrane domain of the FGFR3 in three affected unrelated individuals. 13 refs., 1 tab.

  8. Effect of Linkage Disequilibrium on the Identification of Functional Variants

    Science.gov (United States)

    Thomas, Alun; Abel, Haley J; Di, Yanming; Faye, Laura L; Jin, Jing; Liu, Jin; Wu, Zheyan; Paterson, Andrew D

    2011-01-01

    We summarize the contributions of Group 9 of Genetic Analysis Workshop 17. This group addressed the problems of linkage disequilibrium and other longer range forms of allelic association when evaluating the effects of genotypes on phenotypes. Issues raised by long-range associations, whether a result of selection, stratification, possible technical errors, or chance, were less expected but proved to be important. Most contributors focused on regression methods of various types to illustrate problematic issues or to develop adaptations for dealing with high-density genotype assays. Study design was also considered, as was graphical modeling. Although no method emerged as uniformly successful, most succeeded in reducing false-positive results either by considering clusters of loci within genes or by applying smoothing metrics that required results from adjacent loci to be similar. Two unexpected results that questioned our assumptions of what is required to model linkage disequilibrium were observed. The first was that correlations between loci separated by large genetic distances can greatly inflate single-locus test statistics, and, whether the result of selection, stratification, possible technical errors, or chance, these correlations seem overabundant. The second unexpected result was that applying principal components analysis to genome-wide genotype data can apparently control not only for population structure but also for linkage disequilibrium. PMID:22128051

  9. Comparing linkage designs based on land facets to linkage designs based on focal species.

    Science.gov (United States)

    Brost, Brian M; Beier, Paul

    2012-01-01

    Least-cost modeling for focal species is the most widely used method for designing conservation corridors and linkages. However, these designs depend on today's land covers, which will be altered by climate change. We recently proposed an alternative approach based on land facets (recurring landscape units of relatively uniform topography and soils). The rationale is that corridors with high continuity of individual land facets will facilitate movement of species associated with each facet today and in the future. Conservation practitioners might like to know whether a linkage design based on land facets is likely to provide continuity of modeled breeding habitat for species needing connectivity today, and whether a linkage for focal species provides continuity and interspersion of land facets. To address these questions, we compared linkages designed for focal species and land facets in three landscapes in Arizona, USA. We used two variables to measure linkage utility, namely distances between patches of modeled breeding habitat for 5-16 focal species in each linkage, and resistance profiles for focal species and land facets between patches connected by the linkage. Compared to focal species designs, linkage designs based on land facets provided as much or more modeled habitat connectivity for 25 of 28 species-landscape combinations, failing only for the three species with the most narrowly distributed habitat. Compared to land facets designs, focal species linkages provided lower connectivity for about half the land facets in two landscapes. In areas where a focal species approach to linkage design is not possible, our results suggest that conservation practitioners may be able to implement a land facets approach with some confidence that the linkage design would serve most potential focal species. In areas where focal species designs are possible, we recommend using the land facet approach to complement, rather than replace, focal species approaches.

  10. 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.

  11. Cytogenetical anchoring of sheep linkage map and syntenic groups using a sheep BAC library

    Directory of Open Access Journals (Sweden)

    Cribiu Edmond-Paul

    2000-07-01

    Full Text Available Abstract In order to simultaneously integrate linkage and syntenic groups to the ovine chromosomal map, a sheep bacterial artificial chromosome (BAC library was screened with previously assigned microsatellites using a sheep-hamster hybrid panel and genetic linkage. Thirty-three BACs were obtained, fluorescently labelled and hybridised on sheep-goat hybrid metaphases (2n = 57. This study allowed us, (i, to anchor all linkage groups on sheep chromosomes, (ii, to give information on the probable position of the centromere on the linkage map for the centromeric chromosomes, (iii, to contradict the previous orientation of the ovine × linkage group by the mapping of BMS1008 on OARXq38. Concerning our somatic cell hybrid panel, this study resulted in the assignment of all the previously unassigned groups to ovine chromosomes and a complete characterisation of the hybrid panel. In addition, since hybridisations were performed on a sheep-goat hybrid, new marker/anchoring points were added to the caprine cytogenetic map.

  12. Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22.

    Directory of Open Access Journals (Sweden)

    Mine S Cicek

    Full Text Available A substantial proportion of familial colorectal cancer (CRC is not a consequence of known susceptibility loci, such as mismatch repair (MMR genes, supporting the existence of additional loci. To identify novel CRC loci, we conducted a genome-wide linkage scan in 356 white families with no evidence of defective MMR (i.e., no loss of tumor expression of MMR proteins, no microsatellite instability (MSI-high tumors, or no evidence of linkage to MMR genes. Families were ascertained via the Colon Cancer Family Registry multi-site NCI-supported consortium (Colon CFR, the City of Hope Comprehensive Cancer Center, and Memorial University of Newfoundland. A total of 1,612 individuals (average 5.0 per family including 2.2 affected were genotyped using genome-wide single nucleotide polymorphism linkage arrays; parametric and non-parametric linkage analysis used MERLIN in a priori-defined family groups. Five lod scores greater than 3.0 were observed assuming heterogeneity. The greatest were among families with mean age of diagnosis less than 50 years at 4q21.1 (dominant HLOD = 4.51, α = 0.84, 145.40 cM, rs10518142 and among all families at 12q24.32 (dominant HLOD = 3.60, α = 0.48, 285.15 cM, rs952093. Among families with four or more affected individuals and among clinic-based families, a common peak was observed at 15q22.31 (101.40 cM, rs1477798; dominant HLOD = 3.07, α = 0.29; dominant HLOD = 3.03, α = 0.32, respectively. Analysis of families with only two affected individuals yielded a peak at 8q13.2 (recessive HLOD = 3.02, α = 0.51, 132.52 cM, rs1319036. These previously unreported linkage peaks demonstrate the continued utility of family-based data in complex traits and suggest that new CRC risk alleles remain to be elucidated.

  13. Colorectal Cancer Linkage on Chromosomes 4q21, 8q13, 12q24, and 15q22

    Science.gov (United States)

    Cicek, Mine S.; Cunningham, Julie M.; Fridley, Brooke L.; Serie, Daniel J.; Bamlet, William R.; Diergaarde, Brenda; Haile, Robert W.; Le Marchand, Loic; Krontiris, Theodore G.; Younghusband, H. Banfield; Gallinger, Steven; Newcomb, Polly A.; Hopper, John L.; Jenkins, Mark A.; Casey, Graham; Schumacher, Fredrick; Chen, Zhu; DeRycke, Melissa S.; Templeton, Allyson S.; Winship, Ingrid; Green, Roger C.; Green, Jane S.; Macrae, Finlay A.; Parry, Susan; Young, Graeme P.; Young, Joanne P.; Buchanan, Daniel; Thomas, Duncan C.; Bishop, D. Timothy; Lindor, Noralane M.; Thibodeau, Stephen N.; Potter, John D.; Goode, Ellen L.

    2012-01-01

    A substantial proportion of familial colorectal cancer (CRC) is not a consequence of known susceptibility loci, such as mismatch repair (MMR) genes, supporting the existence of additional loci. To identify novel CRC loci, we conducted a genome-wide linkage scan in 356 white families with no evidence of defective MMR (i.e., no loss of tumor expression of MMR proteins, no microsatellite instability (MSI)-high tumors, or no evidence of linkage to MMR genes). Families were ascertained via the Colon Cancer Family Registry multi-site NCI-supported consortium (Colon CFR), the City of Hope Comprehensive Cancer Center, and Memorial University of Newfoundland. A total of 1,612 individuals (average 5.0 per family including 2.2 affected) were genotyped using genome-wide single nucleotide polymorphism linkage arrays; parametric and non-parametric linkage analysis used MERLIN in a priori-defined family groups. Five lod scores greater than 3.0 were observed assuming heterogeneity. The greatest were among families with mean age of diagnosis less than 50 years at 4q21.1 (dominant HLOD = 4.51, α = 0.84, 145.40 cM, rs10518142) and among all families at 12q24.32 (dominant HLOD = 3.60, α = 0.48, 285.15 cM, rs952093). Among families with four or more affected individuals and among clinic-based families, a common peak was observed at 15q22.31 (101.40 cM, rs1477798; dominant HLOD = 3.07, α = 0.29; dominant HLOD = 3.03, α = 0.32, respectively). Analysis of families with only two affected individuals yielded a peak at 8q13.2 (recessive HLOD = 3.02, α = 0.51, 132.52 cM, rs1319036). These previously unreported linkage peaks demonstrate the continued utility of family-based data in complex traits and suggest that new CRC risk alleles remain to be elucidated. PMID:22675446

  14. Dimensional threshold for fracture linkage and hooking

    Science.gov (United States)

    Lamarche, Juliette; Chabani, Arezki; Gauthier, Bertrand D. M.

    2018-03-01

    Fracture connectivity in rocks depends on spatial properties of the pattern including length, abundance and orientation. When fractures form a single-strike set, they hardly cross-cut each other and the connectivity is limited. Linkage probability increases with increasing fracture abundance and length as small fractures connect to each other to form longer ones. A process for parallel fracture linkage is the "hooking", where two converging fracture tips mutually deviate and then converge to connect due to the interaction of their crack-tip stresses. Quantifying the processes and conditions for fracture linkage in single-strike fracture sets is crucial to better predicting fluid flow in Naturally Fractured Reservoirs. For 1734 fractures in Permian shales of the Lodève Basin, SE France, we measured geometrical parameters in 2D, characterizing three stages of the hooking process: underlapping, overlapping and linkage. We deciphered the threshold values, shape ratios and limiting conditions to switch from one stage to another one. The hook set up depends on the spacing (S) and fracture length (Lh) with the relation S ≈ 0.15 Lh. Once the hooking is initiated, with the fracture deviation length (L) L ≈ 0.4 Lh, the fractures reaches the linkage stage only when the spacing is reduced to S ≈ 0.02 Lh and the convergence (C) is < 0.1 L. These conditions apply to multi-scale fractures with a shape ratio L/S = 10 and for fracture curvature of 10°-20°.

  15. Preoperative screening: value of previous tests.

    Science.gov (United States)

    Macpherson, D S; Snow, R; Lofgren, R P

    1990-12-15

    To determine the frequency of tests done in the year before elective surgery that might substitute for preoperative screening tests and to determine the frequency of test results that change from a normal value to a value likely to alter perioperative management. Retrospective cohort analysis of computerized laboratory data (complete blood count, sodium, potassium, and creatinine levels, prothrombin time, and partial thromboplastin time). Urban tertiary care Veterans Affairs Hospital. Consecutive sample of 1109 patients who had elective surgery in 1988. At admission, 7549 preoperative tests were done, 47% of which duplicated tests performed in the previous year. Of 3096 previous results that were normal as defined by hospital reference range and done closest to the time of but before admission (median interval, 2 months), 13 (0.4%; 95% CI, 0.2% to 0.7%), repeat values were outside a range considered acceptable for surgery. Most of the abnormalities were predictable from the patient's history, and most were not noted in the medical record. Of 461 previous tests that were abnormal, 78 (17%; CI, 13% to 20%) repeat values at admission were outside a range considered acceptable for surgery (P less than 0.001, frequency of clinically important abnormalities of patients with normal previous results with those with abnormal previous results). Physicians evaluating patients preoperatively could safely substitute the previous test results analyzed in this study for preoperative screening tests if the previous tests are normal and no obvious indication for retesting is present.

  16. 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...... adulthood, asthma is frequently associated also with quantitative measures of atopy. Genome wide quantitative multipoint linkage analysis was conducted for serum IgE levels and percentage of positive skin prick test (SPT(per)) using three large groups of families originally ascertained for asthma....... In this report, 438 and 429 asthma families were informative for linkage using IgE and SPT(per) which represents 690 independent families. Suggestive linkage (LOD >/= 2) was found on chromosomes 1, 3, and 8q with maximum LODs of 2.34 (IgE), 2.03 (SPT(per)), and 2.25 (IgE) near markers D1S1653, D3S2322-D3S1764...

  17. A microsatellite linkage map of Drosophila mojavensis

    Directory of Open Access Journals (Sweden)

    Schully Sheri

    2004-05-01

    Full Text Available Abstract Background Drosophila mojavensis has been a model system for genetic studies of ecological adaptation and speciation. However, despite its use for over half a century, no linkage map has been produced for this species or its close relatives. Results We have developed and mapped 90 microsatellites in D. mojavensis, and we present a detailed recombinational linkage map of 34 of these microsatellites. A slight excess of repetitive sequence was observed on the X-chromosome relative to the autosomes, and the linkage groups have a greater recombinational length than the homologous D. melanogaster chromosome arms. We also confirmed the conservation of Muller's elements in 23 sequences between D. melanogaster and D. mojavensis. Conclusions The microsatellite primer sequences and localizations are presented here and made available to the public. This map will facilitate future quantitative trait locus mapping studies of phenotypes involved in adaptation or reproductive isolation using this species.

  18. Intragroup Emotions: Physiological Linkage and Social Presence

    Science.gov (United States)

    Järvelä, Simo; Kätsyri, Jari; Ravaja, Niklas; Chanel, Guillaume; Henttonen, Pentti

    2016-01-01

    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. PMID:26903913

  19. A reference linkage map for Eucalyptus.

    Science.gov (United States)

    Hudson, Corey J; Freeman, Jules S; Kullan, Anand R K; Petroli, César D; Sansaloni, Carolina P; Kilian, Andrzej; Detering, Frank; Grattapaglia, Dario; Potts, Brad M; Myburg, Alexander A; Vaillancourt, René E

    2012-06-15

    Genetic linkage maps are invaluable resources in plant research. They provide a key tool for many genetic applications including: mapping quantitative trait loci (QTL); comparative mapping; identifying unlinked (i.e. independent) DNA markers for fingerprinting, population genetics and phylogenetics; assisting genome sequence assembly; relating physical and recombination distances along the genome and map-based cloning of genes. Eucalypts are the dominant tree species in most Australian ecosystems and of economic importance globally as plantation trees. The genome sequence of E. grandis has recently been released providing unprecedented opportunities for genetic and genomic research in the genus. A robust reference linkage map containing sequence-based molecular markers is needed to capitalise on this resource. Several high density linkage maps have recently been constructed for the main commercial forestry species in the genus (E. grandis, E. urophylla and E. globulus) using sequenced Diversity Arrays Technology (DArT) and microsatellite markers. To provide a single reference linkage map for eucalypts a composite map was produced through the integration of data from seven independent mapping experiments (1950 individuals) using a marker-merging method. The composite map totalled 1107 cM and contained 4101 markers; comprising 3880 DArT, 213 microsatellite and eight candidate genes. Eighty-one DArT markers were mapped to two or more linkage groups, resulting in the 4101 markers being mapped to 4191 map positions. Approximately 13% of DArT markers mapped to identical map positions, thus the composite map contained 3634 unique loci at an average interval of 0.31 cM. The composite map represents the most saturated linkage map yet produced in Eucalyptus. As the majority of DArT markers contained on the map have been sequenced, the map provides a direct link to the E. grandis genome sequence and will serve as an important reference for progressing eucalypt research.

  20. Genotyping-by-sequencing enables linkage mapping in three octoploid cultivated strawberry families

    Directory of Open Access Journals (Sweden)

    Kelly J. Vining

    2017-08-01

    Full Text Available Genotyping-by-sequencing (GBS was used to survey genome-wide single-nucleotide polymorphisms (SNPs in three biparental strawberry (Fragaria × ananassa populations with the goal of evaluating this technique in a species with a complex octoploid genome. GBS sequence data were aligned to the F. vesca ‘Fvb’ reference genome in order to call SNPs. Numbers of polymorphic SNPs per population ranged from 1,163 to 3,190. Linkage maps consisting of 30–65 linkage groups were produced from the SNP sets derived from each parent. The linkage groups covered 99% of the Fvb reference genome, with three to seven linkage groups from a given parent aligned to any particular chromosome. A phylogenetic analysis performed using the POLiMAPS pipeline revealed linkage groups that were most similar to ancestral species F. vesca for each chromosome. Linkage groups that were most similar to a second ancestral species, F. iinumae, were only resolved for Fvb 4. The quantity of missing data and heterogeneity in genome coverage inherent in GBS complicated the analysis, but POLiMAPS resolved F. × ananassa chromosomal regions derived from diploid ancestor F. vesca.

  1. 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

  2. HLA region excluded by linkage analyses of early onset periodontitis

    Energy Technology Data Exchange (ETDEWEB)

    Sun, C.; Wang, S.; Lopez, N.

    1994-09-01

    Previous studies suggested that HLA genes may influence susceptibility to early-onset periodontitis (EOP). Segregation analyses indicate that EOP may be due to a single major gene. We conducted linkage analyses to assess possible HLA effects on EOP. Fifty families with two or more close relatives affected by EOP were ascertained in Virginia and Chile. A microsatellite polymorphism within the HLA region (at the tumor necrosis factor beta locus) was typed using PCR. Linkage analyses used a donimant model most strongly supported by previous studies. Assuming locus homogeneity, our results exclude a susceptibility gene within 10 cM on either side of our marker locus. This encompasses all of the HLA region. Analyses assuming alternative models gave qualitatively similar results. Allowing for locus heterogeneity, our data still provide no support for HLA-region involvement. However, our data do not statistically exclude (LOD <-2.0) hypotheses of disease-locus heterogeneity, including models where up to half of our families could contain an EOP disease gene located in the HLA region. This is due to the limited power of even our relatively large collection of families and the inherent difficulties of mapping genes for disorders that have complex and heterogeneous etiologies. Additional statistical analyses, recruitment of families, and typing of flanking DNA markers are planned to more conclusively address these issues with respect to the HLA region and other candidate locations in the human genome. Additional results for markers covering most of the human genome will also be presented.

  3. Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial.

    Science.gov (United States)

    Shaverdian, Narek; Lisberg, Aaron E; Bornazyan, Krikor; Veruttipong, Darlene; Goldman, Jonathan W; Formenti, Silvia C; Garon, Edward B; Lee, Percy

    2017-07-01

    Preclinical studies have found radiotherapy enhances antitumour immune responses. We aimed to assess disease control and pulmonary toxicity in patients who previously received radiotherapy for non-small-cell lung cancer (NSCLC) before receiving pembrolizumab. We assessed patients with advanced NSCLC treated on the phase 1 KEYNOTE-001 trial at a single institution (University of California, Los Angeles, CA, USA). Patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 1 or less, had adequate organ function, and no history of pneumonitis. Patients received pembrolizumab at a dose of either 2 mg/kg of bodyweight or 10 mg/kg every 3 weeks, or 10 mg/kg every 2 weeks, until disease progression, unacceptable toxicity, or other protocol-defined reasons for discontinuation. Disease response and pulmonary toxicity were prospectively assessed by Immune-related Response Criteria and Common Terminology Criteria for Adverse Events version 4.0. The primary objective of the KEYNOTE-001 trial was to assess the safety, side-effect profile, and antitumour activity of pembrolizumab. For our secondary analysis, patients were divided into subgroups to compare patients who previously received radiotherapy with patients who had not. Our primary objective was to determine whether previous radiotherapy affected progression-free survival, overall survival, and pulmonary toxicity in the intention-to-treat population. The KEYNOTE-001 trial was registered with ClinicalTrials.gov, number NCT01295827. Between May 22, 2012, and July 11, 2014, 98 patients were enrolled and received their first cycle of pembrolizumab. One patient was lost to follow-up. 42 (43%) of 97 patients had previously received any radiotherapy for the treatment of NSCLC before the first cycle of pembrolizumab. 38 (39%) of 97 patients received extracranial radiotherapy and 24 (25%) of 97 patients received thoracic radiotherapy. Median follow-up for surviving patients was 32·5

  4. Exploring the linkage between cell culture process parameters and downstream processing utilizing a plackett-burman design for a model monoclonal antibody.

    Science.gov (United States)

    Agarabi, Cyrus D; Chavez, Brittany K; Lute, Scott C; Read, Erik K; Rogstad, Sarah; Awotwe-Otoo, David; Brown, Matthew R; Boyne, Michael T; Brorson, Kurt A

    2017-01-01

    Linkage of upstream cell culture with downstream processing and purification is an aspect of Quality by Design crucial for efficient and consistent production of high quality biopharmaceutical proteins. In a previous Plackett-Burman screening study of parallel bioreactor cultures we evaluated main effects of 11 process variables, such as agitation, sparge rate, feeding regimens, dissolved oxygen set point, inoculation density, supplement addition, temperature, and pH shifts. In this follow-up study, we observed linkages between cell culture process parameters and downstream capture chromatography performance and subsequent antibody attributes. In depth analysis of the capture chromatography purification of harvested cell culture fluid yielded significant effects of upstream process parameters on host cell protein abundance and behavior. A variety of methods were used to characterize the antibody both after purification and buffer formulation. This analysis provided insight in to the significant impacts of upstream process parameters on aggregate formation, impurities, and protein structure. This report highlights the utility of linkage studies in identifying how changes in upstream parameters can impact downstream critical quality attributes. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:163-170, 2017. © 2016 American Institute of Chemical Engineers.

  5. Confirmation and Fine Mapping of a Major QTL for Aflatoxin Resistance in Maize Using a Combination of Linkage and Association Mapping

    Directory of Open Access Journals (Sweden)

    Yu Zhang

    2016-09-01

    Full Text Available Maize grain contamination with aflatoxin from Aspergillus flavus (A. flavus is a serious health hazard to animals and humans. To map the quantitative trait loci (QTLs associated with resistance to A. flavus, we employed a powerful approach that differs from previous methods in one important way: it combines the advantages of the genome-wide association analysis (GWAS and traditional linkage mapping analysis. Linkage mapping was performed using 228 recombinant inbred lines (RILs, and a highly significant QTL that affected aflatoxin accumulation, qAA8, was mapped. This QTL spanned approximately 7 centi-Morgan (cM on chromosome 8. The confidence interval was too large for positional cloning of the causal gene. To refine this QTL, GWAS was performed with 558,629 single nucleotide polymorphisms (SNPs in an association population comprising 437 maize inbred lines. Twenty-five significantly associated SNPs were identified, most of which co-localised with qAA8 and explained 6.7% to 26.8% of the phenotypic variation observed. Based on the rapid linkage disequilibrium (LD and the high density of SNPs in the association population, qAA8 was further localised to a smaller genomic region of approximately 1500 bp. A high-resolution map of the qAA8 region will be useful towards a marker-assisted selection (MAS of A. flavus resistance and a characterisation of the causal gene.

  6. A Genetic Linkage Map of Mycosphaerella Fijiensis, using SSR and DArT Markers

    Science.gov (United States)

    Mycosphaerella fijiensis is the causal agent of black leaf streak or Black Sigatoka disease in bananas. This pathogen threatens global banana production as the main export Cavendish cultivars are highly susceptible. Previously a genetic linkage map was generated predominantly using anonymous AFLP ma...

  7. Heritability and whole genome linkage of pulse pressure in chinese twin pairs.

    Science.gov (United States)

    Jiang, Wenjie; Jiang, Wengjie; Zhang, Dongfeng; Pang, Zengchang; Li, Shuxia; Duan, Haiping; Wang, Shaojie; Tan, Qihua

    2012-12-01

    Elevated pulse pressure is associated with cardiovascular disorders and mortality in various populations. The genetic influence on pulse pressure has been confirmed by heritability estimates using related individuals.Recently, efforts have been made in mapping genes that are linked to the phenotype. We report results on our heritability and linkage study conducted on the Chinese population in mainland China where cardiovascular and cerebrovascular diseases are becoming the leading cause of death. A total of 630 pairs of middle-aged Chinese twins were collected for heritability analysis, from which 63 dizygotic twin pairs were randomly selected for genome-wide linkage analysis using Affymetrix 6.0 SNP array. Regression analysis reconfirmed the significant effects of age, sex, and BMI on pulse pressure. Comparison of twin models suggested the parsimonious AE model as the best model with a heritability estimate of 0.45.Genome-wide non-parametric linkage analysis identified three significant linkage peaks on chromosome11 (lod score 4.06 at 30.5 eM), chromosome 12 (lod score 3. 97 at 100.7 eM), and chromosome 18 (lod score 4.01 at 70.7 eM) with the last two peaks closely overlapping with linkage peaks reported by two American studies. In addition, multiple regions with suggestive linkage were identified with many of them overlapping with published linkage regions. Our results provide both epidemiological and molecular genetic evidence for the genetic dissection of pulse pressure in the Chinese population, which could help in fine mapping and in characterizing genes that are involved in the regulation of pulse pressure.

  8. Linkage disequilibrium and association mapping of drought ...

    African Journals Online (AJOL)

    Drought stress is a major abiotic stress that limits crop production. Molecular association mapping techniques through linkage disequilibrium (LD) can be effectively used to tag genomic regions involved in drought stress tolerance. With the association mapping approach, 90 genotypes of cotton Gossypium hirsutum, from ...

  9. Dialogic Linkage and Resonance in Autism

    Science.gov (United States)

    Hobson, R. Peter; Hobson, Jessica A.; Garcia-Perez, Rosa; Du Bois, John

    2012-01-01

    We evaluated how children with autism make linguistic adjustments when talking with someone else. We devised two novel measures to assess (a) overall conversational linkage and (b) utterance-by-utterance resonance within dialogue between an adult and matched participants with and without autism (n = 12 per group). Participants with autism were…

  10. Producer Services, Manufacturing Linkages, and Trade

    NARCIS (Netherlands)

    J.F. François (Joseph); J. Kepler; J. Woerz

    2007-01-01

    textabstractWorking with a mix of panel data on goods and services trade for the OECD for 1994-2004, combined with social accounts data (i.e. data on intermediate linkages) for 78 countries benchmarked to the panel midpoint, we examine the role of services as inputs in manufacturing, with a

  11. Linkage between psychological contract and employee retention ...

    African Journals Online (AJOL)

    The study examines the linkage between psychological contract and employees' retention, performance and productivity in organizations in Nigeria. It studies the interplay between psychological contract and the variables with a view to understanding their interactions and impacts in organizations. The methodology is ...

  12. Utilizing linkage disequilibrium information from Indian Genome ...

    Indian Academy of Sciences (India)

    Utilizing linkage disequilibrium information from Indian Genome. Variation Database for mapping mutations: SCA12 case study. SAMIRA BAHL1, IKHLAK AHMED2, THE INDIAN GENOME VARIATION CONSORTIUM3 and MITALI MUKERJI1. 1Functional Genomics Unit, Institute of Genomics and Integrative Biology (CSIR), ...

  13. principles, realities and challenges regarding institutional linkages ...

    African Journals Online (AJOL)

    p2333147

    (2) Compromise between proximity to community and effective coordination. If organisational linkage structures are to facilitate effective participation and ownership, it stands to reason that they should be as close to the grassroots community as possible. Unless community members regard such organisational structures as.

  14. agricultural research and extension linkage in ethiopia

    African Journals Online (AJOL)

    AUA

    aimed at strengthening research and extension linkages will differ from country to country depending on historical working relationships between research and extension organisations as well as their organizational structures, responsiveness to the ever- growing challenges and how divergent or convergent their goals are ...

  15. 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

  16. Visualization of pairwise and multilocus linkage disequilibrium structure using latent forests.

    Directory of Open Access Journals (Sweden)

    Raphaël Mourad

    Full Text Available Linkage disequilibrium study represents a major issue in statistical genetics as it plays a fundamental role in gene mapping and helps us to learn more about human history. The linkage disequilibrium complex structure makes its exploratory data analysis essential yet challenging. Visualization methods, such as the triangular heat map implemented in Haploview, provide simple and useful tools to help understand complex genetic patterns, but remain insufficient to fully describe them. Probabilistic graphical models have been widely recognized as a powerful formalism allowing a concise and accurate modeling of dependences between variables. In this paper, we propose a method for short-range, long-range and chromosome-wide linkage disequilibrium visualization using forests of hierarchical latent class models. Thanks to its hierarchical nature, our method is shown to provide a compact view of both pairwise and multilocus linkage disequilibrium spatial structures for the geneticist. Besides, a multilocus linkage disequilibrium measure has been designed to evaluate linkage disequilibrium in hierarchy clusters. To learn the proposed model, a new scalable algorithm is presented. It constrains the dependence scope, relying on physical positions, and is able to deal with more than one hundred thousand single nucleotide polymorphisms. The proposed algorithm is fast and does not require phase genotypic data.

  17. Efficient sequential and parallel algorithms for record linkage.

    Science.gov (United States)

    Mamun, Abdullah-Al; Mi, Tian; Aseltine, Robert; Rajasekaran, Sanguthevar

    2014-01-01

    Integrating data from multiple sources is a crucial and challenging problem. Even though there exist numerous algorithms for record linkage or deduplication, they suffer from either large time needs or restrictions on the number of datasets that they can integrate. In this paper we report efficient sequential and parallel algorithms for record linkage which handle any number of datasets and outperform previous algorithms. Our algorithms employ hierarchical clustering algorithms as the basis. A key idea that we use is radix sorting on certain attributes to eliminate identical records before any further processing. Another novel idea is to form a graph that links similar records and find the connected components. Our sequential and parallel algorithms have been tested on a real dataset of 1,083,878 records and synthetic datasets ranging in size from 50,000 to 9,000,000 records. Our sequential algorithm runs at least two times faster, for any dataset, than the previous best-known algorithm, the two-phase algorithm using faster computation of the edit distance (TPA (FCED)). The speedups obtained by our parallel algorithm are almost linear. For example, we get a speedup of 7.5 with 8 cores (residing in a single node), 14.1 with 16 cores (residing in two nodes), and 26.4 with 32 cores (residing in four nodes). We have compared the performance of our sequential algorithm with TPA (FCED) and found that our algorithm outperforms the previous one. The accuracy is the same as that of this previous best-known algorithm.

  18. An integrated linkage map reveals candidate genes underlying adaptive variation in Chinook salmon (Oncorhynchus tshawytscha)

    DEFF Research Database (Denmark)

    Mckinney, G. J.; Seeb, L. W.; Larson, W. A.

    2016-01-01

    Salmonids are an important cultural and ecological resource exhibiting near worldwide distribution between their native and introduced range. Previous research has generated linkage maps and genomic resources for several species as well as genome assemblies for two species. We first leveraged imp...... traits such as stress response, growth and behaviour. Collectively, these results demonstrate the utility of combining genomic resources with linkage maps to enhance evolutionary inferences....

  19. 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.

  20. SSR genetic linkage map construction of pea (Pisum sativum L. based on Chinese native varieties

    Directory of Open Access Journals (Sweden)

    Xuelian Sun

    2014-04-01

    Full Text Available Simple sequence repeat (SSR markers have previously been applied to linkage mapping of the pea (Pisum sativum L. genome. However, the transferability of existing loci to the molecularly distinct Chinese winter pea gene pool was limited. A novel set of pea SSR markers was accordingly developed. Together with existing SSR sequences, the genome of the G0003973 (winter hardy × G0005527 (cold sensitive cross was mapped using 190 F2 individuals. In total, 157 SSR markers were placed in 11 linkage groups with an average interval of 9.7 cM and total coverage of 1518 cM. The novel markers and genetic linkage map will be useful for marker-assisted pea breeding.

  1. Effect of Linkage Groups on Motional Cooperativity in Secondary Relaxations of Some Glassy Polymers

    Science.gov (United States)

    Li, Lei; Yee, Albert F.

    2000-03-01

    In our previous research we found that the secondary relaxation of bisphenol-A (BPA) polycarbonate is due to a cooperative motion which includes several repeat units. Clearly the linkage between neighboring BPA segments must play an important role. It is expected that a more flexible linkage would require less motional cooperativity. To demonstrate this idea, polyformals based on the comonomers BPA, tetramethyl-BPA and methylenechloride with controlled sequence structure were synthesized and DMA studies were conducted. The results show that the secondary relaxation behavior of copolyformals is not dependent on the block length of BPA segments, which suggest that the molecular motion does not require in-chain cooperation. The lower in-chain motional cooperativity of BPA-polyformal is attributed to the lower rotational energy barrier of the formal linkage.

  2. 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

  3. VAGINAL PROGESTERONE VERSUS CERVICAL CERCLAGE FOR THE PREVENTION OF PRETERM BIRTH IN WOMEN WITH A SONOGRAPHIC SHORT CERVIX, SINGLETON GESTATION, AND PREVIOUS PRETERM BIRTH: A SYSTEMATIC REVIEW AND INDIRECT COMPARISON META-ANALYSIS

    Science.gov (United States)

    CONDE-AGUDELO, Agustin; ROMERO, Roberto; NICOLAIDES, Kypros; CHAIWORAPONGSA, Tinnakorn; O'BRIEN, John M.; CETINGOZ, Elcin; DA FONSECA, Eduardo; CREASY, George; SOMA-PILLAY, Priya; FUSEY, Shalini; CAM, Cetin; ALFIREVIC, Zarko; HASSAN, Sonia S.

    2012-01-01

    OBJECTIVE No randomized controlled trial has directly compared vaginal progesterone and cervical cerclage for the prevention of preterm birth in women with a sonographic short cervix in the midtrimester, singleton gestation, and previous spontaneous preterm birth. We performed an indirect comparison of vaginal progesterone versus cerclage, using placebo/no cerclage as the common comparator. STUDY DESIGN Adjusted indirect meta-analysis of randomized controlled trials. RESULTS Four studies evaluating vaginal progesterone versus placebo (158 patients) and five evaluating cerclage versus no cerclage (504 patients) were included. Both interventions were associated with a statistically significant reduction in the risk of preterm birth <32 weeks of gestation and composite perinatal morbidity and mortality compared with placebo/no cerclage. Adjusted indirect meta-analyses did not show statistically significant differences between vaginal progesterone and cerclage in reducing preterm birth or adverse perinatal outcomes. CONCLUSION Based on state-of-the-art methodology for indirect comparisons, either vaginal progesterone or cerclage are equally efficacious in the prevention of preterm birth in women with a sonographic short cervix in the midtrimester, singleton gestation, and previous preterm birth. The selection of the optimal treatment may depend upon adverse events, cost and patient/clinician preferences. PMID:23157855

  4. Actors affecting the effectiveness of extension linkages between ...

    African Journals Online (AJOL)

    Actors affecting the effectiveness of extension linkages between agricultural development programmes (ADPs) and universites in South-Eastern Nigeria. ... as facilitators of linkage effectiveness, indicated that for linkages to be effective, all the physical, psychological and social factors of human relationships must be made to ...

  5. Long-term effectiveness of bee venom acupuncture and physiotherapy in the treatment of adhesive capsulitis: a one-year follow-up analysis of a previous randomized controlled trial.

    Science.gov (United States)

    Park, Yeon Cheol; Koh, Pil Seong; Seo, Byung Kwan; Lee, Jung Woo; Cho, Nam Su; Park, Hyung Soon; Park, Dong Suk; Baek, Yong Hyeon

    2014-12-01

    An earlier randomized controlled trial (RCT) study showed that bee venom acupuncture (BVA) in combination with physiotherapy can be more effective in functional improvement and pain reduction in patients with adhesive capsulitis (AC). The objective of the current study was to examine the long-term effect of BVA in combination with physiotherapy on AC of the shoulder. Retrospective 1-year follow-up analysis of a previous RCT using a telephone interview method. Outpatient joint center at the Gang Dong Kyung Hee University Hospital of Seoul, Republic of Korea. A total of 192 patients had been enrolled in the previous study, and 124 of these were excluded from the current study. Sixty-eight patients who had been treated with combined BVA and physiotherapy for AC of the shoulder for 2 months were interviewed at approximately 1 year after treatment by telephone. Sixty of 68 patients were included in the follow-up analysis. Twenty received BV 1 treatment (1:10,000 concentration BVA plus physiotherapy), 22 received BV 2 treatment (1:30,000 concentration BVA plus physiotherapy), and 18 received control treatment (normal saline injection plus physiotherapy). The primary outcome measure was Shoulder Pain And Disability Index (SPADI) score. Secondary outcome measure was score on verbal rating scale for pain and patient satisfaction. Baseline characteristics of the groups did not significantly differ. SPADI scores at 1 year significantly differed between the BV 1 group and the control group (p=0.043). No significant differences were found in pain verbal rating scores after 1 year. Treatment satisfaction with therapy was also assessed, and the BV 1 and BV 2 groups showed significantly greater satisfaction compared with the control group. BVA combined with physiotherapy remains clinically effective 1 year after treatment and may help improve long-term quality of life in patients with AC of the shoulder.

  6. The Importance of Geographical Proximity for New Product Development Activities within Inter-firm Linkages

    DEFF Research Database (Denmark)

    Dahlgren, Johan Henrich

    important as a resource and where collaboration partners are important. Hypotheses are tested by means of a quantitative analysis of a data set containing information about 4842 domestic and international inter-firm linkages of Danish firms in manufacturing industries. The findings in this analysis exhibit...

  7. Components of selection in the evolution of the influenza virus: linkage effects beat inherent selection.

    Directory of Open Access Journals (Sweden)

    Christopher J R Illingworth

    2012-12-01

    Full Text Available The influenza virus is an important human pathogen, with a rapid rate of evolution in the human population. The rate of homologous recombination within genes of influenza is essentially zero. As such, where two alleles within the same gene are in linkage disequilibrium, interference between alleles will occur, whereby selection acting upon one allele has an influence upon the frequency of the other. We here measured the relative importance of selection and interference effects upon the evolution of influenza. We considered time-resolved allele frequency data from the global evolutionary history of the haemagglutinin gene of human influenza A/H3N2, conducting an in-depth analysis of sequences collected since 1996. Using a model that accounts for selection-caused interference between alleles in linkage disequilibrium, we estimated the inherent selective benefit of individual polymorphisms in the viral population. These inherent selection coefficients were in turn used to calculate the total selective effect of interference acting upon each polymorphism, considering the effect of the initial background upon which a mutation arose, and the subsequent effect of interference from other alleles that were under selection. Viewing events in retrospect, we estimated the influence of each of these components in determining whether a mutant allele eventually fixed or died in the global viral population. Our inherent selection coefficients, when combined across different regions of the protein, were consistent with previous measurements of dN/dS for the same system. Alleles going on to fix in the global population tended to be under more positive selection, to arise on more beneficial backgrounds, and to avoid strong negative interference from other alleles under selection. However, on average, the fate of a polymorphism was determined more by the combined influence of interference effects than by its inherent selection coefficient.

  8. Have North-South Growth Linkages Changed?

    OpenAIRE

    Willy W. Hoffmaister; Mahmood Pradhan; Hossein Samiei

    1996-01-01

    This paper provides preliminary econometric evidence suggesting that the traditional trade-based business cycle linkages between the North and the South have changed. Many countries in the South, in particular in Asia, appear to have become more resilient to cyclical movements in the North, and to have come to play a more significant role in sustaining global activity, in particular during the 1991-93 slowdown. A number of factors may have contributed to these changes: improved domestic polic...

  9. Commodities and Linkages: Meeting the Policy Challenge

    OpenAIRE

    Kaplinsky, Raphael; Morris, Adam; Kaplan, David

    2011-01-01

    The results of detailed empirical enquiry into the nature and determinants of the breadth and depth of linkages in and out of the commodities sector in eight SSA countries (Angola, Botswana, Gabon, Ghana, Nigeria, South Africa Tanzania, and Zambia) and six sectors (copper, diamonds, gold, oil and gas, mining services and timber) has shown extensive scope for industrial development (MMCP DP 13, 2011). A primary conclusion of this research was that policy in both the private and public realm wa...

  10. 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

  11. Prioritizing Tiger Conservation through Landscape Genetics and Habitat Linkages

    Science.gov (United States)

    Yumnam, Bibek; Jhala, Yadvendradev V.; Qureshi, Qamar; Maldonado, Jesus E.; Gopal, Rajesh; Saini, Swati; Srinivas, Y.; Fleischer, Robert C.

    2014-01-01

    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 km2 of forest habitat was found to be only 21,290 km2. 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 (F ST) 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 provide legal status to

  12. Prioritizing tiger conservation through landscape genetics and habitat linkages.

    Science.gov (United States)

    Yumnam, Bibek; Jhala, Yadvendradev V; Qureshi, Qamar; Maldonado, Jesus E; Gopal, Rajesh; Saini, Swati; Srinivas, Y; Fleischer, Robert C

    2014-01-01

    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 provide legal status

  13. Genotyping by Sequencing in Almond: SNP Discovery, Linkage Mapping, and Marker Design

    Directory of Open Access Journals (Sweden)

    Shashi N. Goonetilleke

    2018-01-01

    Full Text Available In crop plant genetics, linkage maps provide the basis for the mapping of loci that affect important traits and for the selection of markers to be applied in crop improvement. In outcrossing species such as almond (Prunus dulcis Mill. D. A. Webb, application of a double pseudotestcross mapping approach to the F1 progeny of a biparental cross leads to the construction of a linkage map for each parent. Here, we report on the application of genotyping by sequencing to discover and map single nucleotide polymorphisms in the almond cultivars “Nonpareil” and “Lauranne.” Allele-specific marker assays were developed for 309 tag pairs. Application of these assays to 231 Nonpareil × Lauranne F1 progeny provided robust linkage maps for each parent. Analysis of phenotypic data for shell hardness demonstrated the utility of these maps for quantitative trait locus mapping. Comparison of these maps to the peach genome assembly confirmed high synteny and collinearity between the peach and almond genomes. The marker assays were applied to progeny from several other Nonpareil crosses, providing the basis for a composite linkage map of Nonpareil. Applications of the assays to a panel of almond clones and a panel of rootstocks used for almond production demonstrated the broad applicability of the markers and provide subsets of markers that could be used to discriminate among accessions. The sequence-based linkage maps and single nucleotide polymorphism assays presented here could be useful resources for the genetic analysis and genetic improvement of almond.

  14. Short Communication: Genetic linkage map of Cucurbita maxima with molecular and morphological markers.

    Science.gov (United States)

    Ge, Y; Li, X; Yang, X X; Cui, C S; Qu, S P

    2015-05-22

    Cucurbita maxima is one of the most widely cultivated vegetables in China and exhibits distinct morphological characteristics. In this study, genetic linkage analysis with 57 simple-sequence repeats, 21 amplified fragment length polymorphisms, 3 random-amplified polymorphic DNA, and one morphological marker revealed 20 genetic linkage groups of C. maxima covering a genetic distance of 991.5 cM with an average of 12.1 cM between adjacent markers. Genetic linkage analysis identified the simple-sequence repeat marker 'PU078072' 5.9 cM away from the locus 'Rc', which controls rind color. The genetic map in the present study will be useful for better mapping, tagging, and cloning of quantitative trait loci/gene(s) affecting economically important traits and for breeding new varieties of C. maxima through marker-assisted selection.

  15. Renal brush border enzyme-cleavable linkages for low renal radioactivity levels of radiolabeled antibody fragments.

    Science.gov (United States)

    Akizawa, Hiromichi; Imajima, Mitsuo; Hanaoka, Hirofumi; Uehara, Tomoya; Satake, Satoshi; Arano, Yasushi

    2013-02-20

    We previously demonstrated that Fab fragments labeled with 3'-[(131)I]iodohippuryl N(ε)-maleoyl-l-lysine ([(131)I]HML) showed low renal radioactivity from early postinjection time, due to a liberation of m-[(131)I]iodohippuric acid by the action of renal brush border enzymes. Since there are lots of enzymes on renal brush border membrane, peptide linkages other than the glycyl-l-lysine were evaluated as the cleavable linkages to explore the chemical design. In this study, we evaluated four peptide linkages with a general formula of m-iodobenzoyl-glycyl-X (X: l-tyosine O-methyl, l-asparagine, l-glutamine, and N(ε)-Boc-l-lysine). In vitro studies using renal brush border membrane vesicles (BBMVs) demonstrated that 3'-[(125)I]iodohippuryl O-methyl-l-tyrosine (2c) liberated the highest amount of m-[(125)I]iodohippuric acid among the four substrates and the change in the linkage structure altered enzyme species responsible for the hydrolysis reaction. To further assess the applicability of the linkage, a radioiodination reagent containing a glycyl-tyrosine linkage, 3'-[(125)I]iodohippuryl O-((2-maleimidoethyl)carbamoyl)methyl-l-tyrosine (HMT, 12c), was designed, synthesized, and subsequently conjugated to an Fab fragment. [(125)I]HMT-Fab exhibited renal radioactivity levels similar to and significantly lower than [(125)I]HML-Fab and directly radioiodinated Fab, while the blood clearance rates of the three were similar. The analyses of urine for 24 h postinjection of [(125)I]HMT-Fab showed that m-[(125)I]iodohippuric acid was excreted as the major radiometabolite. The findings indicated that glycyl-tyrosine linkage is also available to reduce renal radioactivity levels of radioiodinated Fab fragments, due to liberation of m-iodohippuric acid by the action of enzymes present on renal brush border membrane. These findings suggest that an appropriate selection of peptide linkages would allow the liberation of a designed radiolabeled compound from covalently conjugated

  16. Impact of the Hepatitis Testing and Linkage to Care (HepTLC) Initiative on Linkage to Care for Minnesota Refugees with Hepatitis B, 2012–2014

    Science.gov (United States)

    Sweet, Kristin A.; Nelson, Kailey; Mamo, Blain; Chute, Sara M.

    2016-01-01

    Objective The Hepatitis Testing and Linkage to Care (HepTLC) initiative promoted viral hepatitis B and hepatitis C screening, posttest counseling, and linkage to care at 34 U.S. sites from 2012 to 2014. Through the HepTLC initiative, the Minnesota Department of Health (MDH) and clinic partners began conducting linkage-to-care activities with hepatitis B-positive refugees in October 2012. This intervention provided culturally appropriate support to link refugees to follow-up care for hepatitis B. Methods MDH refugee health and viral hepatitis surveillance programs, along with clinics that screened newly arrived refugees in Hennepin and Ramsey counties in Minnesota, collaborated on the project, which took place from October 1, 2012, through September 30, 2014. Bilingual care navigators contacted refugees to provide education, make appointments, and arrange transportation. We compared the linkage-to-care rate for participants with the rates for refugees screened the year before project launch using a two-sample test of proportions. Results In the year preceding the project (October 2011 through September 2012), 87 newly arrived refugees had a positive hepatitis B surface antigen (HBsAg) test. Fifty-six (64%) refugees received follow-up care, 12 (14%) refugees did not receive follow-up care, and 19 (22%) refugees could not be located and had no record of follow-up care. During the project, 174 HBsAg-positive, newly arrived refugees were screened. Of those 174 refugees, 162 (93%) received follow-up care, seven (4%) did not receive follow-up care, and five (3%) could not be located and had no record of follow-up care. The one-year linkage-to-care rate for project participants (93%) was significantly higher than the rate for refugees screened the previous year (64%) (prefugees. PMID:27168670

  17. Impact of the Hepatitis Testing and Linkage to Care (HepTLC) Initiative on Linkage to Care for Minnesota Refugees with Hepatitis B, 2012-2014.

    Science.gov (United States)

    Linde, Ann C; Sweet, Kristin A; Nelson, Kailey; Mamo, Blain; Chute, Sara M

    2016-01-01

    The Hepatitis Testing and Linkage to Care (HepTLC) initiative promoted viral hepatitis B and hepatitis C screening, posttest counseling, and linkage to care at 34 U.S. sites from 2012 to 2014. Through the HepTLC initiative, the Minnesota Department of Health (MDH) and clinic partners began conducting linkage-to-care activities with hepatitis B-positive refugees in October 2012. This intervention provided culturally appropriate support to link refugees to follow-up care for hepatitis B. MDH refugee health and viral hepatitis surveillance programs, along with clinics that screened newly arrived refugees in Hennepin and Ramsey counties in Minnesota, collaborated on the project, which took place from October 1, 2012, through September 30, 2014. Bilingual care navigators contacted refugees to provide education, make appointments, and arrange transportation. We compared the linkage-to-care rate for participants with the rates for refugees screened the year before project launch using a two-sample test of proportions. In the year preceding the project (October 2011 through September 2012), 87 newly arrived refugees had a positive hepatitis B surface antigen (HBsAg) test. Fifty-six (64%) refugees received follow-up care, 12 (14%) refugees did not receive follow-up care, and 19 (22%) refugees could not be located and had no record of follow-up care. During the project, 174 HBsAg-positive, newly arrived refugees were screened. Of those 174 refugees, 162 (93%) received follow-up care, seven (4%) did not receive follow-up care, and five (3%) could not be located and had no record of follow-up care. The one-year linkage-to-care rate for project participants (93%) was significantly higher than the rate for refugees screened the previous year (64%) (prefugees.

  18. Probabilistic linkage to enhance deterministic algorithms and reduce data linkage errors in hospital administrative data.

    Science.gov (United States)

    Hagger-Johnson, Gareth; Harron, Katie; Goldstein, Harvey; Aldridge, Robert; Gilbert, Ruth

    2017-06-30

     BACKGROUND: The pseudonymisation algorithm used to link together episodes of care belonging to the same patients in England (HESID) has never undergone any formal evaluation, to determine the extent of data linkage error. To quantify improvements in linkage accuracy from adding probabilistic linkage to existing deterministic HESID algorithms. Inpatient admissions to NHS hospitals in England (Hospital Episode Statistics, HES) over 17 years (1998 to 2015) for a sample of patients (born 13/28th of months in 1992/1998/2005/2012). We compared the existing deterministic algorithm with one that included an additional probabilistic step, in relation to a reference standard created using enhanced probabilistic matching with additional clinical and demographic information. Missed and false matches were quantified and the impact on estimates of hospital readmission within one year were determined. HESID produced a high missed match rate, improving over time (8.6% in 1998 to 0.4% in 2015). Missed matches were more common for ethnic minorities, those living in areas of high socio-economic deprivation, foreign patients and those with 'no fixed abode'. Estimates of the readmission rate were biased for several patient groups owing to missed matches, which was reduced for nearly all groups. CONCLUSION: Probabilistic linkage of HES reduced missed matches and bias in estimated readmission rates, with clear implications for commissioning, service evaluation and performance monitoring of hospitals. The existing algorithm should be modified to address data linkage error, and a retrospective update of the existing data would address existing linkage errors and their implications.

  19. Linkage to HIV care after home-based HIV counselling and testing in sub-Saharan Africa: a systematic review.

    Science.gov (United States)

    Ruzagira, Eugene; Baisley, Kathy; Kamali, Anatoli; Biraro, Samuel; Grosskurth, Heiner

    2017-07-01

    Home-based HIV counselling and testing (HBHCT) has the potential to increase HIV testing uptake in sub-Saharan Africa (SSA), but data on linkage to HIV care after HBHCT are scarce. We conducted a systematic review of linkage to care after HBHCT in SSA. Five databases were searched for studies published between 1st January 2000 and 19th August 2016 that reported on linkage to care among adults newly identified with HIV infection through HBHCT. Eligible studies were reviewed, assessed for risk of bias and findings summarised using the PRISMA guidelines. A total of 14 studies from six countries met the eligibility criteria; nine used specific strategies (point-of-care CD4 count testing, follow-up counselling, provision of transport funds to clinic and counsellor facilitation of HIV clinic visit) in addition to routine referral to facilitate linkage to care. Time intervals for ascertaining linkage ranged from 1 week to 12 months post-HBHCT. Linkage ranged from 8.2% [95% confidence interval (CI), 6.8-9.8%] to 99.1% (95% CI, 96.9-99.9%). Linkage was generally lower (80%) if additional strategies were used. Only one study assessed linkage by means of a randomised trial. Five studies had data on cotrimoxazole (CTX) prophylaxis and 12 on ART eligibility and initiation. CTX uptake among those eligible ranged from 0% to 100%. The proportion of persons eligible for ART ranged from 16.5% (95% CI, 12.1-21.8) to 77.8% (95% CI, 40.0-97.2). ART initiation among those eligible ranged from 14.3% (95% CI, 0.36-57.9%) to 94.9% (95% CI, 91.3-97.4%). Additional linkage strategies, whilst seeming to increase linkage, were not associated with higher uptake of CTX and/or ART. Most of the studies were susceptible to risk of outcome ascertainment bias. A pooled analysis was not performed because of heterogeneity across studies with regard to design, setting and the key variable definitions. Only few studies from SSA investigated linkage to care among adults newly diagnosed with HIV through

  20. Linkage of autosomal recessive lamellar ichthyosis to chromosome 14q

    Energy Technology Data Exchange (ETDEWEB)

    Russell, L.J.; Compton, J.G.; Bale, S.J. [National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD (United States); DiGiovanna, J.J. [National Cancer Institute, Bethesda, MD (United States); Hashem, N. [Ains-Shams Univ. Medical Genetics Center, Cairo (Egypt)

    1994-12-01

    The authors have mapped the locus for lamellar ichthyosis (LI), an autosomal recessive skin disease characterized by abnormal cornification of the epidermis. Analysis using both inbred and outbred families manifesting severe LI showed complete linkage to several markers within a 9.3-cM region on chromosome 14q11. Affected individuals in inbred families were also found to have striking homozygosity for markers in this region. Linkage-based genetic counseling and prenatal diagnosis is now available for informative at-risk families. Several transcribed genes have been mapped to the chromosome 14 region containing the LI gene. The transglutaminase 1 gene (TGM1), which encodes one of the enzymes responsible for cross-linking epidermal proteins during formation of the stratum corneum, maps to this interval. The TGM1 locus was completely linked to LI (Z = 9.11), suggesting that TGM1 is a good candidate for further investigation of this disorder. The genes for four serine proteases also map to this region but are expressed only in hematopoietic or mast cells, making them less likely candidates.

  1. Mapping Mendelian Factors Underlying Quantitative Traits Using RFLP Linkage Maps

    Science.gov (United States)

    Lander, E. S.; Botstein, D.

    1989-01-01

    The advent of complete genetic linkage maps consisting of codominant DNA markers [typically restriction fragment length polymorphisms (RFLPs)] has stimulated interest in the systematic genetic dissection of discrete Mendelian factors underlying quantitative traits in experimental organisms. We describe here a set of analytical methods that modify and extend the classical theory for mapping such quantitative trait loci (QTLs). These include: (i) a method of identifying promising crosses for QTL mapping by exploiting a classical formula of SEWALL WRIGHT; (ii) a method (interval mapping) for exploiting the full power of RFLP linkage maps by adapting the approach of LOD score analysis used in human genetics, to obtain accurate estimates of the genetic location and phenotypic effect of QTLs; and (iii) a method (selective genotyping) that allows a substantial reduction in the number of progeny that need to be scored with the DNA markers. In addition to the exposition of the methods, explicit graphs are provided that allow experimental geneticists to estimate, in any particular case, the number of progeny required to map QTLs underlying a quantitative trait. PMID:2563713

  2. Whole Exome Sequencing and Segregation Analysis Confirms That a Mutation in COL17A1 Is the Cause of Epithelial Recurrent Erosion Dystrophy in a Large Dominant Pedigree Previously Mapped to Chromosome 10q23-q24.

    Directory of Open Access Journals (Sweden)

    Benjamin R Lin

    Full Text Available To report identification of a COL17A1 mutation in a family with a corneal dystrophy previously mapped to chromosome 10q23-q24.Whole-exome sequencing was performed on DNA samples from five affected family members and two unrelated, unaffected individuals. Identified variants were filtered for those that were: located in the linked interval on chromosome 10q23-q24; novel or rare (minor allele frequency ≤0.01; heterozygous; present in all affected individuals and not in controls; and present in genes that encode proteins expressed in human corneal epithelial cells (reads per kilobase per million ≥1. Sanger sequencing of identified variants (SNVs was performed in additional family members. In silico analysis was used to predict the functional impact of non-synonymous variants.Three SNVs located in two genes were identified that met the filtering criteria: one rare synonymous c.3156C>T variant in the collagen, type XVII, alpha I (COL17A1 gene; and two rare variants, one synonymous and one missense, in the dynamin binding protein (DNMBP gene. Sanger sequencing of additional family members determined that only the COL17A1 variant segregates with the affected phenotype. In silico analysis predicts that the missense variant in DNMBP would be tolerated.The corneal dystrophy mapped to chromosome 10q23-q24 is associated with the c.3156C>T variant in COL17A1. As this variant has recently been identified in five other families with early onset recurrent corneal erosions, and has been shown in vitro to introduce a cryptic splice donor site, this dystrophy is likely caused by aberrant splicing of COL17A1 and should be classified as epithelial recurrent erosion dystrophy.

  3. 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.

  4. Biosynthesis of riboflavin: mechanism of formation of the ribitylamino linkage

    International Nuclear Information System (INIS)

    Keller, P.J.; Van, Q.L.; Kim, S.U.; Bown, D.H.; Chen, H.C.; Kohnle, A.; Bacher, A.; Floss, H.G.

    1988-01-01

    Feeding experiments with Ashbya gossypii followed by NMR analysis of the resulting riboflavin showed incorporation of deuterium from D-[2- 2 H]ribose at C-2' and from D-[1- 2 H] ribose in the pro-R position at C-1' of the ribityl side chain. The results rule out an Amadori rearrangement mechanism for the reduction of the ribosylamino to the ribitylamino linkage and point to formation of a Schiff base that is reduced stereospecifically opposite to the face from which the oxygen has departed. As prerequisite for the analysis, the 1 H NMR signals for the pro-R and pro-S hydrogens at C-1' of 6,7-dimethyl-8-ribityllumazine and riboflavin and its tetraacetate were assigned with the aid of synthetic stereospecifically deuteriated samples

  5. Elastodynamic Effects of Mass-Balancing: Experimental Investigation of a Four-Bar Linkage

    Directory of Open Access Journals (Sweden)

    Alberto Martini

    2013-01-01

    Full Text Available This paper deals with static balancing of closed-loop mechanisms. The long-term goal of the research is enhancing the performance of parallel robots by means of effective static balancing strategies that take into account the system dynamic behaviour. In this contribution, the influence of mass-balancing on the elastodynamic performance of a four-bar linkage, intended as the simplest example of closed-loop mechanism, is experimentally investigated. The design of the experimental apparatus is discussed and the results of tests on both an unbalanced linkage and its balanced variant are presented. Base-transmitted forces and vibrations are monitored for constant-speed operations and for velocity ramp tests in order to characterize the elastodynamic behaviour of the linkages. The analysis is supported by implementing a flexible multibody model of the experimental apparatus that enhances the interpretation of the experimental data.

  6. Is a Previously or Currently Reduced Testosterone Level in Male Patients with Type 2 Diabetes Mellitus a Risk Factor for the Development of Coronary Artery Disease? A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Huang, Feng

    2018-04-04

    We aimed to systematically investigate the association between testosterone level and cardiovascular risk in male patients with type 2 diabetes mellitus (T2DM) by comparing male T2DM patients with low testosterone levels to male T2DM patients with normal testosterone levels at baseline in terms of the number of cases of coronary artery disease (CAD). Online databases were carefully searched for studies relating to testosterone, diabetes mellitus, and cardiovascular risk by using the search terms 'testosterone,' 'diabetes mellitus,' and 'coronary artery/cardiovascular disease.' The only endpoint in this analysis was CAD/atherosclerosis/coronary plaque/major adverse coronary event prior to or following testosterone reduction at baseline. The analytical parameters used in this analysis were the risk ratio (RR) with the 95% confidence interval (CI), as obtained using the RevMan 5.3 software. 3467 male patients with T2DM (1079 patients with a low testosterone level versus 2388 patients with a normal testosterone level) were included. The results of this analysis showed that when a random effects model was used, a higher risk of CAD/cardiovascular disease was observed in diabetic patients with a low testosterone level than in those with a normal testosterone level (RR 1.24, 95% CI 0.94-1.63; P = 0.13). However, the difference in risk was not statistically significant. Similarly, with a fixed effects model, a low testosterone level was associated with a higher CAD/cardiovascular risk of disease (RR 1.12, 95% CI 0.98-1.34; P = 0.08); in this case, the difference in risk between the T2DM patients with low and normal testosterone levels approached statistical significance. A previously or currently reduced testosterone level was not found to be statistically significantly associated with a high risk of CAD/cardiovascular disease in male patients with T2DM. However, the difference in risk between the T2DM patients with low and normal testosterone levels was observed

  7. Blood pressure and fasting lipid changes after 24 weeks’ treatment with vildagliptin: a pooled analysis in >2,000 previously drug-naïve patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Evans M

    2016-08-01

    Full Text Available Marc Evans,1 Anja Schweizer,2 James E Foley3 1Diabetes Resource Centre, Llandough Hospital, Cardiff, UK; 2Medical Affairs Cardio Metabolic, Novartis Pharma AG, Basel, Switzerland; 3Medical Affairs Cardio-Metabolic, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA Introduction: We have previously shown modest weight loss with vildagliptin treatment. Since body weight balance is associated with changes in blood pressure (BP and fasting lipids, we have assessed these parameters following vildagliptin treatment. Methods: Data were pooled from all double-blind, randomized, controlled, vildagliptin monotherapy trials on previously drug-naïve patients with type 2 diabetes mellitus who received vildagliptin 50 mg once daily (qd or twice daily (bid; n=2,108 and wherein BP and fasting lipid data were obtained. Results: Data from patients receiving vildagliptin 50 mg qd or bid showed reductions from baseline to week 24 in systolic BP (from 132.5±0.32 to 129.8±0.34 mmHg; P<0.0001, diastolic BP (from 81.2±0.18 to 79.6±0.19 mmHg; P<0.0001, fasting triglycerides (from 2.00±0.02 to 1.80±0.02 mmol/L; P<0.0001, very low density lipoprotein cholesterol (from 0.90±0.01 to 0.83±0.01 mmol/L; P<0.0001, and low density lipoprotein cholesterol (from 3.17±0.02 to 3.04±0.02 mmol/L; P<0.0001, whereas high density lipoprotein cholesterol increased (from 1.19±0.01 to 1.22±0.01 mmol/L; P<0.001. Weight decreased by 0.48±0.08 kg (P<0.001. Conclusion: This large pooled analysis demonstrated that vildagliptin shows a significant reduction in BP and a favorable fasting lipid profile that are associated with modest weight loss. Keywords: TG, HDL, LDL, body weight DPP-4 inhibitor, GLP-1 

  8. Linkages to Public Land Framework: toward embedding humans in ecosystem analyses by using “inside-out social assessment.”

    Science.gov (United States)

    Joanna Endter-Wada; Dale J. Blahna

    2011-01-01

    This article presents the " Linkages to Public Land" (LPL) Framework, a general but comprehensive data-gathering and analysis approach aimed at informing citizen and agency decision making about the social environment of public land. This social assessment and planning approach identifies and categorizes various types of linkages that people have to public...

  9. Mixed-linkage (1-->3),(1-->4)-beta-D-glucan is not unique to the Poales and is an abundant component of Equisetum arvense cell walls

    DEFF Research Database (Denmark)

    Sørensen, Iben; Pettolino, Filomena A; Wilson, Sarah M

    2008-01-01

    of the horsetail Equisetum arvense. MALDI-TOF MS and monosaccharide linkage analysis revealed that MLG in E. arvense is an unbranched homopolymer that consists of short blocks of contiguous 1,4-beta-linked glucose residues joined by 1,3-beta linkages. However, in contrast to Poaceae species, MLG in E. arvense...

  10. 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…

  11. Linkage and mapping analyses of the no glue egg gene Ng in the ...

    African Journals Online (AJOL)

    In the silkworm, Bombyx mori, no glue egg is mainly controlled by Ng (No glue) gene, which is located on the 12th chromosome. Owning to a lack of crossing over in females, reciprocal backcrossed F1 (BC1) progenies were used for linkage analysis and mapping of the Ng gene based on the simple sequence repeats ...

  12. Maximum-likelihood estimation in linkage heterogeneity models including additional information via the EM algorithm

    NARCIS (Netherlands)

    Houwing-Duistermaat, J. J.; Sandkuijl, L. A.; Bergen, A. A.; van Houwelingen, H. C.

    1995-01-01

    In linkage analysis, estimated recombination fractions between a disease gene and several markers are used to assign the disease gene to a particular chromosome region. For rare diseases, locus heterogeneity leads to different recombination fractions in different families, and a set of pedigrees can

  13. 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

  14. Indian migrants in britain: mirror image of social linkages between Gujarat and London

    NARCIS (Netherlands)

    Rutten, M.; Patel, P.J.

    2003-01-01

    This article discusses the social linkages between Gujarati migrants in Britain and their family members in India. It considers the home and the migrant community in the same unit of analysis rather than as separate communities. It is based on fieldwork conducted in 1998 among members of the Patidar

  15. 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, Jonas; 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

  16. 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...

  17. 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

  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

    2011-03-01

    Full Text Available 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.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.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

  19. Effect of long-term GH replacement therapy on cardiovascular outcomes in GH-deficient patients previously treated for acromegaly: a sub-analysis from the Dutch National Registry of Growth Hormone Treatment in Adults.

    Science.gov (United States)

    van Bunderen, Christa C; van Varsseveld, Nadège C; Heymans, Martijn W; Franken, Anton A M; Koppeschaar, Hans P F; van der Lely, Aart J; Drent, Madeleine L

    2014-12-01

    The effect of GH deficiency (GHD) on the metabolic profile of acromegaly patients is unclear in patients previously treated for acromegaly, as are the efficacy and safety of GH treatment in this particular group. The aim of the study is to describe the characteristics of patients with severe GHD who were previously treated for acromegaly, and to investigate the effects of long-term GH treatment on cardiovascular risk factors and morbidity, compared with patients who were treated for a nonfunctioning pituitary adenoma (NFPA). A nationwide surveillance study. Sixty-five patients from the Dutch National Registry of Growth Hormone Treatment in Adults with previous acromegaly were compared with 778 patients with previous NFPA. Cardiovascular indices, including body composition, lipid profile, glucose metabolism, blood pressure, and morbidity were investigated. GHD patients with previous acromegaly had an unfavorable metabolic profile comparable with or more than GHD patients with previous NFPA. GH treatment led to improvement of the lipid profile in both groups, also after excluding patients using lipid-lowering medication. In patients with previous acromegaly, HbA1c levels increased more than in patients with previous NFPA (estimate 0.03, 95% CI 0.002-0.06, P=0.04). The risk for developing cardiovascular diseases was not different between the groups. The patients with GHD after previous acromegaly have an unfavorable metabolic profile comparable with patients with GHD after previous NFPA. In both groups, the lipid profile improves during GH treatment. Changes in glucose metabolism should be monitored closely. GH treatment in patients with GHD previously treated for acromegaly had no deleterious effect on cardiovascular morbidity. © 2014 European Society of Endocrinology.

  20. A second-generation anchored genetic linkage map of the tammar wallaby (Macropus eugenii

    Directory of Open Access Journals (Sweden)

    Patel Hardip R

    2011-08-01

    Full Text Available Abstract Background The tammar wallaby, Macropus eugenii, a small kangaroo used for decades for studies of reproduction and metabolism, is the model Australian marsupial for genome sequencing and genetic investigations. The production of a more comprehensive cytogenetically-anchored genetic linkage map will significantly contribute to the deciphering of the tammar wallaby genome. It has great value as a resource to identify novel genes and for comparative studies, and is vital for the ongoing genome sequence assembly and gene ordering in this species. Results A second-generation anchored tammar wallaby genetic linkage map has been constructed based on a total of 148 loci. The linkage map contains the original 64 loci included in the first-generation map, plus an additional 84 microsatellite loci that were chosen specifically to increase coverage and assist with the anchoring and orientation of linkage groups to chromosomes. These additional loci were derived from (a sequenced BAC clones that had been previously mapped to tammar wallaby chromosomes by fluorescence in situ hybridization (FISH, (b End sequence from BACs subsequently FISH-mapped to tammar wallaby chromosomes, and (c tammar wallaby genes orthologous to opossum genes predicted to fill gaps in the tammar wallaby linkage map as well as three X-linked markers from a published study. Based on these 148 loci, eight linkage groups were formed. These linkage groups were assigned (via FISH-mapped markers to all seven autosomes and the X chromosome. The sex-pooled map size is 1402.4 cM, which is estimated to provide 82.6% total coverage of the genome, with an average interval distance of 10.9 cM between adjacent markers. The overall ratio of female/male map length is 0.84, which is comparable to the ratio of 0.78 obtained for the first-generation map. Conclusions Construction of this second-generation genetic linkage map is a significant step towards complete coverage of the tammar wallaby

  1. Primary angioplasty vs. fibrinolysis in very old patients with acute myocardial infarction: TRIANA (TRatamiento del Infarto Agudo de miocardio eN Ancianos) randomized trial and pooled analysis with previous studies.

    Science.gov (United States)

    Bueno, Héctor; Betriu, Amadeo; Heras, Magda; Alonso, Joaquín J; Cequier, Angel; García, Eulogio J; López-Sendón, José L; Macaya, Carlos; Hernández-Antolín, Rosana

    2011-01-01

    To compare primary percutaneous coronary intervention (pPCI) and fibrinolysis in very old patients with ST-segment elevation myocardial infarction (STEMI), in whom head-to-head comparisons between both strategies are scarce. Patients ≥75 years old with STEMI <6 h were randomized to pPCI or fibrinolysis. The primary endpoint was a composite of all-cause mortality, re-infarction, or disabling stroke at 30 days. The trial was prematurely stopped due to slow recruitment after enrolling 266 patients (134 allocated to pPCI and 132 to fibrinolysis). Both groups were well balanced in baseline characteristics. Mean age was 81 years. The primary endpoint was reached in 25 patients in the pPCI group (18.9%) and 34 (25.4%) in the fibrinolysis arm [odds ratio (OR), 0.69; 95% confidence interval (CI) 0.38-1.23; P = 0.21]. Similarly, non-significant reductions were found in death (13.6 vs. 17.2%, P = 0.43), re-infarction (5.3 vs. 8.2%, P = 0.35), or disabling stroke (0.8 vs. 3.0%, P = 0.18). Recurrent ischaemia was less common in pPCI-treated patients (0.8 vs. 9.7%, P< 0.001). No differences were found in major bleeds. A pooled analysis with the two previous reperfusion trials performed in older patients showed an advantage of pPCI over fibrinolysis in reducing death, re-infarction, or stroke at 30 days (OR, 0.64; 95% CI 0.45-0.91). Primary PCI seems to be the best reperfusion therapy for STEMI even for the oldest patients. Early contemporary fibrinolytic therapy may be a safe alternative to pPCI in the elderly when this is not available.

  2. A Novel Flux Linkage Indirect Measurement for Switched Reluctance Motor

    Science.gov (United States)

    Li, Pang; Zhang, Lei; Yu, Yue

    2017-05-01

    This paper presents a indirect detection system of flux linkage characteristic of switched reluctance motor based on dsPACE, fixed rotor position by mechanical indexing for Static flux linkage detection, the phase windings is excited by the step voltage signal, the voltage and phase current are collected real -time, and calculate flux linkage. The advantages of the method is that the parameters are optimized by ControlDesk, the flux linkage detection model is built by Simulink, no writing program, simple, easy implementation. An 1.5kw three-phase 12/8 SRM experimental prototype was constructed, the detection results of the Static flux linkage and dynamic flux linkage verified its validity and feasibility.

  3. Classification and Regression Tree Analysis of Clinical Patterns that Predict Survival in 127 Chinese Patients with Advanced Non-small Cell Lung Cancer Treated by Gefitinib Who Failed to Previous Chemotherapy

    Directory of Open Access Journals (Sweden)

    Ziping WANG

    2011-09-01

    Full Text Available Background and objective It has been proven that gefitinib produces only 10%-20% tumor regression in heavily pretreated, unselected non-small cell lung cancer (NSCLC patients as the second- and third-line setting. Asian, female, nonsmokers and adenocarcinoma are favorable factors; however, it is difficult to find a patient satisfying all the above clinical characteristics. The aim of this study is to identify novel predicting factors, and to explore the interactions between clinical variables and their impact on the survival of Chinese patients with advanced NSCLC who were heavily treated with gefitinib in the second- or third-line setting. Methods The clinical and follow-up data of 127 advanced NSCLC patients referred to the Cancer Hospital & Institute, Chinese Academy of Medical Sciences from March 2005 to March 2010 were analyzed. Multivariate analysis of progression-free survival (PFS was performed using recursive partitioning, which is referred to as the classification and regression tree (CART analysis. Results The median PFS of 127 eligible consecutive advanced NSCLC patients was 8.0 months (95%CI: 5.8-10.2. CART was performed with an initial split on first-line chemotherapy outcomes and a second split on patients’ age. Three terminal subgroups were formed. The median PFS of the three subsets ranged from 1.0 month (95%CI: 0.8-1.2 for those with progressive disease outcome after the first-line chemotherapy subgroup, 10 months (95%CI: 7.0-13.0 in patients with a partial response or stable disease in first-line chemotherapy and age <70, and 22.0 months for patients obtaining a partial response or stable disease in first-line chemotherapy at age 70-81 (95%CI: 3.8-40.1. Conclusion Partial response, stable disease in first-line chemotherapy and age ≥ 70 are closely correlated with long-term survival treated by gefitinib as a second- or third-line setting in advanced NSCLC. CART can be used to identify previously unappreciated patient

  4. Linkage design effect on the reliability of surface micromachined microengines driving a load

    Energy Technology Data Exchange (ETDEWEB)

    Tanner, D.M.; Peterson, K.A.; Irwin, L.W.; Tangyunyong, P.; Miller, W.M.; Eaton, W.P.; Smith, N.F.; Rodgers, M.S.

    1998-08-01

    The reliability of microengines is a function of the design of the mechanical linkage used to connect the electrostatic actuator to the drive. The authors have completed a series of reliability stress tests on surface micromachined microengines driving an inertial load. In these experiments, the authors used microengines that had pin mechanisms with guides connecting the drive arms to the electrostatic actuators. Comparing this data to previous results using flexure linkages revealed that the pin linkage design was less reliable. The devices were stressed to failure at eight frequencies, both above and below the measured resonance frequency of the microengine. Significant amounts of wear debris were observed both around the hub and pin joint of the drive gear. Additionally, wear tracks were observed in the area where the moving shuttle rubbed against the guides of the pin linkage. At each frequency, they analyzed the statistical data yielding a lifetime (t{sub 50}) for median cycles to failure and {sigma}, the shape parameter of the distribution. A model was developed to describe the failure data based on fundamental wear mechanisms and forces exhibited in mechanical resonant systems. The comparison to the model will be discussed.

  5. Association between cancer and contact allergy: a linkage study

    DEFF Research Database (Denmark)

    Engkilde, Kaare; Thyssen, Jacob P; Menné, Torkil

    2011-01-01

    by logistic regression analysis. Results An inverse association between contact allergy and non-melanoma skin- and breast cancer, respectively, was identified in both sexes, and an inverse trend for brain cancer was found in women with contact allergy. Additionally, a positive association between contact......Background Contact allergy is a prevalent disorder. It is estimated that about 20% of the general population are allergic to one or more of the chemicals that constitute the European baseline patch test panel. While many studies have investigated associations between type I allergic disorders...... and cancer, few have looked into the association between cancer and contact allergy, a type IV allergy. By linking two clinical databases, the authors investigate the possible association between contact allergy and cancer. Methods Record linkage of two different registers was performed: (1) a tertiary...

  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

    2017-07-01

    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. Quantifying the Correctness, Computational Complexity, and Security of Privacy-Preserving String Comparators for Record Linkage

    Science.gov (United States)

    Durham, Elizabeth; Xue, Yuan; Kantarcioglu, Murat; Malin, Bradley

    2011-01-01

    Record linkage is the task of identifying records from disparate data sources that refer to the same entity. It is an integral component of data processing in distributed settings, where the integration of information from multiple sources can prevent duplication and enrich overall data quality, thus enabling more detailed and correct analysis. Privacy-preserving record linkage (PPRL) is a variant of the task in which data owners wish to perform linkage without revealing identifiers associated with the records. This task is desirable in various domains, including healthcare, where it may not be possible to reveal patient identity due to confidentiality requirements, and in business, where it could be disadvantageous to divulge customers' identities. To perform PPRL, it is necessary to apply string comparators that function in the privacy-preserving space. A number of privacy-preserving string comparators (PPSCs) have been proposed, but little research has compared them in the context of a real record linkage application. This paper performs a principled and comprehensive evaluation of six PPSCs in terms of three key properties: 1) correctness of record linkage predictions, 2) computational complexity, and 3) security. We utilize a real publicly-available dataset, derived from the North Carolina voter registration database, to evaluate the tradeoffs between the aforementioned properties. Among our results, we find that PPSCs that partition, encode, and compare strings yield highly accurate record linkage results. However, as a tradeoff, we observe that such PPSCs are less secure than those that map and compare strings in a reduced dimensional space. PMID:22904698

  8. A análise seminal deve ser requisitada para homens com histórico de fertilidade prévia? Should semen analysis be requested for men with a history of previous fertility?

    Directory of Open Access Journals (Sweden)

    Eleonora Bedin Pasqualotto

    2006-11-01

    ão devem presumir que um paciente possui uma análise seminal normal, baseados no fato de este possuir história de estabelecimento de uma gravidez no passado.PURPOSE: to determine if the previous fertility history can predict current fertility status of a patient examined for couple’s infertility. METHODS: retrospective study involving semen analyses from 183 consecutive subfertile patients evaluated from September 2002 to March 2004. We excluded those patients who had undergone radio or chemotherapy, orchiectomy or vasectomy. Mean values of all analyses were used for patients with multiple semen analysis. Patients with more than 20x10(6 sperm/mL, motility higher than 50% and with normal strict sperm morphology higher than 14% were considered normal. Patients were divided into two groups, according to the fertility status: primary infertility (118 patients and secondary infertility (65 patients. Data were analyzed according to the chi2 test and the Student t-test. RESULTS: no differences were detected in the mean age between patients with primary infertility, 37.3±6.3, and secondary infertility, 38.1±5.9; p=0.08. In the group of patients with primary infertility, 51.9% (61 patients had a normal sperm concentration, 70.3% (83 patients had normal sperm motility and 26.3% (31 patients had normal sperm morphology. In the group of patients with secondary infertility, 53.8% (35 patients had normal sperm concentration, 75.4% (49 patients had normal sperm motility and 32.3% (21 patients had normal sperm morphology. No significant differences were detected in sperm concentration (21.3x10(6/mL versus 23.1x10(6/mL; p=0.07, motility (45.2 versus 48.1%; p=0.08 and morphology (6.1 versus 6.4%; p=0.09 between groups of patients with primary and secondary infertility. CONCLUSIONS: semen analysis should be requested even in cases of prior male fertility. Physicians should not presume a patient to have a normal semen analysis based on his previous history of initiating a pregnancy.

  9. Assessing the feasibility of linkage disequilibrium methods for mapping complex traits: an initial screen for bipolar disorder loci on chromosome 18.

    Science.gov (United States)

    Escamilla, M A; McInnes, L A; Spesny, M; Reus, V I; Service, S K; Shimayoshi, N; Tyler, D J; Silva, S; Molina, J; Gallegos, A; Meza, L; Cruz, M L; Batki, S; Vinogradov, S; Neylan, T; Nguyen, J B; Fournier, E; Araya, C; Barondes, S H; Leon, P; Sandkuijl, L A; Freimer, N B

    1999-06-01

    Linkage disequilibrium (LD) analysis has been promoted as a method of mapping disease genes, particularly in isolated populations, but has not yet been used for genome-screening studies of complex disorders. We present results of a study to investigate the feasibility of LD methods for genome screening using a sample of individuals affected with severe bipolar mood disorder (BP-I), from an isolated population of the Costa Rican central valley. Forty-eight patients with BP-I were genotyped for markers spaced at approximately 6-cM intervals across chromosome 18. Chromosome 18 was chosen because a previous genome-screening linkage study of two Costa Rican families had suggested a BP-I locus on this chromosome. Results of the current study suggest that LD methods will be useful for mapping BP-I in a larger sample. The results also support previously reported possible localizations (obtained from a separate collection of patients) of BP-I-susceptibility genes at two distinct sites on this chromosome. Current limitations of LD screening for identifying loci for complex traits are discussed, and recommendations are made for future research with these methods.

  10. Combining powers of linkage and association mapping for precise dissection of QTL controlling resistance to gray leaf spot disease in maize (Zea mays L.).

    Science.gov (United States)

    Mammadov, Jafar; Sun, Xiaochun; Gao, Yanxin; Ochsenfeld, Cherie; Bakker, Erica; Ren, Ruihua; Flora, Jonathan; Wang, Xiujuan; Kumpatla, Siva; Meyer, David; Thompson, Steve

    2015-11-10

    Gray Leaf Spot (GLS causal agents Cercospora zeae-maydis and Cercospora zeina) is one of the most important foliar diseases of maize in all areas where the crop is being cultivated. Although in the USA the situation with GLS severity is not as critical as in sub-Saharan Africa or Brazil, the evidence of climate change, increasing corn monoculture as well as the narrow genetic base of North American resistant germplasm can turn the disease into a serious threat to US corn production. The development of GLS resistant cultivars is one way to control the disease. In this study we combined the high QTL detection power of genetic linkage mapping with the high resolution power of genome-wide association study (GWAS) to precisely dissect QTL controlling GLS resistance and identify closely linked molecular markers for robust marker-assisted selection and trait introgression. Using genetic linkage analysis with a small bi-parental mapping population, we identified four GLS resistance QTL on chromosomes 1, 6, 7, and 8, which were validated by GWAS. GWAS enabled us to dramatically increase the resolution within the confidence intervals of the above-mentioned QTL. Particularly, GWAS revealed that QTLGLSchr8, detected by genetic linkage mapping as a locus with major effect, was likely represented by two QTL with smaller effects. Conducted in parallel, GWAS of days-to-silking demonstrated the co-localization of flowering time QTL with GLS resistance QTL on chromosome 7 indicating that either QTLGLSchr7 is a flowering time QTL or it is a GLS resistance QTL that co-segregates with the latter. As a result, this genetic linkage - GWAS hybrid mapping system enabled us to identify one novel GLS resistance QTL (QTLGLSchr8a) and confirm with more refined positions four more previously mapped QTL (QTLGLSchr1, QTLGLSchr6, QTLGLSchr7, and QTLGLSchr8b). Through the novel Single Donor vs. Elite Panel method we were able to identify within QTL confidence intervals SNP markers that would be

  11. PhenoDB: an integrated client/server database for linkage and population genetics.

    Science.gov (United States)

    Cheung, K H; Nadkarni, P; Silverstein, S; Kidd, J R; Pakstis, A J; Miller, P; Kidd, K K

    1996-08-01

    In this paper we describe PhenoDB, an Internet-accessible client/server database application for population and linkage genetics. PhenoDB stores genetic marker data on pedigrees and populations. A database for population and linkage genetics requires two core functions: data management tasks, such as interactive validation during data entry and editing, and data analysis tasks, such as generating summary population statistics and performing linkage analyses. In PhenoDB we attempt to make these tasks as easy as possible. The client/server architecture allows efficient management and manipulation of large datasets via an easy-to-use graphical interface. PhenoDB data (73 populations, 34 pedigrees, approximately 4200 individuals, and close to 80,000 typings) are stored in a generic format that can be readily exported to (or imported from) the file formats required by various existing analysis programs such as LIPED and Lathrop and Lalouel's Multipoint Linkage. PhenoDB allows performance of complex ad-hoc queries and can generate reports for use in project management. Finally, PhenoDB can produce statistical summaries such as allele frequencies, phenotype frequencies, and Chi-square tests of Hardy-Weinberg ratios of population/pedigree data.

  12. Linkage maps of the Atlantic salmon (Salmo salar) genome derived from RAD sequencing.

    Science.gov (United States)

    Gonen, Serap; Lowe, Natalie R; Cezard, Timothé; Gharbi, Karim; Bishop, Stephen C; Houston, Ross D

    2014-02-27

    Genetic linkage maps are useful tools for mapping quantitative trait loci (QTL) influencing variation in traits of interest in a population. Genotyping-by-sequencing approaches such as Restriction-site Associated DNA sequencing (RAD-Seq) now enable the rapid discovery and genotyping of genome-wide SNP markers suitable for the development of dense SNP linkage maps, including in non-model organisms such as Atlantic salmon (Salmo salar). This paper describes the development and characterisation of a high density SNP linkage map based on SbfI RAD-Seq SNP markers from two Atlantic salmon reference families. Approximately 6,000 SNPs were assigned to 29 linkage groups, utilising markers from known genomic locations as anchors. Linkage maps were then constructed for the four mapping parents separately. Overall map lengths were comparable between male and female parents, but the distribution of the SNPs showed sex-specific patterns with a greater degree of clustering of sire-segregating SNPs to single chromosome regions. The maps were integrated with the Atlantic salmon draft reference genome contigs, allowing the unique assignment of ~4,000 contigs to a linkage group. 112 genome contigs mapped to two or more linkage groups, highlighting regions of putative homeology within the salmon genome. A comparative genomics analysis with the stickleback reference genome identified putative genes closely linked to approximately half of the ordered SNPs and demonstrated blocks of orthology between the Atlantic salmon and stickleback genomes. A subset of 47 RAD-Seq SNPs were successfully validated using a high-throughput genotyping assay, with a correspondence of 97% between the two assays. This Atlantic salmon RAD-Seq linkage map is a resource for salmonid genomics research as genotyping-by-sequencing becomes increasingly common. This is aided by the integration of the SbfI RAD-Seq SNPs with existing reference maps and the draft reference genome, as well as the identification of

  13. Rates of induced abortion in Denmark according to age, previous births and previous abortions

    Directory of Open Access Journals (Sweden)

    Marie-Louise H. Hansen

    2009-11-01

    Full Text Available Background: Whereas the effects of various socio-demographic determinants on a woman's risk of having an abortion are relatively well-documented, less attention has been given to the effect of previous abortions and births. Objective: To study the effect of previous abortions and births on Danish women's risk of an abortion, in addition to a number of demographic and personal characteristics. Data and methods: From the Fertility of Women and Couples Dataset we obtained data on the number of live births and induced abortions by year (1981-2001, age (16-39, county of residence and marital status. Logistic regression analysis was used to estimate the influence of the explanatory variables on the probability of having an abortion in a relevant year. Main findings and conclusion: A woman's risk of having an abortion increases with the number of previous births and previous abortions. Some interactions were was found in the way a woman's risk of abortion varies with calendar year, age and parity. The risk of an abortion for women with no children decreases while the risk of an abortion for women with children increases over time. Furthermore, the risk of an abortion decreases with age, but relatively more so for women with children compared to childless women. Trends for teenagers are discussed in a separate section.

  14. 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...... 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...... the whole population based on LDC. The results showed that selecting individuals with similar haplotypes to the paternal haplotypes (minimum recombination criterion) using LAC compared to random phenotyping gave at least the same power to detect a QTL but decreased the accuracy of the QTL position. However...

  15. The kinematics of the rigid feedback linkage, the impedance of the hydraulic servomechanism and the flutter occurrence

    Directory of Open Access Journals (Sweden)

    Ioan URSU

    2012-09-01

    Full Text Available The paper brought to light a previous result of the author, used in the design of hydraulicservos actuating flight controls of the airplanes IAR 93 and IAR 99. The results highlights theimportance of the the kinematics of the rigid feedback linkage of the hydraulic servo in anaeroservoelastic frame.

  16. Linkages between Approaches to Learning, Perceived Stress and Expected and Actual Academic Outcomes among First-Semester Psychology Students

    Science.gov (United States)

    Öhrstedt, Maria; Lindfors, Petra

    2018-01-01

    Previous research indicates that higher educational students' perceptions of stress are in part related to the teaching and learning context, and influence academic outcomes. This study intends to deepen our understanding of these processes by examining the linkages between approaches to learning, perceived stress and expected and actual academic…

  17. Evolution of levers and linkages in the feeding mechanisms of fishes.

    Science.gov (United States)

    Westneat, Mark W

    2004-11-01

    The evolution of feeding mechanisms in the ray-finned fishes (Actinopterygii) is a compelling example of transformation in a musculoskeletal complex involving multiple skeletal elements and numerous muscles that power skull motion. Biomechanical models of jaw force and skull kinetics aid our understanding of these complex systems and enable broad comparison of feeding mechanics across taxa. Mechanical models characterize how muscles move skeletal elements by pulling bones around points of rotation in lever mechanisms, or by transmitting force through skeletal elements connected in a linkage. Previous work has focused on the feeding biomechanics of several lineages of fishes, but a broader survey of skull function in the context of quantitative models has not been attempted. This study begins such a survey by examining the diversity of mechanical design of the oral jaws in 35 species of ray-finned fishes with three main objectives: (1) analyze lower jaw lever models in a broad phylogenetic range of taxa, (2) identify the origin and evolutionary patterns of change in the linkage systems that power maxillary rotation and upper jaw protrusion, and (3) analyze patterns of change in feeding design in the context of actinopterygian phylogeny. The mandibular lever is present in virtually all actinopterygians, and the diversity in lower jaw closing force transmission capacity, with mechanical advantage ranging from 0.04 to 0.68, has important functional consequences. A four-bar linkage for maxillary rotation arose in the Amiiformes and persists in various forms in many teleost species. Novel mechanisms for upper jaw protrusion based on this linkage for maxillary rotation have evolved independently at least five times in teleosts. The widespread anterior jaws linkage for jaw protrusion in percomorph fishes arose initially in Zeiformes and subsequently radiated into a wide range of premaxillary protrusion capabilities.

  18. 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.

  19. Preliminary genetic linkage maps of Chinese herb Dendrobium ...

    Indian Academy of Sciences (India)

    2013-08-05

    Aug 5, 2013 ... [Feng S., Zhao H., Lu J., Liu J., Shen B. and Wang H. 2013 Preliminary genetic linkage maps of Chinese herb Dendrobium nobile and. D. moniliforme. J. Genet. 92, 205–212]. Introduction ..... ity, and inbreeding depression make F2 or backcross popu- lations rarely available for genetic linkage mapping ...

  20. 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. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Construction of genetic linkage map of the medicinal and ...

    Indian Academy of Sciences (India)

    got placed on 2 linkage groups, LLS and LPS on LG1 and. LLP, STP, POL and CPC on LG8. Discussion. Detailed genetic linkage maps of crop plant, on which molec- ular DNA markers are tightly placed and in which loci for morphological features, quantitative traits and specific genes have been located with reference to ...

  2. Linkages and Networks in the Structure of Personal Power.

    Science.gov (United States)

    MacConkey, Dorothy I.

    1980-01-01

    People in academic social systems who are interested in promotions learn about decision-making processes in academe, and about communication linkages. They learn to grasp the impact of these linkages and the support networks. An irrefutable ingredient is a sterling professional performance. Applying personal power requires individual tailoring.…

  3. 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.

  4. Agriculture–Tourism Linkages in Botswana: Evidence from the ...

    African Journals Online (AJOL)

    This article examines the linkages between the tourism and agriculture sectors in Botswana using evidence gathered from the country's growing safari lodge accommodation sector. The findings reveal limited local linkages between agriculture and tourism, and instead the existence of high levels of food imports from ...

  5. Identifying and Mapping Linkages between Actors in the Climate ...

    African Journals Online (AJOL)

    Promoting innovations in climate change requires innovation partnerships and linkages and also creating an enabling environment for actors. The paper reviewed available information on the identification and mapping of linkages between actors in the climate change innovation system. The findings showed different ...

  6. Effects of aquaculture researchers' job characteristics on linkage ...

    African Journals Online (AJOL)

    The study examined the effects of researchers' job characteristics on linkage activities in Nigeria due to the fact that many fish farmers have not been properly reached with technologies and the problem of poor fish production has been attributed to the weak linkages existing between research, extension and fish farmers.

  7. Construction of genetic linkage map of the medicinal and ...

    Indian Academy of Sciences (India)

    An integrated genetic linkage map of the medicinal and ornamental plant Catharanthus roseus, based on different types of molecular and morphological markers was constructed, using a F2 population of 144 plants. The map defines 14 linkage groups (LGs) and consists of 131 marker loci, including 125 molecular DNA ...

  8. A preliminary linkage map using spotted melanic laboratory strains ...

    Indian Academy of Sciences (India)

    Kondo S. et al. 2000 A detailed linkage map of Medaka, Oryzias latipes: comparative genomics and genome evolution. Genetics. 154, 1773–1784. Nichols K. M., Young W. P., Danzmann R. G., Robison B. D.,. Rexroad C., Noakes M. et al. 2003 A consolidated linkage map for rainbow trout (Oncorhynchus mykiss). Anim.

  9. An instrumented spatial linkage for measuring knee joint kinematics.

    Science.gov (United States)

    Rosvold, Joshua M; Atarod, Mohammad; Frank, Cyril B; Shrive, Nigel G

    2016-01-01

    In this study, the design and development of a highly accurate instrumented spatial linkage (ISL) for kinematic analysis of the ovine stifle joint is described. The ovine knee is a promising biomechanical model of the human knee joint. The ISL consists of six digital rotational encoders providing six degrees of freedom (6-DOF) to its motion. The ISL makes use of the complete and parametrically continuous (CPC) kinematic modeling method to describe the kinematic relationship between encoder readings and the relative positions and orientation of its two ends. The CPC method is useful when calibrating the ISL, because a small change in parameters corresponds to a small change in calculated positions and orientations and thus a smaller optimization error, compared to other kinematic models. The ISL is attached rigidly to the femur and the tibia for motion capture, and the CPC kinematic model is then employed to transform the angle sensor readings to relative motion of the two ends of the linkage, and thereby, the stifle joint motion. The positional accuracy for ISL after calibration and optimization was 0.3±0.2mm (mean +/- standard deviation). The ISL was also evaluated dynamically to ensure that accurate results were maintained, and achieved an accuracy of 0.1mm. Compared to the traditional motion capture methods, this system provides increased accuracy, reduced processing time, and ease of use. Future work will be on the application of the ISL to the ovine gait and determination of in vivo joint motions and tissue loads. Accurate measurement of knee joint kinematics is essential in understanding injury mechanisms and development of potential preventive or treatment strategies. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. BRIDGES: Evolution of basic and applied linkages in benthic science

    Science.gov (United States)

    Aumen, Nicholas G.; Gurtz, Martin E.; Barbour, Michael T.; Moerke, Ashley

    2010-01-01

    Growing awareness of environmental degradation resulted in stricter environmental regulations and laws for aquatic ecosystems. These regulations were followed by an increase in applied research and monitoring beginning in the early 1970s. The number of applied scientists who were members of the North American Benthological Society grew at a commensurate rate. The editors of J-NABS recognized that, despite these increases, submitted manuscripts mostly addressed basic science. In response, the BRIDGES section of J-NABS was created in 1994 to provide a forum for linking basic ecological principles to applied science problems and issues. We examined the emergence of applied science topics in J-NABS and its predecessor, Freshwater Invertebrate Biology, from their beginning in 1982 to 2009. We classified papers among 11 categories that included a basic/applied science linkage. In the 1980s, applied papers were predominantly on effects of eutrophication/pollution and landuse changes. When BRIDGES was established in 1994, papers were solicited by editors and BRIDGES sections usually included >1 paper on a common theme to express complementary or alternate viewpoints. Forty-two papers appeared in BRIDGES between 1994 and 2009, but the number per issue declined after 2001. The total number of applied science papers in J-NABS has increased since ∼1994. Citation analysis of BRIDGES papers illustrates how information is being cited, but applied papers often are used in ways that might not lead to citations. BRIDGES transitioned to a new format in September 2009 to address new types of complex, multifaceted linkages. All new BRIDGES articles will be open access, and authors will be encouraged to produce lay-language fact sheets and to post them on the web.

  11. Intracranial Aneurysms in Finnish Families: Confirmation of Linkage and Refinement of the Interval to Chromosome 19q13.3

    Science.gov (United States)

    van der Voet, Monique; Olson, Jane M.; Kuivaniemi, Helena; Dudek, Doreen M.; Skunca, Magdalena; Ronkainen, Antti; Niemelä, Mika; Jääskeläinen, Juha; Hernesniemi, Juha; Helin, Katariina; Leinonen, Eira; Biswas, Moumita; Tromp, Gerard

    2004-01-01

    We recently reported a two-stage genomewide screen of 48 sib pairs affected with intracranial aneurysms (IAs) that revealed suggestive linkage to chromosome 19q13, with a LOD score of 2.58. The region supporting linkage spanned ∼22 cM. Here, we report a follow-up study of the locus at 19q13, with a sample size expanded to 139 affected sib pairs, along with 83 other affected relative pairs (222 affected relative pairs in total). Suggestive linkage was observed in both independent sample sets, and linkage was significant in the combined set at 70 cM (LOD score 3.50; P=.00006) and at 80 cM (LOD score 3.93; P=.00002). Linkage was highly significant at 70 cM (LOD score 5.70; P=.000001) and at 80 cM (LOD score 3.99; P=.00005) when a covariate measuring the number of affected individuals in the nuclear family was included. To evaluate further the contribution to the linkage signal from families with more than two affected relatives, we performed model-based linkage analysis with a recessive model and a range of penetrances, and we obtained maximum linkage at 70 cM (LOD score 3.16; P=.00007) with a penetrance of 0.3. We then estimated location by using GENEFINDER. The most likely location for a gene predisposing to IAs in the Finnish population is in a region with a 95% confidence interval of 11.6 cM (P=.00007) centered 2.0 cM proximal to D19S246. PMID:14872410

  12. Placental complications after a previous cesarean section

    OpenAIRE

    Milošević Jelena; Lilić Vekoslav; Tasić Marija; Radović-Janošević Dragana; Stefanović Milan; Antić Vladimir

    2009-01-01

    Introduction The incidence of cesarean section has been rising in the past 50 years. With the increased number of cesarean sections, the number of pregnancies with the previous cesarean section rises as well. The aim of this study was to establish the influence of the previous cesarean section on the development of placental complications: placenta previa, placental abruption and placenta accreta, as well as to determine the influence of the number of previous cesarean sections on the complic...

  13. Genomewide Linkage Disequilibrium Mapping of Severe Bipolar Disorder in a Population Isolate

    Science.gov (United States)

    Ophoff, Roel A.; Escamilla, Michael A.; Service, Susan K.; Spesny, Mitzi; Meshi, Dar B.; Poon, Wingman; Molina, Julio; Fournier, Eduardo; Gallegos, Alvaro; Mathews, Carol; Neylan, Thomas; Batki, Steven L.; Roche, Erin; Ramirez, Margarita; Silva, Sandra; De Mille, Melissa C.; Dong, Penny; Leon, Pedro E.; Reus, Victor I.; Sandkuijl, Lodewijk A.; Freimer, Nelson B.

    2002-01-01

    Genomewide association studies may offer the best promise for genetic mapping of complex traits. Such studies in outbred populations require very densely spaced single-nucleotide polymorphisms. In recently founded population isolates, however, extensive linkage disequilibrium (LD) may make these studies feasible with currently available sets of short tandem repeat markers, spaced at intervals as large as a few centimorgans. We report the results of a genomewide association study of severe bipolar disorder (BP-I), using patients from the isolated population of the central valley of Costa Rica. We observed LD with BP-I on several chromosomes; the most striking results were in proximal 8p, a region that has previously shown linkage to schizophrenia. This region could be important for severe psychiatric disorders, rather than for a specific phenotype. PMID:12119601

  14. Confirmation of linkage and refinement of the RP28 locus for autosomal recessive retinitis pigmentosa on chromosome 2p14-p15 in an Indian family.

    Science.gov (United States)

    Kumar, Arun; Shetty, Jyoti; Kumar, Bharath; Blanton, Susan Halloran

    2004-06-15

    To report the linkage analysis of retinitis pigmentosa (RP) in an Indian family. Individuals were examined for symptoms of retinitis pigmentosa and their blood samples were withdrawn for genetic analysis. The disorder was tested for linkage to known 14 adRP and 22 arRP loci using microsatellite markers. Seventeen individuals including seven affecteds participated in the study. All affected individuals had typical RP. The age of onset of the disease ranged from 8-18 years. The disorder in this family segregated either as an autosomal recessive trait with pseudodominance or an autosomal dominant trait. Linkage to an autosomal recessive locus RP28 on chromosome 2p14-p15 was positive with a maximum two-point lod score of 3.96 at theta=0 for D2S380. All affected individuals were homozygous for alleles at D2S2320, D2S2397, D2S380, and D2S136. Recombination events placed the minimum critical region (MCR) for the RP28 gene in a 1.06 cM region between D2S2225 and D2S296. The present data confirmed linkage of arRP to the RP28 locus in a second Indian family. The RP28 locus was previously mapped to a 16 cM region between D2S1337 and D2S286 in a single Indian family. Haplotype analysis in this family has further narrowed the MCR for the RP28 locus to a 1.06 cM region between D2S2225 and D2S296. Of 15 genes reported in the MCR, 14 genes (KIAA0903, OTX1, MDH1, UGP2, VPS54, PELI1, HSPC159, FLJ20080, TRIP-Br2, SLC1A4, KIAA0582, RAB1A, ACTR2, and SPRED2) are either expressed in the eye or retina. Further study needs to be done to test which of these genes is mutated in patients with RP linked to the RP28 locus.

  15. A gene-derived SNP-based high resolution linkage map of carrot including the location of QTL conditioning root and leaf anthocyanin pigmentation.

    Science.gov (United States)

    Cavagnaro, Pablo F; Iorizzo, Massimo; Yildiz, Mehtap; Senalik, Douglas; Parsons, Joshua; Ellison, Shelby; Simon, Philipp W

    2014-12-16

    Purple carrots accumulate large quantities of anthocyanins in their roots and leaves. These flavonoid pigments possess antioxidant activity and are implicated in providing health benefits. Informative, saturated linkage maps associated with well characterized populations segregating for anthocyanin pigmentation have not been developed. To investigate the genetic architecture conditioning anthocyanin pigmentation we scored root color visually, quantified root anthocyanin pigments by high performance liquid chromatography in segregating F2, F3 and F4 generations of a mapping population, mapped quantitative trait loci (QTL) onto a dense gene-derived single nucleotide polymorphism (SNP)-based linkage map, and performed comparative trait mapping with two unrelated populations. Root pigmentation, scored visually as presence or absence of purple coloration, segregated in a pattern consistent with a two gene model in an F2, and progeny testing of F3-F4 families confirmed the proposed genetic model. Purple petiole pigmentation was conditioned by a single dominant gene that co-segregates with one of the genes conditioning root pigmentation. Root total pigment estimate (RTPE) was scored as the percentage of the root with purple color.All five anthocyanin glycosides previously reported in carrot, as well as RTPE, varied quantitatively in the F2 population. For the purpose of QTL analysis, a high resolution gene-derived SNP-based linkage map of carrot was constructed with 894 markers covering 635.1 cM with a 1.3 cM map resolution. A total of 15 significant QTL for all anthocyanin pigments and for RTPE mapped to six chromosomes. Eight QTL with the largest phenotypic effects mapped to two regions of chromosome 3 with co-localized QTL for several anthocyanin glycosides and for RTPE. A single dominant gene conditioning anthocyanin acylation was identified and mapped.Comparative mapping with two other carrot populations segregating for purple color indicated that carrot anthocyanin

  16. Rates, intrinsic linkages, and multistate population dynamics.

    Science.gov (United States)

    Schoen, Robert

    2017-01-01

    Demographic analyses of multistate populations are commonplace, as are situations where population stocks are known but population flows are not. Still, demographic models for multistate populations with changing rates remain at an early stage of development, limiting dynamic analyses and analytical projections. Here, a new approach, the Intrinsic Linkage-Rate Ratio (IL-RR) model, is presented and explored. The key IL parameter, w , is a simple weight for projecting populations. Using the ultimate state composition implied by the prevailing rates, the IL-RR model provides new relationships that connect multistate populations over time and allow analytical population projections. Parameter w reflects population metabolism and scales the level of the transfer rates. Compositional change is driven by the sequence of implicit stable population compositions. The IL-RR approach also provides a new method for estimating transfer rates within an interval from population numbers at the beginning and end of the interval. The new relationships developed advance the ability of demographers to model multistate populations with changing rates and to relate population stocks and flows.

  17. A transparent and transportable methodology for evaluating Data Linkage software.

    Science.gov (United States)

    Ferrante, Anna; Boyd, James

    2012-02-01

    There has been substantial growth in Data Linkage (DL) activities in recent years. This reflects growth in both the demand for, and the supply of, linked or linkable data. Increased utilisation of DL "services" has brought with it increased need for impartial information about the suitability and performance capabilities of DL software programs and packages. Although evaluations of DL software exist; most have been restricted to the comparison of two or three packages. Evaluations of a large number of packages are rare because of the time and resource burden placed on the evaluators and the need for a suitable "gold standard" evaluation dataset. In this paper we present an evaluation methodology that overcomes a number of these difficulties. Our approach involves the generation and use of representative synthetic data; the execution of a series of linkages using a pre-defined linkage strategy; and the use of standard linkage quality metrics to assess performance. The methodology is both transparent and transportable, producing genuinely comparable results. The methodology was used by the Centre for Data Linkage (CDL) at Curtin University in an evaluation of ten DL software packages. It is also being used to evaluate larger linkage systems (not just packages). The methodology provides a unique opportunity to benchmark the quality of linkages in different operational environments. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Clinical and economic analysis of effectiveness of Nivolumab (Opdivo® use as second-line monotherapy in adult patients with advanced renal cell carcinoma after previous systemic therapy

    Directory of Open Access Journals (Sweden)

    M. Yu. Frolov

    2017-01-01

    Full Text Available Objecktive. To conduct a comparative pharmacoeconomic analysis of using nivolumab (Opdivo® as monotherapy in advanced renal cell carcinoma (RCC in adult patients 2-line therapy.Materials and methods. “Cost–effectiveness” was assessed using a Markov model for one patient with advanced RCC. “Cost–effectiveness” analysis, “cost–utility” analysis “budget impact” analysis were performed. Overall survival and QALYs were included into the model as the effectiveness criteria. All the direct costs were calculated from the Russian healthcare system perspective.Results. Treatment with nivolumab was associated with lower total direct costs, less frequent adverse events compared with the combination lenvatinib + everolimus. Total costs per patient were 2 451 712 rubles and 5232592 rubles for nivolumab and the combination lenvatinib + everolimus, respectively. The incremental “cost–effectiveness” ratio was 5 561760 rubles per life-months gained and 2339823 rubles per quality-adjusted life month. A sensitivity analysis confirmed the base case results. “Budget impact” analysis showed that the using of nivolumab allows to save budget costs and to treat additional 198 patients without spending healthcare resources.Conclusion. The results of the study showed that using nivolumab (Opdivo® as monotherapy in advanced RCC in adult patients as 2-line therapy is clinically effective and “cost–effective” method of treatment of adult patients with RCC in theRussian Federation. 

  19. Linkages from DOE’s Vehicle Technologies R&D in Advanced Combustion to More Efficient, Cleaner-Burning Engines

    Energy Technology Data Exchange (ETDEWEB)

    Ruegg, Rosalie [TIA Consulting Inc., Emerald Isle, NC (United States); Thomas, Patrick [1790 Analytics LLC., Haddonfield, NC (United States)

    2011-06-01

    This report uses bibliometric analysis, supported by interview and review of documents and databases, to trace linkages from knowledge outputs resulting from DOE's advances in vehicle engine combustion to downstream innovations in commercial diesel engines and other areas. This analysis covers the period from 1974 through 2008 (and in some cases to early 2009).

  20. 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.

  1. Comprehensive linkage and association analyses identify haplotype, near to the TNFSF15 gene, significantly associated with spondyloarthritis.

    Directory of Open Access Journals (Sweden)

    Elena Zinovieva

    2009-06-01

    Full Text Available Spondyloarthritis (SpA is a chronic inflammatory disorder with a strong genetic predisposition dominated by the role of HLA-B27. However, the contribution of other genes to the disease susceptibility has been clearly demonstrated. We previously reported significant evidence of linkage of SpA to chromosome 9q31-34. The current study aimed to characterize this locus, named SPA2. First, we performed a fine linkage mapping of SPA2 (24 cM with 28 microsatellite markers in 149 multiplex families, which allowed us to reduce the area of investigation to an 18 cM (13 Mb locus delimited by the markers D9S279 and D9S112. Second, we constructed a linkage disequilibrium (LD map of this region with 1,536 tag single-nucleotide polymorphisms (SNPs in 136 families (263 patients. The association was assessed using a transmission disequilibrium test. One tag SNP, rs4979459, yielded a significant P-value (4.9 x 10(-5. Third, we performed an extension association study with rs4979459 and 30 surrounding SNPs in LD with it, in 287 families (668 patients, and in a sample of 139 cases and 163 controls. Strong association was observed in both familial and case/control datasets for several SNPs. In the replication study, carried with 8 SNPs in an independent sample of 232 cases and 149 controls, one SNP, rs6478105, yielded a nominal P-value<3 x 10(-2. Pooled case/control study (371 cases and 312 controls as well as combined analysis of extension and replication data showed very significant association (P<5 x 10(-4 for 6 of the 8 latter markers (rs7849556, rs10817669, rs10759734, rs6478105, rs10982396, and rs10733612. Finally, haplotype association investigations identified a strongly associated haplotype (P<8.8 x 10(-5 consisting of these 6 SNPs and located in the direct vicinity of the TNFSF15 gene. In conclusion, we have identified within the SPA2 locus a haplotype strongly associated with predisposition to SpA which is located near to TNFSF15, one of the major

  2. 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

    Migraine and Bipolar Disorder (BPAD) are clinically heterogeneous disorders of the brain with a significant, but complex, genetic component. Epidemiological and clinical studies have demonstrated a high degree of co-morbidity between migraine and BPAD. Several genomewide linkage studies in BPAD...... that using migraine comorbidity to look at subsets of BPAD families in a genetic linkage analysis would prove useful in identifying genetic susceptibility regions in both of these disorders. We used BPAD with comorbid migraine as an alternative phenotype definition in a re-analysis of the NIMH Bipolar...... osome 4 (not co-segregating with BPAD) in a sample of BPAD families with comorbid migraine, and suggest a susceptibility locus on chromosome 20, harboring a gene for the migraine/BPAD phenotype. Together these data suggest that some genes may predispose to both bipolar disorder and migraine....

  3. Conversion of chromosome-specific RAPDs into SCAR-based anchor markers for onion linkage maps and its application to genetic analyses inother Allium species

    NARCIS (Netherlands)

    Masuzaki, S.; Miyazaki, T.; McCallum, J.; Heusden, van A.W.; Kik, C.; Yamashita, K.; Tashiro, Y.

    2008-01-01

    Integration of previously developed Allium cepa linkage maps requires the availability of anchor markers for each of the eight chromosomes of shallot (A. cepa L. common group Aggregatum). To this end, eight RAPD markers originating from our previous research were converted into SCAR markers via

  4. Automatic electromagnetic valve for previous vacuum

    International Nuclear Information System (INIS)

    Granados, C. E.; Martin, F.

    1959-01-01

    A valve which permits the maintenance of an installation vacuum when electric current fails is described. It also lets the air in the previous vacuum bomb to prevent the oil ascending in the vacuum tubes. (Author)

  5. Geographic stratification of linkage disequilibrium: a worldwide population study in a region of chromosome 22

    Directory of Open Access Journals (Sweden)

    González-Neira Anna

    2004-11-01

    Full Text Available Abstract Recent studies of haplotype diversity in a number of genomic regions have suggested that long stretches of DNA are preserved in the same chromosome, with little evidence of recombination events. The knowledge of the extent and strength of these haplotypes could become a powerful tool for future genetic analysis of complex traits. Different patterns of linkage disequilibrium (LD have been found when comparing individuals of African and European descent, but there is scarce knowledge about the worldwide population stratification. Thus, the study of haplotype composition and the pattern of LD from a global perspective are relevant for elucidating their geographical stratification, as it may have implications in the future analysis of complex traits. We have typed 12 single nucleotide polymorphisms in a chromosome 22 region--previously described as having high LD levels in European populations -- in 39 different world populations. Haplotype structure has a clear continental structure with marked heterogeneity within some continents (Africa, America. The pattern of LD among neighbouring markers exhibits a strong clustering of all East Asian populations on the one hand and of Western Eurasian populations (including Europe on the other, revealing only two major LD patterns, but with some very specific outliers due to specific demographic histories. Moreover, it should be taken into account that African populations are highly heterogeneous. The present results support the existence of a wide (but not total communality in LD patterns in human populations from different continental regions, despite differences in their demographic histories, as population factors seem to be less relevant compared with genomic forces in shaping the patterns of LD.

  6. Linkage and whole genome sequencing identify a locus on 6q25-26 for formal thought disorder and implicate MEF2A regulation

    DEFF Research Database (Denmark)

    Thygesen, Johan Hilge; Zambach, Sine Katharina; Ingason, Andrés

    2015-01-01

    Formal thought disorder is a major feature of schizophrenia and other psychotic disorders. It is heritable, found in healthy relatives of patients with schizophrenia and other mental disorders but knowledge of specific genetic factors is lacking. The aim of this study was to search for biologically...... relevant high-risk variants. Formal thought disorder was assessed in participants in the Copenhagen Schizophrenia Linkage Study (N=236), a unique high-risk family study comprised of six large pedigrees. Microsatellite linkage analysis of formal thought disorder was performed and subsequent haplotype...... analysis of the implicated region using phased microsatellite and SNP genotypes. Whole genome sequencing (N=3) was used in the attempt to identify causative variants in the linkage region. Linkage analysis of formal thought disorder resulted in a single peak at chromosome 6(q26-q27) centred on marker D6S...

  7. EST-derived SSR markers used as anchor loci for the construction of a consensus linkage map in ryegrass (Lolium spp.)

    DEFF Research Database (Denmark)

    Studer, Bruno; Kölliker, Roland; Muylle, Hilde

    2010-01-01

    Background Genetic markers and linkage mapping are basic prerequisites for marker-assisted selection and map-based cloning. In the case of the key grassland species Lolium spp., numerous mapping populations have been developed and characterised for various traits. Although some genetic linkage maps...... 284 EST-derived and genomic SSR markers. The total map length was 742 centiMorgan (cM), ranging for individual chromosomes from 70 cM of linkage group (LG) 6 to 171 cM of LG 2. Conclusions The consensus linkage map for ryegrass based on eight mapping populations and constructed using a large set...... of publicly available Lolium EST-SSRs mapped for the first time together with previously mapped SSR markers will allow for consolidating existing mapping and QTL information in ryegrass. Map and markers presented here will prove to be an asset in the development for both molecular breeding of ryegrass as well...

  8. A novel linkage map of sugarcane with evidence for clustering of retrotransposon-based markers

    Directory of Open Access Journals (Sweden)

    Palhares Alessandra C

    2012-06-01

    Full Text Available Abstract Background The development of sugarcane as a sustainable crop has unlimited applications. The crop is one of the most economically viable for renewable energy production, and CO2 balance. Linkage maps are valuable tools for understanding genetic and genomic organization, particularly in sugarcane due to its complex polyploid genome of multispecific origins. The overall objective of our study was to construct a novel sugarcane linkage map, compiling AFLP and EST-SSR markers, and to generate data on the distribution of markers anchored to sequences of scIvana_1, a complete sugarcane transposable element, and member of the Copia superfamily. Results The mapping population parents (‘IAC66-6’ and ‘TUC71-7’ contributed equally to polymorphisms, independent of marker type, and generated markers that were distributed into nearly the same number of co-segregation groups (or CGs. Bi-parentally inherited alleles provided the integration of 19 CGs. The marker number per CG ranged from two to 39. The total map length was 4,843.19 cM, with a marker density of 8.87 cM. Markers were assembled into 92 CGs that ranged in length from 1.14 to 404.72 cM, with an estimated average length of 52.64 cM. The greatest distance between two adjacent markers was 48.25 cM. The scIvana_1-based markers (56 were positioned on 21 CGs, but were not regularly distributed. Interestingly, the distance between adjacent scIvana_1-based markers was less than 5 cM, and was observed on five CGs, suggesting a clustered organization. Conclusions Results indicated the use of a NBS-profiling technique was efficient to develop retrotransposon-based markers in sugarcane. The simultaneous maximum-likelihood estimates of linkage and linkage phase based strategies confirmed the suitability of its approach to estimate linkage, and construct the linkage map. Interestingly, using our genetic data it was possible to calculate the number of retrotransposon scIvana_1 (~60

  9. X-linked mental retardation with thin habitus, osteoporosis, and kyphoscoliosis: Linkage to Xp21.3-p22.12

    Energy Technology Data Exchange (ETDEWEB)

    Arena, J.F.; Lubs, H. [Univ. of Miami School of Medicine, Miami, FL (United States); Schwartz, C. [Greenwood Genetic Center, SC (United States)] [and others

    1996-07-12

    We reevaluated a family previously described as having nonspecific X-linked mental retardation (XLMR) by Snyder and Robinson (MINI 309583). Clinical and DNA studies were conducted on 17 relatives, including 6 males with mild-to-moderate mental retardation, 3 carrier females, and 8 normal males. In contrast to the normal appearance and minimal clinical findings reported 22 years ago, affected males were found to have a characteristic set of clinical findings. These developed gradually over the first 2 decades, and included thin body build with diminished muscle mass, osteoporosis and kyphoscoliosis, slight facial asymmetry with a prominent lower lip, nasal speech, high narrow or cleft palate, and long great toes. Carrier females were clinically normal. Multipoint linkage analysis indicated linkage to markers distal to the 3{prime} end of DMD (DXS41 and DXS989), with a maximal lod score of 4.7. On the basis of these findings, this entity is redefined as XLMR syndrome. 22 refs., 6 figs., 2 tabs.

  10. LINKAGES: An Individual-based Forest Ecosystem Biogeochemistry Model

    Data.gov (United States)

    National Aeronautics and Space Administration — ABSTRACT: This model product contains the source codes for version 1 of the individual-based forest ecosystem biogeochemistry model LINKAGES and two subsequent...

  11. 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.

  12. 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

    , approximate centromere placement is possible by phasing the same data used to generate linkage maps. Assuming one obligate crossover per chromosome arm, information about centromere location can be revealed by tracking the accumulated recombination frequency along linkage groups, similar to half......Linkage mapping is often used to identify genes associated with phenotypic traits and for aiding genome assemblies. Still, many emerging maps do not locate centromeres – an essential component of the genomic landscape. Here, we demonstrate that for genomes with strong chiasma interference....... 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...

  13. LINKAGES: An Individual-based Forest Ecosystem Biogeochemistry Model

    Data.gov (United States)

    National Aeronautics and Space Administration — This model product contains the source codes for version 1 of the individual-based forest ecosystem biogeochemistry model LINKAGES and two subsequent versions as...

  14. FHWA planning and environmental linkages annual report fiscal year 2011.

    Science.gov (United States)

    2012-01-20

    This report highlights the Federal Highway Administration's (FHWA) Planning and Environment Linkages (PEL) program activities for Fiscal Year 2011 (FY11). The PEL program's purpose is to provide transportation agencies with tools and resources to int...

  15. Underreporting of maternal mortality in Taiwan: A data linkage study

    Directory of Open Access Journals (Sweden)

    Tung-Pi Wu

    2015-12-01

    Conclusion: Approximately two-thirds of the maternal deaths in Taiwan were unreported in the officially published mortality data. Hence, routine nationwide data linkage is essential to monitor maternal mortality in Taiwan accurately.

  16. Concomitant and previous osteoporotic vertebral fractures.

    Science.gov (United States)

    Lenski, Markus; Büser, Natalie; Scherer, Michael

    2017-04-01

    Background and purpose - Patients with osteoporosis who present with an acute onset of back pain often have multiple fractures on plain radiographs. Differentiation of an acute osteoporotic vertebral fracture (AOVF) from previous fractures is difficult. The aim of this study was to investigate the incidence of concomitant AOVFs and previous OVFs in patients with symptomatic AOVFs, and to identify risk factors for concomitant AOVFs. Patients and methods - This was a prospective epidemiological study based on the Registry of Pathological Osteoporotic Vertebral Fractures (REPAPORA) with 1,005 patients and 2,874 osteoporotic vertebral fractures, which has been running since February 1, 2006. Concomitant fractures are defined as at least 2 acute short-tau inversion recovery (STIR-) positive vertebral fractures that happen concomitantly. A previous fracture is a STIR-negative fracture at the time of initial diagnostics. Logistic regression was used to examine the influence of various variables on the incidence of concomitant fractures. Results - More than 99% of osteoporotic vertebral fractures occurred in the thoracic and lumbar spine. The incidence of concomitant fractures at the time of first patient contact was 26% and that of previous fractures was 60%. The odds ratio (OR) for concomitant fractures decreased with a higher number of previous fractures (OR =0.86; p = 0.03) and higher dual-energy X-ray absorptiometry T-score (OR =0.72; p = 0.003). Interpretation - Concomitant and previous osteoporotic vertebral fractures are common. Risk factors for concomitant fractures are a low T-score and a low number of previous vertebral fractures in cases of osteoporotic vertebral fracture. An MRI scan of the the complete thoracic and lumbar spine with STIR sequence reduces the risk of under-diagnosis and under-treatment.

  17. A microsatellite-based genetic linkage map and putative sex-determining genomic regions in Lake Victoria cichlids.

    Science.gov (United States)

    Kudo, Yu; Nikaido, Masato; Kondo, Azusa; Suzuki, Hikoyu; Yoshida, Kohta; Kikuchi, Kiyoshi; Okada, Norihiro

    2015-04-15

    Cichlid fishes in East Africa have undergone extensive adaptive radiation, which has led to spectacular diversity in their morphology and ecology. To date, genetic linkage maps have been constructed for several tilapias (riverine), Astatotilapia burtoni (Lake Tanganyika), and hybrid lines of Lake Malawi cichlids to facilitate genome-wide comparative analyses. In the present study, we constructed a genetic linkage map of the hybrid line of Lake Victoria cichlids, so that maps of cichlids from all the major areas of East Africa will be available. The genetic linkage map shown here is derived from the F2 progeny of an interspecific cross between Haplochromis chilotes and Haplochromis sauvagei and is based on 184 microsatellite and two single-nucleotide polymorphism (SNP) markers. Most of the microsatellite markers used in the present study were originally designed for other genetic linkage maps, allowing us to directly compare each linkage group (LG) among different cichlid groups. We found 25 LGs, the total length of which was 1133.2cM with an average marker spacing of about 6.09cM. Our subsequent linkage mapping analysis identified two putative sex-determining loci in cichlids. Interestingly, one of these two loci is located on cichlid LG5, on which the female heterogametic ZW locus and several quantitative trait loci (QTLs) related to adaptive evolution have been reported in Lake Malawi cichlids. We also found that V1R1 and V1R2, candidate genes for the fish pheromone receptor, are located very close to the recently detected sex-determining locus on cichlid LG5. The genetic linkage map study presented here may provide a valuable foundation for studying the chromosomal evolution of East African cichlids and the possible role of sex chromosomes in generating their genomic diversity. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Estimating parameters for probabilistic linkage of privacy-preserved datasets.

    Science.gov (United States)

    Brown, Adrian P; Randall, Sean M; Ferrante, Anna M; Semmens, James B; Boyd, James H

    2017-07-10

    Probabilistic record linkage is a process used to bring together person-based records from within the same dataset (de-duplication) or from disparate datasets using pairwise comparisons and matching probabilities. The linkage strategy and associated match probabilities are often estimated through investigations into data quality and manual inspection. However, as privacy-preserved datasets comprise encrypted data, such methods are not possible. In this paper, we present a method for estimating the probabilities and threshold values for probabilistic privacy-preserved record linkage using Bloom filters. Our method was tested through a simulation study using synthetic data, followed by an application using real-world administrative data. Synthetic datasets were generated with error rates from zero to 20% error. Our method was used to estimate parameters (probabilities and thresholds) for de-duplication linkages. Linkage quality was determined by F-measure. Each dataset was privacy-preserved using separate Bloom filters for each field. Match probabilities were estimated using the expectation-maximisation (EM) algorithm on the privacy-preserved data. Threshold cut-off values were determined by an extension to the EM algorithm allowing linkage quality to be estimated for each possible threshold. De-duplication linkages of each privacy-preserved dataset were performed using both estimated and calculated probabilities. Linkage quality using the F-measure at the estimated threshold values was also compared to the highest F-measure. Three large administrative datasets were used to demonstrate the applicability of the probability and threshold estimation technique on real-world data. Linkage of the synthetic datasets using the estimated probabilities produced an F-measure that was comparable to the F-measure using calculated probabilities, even with up to 20% error. Linkage of the administrative datasets using estimated probabilities produced an F-measure that was higher

  19. 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 famil