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Sample records for linkage analysis showed

  1. A Formalization of Linkage Analysis

    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 ...

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

    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.

  3. Methods for genetic linkage analysis using trisomies.

    Feingold, E; Lamb, N E; Sherman, S L

    1995-01-01

    Certain genetic disorders are rare in the general population, but more common in individuals with specific trisomies. Examples of this include leukemia and duodenal atresia in trisomy 21. This paper presents a linkage analysis method for using trisomic individuals to map genes for such traits. It is based on a very general gene-specific dosage model that posits that the trait is caused by specific effects of different alleles at one or a few loci and that duplicate copies of "susceptibility" ...

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

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

    1994-09-01

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

  5. The score statistic of the LD-lod analysis: detecting linkage adaptive to linkage disequilibrium.

    Huang, J; Jiang, Y

    2001-01-01

    We study the properties of a modified lod score method for testing linkage that incorporates linkage disequilibrium (LD-lod). By examination of its score statistic, we show that the LD-lod score method adaptively combines two sources of information: (a) the IBD sharing score which is informative for linkage regardless of the existence of LD and (b) the contrast between allele-specific IBD sharing scores which is informative for linkage only in the presence of LD. We also consider the connection between the LD-lod score method and the transmission-disequilibrium test (TDT) for triad data and the mean test for affected sib pair (ASP) data. We show that, for triad data, the recessive LD-lod test is asymptotically equivalent to the TDT; and for ASP data, it is an adaptive combination of the TDT and the ASP mean test. We demonstrate that the LD-lod score method has relatively good statistical efficiency in comparison with the ASP mean test and the TDT for a broad range of LD and the genetic models considered in this report. Therefore, the LD-lod score method is an interesting approach for detecting linkage when the extent of LD is unknown, such as in a genome-wide screen with a dense set of genetic markers. Copyright 2001 S. Karger AG, Basel

  6. Distribution of lod scores in oligogenic linkage analysis.

    Williams, J T; North, K E; Martin, L J; Comuzzie, A G; Göring, H H; Blangero, J

    2001-01-01

    In variance component oligogenic linkage analysis it can happen that the residual additive genetic variance bounds to zero when estimating the effect of the ith quantitative trait locus. Using quantitative trait Q1 from the Genetic Analysis Workshop 12 simulated general population data, we compare the observed lod scores from oligogenic linkage analysis with the empirical lod score distribution under a null model of no linkage. We find that zero residual additive genetic variance in the null model alters the usual distribution of the likelihood-ratio statistic.

  7. Bayesian linkage and segregation analysis: factoring the problem.

    Matthysse, S

    2000-01-01

    Complex segregation analysis and linkage methods are mathematical techniques for the genetic dissection of complex diseases. They are used to delineate complex modes of familial transmission and to localize putative disease susceptibility loci to specific chromosomal locations. The computational problem of Bayesian linkage and segregation analysis is one of integration in high-dimensional spaces. In this paper, three available techniques for Bayesian linkage and segregation analysis are discussed: Markov Chain Monte Carlo (MCMC), importance sampling, and exact calculation. The contribution of each to the overall integration will be explicitly discussed.

  8. ANALYSIS OF INTER SECTORAL LINKAGES IN SEMARANG REGENCY

    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

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

    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.

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

    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

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

    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...

  12. Robust LOD scores for variance component-based linkage analysis.

    Blangero, J; Williams, J T; Almasy, L

    2000-01-01

    The variance component method is now widely used for linkage analysis of quantitative traits. Although this approach offers many advantages, the importance of the underlying assumption of multivariate normality of the trait distribution within pedigrees has not been studied extensively. Simulation studies have shown that traits with leptokurtic distributions yield linkage test statistics that exhibit excessive Type I error when analyzed naively. We derive analytical formulae relating the deviation from the expected asymptotic distribution of the lod score to the kurtosis and total heritability of the quantitative trait. A simple correction constant yields a robust lod score for any deviation from normality and for any pedigree structure, and effectively eliminates the problem of inflated Type I error due to misspecification of the underlying probability model in variance component-based linkage analysis.

  13. Markov chain Monte Carlo linkage analysis: effect of bin width on the probability of linkage.

    Slager, S L; Juo, S H; Durner, M; Hodge, S E

    2001-01-01

    We analyzed part of the Genetic Analysis Workshop (GAW) 12 simulated data using Monte Carlo Markov chain (MCMC) methods that are implemented in the computer program Loki. The MCMC method reports the "probability of linkage" (PL) across the chromosomal regions of interest. The point of maximum PL can then be taken as a "location estimate" for the location of the quantitative trait locus (QTL). However, Loki does not provide a formal statistical test of linkage. In this paper, we explore how the bin width used in the calculations affects the max PL and the location estimate. We analyzed age at onset (AO) and quantitative trait number 5, Q5, from 26 replicates of the general simulated data in one region where we knew a major gene, MG5, is located. For each trait, we found the max PL and the corresponding location estimate, using four different bin widths. We found that bin width, as expected, does affect the max PL and the location estimate, and we recommend that users of Loki explore how their results vary with different bin widths.

  14. LINKAGE ANALYSIS BY 2-DIMENSIONAL DNA TYPING

    MEERMAN, GJT; MULLAART, E; VANDERMEULEN, MA; DENDAAS, JHG; MOROLLI, B; UITTERLINDEN, AG; VIJG, J

    1993-01-01

    In two-dimensional (2-D) DNA typing, genomic DNA fragments are separated, first according to size by electrophoresis in a neutral polyacrylamide gel and second according to sequence by denaturing gradient gel electrophoresis, followed by hybridization analysis using micro- and minisatellite core

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

    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. Countering Islamic State Messaging Through “Linkage-Based” Analysis

    J.M. Berger

    2017-08-01

    Full Text Available The Islamic State’s recent losses on the battlefield, including significant casualties within its media and propaganda division, offer a unique opportunity to inject competing and alternative messages into the information space. This paper proposes that the content of such messages should be guided by a linkage-based analysis of existing Islamic State messaging. A linkage-based analysis of a top-level 2017 audio message by Islamic State spokesperson Abu Hasan al Muhajir offers several potential insights into crafting effective content for competing and alternative messages. A comparison of the 2017 work to earlier Islamic State messaging also reveals specific opportunities to undermine the credibility of the organisation’s broader propaganda programme by highlighting the organisation’s repeated failure to follow through on its extravagantly promised commitment to achieving its stated goals.

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

    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. Genetic counseling in Usher syndrome: linkage and mutational analysis of 10 Colombian families.

    Tamayo, M L; Lopez, G; Gelvez, N; Medina, D; Kimberling, W J; Rodríguez, V; Tamayo, G E; Bernal, J E

    2008-01-01

    Usher Syndrome (US), an autosomal recessive disease, is characterized by retinitis pigmentosa (RP), vestibular dysfunction, and congenital sensorineural deafness. There are three recognized clinical types of the disorder. In order to improve genetic counseling for affected families, we conducted linkage analysis and DNA sequencing in 10 Colombian families with confirmed diagnosis of US (4 type I and 6 type II). Seventy-five percent of the US1 families showed linkage to locus USH1B, while the remaining 25% showed linkage to loci USH1B and USH1C. Among families showing linkage to USH1B we found two different mutations in the MYO7A gene: IVS42-26insTTGAG in exon 43 (heterozygous state) and R634X (CGA-TGA) in exon 16 (homozygous state). All six US2 families showed linkage to locus USH2A. Of them, 4 had c.2299delG mutation (1 homozygote state and 3 heterozygous); in the remaining 2 we did not identify any pathologic DNA variant. USH2A individuals with a 2299delG mutation presented a typical and homogeneous retinal phenotype with bilateral severe hearing loss, except for one individual with a heterozygous 2299delG mutation, whose hearing loss was asymmetric, but more profound than in the other cases. The study of these families adds to the genotype-phenotype characterization of the different types and subtypes of US and facilitates genetic counseling in these families. We would like to emphasize the need to perform DNA studies as a prerequisite for genetic counseling in affected families.

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

    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.

  1. X linked exudative vitreoretinopathy: clinical features and genetic linkage analysis.

    Fullwood, P; Jones, J; Bundey, S; Dudgeon, J; Fielder, A R; Kilpatrick, M W

    1993-03-01

    A four generation family in which familial exudative vitreoretinopathy is inherited as an X linked condition is described. Essentially the condition is one of abnormal vascularisation and signs at birth are those of a retinopathy superficially resembling retinopathy of prematurity, retinal folds, or, in advanced cases, enophthalmos or even phthisis. Prognosis depends on the progression of the retinal changes. The family members, including seven affected males and five obligate carrier females, have been types for 20 DNA markers, and linkage analysis suggests a gene locus either at Xq21.3 or at Xp11. As the latter region includes the locus for the gene for Norrie disease, it is possible that this and X linked vitreoretinopathy are allelic. We can further speculate that the differences in severity of the clinical manifestations are dependent only upon the timing of the insult.

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

    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.

  3. Meta-analysis of genome-wide linkage studies in BMI and obesity.

    Saunders, Catherine L; Chiodini, Benedetta D; Sham, Pak; Lewis, Cathryn M; Abkevich, Victor; Adeyemo, Adebowale A; de Andrade, Mariza; Arya, Rector; Berenson, Gerald S; Blangero, John; Boehnke, Michael; Borecki, Ingrid B; Chagnon, Yvon C; Chen, Wei; Comuzzie, Anthony G; Deng, Hong-Wen; Duggirala, Ravindranath; Feitosa, Mary F; Froguel, Philippe; Hanson, Robert L; Hebebrand, Johannes; Huezo-Dias, Patricia; Kissebah, Ahmed H; Li, Weidong; Luke, Amy; Martin, Lisa J; Nash, Matthew; Ohman, Miina; Palmer, Lyle J; Peltonen, Leena; Perola, Markus; Price, R Arlen; Redline, Susan; Srinivasan, Sathanur R; Stern, Michael P; Stone, Steven; Stringham, Heather; Turner, Stephen; Wijmenga, Cisca; Collier, David A

    2007-09-01

    The objective was to provide an overall assessment of genetic linkage data of BMI and BMI-defined obesity using a nonparametric genome scan meta-analysis. We identified 37 published studies containing data on over 31,000 individuals from more than >10,000 families and obtained genome-wide logarithm of the odds (LOD) scores, non-parametric linkage (NPL) scores, or maximum likelihood scores (MLS). BMI was analyzed in a pooled set of all studies, as a subgroup of 10 studies that used BMI-defined obesity, and for subgroups ascertained through type 2 diabetes, hypertension, or subjects of European ancestry. Bins at chromosome 13q13.2- q33.1, 12q23-q24.3 achieved suggestive evidence of linkage to BMI in the pooled analysis and samples ascertained for hypertension. Nominal evidence of linkage to these regions and suggestive evidence for 11q13.3-22.3 were also observed for BMI-defined obesity. The FTO obesity gene locus at 16q12.2 also showed nominal evidence for linkage. However, overall distribution of summed rank p values <0.05 is not different from that expected by chance. The strongest evidence was obtained in the families ascertained for hypertension at 9q31.1-qter and 12p11.21-q23 (p < 0.01). Despite having substantial statistical power, we did not unequivocally implicate specific loci for BMI or obesity. This may be because genes influencing adiposity are of very small effect, with substantial genetic heterogeneity and variable dependence on environmental factors. However, the observation that the FTO gene maps to one of the highest ranking bins for obesity is interesting and, while not a validation of this approach, indicates that other potential loci identified in this study should be investigated further.

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

    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.

  5. Genome-wide linkage analysis for human longevity

    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...

  6. Multipoint linkage analysis and homogeneity tests in 15 Dutch X-linked retinitis pigmentosa families

    Bergen, A. A.; van den Born, L. I.; Schuurman, E. J.; Pinckers, A. J.; van Ommen, G. J.; Bleekers-Wagemakers, E. M.; Sandkuijl, L. A.

    1995-01-01

    Linkage analysis and homogeneity tests were carried out in 15 Dutch families segregating X-linked retinitis pigmentosa (X L R P). The study included segregation data for eight polymorphic DNA markers from the short arm of the human X chromosome. The results of both multipoint linkage analysis in

  7. Direct power comparisons between simple LOD scores and NPL scores for linkage analysis in complex diseases.

    Abreu, P C; Greenberg, D A; Hodge, S E

    1999-09-01

    Several methods have been proposed for linkage analysis of complex traits with unknown mode of inheritance. These methods include the LOD score maximized over disease models (MMLS) and the "nonparametric" linkage (NPL) statistic. In previous work, we evaluated the increase of type I error when maximizing over two or more genetic models, and we compared the power of MMLS to detect linkage, in a number of complex modes of inheritance, with analysis assuming the true model. In the present study, we compare MMLS and NPL directly. We simulated 100 data sets with 20 families each, using 26 generating models: (1) 4 intermediate models (penetrance of heterozygote between that of the two homozygotes); (2) 6 two-locus additive models; and (3) 16 two-locus heterogeneity models (admixture alpha = 1.0,.7,.5, and.3; alpha = 1.0 replicates simple Mendelian models). For LOD scores, we assumed dominant and recessive inheritance with 50% penetrance. We took the higher of the two maximum LOD scores and subtracted 0.3 to correct for multiple tests (MMLS-C). We compared expected maximum LOD scores and power, using MMLS-C and NPL as well as the true model. Since NPL uses only the affected family members, we also performed an affecteds-only analysis using MMLS-C. The MMLS-C was both uniformly more powerful than NPL for most cases we examined, except when linkage information was low, and close to the results for the true model under locus heterogeneity. We still found better power for the MMLS-C compared with NPL in affecteds-only analysis. The results show that use of two simple modes of inheritance at a fixed penetrance can have more power than NPL when the trait mode of inheritance is complex and when there is heterogeneity in the data set.

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

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

    2014-03-01

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

  9. A tetranucleotide repeat (D4S1652) is linked to facioscapulohumeral dystrophy and shows no linkage disequilibrium with the disease

    Mathews, K.D.; Bailey, H.L.; Mills, K.A. [and others

    1994-09-01

    Facioscapulohumeral dystrophy (FSHD) is an autosomal dominant dystrophy which is associated with a deletion in a subtelomeric repeat element on 4q35. The gene has not yet been identified. The probe detecting this deletion (D4F104S1) is not chromosome 4-specific, and at least one large family has been identified which is not linked to chromosome 4. Thus, persymptomatic/prenatal diagnosis can only be provided to families that are proven to be chromosome 4-linked or where a new mutation is demonstrated. The markers available to demonstrate linkage to chromosome 4, D4S139, D4S163, and D4F35S1, are VNTRs. We have used D4S1652, a tetranucleotide repeat recently identified by the Cooperative Human Linkage Center, in our FSHD families. We found it is completely linked to the 4q35 VNTRs and to the disease phenotype. Physical mapping, using radiation hybrids and somatic cell hybrids, places D4S1652 between D4S139, an interval of approximately 1 Mb. We have used D4S1652 to look for linkage disequilibrium in our FSHD patient population. This result is of interest because of our hypothesis that the deletion in the subtelomeric repeat element alters transcription of a more proximal gene through a position effect. Previously available markers have been unsatisfactory for this experiment because of difficulty comparing numerous VNTR alleles across families. We observed 4, easily distinguished, D4S1652 alleles in our families. We studied 14 chromosomes associated with disease phenotype and 55 chromosomes from nontransmitting parents. We found no evidence for linkage disequilibrium ({chi}{sup 2}=1.313, nonsignificant). This result will need confirmation with a larger patient population, but is consistent with the clinical observation that there is a high rate of a new mutation in this disorder.

  10. A Family with Mental Retardation, Epilepsy and Cerebellar Hypoplasia Showing Linkage to Chromosome 20p11.21-q11.23

    Fatih Bayrakli

    2014-01-01

    Full Text Available Background: Cerebellar hypoplasia (CH is a rare malformation caused by various etiologies, usually manifesting clinically as nonprogressive cerebellar ataxia with or without mental retardation. The molecular pathogenesis of the autosomal recessive cerebellar ataxias has a wide range of mechanisms. Differential diagnosis and categorization of the recessive cerebellar ataxias, however, need more specific, biochemical and genetic investigation. Methods: This study applied whole-genome linkage analysis to study a family with nonprogressive cerebellar ataxia and additional mental retardation, epilepsy, and facial dysmorphic features. Genotyping and linkage analysis was done using the GeneChip Mapping 250K NspI Array (Affymetrix Inc., Santa Clara, Calif., USA for genome-wide linkage analysis of the genotyping data from the affected children and their parents. Results: Allegro software version 1.2 was used for multipoint linkage analysis. We assumed an autosomal recessive inheritance pattern and assigned a penetrance of 0.999. Single-nucleotide polymorphism allele frequencies were estimated from the Affymetrix data of the Caucasian family studied. Using these parameters, a theoretical maximum logarithm of the odds score of 2.69 was identified at chromosome 20p11.21-q11.23. Conclusions: This chromosomal locus is unprecedented in autosomal recessive and nonprogressive ataxia disorder. Further investigation might reveal a new causative gene generating the CH phenotype.

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

    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

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

    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.

  13. Leontief Input-Output Method for The Fresh Milk Distribution Linkage Analysis

    Riski Nur Istiqomah

    2016-11-01

    Full Text Available This research discusses about linkage analysis and identifies the key sector in the fresh milk distribution using Leontief Input-Output method. This method is one of the application of Mathematics in economy. The current fresh milk distribution system includes dairy farmers →collectors→fresh milk processing industries→processed milk distributors→consumers. Then, the distribution is merged between the collectors’ axctivity and the fresh milk processing industry. The data used are primary and secondary data taken in June 2016 in Kecamatan Jabung Kabupaten Malang. The collected data are then analysed using Leontief Input-Output Matriks and Python (PYIO 2.1 software. The result is that the merging of the collectors’ and the fresh milk processing industry’s activities shows high indices of forward linkages and backward linkages. It is shown that merging of the two activities is the key sector which has an important role in developing the whole activities in the fresh milk distribution.

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

    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. A microsatellite linkage map for Drosophila montana shows large variation in recombination rates, and a courtship song trait maps to an area of low recombination.

    Schäfer, M A; Mazzi, D; Klappert, K; Kauranen, H; Vieira, J; Hoikkala, A; Ritchie, M G; Schlötterer, C

    2010-03-01

    Current advances in genetic analysis are opening up our knowledge of the genetics of species differences, but challenges remain, particularly for out-bred natural populations. We constructed a microsatellite-based linkage map for two out-bred lines of Drosophila montana derived from divergent populations by taking advantage of the Drosophila virilis genome and available cytological maps of both species. Although the placement of markers was quite consistent with cytological predictions, the map indicated large heterogeneity in recombination rates along chromosomes. We also performed a quantitative trait locus (QTL) analysis on a courtship song character (carrier frequency), which differs between populations and is subject to strong sexual selection. Linkage mapping yielded two significant QTLs, which explained 3% and 14% of the variation in carrier frequency, respectively. Interestingly, as in other recent studies of traits which can influence speciation, the strongest QTL mapped to a genomic region partly covered by an inversion polymorphism.

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

    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

  17. Identification of Sex-determining Loci in Pacific White Shrimp Litopeneaus vannamei Using Linkage and Association Analysis.

    Yu, Yang; Zhang, Xiaojun; Yuan, Jianbo; Wang, Quanchao; Li, Shihao; Huang, Hao; Li, Fuhua; Xiang, Jianhai

    2017-06-01

    The Pacific white shrimp Litopenaeus vannamei is a predominant aquaculture shrimp species in the world. Like other animals, the L. vannamei exhibited sexual dimorphism in growth trait. Mapping of the sex-determining locus will be very helpful to clarify the sex determination system and further benefit the shrimp aquaculture industry towards the production of mono-sex stocks. Based on the data used for high-density linkage map construction, linkage-mapping analysis was conducted. The sex determination region was mapped in linkage group (LG) 18. A large region from 0 to 21.205 cM in LG18 showed significant association with sex. However, none of the markers in this region showed complete association with sex in the other populations. So an association analysis was designed using the female parent, pool of female progenies, male parent, and pool of male progenies. Markers were de novo developed and those showing significant differences between female and male pools were identified. Among them, three sex-associated markers including one fully associated marker were identified. Integration of linkage and association analysis showed that the sex determination region was fine-mapped in a small region along LG18. The identified sex-associated marker can be used for the sex detection of this species at genetic level. The fine-mapped sex-determining region will contribute to the mapping of sex-determining gene and help to clarify sex determination system for L. vannamei.

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

    Shastry, B S; Hejtmancik, J F; Plager, D A; Hartzer, M K; Trese, M T

    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 (Zmax = 2.1, theta max = 0) and DXS228 (Zmax = 0.5, theta max = 0.11), and this was further confirmed by multipoint analysis with these same markers (Zmax = 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.

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

    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.

  20. A combined linkage and exome sequencing analysis for electrocardiogram parameters in the Erasmus Rucphen Family study

    Claudia Tamar Silva

    2016-11-01

    Full Text Available 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 (GWAS 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 Ca2+ 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.

  1. Nonlinear Analysis of Time Series in Genome-Wide Linkage Disequilibrium Data

    Hernández-Lemus, Enrique; Estrada-Gil, Jesús K.; Silva-Zolezzi, Irma; Fernández-López, J. Carlos; Hidalgo-Miranda, Alfredo; Jiménez-Sánchez, Gerardo

    2008-02-01

    The statistical study of large scale genomic data has turned out to be a very important tool in population genetics. Quantitative methods are essential to understand and implement association studies in the biomedical and health sciences. Nevertheless, the characterization of recently admixed populations has been an elusive problem due to the presence of a number of complex phenomena. For example, linkage disequilibrium structures are thought to be more complex than their non-recently admixed population counterparts, presenting the so-called ancestry blocks, admixed regions that are not yet smoothed by the effect of genetic recombination. In order to distinguish characteristic features for various populations we have implemented several methods, some of them borrowed or adapted from the analysis of nonlinear time series in statistical physics and quantitative physiology. We calculate the main fractal dimensions (Kolmogorov's capacity, information dimension and correlation dimension, usually named, D0, D1 and D2). We also have made detrended fluctuation analysis and information based similarity index calculations for the probability distribution of correlations of linkage disequilibrium coefficient of six recently admixed (mestizo) populations within the Mexican Genome Diversity Project [1] and for the non-recently admixed populations in the International HapMap Project [2]. Nonlinear correlations showed up as a consequence of internal structure within the haplotype distributions. The analysis of these correlations as well as the scope and limitations of these procedures within the biomedical sciences are discussed.

  2. Familial aggregation and linkage analysis with covariates for metabolic syndrome risk factors.

    Naseri, Parisa; Khodakarim, Soheila; Guity, Kamran; Daneshpour, Maryam S

    2018-06-15

    Mechanisms of metabolic syndrome (MetS) causation are complex, genetic and environmental factors are important factors for the pathogenesis of MetS In this study, we aimed to evaluate familial and genetic influences on metabolic syndrome risk factor and also assess association between FTO (rs1558902 and rs7202116) and CETP(rs1864163) genes' single nucleotide polymorphisms (SNP) with low HDL_C in the Tehran Lipid and Glucose Study (TLGS). The design was a cross-sectional study of 1776 members of 227 randomly-ascertained families. Selected families contained at least one affected metabolic syndrome and at least two members of the family had suffered a loss of HDL_C according to ATP III criteria. In this study, after confirming the familial aggregation with intra-trait correlation coefficients (ICC) of Metabolic syndrome (MetS) and the quantitative lipid traits, the genetic linkage analysis of HDL_C was performed using conditional logistic method with adjusted sex and age. The results of the aggregation analysis revealed a higher correlation between siblings than between parent-offspring pairs representing the role of genetic factors in MetS. In addition, the conditional logistic model with covariates showed that the linkage results between HDL_C and three marker, rs1558902, rs7202116 and rs1864163 were significant. In summary, a high risk of MetS was found in siblings confirming the genetic influences of metabolic syndrome risk factor. Moreover, the power to detect linkage increases in the one parameter conditional logistic model regarding the use of age and sex as covariates. Copyright © 2018. Published by Elsevier B.V.

  3. Haplotype analysis and linkage disequilibrium for DGAT1

    Strucken, Eva M.; Rahmatalla, Siham; De Koning, Dirk-Jan; Brockmann, Gudrun A.

    2010-01-01

    This study focused on haplotype effects and linkage disequilibrium (LD) for the K232A locus and the promoter VNTR in the DGAT1 gene. Analyses were carried out in three German Holstein Frisian populations (including 492, 305, and 518 animals) for milk yield, milk fat and protein yield, and milk fat and protein content. We found that effects of the promoter VNTR were not significant and explain only a small amount of the variation of the QTL on BTA14. Haplotype effects were less significant tha...

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

    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.

  5. Strategies for assessing proton linkage to bimolecular interactions by global analysis of isothermal titration calorimetry data

    Coussens, Nathan P.; Schuck, Peter; Zhao, Huaying

    2012-01-01

    Highlights: ► We demonstrate the usefulness of global analysis of ITC data for proton-linked binding study. ► Various experimental strategies are evaluated for their information content. ► Data at multiple temperatures might improve the precision of binding parameters. ► Methods for detailed error analysis of parameter uncertainties are discussed. ► By global modeling, an uncertainty in molecular concentrations can be accounted for. - Abstract: Isothermal titration calorimetry (ITC) is a traditional and powerful method for studying the linkage of ligand binding to proton uptake or release. The theoretical framework has been developed for more than two decades and numerous applications have appeared. In the current work, we explored strategic aspects of experimental design. To this end, we simulated families of ITC data sets that embed different strategies with regard to the number of experiments, range of experimental pH, buffer ionization enthalpy, and temperature. We then re-analyzed the families of data sets in the context of global analysis, employing a proton linkage binding model implemented in the global data analysis platform SEDPHAT, and examined the information content of all data sets by a detailed statistical error analysis of the parameter estimates. In particular, we studied the impact of different assumptions about the knowledge of the exact concentrations of the components, which in practice presents an experimental limitation for many systems. For example, the uncertainty in concentration may reflect imperfectly known extinction coefficients and stock concentrations or may account for different extents of partial inactivation when working with proteins at different pH values. Our results show that the global analysis can yield reliable estimates of the thermodynamic parameters for intrinsic binding and protonation, and that in the context of the global analysis the exact molecular component concentrations may not be required. Additionally

  6. Large-scale linkage analysis of 1302 affected relative pairs with rheumatoid arthritis

    Hamshere, Marian L; Segurado, Ricardo; Moskvina, Valentina; Nikolov, Ivan; Glaser, Beate; Holmans, Peter A

    2007-01-01

    Rheumatoid arthritis is the most common systematic autoimmune disease and its etiology is believed to have both strong genetic and environmental components. We demonstrate the utility of including genetic and clinical phenotypes as covariates within a linkage analysis framework to search for rheumatoid arthritis susceptibility loci. The raw genotypes of 1302 affected relative pairs were combined from four large family-based samples (North American Rheumatoid Arthritis Consortium, United Kingdom, European Consortium on Rheumatoid Arthritis Families, and Canada). The familiality of the clinical phenotypes was assessed. The affected relative pairs were subjected to autosomal multipoint affected relative-pair linkage analysis. Covariates were included in the linkage analysis to take account of heterogeneity within the sample. Evidence of familiality was observed with age at onset (p << 0.001) and rheumatoid factor (RF) IgM (p << 0.001), but not definite erosions (p = 0.21). Genome-wide significant evidence for linkage was observed on chromosome 6. Genome-wide suggestive evidence for linkage was observed on chromosomes 13 and 20 when conditioning on age at onset, chromosome 15 conditional on gender, and chromosome 19 conditional on RF IgM after allowing for multiple testing of covariates. PMID:18466440

  7. Identification of DNA Fragments that Showed Linkage to the Radiation-induced Yellow Vein Mosaic Disease Resistance Mutation in Okra

    Boonsirichai, Kanokporn; Phadvibulya, Valailak; Adthalungrong, Amnuai; Srithongchai, Wanphen; Puripunyavanich, Vichai

    2007-08-01

    Full text: The yellow vein mosaic disease resistant mutant of okra was crossed to Pichit 03, a susceptible variety. Their progeny showed prolonged resistance when compared with Pichit 03. DNA fingerprints of F2 and BC1F1 individuals from the cross indicated that most DNA bands did not segregate with either the resistance or the susceptible characteristics. Nonetheless, polymorphic DNA bands could be identified between the mutant and Okura, the parental variety

  8. Meta-analysis of 32 genome-wide linkage studies of schizophrenia

    Ng, MYM; Levinson, DF; Faraone, SV; Suarez, BK; DeLisi, LE; Arinami, T; Riley, B; Paunio, T; Pulver, AE; Irmansyah; Holmans, PA; Escamilla, M; Wildenauer, DB; Williams, NM; Laurent, C; Mowry, BJ; Brzustowicz, LM; Maziade, M; Sklar, P; Garver, DL; Abecasis, GR; Lerer, B; Fallin, MD; Gurling, HMD; Gejman, PV; Lindholm, E; Moises, HW; Byerley, W; Wijsman, EM; Forabosco, P; Tsuang, MT; Hwu, H-G; Okazaki, Y; Kendler, KS; Wormley, B; Fanous, A; Walsh, D; O’Neill, FA; Peltonen, L; Nestadt, G; Lasseter, VK; Liang, KY; Papadimitriou, GM; Dikeos, DG; Schwab, SG; Owen, MJ; O’Donovan, MC; Norton, N; Hare, E; Raventos, H; Nicolini, H; Albus, M; Maier, W; Nimgaonkar, VL; Terenius, L; Mallet, J; Jay, M; Godard, S; Nertney, D; Alexander, M; Crowe, RR; Silverman, JM; Bassett, AS; Roy, M-A; Mérette, C; Pato, CN; Pato, MT; Roos, J Louw; Kohn, Y; Amann-Zalcenstein, D; Kalsi, G; McQuillin, A; Curtis, D; Brynjolfson, J; Sigmundsson, T; Petursson, H; Sanders, AR; Duan, J; Jazin, E; Myles-Worsley, M; Karayiorgou, M; Lewis, CM

    2009-01-01

    A genome scan meta-analysis (GSMA) was carried out on 32 independent genome-wide linkage scan analyses that included 3255 pedigrees with 7413 genotyped cases affected with schizophrenia (SCZ) or related disorders. The primary GSMA divided the autosomes into 120 bins, rank-ordered the bins within each study according to the most positive linkage result in each bin, summed these ranks (weighted for study size) for each bin across studies and determined the empirical probability of a given summed rank (PSR) by simulation. Suggestive evidence for linkage was observed in two single bins, on chromosomes 5q (142-168 Mb) and 2q (103-134 Mb). Genome-wide evidence for linkage was detected on chromosome 2q (119-152 Mb) when bin boundaries were shifted to the middle of the previous bins. The primary analysis met empirical criteria for ‘aggregate’ genome-wide significance, indicating that some or all of 10 bins are likely to contain loci linked to SCZ, including regions of chromosomes 1, 2q, 3q, 4q, 5q, 8p and 10q. In a secondary analysis of 22 studies of European-ancestry samples, suggestive evidence for linkage was observed on chromosome 8p (16-33 Mb). Although the newer genome-wide association methodology has greater power to detect weak associations to single common DNA sequence variants, linkage analysis can detect diverse genetic effects that segregate in families, including multiple rare variants within one locus or several weakly associated loci in the same region. Therefore, the regions supported by this meta-analysis deserve close attention in future studies. PMID:19349958

  9. A new method of linkage analysis using LOD scores for quantitative traits supports linkage of monoamine oxidase activity to D17S250 in the Collaborative Study on the Genetics of Alcoholism pedigrees.

    Curtis, David; Knight, Jo; Sham, Pak C

    2005-09-01

    Although LOD score methods have been applied to diseases with complex modes of inheritance, linkage analysis of quantitative traits has tended to rely on non-parametric methods based on regression or variance components analysis. Here, we describe a new method for LOD score analysis of quantitative traits which does not require specification of a mode of inheritance. The technique is derived from the MFLINK method for dichotomous traits. A range of plausible transmission models is constructed, constrained to yield the correct population mean and variance for the trait but differing with respect to the contribution to the variance due to the locus under consideration. Maximized LOD scores under homogeneity and admixture are calculated, as is a model-free LOD score which compares the maximized likelihoods under admixture assuming linkage and no linkage. These LOD scores have known asymptotic distributions and hence can be used to provide a statistical test for linkage. The method has been implemented in a program called QMFLINK. It was applied to data sets simulated using a variety of transmission models and to a measure of monoamine oxidase activity in 105 pedigrees from the Collaborative Study on the Genetics of Alcoholism. With the simulated data, the results showed that the new method could detect linkage well if the true allele frequency for the trait was close to that specified. However, it performed poorly on models in which the true allele frequency was much rarer. For the Collaborative Study on the Genetics of Alcoholism data set only a modest overlap was observed between the results obtained from the new method and those obtained when the same data were analysed previously using regression and variance components analysis. Of interest is that D17S250 produced a maximized LOD score under homogeneity and admixture of 2.6 but did not indicate linkage using the previous methods. However, this region did produce evidence for linkage in a separate data set

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

    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.

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

    Soderhall, C.; Korberg, I.B.; Thai, H.T.; Cao, J.; Chen, Y; Zhang, X.; Shulu, Z.; Zanden, L.F.M. van der; Rooij, I.A.L.M. van; Frisen, L.; Roeleveld, N.; Markljung, E.; Kockum, I.; Nordenskjold, A.

    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

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

    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...

  13. Meta-analysis of genome-wide linkage studies in BMI and obesity

    Saunders, Catherine L.; Chiodini, Benedetta D.; Sham, Pak; Lewis, Cathryn M.; Abkevich, Victor; Adeyemo, Adebowale A.; de Andrade, Mariza; Arya, Rector; Berenson, Gerald S.; Blangero, John; Boehnke, Michael; Borecki, Ingrid B.; Chagnon, Yvon C.; Chen, Wei; Comuzzie, Anthony G.; Deng, Hong-Wen; Duggirala, Ravindranath; Feitosa, Mary F.; Froguel, Philippe; Hanson, Robert L.; Hebebrand, Johannes; Huezo-Dias, Patricia; Kissebah, Ahmed H.; Li, Weidong; Luke, Amy; Martin, Lisa J.; Nash, Matthew; Ohman, Muena; Palmer, Lyle J.; Peltonen, Leena; Perola, Markus; Price, R. Arlen; Redline, Susan; Srinivasan, Sathanur R.; Stern, Michael P.; Stone, Steven; Stringham, Heather; Turner, Stephen; Wijmenga, Cisca; Collier, David A.

    Objective: The objective was to provide an overall assessment of genetic linkage data of BMI and BMI-defined obesity using a nonparametric genome scan meta-analysis. Research Methods and Procedures: We identified 37 published studies containing data on over 31,000 individuals from more than >10,000

  14. Linkage studies and mutation analysis of the PDEB gene in 23 families with Leber congenital amaurosis

    Riess, O; Weber, B; Nørremølle, Anne

    1992-01-01

    as to whether mutations in the human PDEB gene might cause LCA. We have previously cloned and characterized the human homologue of the mouse Pdeb gene and have mapped it to chromosome 4p16.3. In this study, a total of 23 LCA families of various ethnic backgrounds have been investigated. Linkage analysis using...

  15. VT Wildlife Linkage Habitat

    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. A visual interface to computer programs for linkage analysis.

    Chapman, C J

    1990-06-01

    This paper describes a visual approach to the input of information about human families into computer data bases, making use of the GEM graphic interface on the Atari ST. Similar approaches could be used on the Apple Macintosh or on the IBM PC AT (to which it has been transferred). For occasional users of pedigree analysis programs, this approach has considerable advantages in ease of use and accessibility. An example of such use might be the analysis of risk in families with Huntington disease using linked RFLPs. However, graphic interfaces do make much greater demands on the programmers of these systems.

  17. Linkage analysis by two-dimensional DNA typing

    te Meerman, G J; Mullaart, E; Meulen ,van der Martin; den Daas, J H; Morolli, B; Uitterlinden, A G; Vijg, J

    1993-01-01

    In two-dimensional (2-D) DNA typing, genomic DNA fragments are separated, first according to size by electrophoresis in a neutral polyacrylamide gel and second according to sequence by denaturing gradient gel electrophoresis, followed by hybridization analysis using micro- and minisatellite core

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

    2Five-Star Animal Health Pharmaceutical Factory of Jilian Province, 5333 Xi'an Road, Changchun, Jilin 130062,. People's .... showed that GH peptide sequence of mature protein in. Rongjiang pig ..... 1, white. (PIC value <0.25, low polymorphism; 0.25

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

    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.

  20. [Linkage analysis of susceptibility loci in 2 target chromosomes in pedigrees with paranoid schizophrenia and undifferentiated schizophrenia].

    Zeng, Li-ping; Hu, Zheng-mao; Mu, Li-li; Mei, Gui-sen; Lu, Xiu-ling; Zheng, Yong-jun; Li, Pei-jian; Zhang, Ying-xue; Pan, Qian; Long, Zhi-gao; Dai, He-ping; Zhang, Zhuo-hua; Xia, Jia-hui; Zhao, Jing-ping; Xia, Kun

    2011-06-01

    To investigate the relationship of susceptibility loci in chromosomes 1q21-25 and 6p21-25 and schizophrenia subtypes in Chinese population. A genomic scan and parametric and non-parametric analyses were performed on 242 individuals from 36 schizophrenia pedigrees, including 19 paranoid schizophrenia and 17 undifferentiated schizophrenia pedigrees, from Henan province of China using 5 microsatellite markers in the chromosome region 1q21-25 and 8 microsatellite markers in the chromosome region 6p21-25, which were the candidates of previous studies. All affected subjects were diagnosed and typed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revised (DSM-IV-TR; American Psychiatric Association, 2000). All subjects signed informed consent. In chromosome 1, parametric analysis under the dominant inheritance mode of all 36 pedigrees showed that the maximum multi-point heterogeneity Log of odds score method (HLOD) score was 1.33 (α = 0.38). The non-parametric analysis and the single point and multi-point nonparametric linkage (NPL) scores suggested linkage at D1S484, D1S2878, and D1S196. In the 19 paranoid schizophrenias pedigrees, linkage was not observed for any of the 5 markers. In the 17 undifferentiated schizophrenia pedigrees, the multi-point NPL score was 1.60 (P= 0.0367) at D1S484. The single point NPL score was 1.95(P= 0.0145) and the multi-point NPL score was 2.39 (P= 0.0041) at D1S2878. Additionally, the multi-point NPL score was 1.74 (P= 0.0255) at D1S196. These same three loci showed suggestive linkage during the integrative analysis of all 36 pedigrees. In chromosome 6, parametric linkage analysis under the dominant and recessive inheritance and the non-parametric linkage analysis of all 36 pedigrees and the 17 undifferentiated schizophrenia pedigrees, linkage was not observed for any of the 8 markers. In the 19 paranoid schizophrenias pedigrees, parametric analysis showed that under recessive

  1. In silico polymorphism analysis for the development of simple sequence repeat and transposon markers and construction of linkage map in cultivated peanut

    Shirasawa Kenta

    2012-06-01

    Full Text Available Abstract Background Peanut (Arachis hypogaea is an autogamous allotetraploid legume (2n = 4x = 40 that is widely cultivated as a food and oil crop. More than 6,000 DNA markers have been developed in Arachis spp., but high-density linkage maps useful for genetics, genomics, and breeding have not been constructed due to extremely low genetic diversity. Polymorphic marker loci are useful for the construction of such high-density linkage maps. The present study used in silico analysis to develop simple sequence repeat-based and transposon-based markers. Results The use of in silico analysis increased the efficiency of polymorphic marker development by more than 3-fold. In total, 926 (34.2% of 2,702 markers showed polymorphisms between parental lines of the mapping population. Linkage analysis of the 926 markers along with 253 polymorphic markers selected from 4,449 published markers generated 21 linkage groups covering 2,166.4 cM with 1,114 loci. Based on the map thus produced, 23 quantitative trait loci (QTLs for 15 agronomical traits were detected. Another linkage map with 326 loci was also constructed and revealed a relationship between the genotypes of the FAD2 genes and the ratio of oleic/linoleic acid in peanut seed. Conclusions In silico analysis of polymorphisms increased the efficiency of polymorphic marker development, and contributed to the construction of high-density linkage maps in cultivated peanut. The resultant maps were applicable to QTL analysis. Marker subsets and linkage maps developed in this study should be useful for genetics, genomics, and breeding in Arachis. The data are available at the Kazusa DNA Marker Database (http://marker.kazusa.or.jp.

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

    Ali, Zafar; Babar, Masroor Ellahi; Ahmad, Jamil; Yousaf, Muhammad Zubair; Asif, Muhammad; Shah, Sajjad Ali

    2011-05-01

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

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

    Anna L Mitchell

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

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

    Mitchell, Anna L; Bøe Wolff, Anette; MacArthur, Katie; Weaver, Jolanta U; Vaidya, Bijay; Erichsen, Martina M; Darlay, Rebecca; Husebye, Eystein S; Cordell, Heather J; Pearce, Simon H S

    2015-01-01

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

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

    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.

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

    Bonné-Tamir, B; Korostishevsky, M; Kalinsky, H; Seroussi, E; Beker, R; Weiss, S; Godel, V

    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 were studied in 10 related sibships. DNA samples 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.

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

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

    1996-07-01

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

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

    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....

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

    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. Linkage analysis in a Dutch family with X-linked recessive congenital stationary night blindness (XL-CSNB).

    Berger, W; van Duijnhoven, G; Pinckers, A; Smits, A; Ropers, H H; Cremers, F

    1995-01-01

    Linkage analysis has been performed in a large Dutch pedigree with X-linked recessive congenital stationary night blindness (CSNB) by utilizing 16 DNA markers from the proximal short arm of the human X chromosome (Xp21.1-11.2). Thirteen polymorphic markers are at least partially informative and have enabled pairwise and multipoint linkage analysis. For three loci, i.e. DXS228, the monoamine oxidase B gene and the Norrie disease gene (NDG), multipoint linkage studies have yielded maximum lod scores of > 3.0 at a recombination fraction of zero. Analysis of recombination events has enabled us to rule out the possibility that the underlying defect in this family is allelic to RP3; the gene defect could also be excluded from the proximal part of the region known to carry RP2. Linkage data are consistent with a possible involvement of the NDG but mutations in the open reading frame of this gene have not been found.

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

    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.

  12. Ascertainment correction for Markov chain Monte Carlo segregation and linkage analysis of a quantitative trait.

    Ma, Jianzhong; Amos, Christopher I; Warwick Daw, E

    2007-09-01

    Although extended pedigrees are often sampled through probands with extreme levels of a quantitative trait, Markov chain Monte Carlo (MCMC) methods for segregation and linkage analysis have not been able to perform ascertainment corrections. Further, the extent to which ascertainment of pedigrees leads to biases in the estimation of segregation and linkage parameters has not been previously studied for MCMC procedures. In this paper, we studied these issues with a Bayesian MCMC approach for joint segregation and linkage analysis, as implemented in the package Loki. We first simulated pedigrees ascertained through individuals with extreme values of a quantitative trait in spirit of the sequential sampling theory of Cannings and Thompson [Cannings and Thompson [1977] Clin. Genet. 12:208-212]. Using our simulated data, we detected no bias in estimates of the trait locus location. However, in addition to allele frequencies, when the ascertainment threshold was higher than or close to the true value of the highest genotypic mean, bias was also found in the estimation of this parameter. When there were multiple trait loci, this bias destroyed the additivity of the effects of the trait loci, and caused biases in the estimation all genotypic means when a purely additive model was used for analyzing the data. To account for pedigree ascertainment with sequential sampling, we developed a Bayesian ascertainment approach and implemented Metropolis-Hastings updates in the MCMC samplers used in Loki. Ascertainment correction greatly reduced biases in parameter estimates. Our method is designed for multiple, but a fixed number of trait loci. Copyright (c) 2007 Wiley-Liss, Inc.

  13. Clinical and genetic linkage analysis of a large Venezuelan kindred with Usher syndrome.

    Keogh, Ivan J; Godinho, R N; Wu, T Po; Diaz de Palacios, A M; Palacios, N; Bello de Alford, M; De Almada, M I; MarPalacios, N; Vazquez, A; Mattei, R; Seidman, C; Seidman, J; Eavey, R D

    2004-08-01

    To undertake a comprehensive investigation into the very high incidence of congenital deafness on the Macano peninsula of Margarita Island, Venezuela. Numerous visits were made to the isolated island community over a 4-year-period. During these visits, it became apparent that a significant number of individuals complained of problems with hearing and vision. Socioeconomic assessments, family pedigrees and clinical histories were recorded on standard questionnaires. All individuals underwent thorough otolaryngologic and ophthalmologic examinations. Twenty milliliters of peripheral venous blood was obtained from each participant. A genome-wide linkage analysis study was performed. Polymorphic microsatellite markers were amplified by polymerase chain reaction and separated on polyacrylamide gels. An ABI 377XL sequencer was used to separate fragments and LOD scores were calculated by using published software. Twenty-four families were identified, comprising 329 individuals, age range 1-80 years, including 184 children. All families were categorized in the lower two (least affluent) socioeconomic categories. A high incidence of consanguinity was detected. Fifteen individuals (11 adults, 4 children) had profound congenital sensorineural hearing loss, vestibular areflexia and retinitis pigmentosa. A maximum LOD score of 6.76 (Linkage >3.0), between markers D11s4186 and D11s911, confirmed linkage to chromosome 11q13.5. The gene myosin VIIA (MYO7A) was confirmed in the interval. Clinical and genetic findings are consistent with a diagnosis of Usher syndrome 1B for those with hearing and vision problems. We report 15 Usher syndrome 1B individuals from a newly detected Latin American socio-demographic origin, with a very high prevalence of 76 per 100,000 population.

  14. Considerations in using linkage analysis as a presymptomatic test for Huntington's disease.

    Farrer, L A; Myers, R H; Cupples, L A; Conneally, P M

    1988-09-01

    The polymorphic locus D4S10 that is genetically linked to the locus for Huntington's disease (HD) has made possible a presymptomatic test for those at risk. Because the symptoms of this progressively debilitating and fatal illness are not usually manifest until adulthood, the outcome of the test will influence major decisions about career, marriage, and procreation. Several differential diagnoses must be considered before using the test if HD is not confirmed in at least one family member. Review of a large number of pedigrees has shown that 40% of persons at risk do not have appropriate family structure for a linkage test. Furthermore, uncooperative or inaccessible relatives may make this test infeasible for many others who wish to be tested. Linkage phase, which must be known in the affected parent for an informative test, can be determined using one or more of 12 probe-enzyme combinations for D4S10. Although the polymorphism information content (PIC) value for any one RFLP is less than 40%, the PIC value for the haplotype of the two G8 HindIII, pK083 EcoRI, and R7 BglII RFLPs is greater than 88%. We have developed a scheme to incorporate linkage data and age at onset information adjusted for censored observations, sex of affected parent, and familial correlation for age at onset, using the computer program MLINK for calculation of risk of having HD. Simulated experiments showed that proper age at onset adjustment is crucial to the calculation of the probability of risk. A formal presymptomatic testing protocol, including pre- and post-test counselling, psychological testing, and paternity testing is recommended. Many of these considerations are illustrated in several actual test cases.

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

    Bianca B Z Vigna

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

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

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

    2016-01-01

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

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

    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

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

    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

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

    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

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

    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.

  1. polymapR - linkage analysis and genetic map construction from F1 populations of outcrossing polyploids.

    Bourke, Peter M; van Geest, Geert; Voorrips, Roeland E; Jansen, Johannes; Kranenburg, Twan; Shahin, Arwa; Visser, Richard G F; Arens, Paul; Smulders, Marinus J M; Maliepaard, Chris

    2018-05-02

    Polyploid species carry more than two copies of each chromosome, a condition found in many of the world's most important crops. Genetic mapping in polyploids is more complex than in diploid species, resulting in a lack of available software tools. These are needed if we are to realise all the opportunities offered by modern genotyping platforms for genetic research and breeding in polyploid crops. polymapR is an R package for genetic linkage analysis and integrated genetic map construction from bi-parental populations of outcrossing autopolyploids. It can currently analyse triploid, tetraploid and hexaploid marker datasets and is applicable to various crops including potato, leek, alfalfa, blueberry, chrysanthemum, sweet potato or kiwifruit. It can detect, estimate and correct for preferential chromosome pairing, and has been tested on high-density marker datasets from potato, rose and chrysanthemum, generating high-density integrated linkage maps in all of these crops. polymapR is freely available under the general public license from the Comprehensive R Archive Network (CRAN) at http://cran.r-project.org/package=polymapR. Chris Maliepaard chris.maliepaard@wur.nl or Roeland E. Voorrips roeland.voorrips@wur.nl. Supplementary data are available at Bioinformatics online.

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

    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...

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

    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.

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

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

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

    2017-01-01

    Key message: 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.Abstract: Construction and use of linkage maps are challenging in hexaploids with polysomic

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

    Zhou, K.; Dempfle, A.; Arcos-Burgos, M.; Bakker, S.C.; Banaschewski, T.; Biederman, J; Buitelaar, J.K.; Castellanos, F.X.; Doyle, A.; Ebstein, R.; Ekholm, J.; Forabosco, P.; Franke, F.; Freitag, C.; Friedel, S.; Gill, M.; Hebebrand, J.; Hinney, A.; Jacob, C.; Lesch, K.P.; Loo, S.K.; Lopera, F.; McCracken, J.T.; McGough, J.J.; Meyer, J.; Mick, E.; Miranda, A.; Muenkel, M.; Mulas, F.; Nelson, S.F.; Nguyen, T.T.; Oades, R.D.; Ogdie, M.N.; Palacio, J.D.; Pineda, D.; Reif, A.; Renner, T.J.; Roeyers, H.; Romanos, M.; Rothenberger, A.; Schäfer, H.; Sergeant, J.A.; Sinke, R.J.; Smalley, S.L.; Sonuga-Barke, E.; Steinhausen, H.C.; van der Meulen, E.; Walitza, S.; Warnke, A.; Lewis, C.M.; Faraone, S.V.; Asherson, P.

    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,

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

    Zhou, K.; Dempfle, A.; Arcos-Burgos, M.; Bakker, S.C.; Banaschewski, T.; Biederman, J.; Buitelaar, J.K.; Castellanos, F.X.; Doyle, A.; Ebstein, R.P.; Ekholm, J.; Forabosco, P.; Franke, B.; Freitag, C.; Friedel, S.; Gill, M.; Hebebrand, J.; Hinney, A.; Jacob, C.; Lesch, K.P.; Loo, S.K.; Lopera, F.; McCracken, J.T.; McGough, J.J.; Meyer, J.; Mick, E.; Miranda, A.; Muenke, M.; Mulas, F.; Nelson, S.F.; Nguyen, T.T.; Oades, R.D.; Ogdie, M.N.; Palacio, J.D.; Pineda, D.; Reif, A.; Renner, T.J.; Roeyers, H.; Romanos, M.; Rothenberger, A.; Schafer, H.; Sergeant, J.A.; Sinke, R.J.; Smalley, S.L.; Sonuga-Barke, E.J.S.; Steinhausen, H.C.; Meulen, E. van der; Walitza, S.; Warnke, A.; Lewis, C.M.; Faraone, S.V.; Asherson, P.

    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,

  8. Prospective Linkages between Peer Victimization and Externalizing Problems in Children: A Meta-Analysis

    Reijntjes, A.; Kamphuis, J.H.; Prinzie, P.; Boelen, P.A.; van der Schoot, M.; Telch, M.J.

    2011-01-01

    Previous meta-analytic research has shown both concurrent and prospective linkages between peer victimization and internalizing problems in youth. However, the linkages between peer victimization and externalizing problems over time have not been systematically examined, and it is therefore unknown

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

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

    2013-12-05

    Hypertriglyceridemia (HTG) is a heritable risk factor for cardiovascular disease. Investigating the genetics of HTG may identify new drug targets. There are ~35 known single-nucleotide variants (SNVs) that explain only ~10% of variation in triglyceride (TG) level. Because of the genetic heterogeneity of HTG, a family study design is optimal for identification of rare genetic variants with large effect size because the same mutation can be observed in many relatives and cosegregation with TG can be tested. We considered HTG in a five-generation family of European American descent (n = 121), ascertained for familial combined hyperlipidemia. By using Bayesian Markov chain Monte Carlo joint oligogenic linkage and association analysis, we detected linkage to chromosomes 7 and 17. Whole-exome sequence data revealed shared, highly conserved, private missense SNVs in both SLC25A40 on chr7 and PLD2 on chr17. Jointly, these SNVs explained 49% of the genetic variance in TG; however, only the SLC25A40 SNV was significantly associated with TG (p = 0.0001). This SNV, c.374A>G, causes a highly disruptive p.Tyr125Cys substitution just outside the second helical transmembrane region of the SLC25A40 inner mitochondrial membrane transport protein. Whole-gene testing in subjects from the Exome Sequencing Project confirmed the association between TG and SLC25A40 rare, highly conserved, coding variants (p = 0.03). These results suggest a previously undescribed pathway for HTG and illustrate the power of large pedigrees in the search for rare, causal variants. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  10. Preimplantation genetic diagnosis of X-linked diseases examined by indirect linkage analysis.

    Borgulova, I; Putzova, M; Soldatova, I; Krautova, L; Pecnova, L; Mika, J; Kren, R; Potuznikova, P; Stejskal, D

    2015-01-01

    Many centers of assisted reproduction in the Czech Republic offer preimplantation genetic diagnosis with fluorescent in situ hybridization (FISH) to couples requiring preimplantation genetic diagnosis (PGD) of X-linked diseases. However, this process results in discarding all male embryos and is not able to distinguish a carrier or healthy female embryo in X-linked recessive disorders. The main aim of this study was to summarize a six-year period of PGD of X-linked monogenic diseases using indirect linkage analysis. We wanted to accentuate the advantage indirect analysis of PGD using multiple displacement amplification (MDA) followed by short tandem repeat (STR) analysis. We present forty-six PGD cycles, including pre-case haplotyping (PGH) panel, for fifteen X-linked diseases. Embryo transfer was made thirty-eight times and gravidity was confirmed in thirteen female probands with a success rate of pregnancy calculated at 42 %. PGD procedure using MDA amplification followed by STR analysis provides help in identifying genetic defects within embryos prior to implantation. The reliability of the method was also supported by high pregnancy rate compared to other publications, which commonly achieved a 30-35 % success rate (Tab. 2, Fig. 1, Ref. 33).

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

    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

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

    Fardeen Ali Malayeri

    2011-03-01

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

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

    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...

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

    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. Clinical reinvestigation and linkage analysis in the family with Episkopi blindness (Norrie disease).

    Wolff, G; Mayerová, A; Wienker, T F; Atalianis, P; Ioannou, P; Warburg, M

    1992-11-01

    We present the results of a clinical and genetic reinvestigation of the Cypriot family affected by an X chromosomally inherited eye disease originally published by Taylor et al, who coined the term Episkopi blindness. The pedigree was extended to 160 members, including 16 affected males out of 48 males at risk for the disease, most of whom were seen by one of us (PA). Affected males are blind with no associated symptoms and apparently are not mentally retarded. Thirty-nine family members agreed to blood sampling for genetic investigations. RFLP analysis was performed using probes from the region known to be deleted in some Norrie patients and polymorphic markers (DXS77, DXS7, MAOA, DXS255) from the proximal short arm of the X chromosome. There was no deletion for any of the probes in the affected males. Linkage analysis yielded positive lod scores for all informative markers (Z (DXS255, theta = 0) = 6.54, Z (MAOA, theta = 0) = 2.23, Z (DXS7, theta = 0) = 2.13). Thus, the conclusion that Episkopi blindness and Norrie disease (NDP, MIM *310600) are the same entity based on clinical evidence is now reinforced by gene mapping.

  16. Estimation of linkage disequilibrium and analysis of genetic diversity in Korean chicken lines

    Seo, Dongwon; Lee, Doo Ho; Choi, Nuri; Sudrajad, Pita; Lee, Seung-Hwan

    2018-01-01

    The development of genetic markers for animal breeding is an effective strategy to reduce the time and cost required to improve economically important traits. To implement genomic selection in the multibreed chicken population of Korea, an understanding of the linkage disequilibrium (LD) status of the target population is essential. In this study, we performed population genetic analyses to investigate LD decay, the effective population size, and breed diversity using 600K high-density single nucleotide polymorphism genotypes of 189 native chickens in 14 lines (including Korean native chicken, imported and adapted purebred and commercial chickens). The results indicated that commercial native chickens have less calculated LD (average, r2 = 0.13–0.26) and purebred native chickens have more calculated LD (average, r2 = 0.24–0.37) across the entire genome. The effective population sizes of the examined lines showed patterns opposite to those of population LD. The phylogeny and admixture analyses showed that commercial and purebred chickens were well distinguished, except for Rhode Island Red (RIR) purebred lines of NC (NIAS_RIR_C) and ND (NIAS_RIR_D). These lines are difficult to distinguish clearly because they originated from the same respective breeds. The results of this study may provide important information for the development of genetic markers that can be used in breeding to improve the economic traits of native chickens. PMID:29425208

  17. Estimation of linkage disequilibrium and analysis of genetic diversity in Korean chicken lines.

    Seo, Dongwon; Lee, Doo Ho; Choi, Nuri; Sudrajad, Pita; Lee, Seung-Hwan; Lee, Jun-Heon

    2018-01-01

    The development of genetic markers for animal breeding is an effective strategy to reduce the time and cost required to improve economically important traits. To implement genomic selection in the multibreed chicken population of Korea, an understanding of the linkage disequilibrium (LD) status of the target population is essential. In this study, we performed population genetic analyses to investigate LD decay, the effective population size, and breed diversity using 600K high-density single nucleotide polymorphism genotypes of 189 native chickens in 14 lines (including Korean native chicken, imported and adapted purebred and commercial chickens). The results indicated that commercial native chickens have less calculated LD (average, r2 = 0.13-0.26) and purebred native chickens have more calculated LD (average, r2 = 0.24-0.37) across the entire genome. The effective population sizes of the examined lines showed patterns opposite to those of population LD. The phylogeny and admixture analyses showed that commercial and purebred chickens were well distinguished, except for Rhode Island Red (RIR) purebred lines of NC (NIAS_RIR_C) and ND (NIAS_RIR_D). These lines are difficult to distinguish clearly because they originated from the same respective breeds. The results of this study may provide important information for the development of genetic markers that can be used in breeding to improve the economic traits of native chickens.

  18. Fat stigmatization in television shows and movies: a content analysis.

    Himes, Susan M; Thompson, J Kevin

    2007-03-01

    To examine the phenomenon of fat stigmatization messages presented in television shows and movies, a content analysis was used to quantify and categorize fat-specific commentary and humor. Fat stigmatization vignettes were identified using a targeted sampling procedure, and 135 scenes were excised from movies and television shows. The material was coded by trained raters. Reliability indices were uniformly high for the seven categories (percentage agreement ranged from 0.90 to 0.98; kappas ranged from 0.66 to 0.94). Results indicated that fat stigmatization commentary and fat humor were often verbal, directed toward another person, and often presented directly in the presence of the overweight target. Results also indicated that male characters were three times more likely to engage in fat stigmatization commentary or fat humor than female characters. To our knowledge, these findings provide the first information regarding the specific gender, age, and types of fat stigmatization that occur frequently in movies and television shows. The stimuli should prove useful in future research examining the role of individual difference factors (e.g., BMI) in the reaction to viewing such vignettes.

  19. Cross border hospital use: analysis using data linkage across four Australian states.

    Spilsbury, Katrina; Rosman, Diana; Alan, Janine; Boyd, James H; Ferrante, Anna M; Semmens, James B

    2015-06-15

    To determine the quality and effectiveness of national data linkage capacity by performing a proof-of-concept project investigating cross-border hospital use and hospital-related deaths. Analysis of person-level linked hospital separation and death registration data of all public and private hospital patients in New South Wales, Queensland and Western Australia and of public hospital patients in South Australia, totalling 7.7 million hospital patients from 1 July 2004 to 30 June 2009. Counts and proportions of hospital stays and patient movement patterns. 223 262 patients (3.0%) travelled across a state border to attend hospitals, in particular, far northern and western NSW patients travelling to Queensland and SA hospitals, respectively. A further 48 575 patients (0.6%) moved their place of residence interstate between hospital visits, particularly to and from areas associated with major mining and tourism industries. Over 11 000 cross-border hospital transfers were also identified. Of patients who travelled across a state border to hospital, 2800 (1.3%) died in that hospital. An additional 496 deaths recorded in one jurisdiction occurred within 30 days of hospital separation from another jurisdiction. Access to person-level data linked across jurisdictions identified geographical hot spots of cross-border hospital use and hospital-related deaths in Australia. This has implications for planning of health service delivery and for longitudinal follow-up studies, particularly those involving mobile populations.

  20. Exome Sequencing and Linkage Analysis Identified Novel Candidate Genes in Recessive Intellectual Disability Associated with Ataxia.

    Jazayeri, Roshanak; Hu, Hao; Fattahi, Zohreh; Musante, Luciana; Abedini, Seyedeh Sedigheh; Hosseini, Masoumeh; Wienker, Thomas F; Ropers, Hans Hilger; Najmabadi, Hossein; Kahrizi, Kimia

    2015-10-01

    Intellectual disability (ID) is a neuro-developmental disorder which causes considerable socio-economic problems. Some ID individuals are also affected by ataxia, and the condition includes different mutations affecting several genes. We used whole exome sequencing (WES) in combination with homozygosity mapping (HM) to identify the genetic defects in five consanguineous families among our cohort study, with two affected children with ID and ataxia as major clinical symptoms. We identified three novel candidate genes, RIPPLY1, MRPL10, SNX14, and a new mutation in known gene SURF1. All are autosomal genes, except RIPPLY1, which is located on the X chromosome. Two are housekeeping genes, implicated in transcription and translation regulation and intracellular trafficking, and two encode mitochondrial proteins. The pathogenesis of these variants was evaluated by mutation classification, bioinformatic methods, review of medical and biological relevance, co-segregation studies in the particular family, and a normal population study. Linkage analysis and exome sequencing of a small number of affected family members is a powerful new technique which can be used to decrease the number of candidate genes in heterogenic disorders such as ID, and may even identify the responsible gene(s).

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

    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.

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

    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,

  3. Analysis of diversity and linkage disequilibrium along chromosome 3B of bread wheat (Triticum aestivum L.).

    Horvath, Aniko; Didier, Audrey; Koenig, Jean; Exbrayat, Florence; Charmet, Gilles; Balfourier, François

    2009-11-01

    A highly polymorphic core collection of bread wheat and a more narrow-based breeding material, gathered from pedigrees of seven modern cultivars, was analysed in order to compare genetic diversity indices and linkage disequilibrium (LD) patterns along the chromosome 3B with microsatellite (SSR) and Diversity Arrays Technology markers. Five ancestral gene pools could be identified within the core collection, indicating a strong geographical structure (Northwest Europe, Southeast Europe, CIMMYT-ICARDA group, Asia, Nepal). The breeding material showed a temporal structure, corresponding to different periods of breeding programmes [old varieties (from old landraces to 1919), semi-modern varieties (1920-1959), modern varieties (1960-2006)]. Basic statistics showed a higher genetic diversity in the core collection than in the breeding material, indicating a stronger selection pressure in this latter material. More generally, the chromosome 3B had a lower diversity than the whole B-genome. LD was weak in all studied materials. Amongst geographical groups, the CIMMYT-ICARDA pool presented the longest ranged LD in contrast to Asian accessions. In the breeding material, LD increased from old cultivars to modern varieties. Genitors of seven modern cultivars were found to be different; most marker pairs in significant LD were observed amongst genitors of Alexandre and Koreli varieties, indicating an important inbreeding effect. At low genetic distances (0-5 cM), the breeding material had higher LD than the core collection, but globally the two materials had similar values in all classes. Marker pairs in significant LD are generally observed around the centromere in both arms and at distal position on the short arm of the chromosome 3B.

  4. Linkage analysis by genotyping of sibling populations: a genetic map for the potato cyst nematode constructed using a "pseudo-F2" mapping strategy.

    Rouppe van der Voort, J N; van Eck, H J; van Zandvoort, P M; Overmars, H; Helder, J; Bakker, J

    1999-07-01

    A mapping strategy is described for the construction of a linkage map of a non-inbred species in which individual offspring genotypes are not amenable to marker analysis. After one extra generation of random mating, the segregating progeny was propagated, and bulked populations of offspring were analyzed. Although the resulting population structure is different from that of commonly used mapping populations, we show that the maximum likelihood formula for a normal F2 is applicable for the estimation of recombination. This "pseudo-F2" mapping strategy, in combination with the development of an AFLP assay for single cysts, facilitated the construction of a linkage map for the potato cyst nematode Globodera rostochiensis. Using 12 pre-selected AFLP primer combinations, a total of 66 segregating markers were identified, 62 of which were mapped to nine linkage groups. These 62 AFLP markers are randomly distributed and cover about 65% of the genome. An estimate of the physical size of the Globodera genome was obtained from comparisons of the number of AFLP fragments obtained with the values for Caenorhabditis elegans. The methodology presented here resulted in the first genomic map for a cyst nematode. The low value of the kilobase/centimorgan (kb/cM) ratio for the Globodera genome will facilitate map-based cloning of genes that mediate the interaction between the nematode and its host plant.

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

    Ganal Martin W

    2006-01-01

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

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

    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

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

    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.

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

    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.

  9. Advertising Discourse Analysis of FES stores: Killing Love, Cowards Show

    Cristian Venegas Ahumada

    2013-08-01

    Full Text Available The objective is to analyze the structural and photographic discourse of the Autumn-Winter campaign 2008 of FES stores for young people. This was done by a semiotic theory and a critical-structural methodology of discourse. An analysis of 4 advertising photographs was done, and at once an analysis of the discourse “FES says no to violence against Women”, which explains the campaign’s target. The result is: The discourse was subjected to production condition (society of control and makes advertising a way to homogenize subjectivity of masses to consume. Recognition conditions demonstrate that this advertising discourse of symbolic violence means a type of violation of Men and Women Rights. An action like this requires commitment of Psychology in order to promote the social humanizing change, by means of university teaching and professional tasks.

  10. application of single-linkage clustering method in the analysis of ...

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    ANALYSIS OF GROWTH RATE OF GROSS DOMESTIC PRODUCT. (GDP) AT ... The end result of the algorithm is a tree of clusters called a dendrogram, which shows how the clusters are ..... Number of cluster sum from from observations of ...

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

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

    2016-01-01

    The hybrids between Luffa acutangula (L.) Roxb. and L.cylindrica (L.) Roem. have strong heterosis effects. However, some reproductive isolation traits hindered their normal hybridization and fructification, which was mainly caused by the flowering time and hybrid pollen sterility. In order to study the genetic basis of two interspecific reproductive isolation traits, we constructed a genetic linkage map using an F2 population derived from a cross between S1174 [L. acutangula (L.) Roxb.] and 9...

  12. Combined segregation and linkage analysis of genetic hemochromatosis using affection status, serum iron, and HLA.

    Borecki, I B; Lathrop, G M; Bonney, G E; Yaouanq, J; Rao, D C

    1990-01-01

    Characterizing the distribution of parameters of iron metabolism by hemochromatosis genotype remains an important goal vis-à-vis potential screening strategies to identify individuals at genetic risk, since a specific marker to detect the abnormal gene has not been identified as yet. In the present investigation, we analyze serum iron values in ascertained families using a method which incorporates both segregation of the clinical affection status and the HLA linkage information to identify t...

  13. Macro-Financial Linkages in Egypt; A Panel Analysis of Economic Shocks and Loan Portfolio Quality

    Inessa Love; Rima Turk-Ariss

    2013-01-01

    This paper investigates macro-financial linkages in Egypt using two complementary methods, assessing the interaction between different macroeconomic aggregates and loan portfolio quality in a multivariate framework as well as through a panel vector autoregressive method that controls for bank-level characteristics. Using a panel of banks over 1993-2010, the authors find that a positive shock to capital inflows and growth in gross domestic product improves banks’ loan portfolio quality, and ...

  14. ROLE OF AGRO-INDUSTRY IN BANGLADESH ECONOMY: AN EMPIRICAL ANALYSIS OF LINKAGES AND MULTIPLIERS

    Quddus, Md. Abdul

    2009-01-01

    The study was undertaken to evaluate the contribution of agro-industry in the Bangladesh economy. The latest two input-output tables of the year 1993-94 and 2001-2002 in Bangladesh were used to calculate inter-industry linkage indices and multiplier effects. Agroindustry contributes a significant portion of national income and the prospect of employment generation is increasing at the higher extent for the sectors food processing, tanning and leather finishing, leather industry, saw milling a...

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

    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.

  16. Bayesian analysis of repairable systems showing a bounded failure intensity

    Guida, Maurizio; Pulcini, Gianpaolo

    2006-01-01

    The failure pattern of repairable mechanical equipment subject to deterioration phenomena sometimes shows a finite bound for the increasing failure intensity. A non-homogeneous Poisson process with bounded increasing failure intensity is then illustrated and its characteristics are discussed. A Bayesian procedure, based on prior information on model-free quantities, is developed in order to allow technical information on the failure process to be incorporated into the inferential procedure and to improve the inference accuracy. Posterior estimation of the model-free quantities and of other quantities of interest (such as the optimal replacement interval) is provided, as well as prediction on the waiting time to the next failure and on the number of failures in a future time interval is given. Finally, numerical examples are given to illustrate the proposed inferential procedure

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

    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

  18. Genome-wide analysis of adolescent psychotic-like experiences shows genetic overlap with psychiatric disorders.

    Pain, Oliver; Dudbridge, Frank; Cardno, Alastair G; Freeman, Daniel; Lu, Yi; Lundstrom, Sebastian; Lichtenstein, Paul; Ronald, Angelica

    2018-03-31

    This study aimed to test for overlap in genetic influences between psychotic-like experience traits shown by adolescents in the community, and clinically-recognized psychiatric disorders in adulthood, specifically schizophrenia, bipolar disorder, and major depression. The full spectra of psychotic-like experience domains, both in terms of their severity and type (positive, cognitive, and negative), were assessed using self- and parent-ratings in three European community samples aged 15-19 years (Final N incl. siblings = 6,297-10,098). A mega-genome-wide association study (mega-GWAS) for each psychotic-like experience domain was performed. Single nucleotide polymorphism (SNP)-heritability of each psychotic-like experience domain was estimated using genomic-relatedness-based restricted maximum-likelihood (GREML) and linkage disequilibrium- (LD-) score regression. Genetic overlap between specific psychotic-like experience domains and schizophrenia, bipolar disorder, and major depression was assessed using polygenic risk score (PRS) and LD-score regression. GREML returned SNP-heritability estimates of 3-9% for psychotic-like experience trait domains, with higher estimates for less skewed traits (Anhedonia, Cognitive Disorganization) than for more skewed traits (Paranoia and Hallucinations, Parent-rated Negative Symptoms). Mega-GWAS analysis identified one genome-wide significant association for Anhedonia within IDO2 but which did not replicate in an independent sample. PRS analysis revealed that the schizophrenia PRS significantly predicted all adolescent psychotic-like experience trait domains (Paranoia and Hallucinations only in non-zero scorers). The major depression PRS significantly predicted Anhedonia and Parent-rated Negative Symptoms in adolescence. Psychotic-like experiences during adolescence in the community show additive genetic effects and partly share genetic influences with clinically-recognized psychiatric disorders, specifically schizophrenia and

  19. 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.

    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.

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

    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.

  1. Joint multi-population analysis for genetic linkage of bipolar disorder or "wellness" to chromosome 4p.

    Visscher, P M; Haley, C S; Ewald, H; Mors, O; Egeland, J; Thiel, B; Ginns, E; Muir, W; Blackwood, D H

    2005-02-05

    To test the hypothesis that the same genetic loci confer susceptibility to, or protection from, disease in different populations, and that a combined analysis would improve the map resolution of a common susceptibility locus, we analyzed data from three studies that had reported linkage to bipolar disorder in a small region on chromosome 4p. Data sets comprised phenotypic information and genetic marker data on Scottish, Danish, and USA extended pedigrees. Across the three data sets, 913 individuals appeared in the pedigrees, 462 were classified, either as unaffected (323) or affected (139) with unipolar or bipolar disorder. A consensus linkage map was created from 14 microsatellite markers in a 33 cM region. Phenotypic and genetic data were analyzed using a variance component (VC) and allele sharing method. All previously reported elevated test statistics in the region were confirmed with one or both analysis methods, indicating the presence of one or more susceptibility genes to bipolar disorder in the three populations in the studied chromosome segment. When the results from both the VC and allele sharing method were considered, there was strong evidence for a susceptibility locus in the data from Scotland, some evidence in the data from Denmark and relatively less evidence in the data from the USA. The test statistics from the Scottish data set dominated the test statistics from the other studies, and no improved map resolution for a putative genetic locus underlying susceptibility in all three studies was obtained. Studies reporting linkage to the same region require careful scrutiny and preferably joint or meta analysis on the same basis in order to ensure that the results are truly comparable. (c) 2004 Wiley-Liss, Inc.

  2. Sectoral linkages of financial services as channels of economic development—An input–output analysis of the Nigerian and Kenyan economies

    Andreas Freytag

    2017-06-01

    Full Text Available Sectoral linkages of financial services of the Nigerian and Kenyan economies are evaluated by means of an input–output analysis for 2007, 2009 and 2011. Backward linkages, forward linkages, multiplier effects and variation indices for the financial services sectors are determined. Due to the increasing importance of mobile money, we additionally investigate these linkages for the communication sector. We find high forward and backward linkages for the Nigerian financial services sector only. Here, changes in final demand for or primary input into the financial sector have a wide and evenly spread impact on the rest of the economy classifying the financial sector as a key sector. Regarding Kenya, however, the sectoral linkages of the financial services sector are lower. This may be due to the well-developed mobile financial market in Kenya. But results for the communication sector, however, yield rather low linkage values and multiplier effects for both economies. All results are confirmed by a robustness test. Nonetheless, they could have been influenced by a lack of data coverage especially with regard to mobile money and a high degree of informal financial transactions. Still, our findings confirm the significance of financial services as channels of economic development for both the economies.

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

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

    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)

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

    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

  6. Pseudoautosomal region in schizophrenia: linkage analysis of seven loci by sib-pair and lod-score methods.

    d'Amato, T; Waksman, G; Martinez, M; Laurent, C; Gorwood, P; Campion, D; Jay, M; Petit, C; Savoye, C; Bastard, C

    1994-05-01

    In a previous study, we reported a nonrandom segregation between schizophrenia and the pseudoautosomal locus DXYS14 in a sample of 33 sibships. That study has been extended by the addition of 16 new sibships from 16 different families. Data from six other loci of the pseudoautosomal region and of the immediately adjacent part of the X specific region have also been analyzed. Two methods of linkage analysis were used: the affected sibling pair (ASP) method and the lod-score method. Lod-score analyses were performed on the basis of three different models--A, B, and C--all shown to be consistent with the epidemiological data on schizophrenia. No clear evidence for linkage was obtained with any of these models. However, whatever the genetic model and the disease classification, maximum lod scores were positive with most of the markers, with the highest scores generally being obtained for the DXYS14 locus. When the ASP method was used, the earlier finding of nonrandom segregation between schizophrenia and the DXYS14 locus was still supported in this larger data set, at an increased level of statistical significance. Findings of ASP analyses were not significant for the other loci. Thus, findings obtained from analyses using the ASP method, but not the lod-score method, were consistent with the pseudoautosomal hypothesis for schizophrenia.

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

    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.

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

    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.

  9. Linkage analysis of Norrie disease with an X-chromosomal ornithine aminotransferase locus.

    Bateman, J B; Kojis, T L; Cantor, R M; Heinzmann, C; Ngo, J T; Spence, M A; Inana, G; Kivlin, J D; Curtis, D; Sparkes, R S

    1993-01-01

    Norrie disease is a rare disease of newborn males caused by prenatal or perinatal retinal detachment, which may be associated with mental retardation, psychosis, and/or hearing loss. DXS7 (L1.28) and MAO A and B loci have been linked to the ND locus on the short arm of the X chromosome. Sequences homologous to OAT also have been mapped to the short arm of the X chromosome. We performed linkage analyses between the ND locus and one of the OAT-like clusters of sequences on the X chromosome (OATL1), using a ScaI RFLP in a ND family, and increased the previously calculated lod score (z) to over 3 (3.38; theta = 0.05). Similarly, we calculated a lod score of 4.06 (theta = 0.01) between the OATL1 and DXS7 loci. Alone, the OATL1 ScaI RFLP system is expected to be informative in 48% of females. If this system were used in combination with the DXS7 TaqI polymorphism, 71% of females would be informative for at least one of the markers and 21% would be informative for both. Because the OATL1 ScaI RFLP is a relatively common polymorphism, this system should be useful for the identification of ND carriers and affected male fetuses and newborns.

  10. Quantitative trait locus mapping of deep rooting by linkage and association analysis in rice.

    Lou, Qiaojun; Chen, Liang; Mei, Hanwei; Wei, Haibin; Feng, Fangjun; Wang, Pei; Xia, Hui; Li, Tiemei; Luo, Lijun

    2015-08-01

    Deep rooting is a very important trait for plants' drought avoidance, and it is usually represented by the ratio of deep rooting (RDR). Three sets of rice populations were used to determine the genetic base for RDR. A linkage mapping population with 180 recombinant inbred lines and an association mapping population containing 237 rice varieties were used to identify genes linked to RDR. Six quantitative trait loci (QTLs) of RDR were identified as being located on chromosomes 1, 2, 4, 7, and 10. Using 1 019 883 single-nucleotide polymorphisms (SNPs), a genome-wide association study of the RDR was performed. Forty-eight significant SNPs of the RDR were identified and formed a clear peak on the short arm of chromosome 1 in a Manhattan plot. Compared with the shallow-rooting group and the whole collection, the deep-rooting group had selective sweep regions on chromosomes 1 and 2, especially in the major QTL region on chromosome 2. Seven of the nine candidate SNPs identified by association mapping were verified in two RDR extreme groups. The findings from this study will be beneficial to rice drought-resistance research and breeding. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

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

    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.

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

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

    2006-01-01

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

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

    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.

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

    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

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

    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.

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

    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.

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

    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.

  18. Discovering the Effects-Endstate Linkage: Using Soft Systems Methodology to Perform EBO Mission Analysis

    Young, Jr, William E

    2005-01-01

    .... EBO mission analysis is shown to be more problem structuring than problem solving. A new mission analysis process is proposed using a modified version of Soft Systems Methodology to meet these challenges...

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

    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....

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

    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) ...

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

    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...

  2. A Simple Linear Regression Method for Quantitative Trait Loci Linkage Analysis With Censored Observations

    Anderson, Carl A.; McRae, Allan F.; Visscher, Peter M.

    2006-01-01

    Standard quantitative trait loci (QTL) mapping techniques commonly assume that the trait is both fully observed and normally distributed. When considering survival or age-at-onset traits these assumptions are often incorrect. Methods have been developed to map QTL for survival traits; however, they are both computationally intensive and not available in standard genome analysis software packages. We propose a grouped linear regression method for the analysis of continuous survival data. Using...

  3. The Linkages between Growth, Poverty and Inequality in Vietnam: An Empirical Analysis

    Hoi Quoc Le

    2010-01-01

    This paper examines how initial inequality and poverty rate are related to subsequent economic growth in the provincial level of Vietnam. The results show a robust negative relationship between initial poverty rate and subsequent economic growth. However, there is no link between initial inequality and subsequent economic growth. The results also show that lower inequality leads to lower poverty rate and poverty reduction could help to reduce inequality. Other determinants of inequality and p...

  4. CONSIDERATIONS OVER THE METHODOLOGY OF FINANCIAL ANALYSIS AND ITS LINKAGE WITH BANKABILITY OF EUROPEAN FUNDED INVESTMENT PROJECTS

    TRENCA Ioan; PETRIA Nicolae; DROJ Laurentiu

    2012-01-01

    European funding is considered to be one of the hot topics in Romania and all over Eastern Europe since its novelty and its expected capacity to improve the life of the newly integrated European citizens. The linkages between the European Financial Support Programmes, the private financing performed by the banking sector and the private companies which are intending to use the structural funds to finance their investments is obvious. The present paper analyzed these linkages, creates a case s...

  5. An analysis of the organizational linkages in the cotton industry in Benin

    Sinzogan, A.A.C.; Jiggins, J.; Vodouhè, S.; Kossou, D.; Totin, G.G.E.; Huis, van A.

    2007-01-01

    A study of the institutional context of the cotton industry in Benin was conducted in 2004, based on an analysis of stakeholders' interests and influence. The impacts on innovation processes and production systems are analysed with respect to farmers' organizations, the research and extension system

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

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

    2016-08-01

    The sustainability of goat farming in marginal areas of southern Africa depends on local breeds that are adapted to specific agro-ecological conditions. Unimproved non-descript goats are the main genetic resources used for the development of commercial meat-type breeds of South Africa. Little is known about genetic diversity and the genetics of adaptation of these indigenous goat populations. This study investigated the genetic diversity, population structure and breed relations, linkage disequilibrium, effective population size and persistence of gametic phase in goat populations of South Africa. Three locally developed meat-type breeds of the Boer (n = 33), Savanna (n = 31), Kalahari Red (n = 40), a feral breed of Tankwa (n = 25) and unimproved non-descript village ecotypes (n = 110) from four goat-producing provinces of the Eastern Cape, KwaZulu-Natal, Limpopo and North West were assessed using the Illumina Goat 50K SNP Bead Chip assay. The proportion of SNPs with minor allele frequencies >0.05 ranged from 84.22% in the Tankwa to 97.58% in the Xhosa ecotype, with a mean of 0.32 ± 0.13 across populations. Principal components analysis, admixture and pairwise FST identified Tankwa as a genetically distinct population and supported clustering of the populations according to their historical origins. Genome-wide FST identified 101 markers potentially under positive selection in the Tankwa. Average linkage disequilibrium was highest in the Tankwa (r(2)  = 0.25 ± 0.26) and lowest in the village ecotypes (r(2) range = 0.09 ± 0.12 to 0.11 ± 0.14). We observed an effective population size of 100 kb with the exception of those in Savanna and Tswana populations. This study highlights the high level of genetic diversity in South African indigenous goats as well as the utility of the genome-wide SNP marker panels in genetic studies of these populations. © 2016 Stichting International Foundation for Animal Genetics.

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

    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...

  8. Genome-Wide Linkage and Association Analysis Identifies Major Gene Loci for Guttural Pouch Tympany in Arabian and German Warmblood Horses

    Metzger, Julia; Ohnesorge, Bernhard; Distl, Ottmar

    2012-01-01

    Equine guttural pouch tympany (GPT) is a hereditary condition affecting foals in their first months of life. Complex segregation analyses in Arabian and German warmblood horses showed the involvement of a major gene as very likely. Genome-wide linkage and association analyses including a high density marker set of single nucleotide polymorphisms (SNPs) were performed to map the genomic region harbouring the potential major gene for GPT. A total of 85 Arabian and 373 German warmblood horses were genotyped on the Illumina equine SNP50 beadchip. Non-parametric multipoint linkage analyses showed genome-wide significance on horse chromosomes (ECA) 3 for German warmblood at 16–26 Mb and 34–55 Mb and for Arabian on ECA15 at 64–65 Mb. Genome-wide association analyses confirmed the linked regions for both breeds. In Arabian, genome-wide association was detected at 64 Mb within the region with the highest linkage peak on ECA15. For German warmblood, signals for genome-wide association were close to the peak region of linkage at 52 Mb on ECA3. The odds ratio for the SNP with the highest genome-wide association was 0.12 for the Arabian. In conclusion, the refinement of the regions with the Illumina equine SNP50 beadchip is an important step to unravel the responsible mutations for GPT. PMID:22848553

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

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

    1996-09-01

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

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

    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

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

    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

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

    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

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

    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.

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

    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.

  15. A simple linear regression method for quantitative trait loci linkage analysis with censored observations.

    Anderson, Carl A; McRae, Allan F; Visscher, Peter M

    2006-07-01

    Standard quantitative trait loci (QTL) mapping techniques commonly assume that the trait is both fully observed and normally distributed. When considering survival or age-at-onset traits these assumptions are often incorrect. Methods have been developed to map QTL for survival traits; however, they are both computationally intensive and not available in standard genome analysis software packages. We propose a grouped linear regression method for the analysis of continuous survival data. Using simulation we compare this method to both the Cox and Weibull proportional hazards models and a standard linear regression method that ignores censoring. The grouped linear regression method is of equivalent power to both the Cox and Weibull proportional hazards methods and is significantly better than the standard linear regression method when censored observations are present. The method is also robust to the proportion of censored individuals and the underlying distribution of the trait. On the basis of linear regression methodology, the grouped linear regression model is computationally simple and fast and can be implemented readily in freely available statistical software.

  16. Transcript-specific, single-nucleotide polymorphism discovery and linkage analysis in hexaploid bread wheat (Triticum aestivum L.).

    Allen, Alexandra M; Barker, Gary L A; Berry, Simon T; Coghill, Jane A; Gwilliam, Rhian; Kirby, Susan; Robinson, Phil; Brenchley, Rachel C; D'Amore, Rosalinda; McKenzie, Neil; Waite, Darren; Hall, Anthony; Bevan, Michael; Hall, Neil; Edwards, Keith J

    2011-12-01

    Food security is a global concern and substantial yield increases in cereal crops are required to feed the growing world population. Wheat is one of the three most important crops for human and livestock feed. However, the complexity of the genome coupled with a decline in genetic diversity within modern elite cultivars has hindered the application of marker-assisted selection (MAS) in breeding programmes. A crucial step in the successful application of MAS in breeding programmes is the development of cheap and easy to use molecular markers, such as single-nucleotide polymorphisms. To mine selected elite wheat germplasm for intervarietal single-nucleotide polymorphisms, we have used expressed sequence tags derived from public sequencing programmes and next-generation sequencing of normalized wheat complementary DNA libraries, in combination with a novel sequence alignment and assembly approach. Here, we describe the development and validation of a panel of 1114 single-nucleotide polymorphisms in hexaploid bread wheat using competitive allele-specific polymerase chain reaction genotyping technology. We report the genotyping results of these markers on 23 wheat varieties, selected to represent a broad cross-section of wheat germplasm including a number of elite UK varieties. Finally, we show that, using relatively simple technology, it is possible to rapidly generate a linkage map containing several hundred single-nucleotide polymorphism markers in the doubled haploid mapping population of Avalon × Cadenza. © 2011 The Authors. Plant Biotechnology Journal © 2011 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

  17. [The Willingness to Consent to the Linkage of Primary and Secondary Data: An Analysis Based on a Survey of Patients with Primary Breast Cancer in Northrhine Westfalia].

    Scholten, N; Pfaff, H; Raabe, N; Kowalski, C

    2017-03-01

    Introduction: By linking data it is possible to merge, for example, survey data with routine data from statutory health insurance (GKV), to gain benefit from the advantages of both. As personal data is involved, it is necessary to obtain consent. Previous studies show that willingness to release this kind of data for scientific research is limited. This fact restricts the number of participants and can cause selection bias. The aim of our study was to analyze willingness to consent to the linkage of survey data with statutory health insurance data in patients with primary breast cancer. Associations between approval and socio-demographic characteristics were explored. Method: In the annual survey of patients with primary breast cancer in certified breast centers in North Rhine-Westphalia, all included patients were questioned concerning their willingness to consent to data linkage. We distinguished between patients insured by AOK Rhineland/Hamburg and all other patients: based on cooperation with AOK Rhineland/Hamburg, we obtained consent to actually link the data for all patients insured there. All other patients were questioned in terms of their insurance and their willingness to consent in general. Results: A total of 2,387 questionnaires were returned, giving a return rate of 49.3%. For the AOK Rhineland/Hamburg-insured patients, the consent rate was at 89.6%. At 75.7%, positive attitudes towards data linkage turned out to be a bit lower for patients with other insurers. Under the assumption that all non-responders disapprove data linkage, still 38.1% of patients showed a positive attitude towards data linkage. As a result of the multivariable model, insurance status (private vs. statutory) and first language turned out to be the only significant factors influencing the response. The consent of patients insured by AOK Rhineland/Hamburg is not significantly influenced by any of the measured socio-demographic factors. Conclusion: Currently, there is not much

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

    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.

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

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

    2016-01-01

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

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

    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

  1. Subsidiary Linkage Patterns

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

    2012-01-01

    channels for spillovers to competitors. We find a curvilinear relationship between the extent of competitive pressure and the quality of a subsidiary's set of local linkages. Furthermore, the extent to which a subsidiary possesses capabilities moderates this relationship: Very capable subsidiaries...... in strongly competitive environments tend to shy away from high quality linkages. We discuss our findings in light of the literature on spillovers and inter-organizational linkages.......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...

  2. Importance Performance Analysis as a Trade Show Performance Evaluation and Benchmarking Tool

    Tafesse, Wondwesen; Skallerud, Kåre; Korneliussen, Tor

    2010-01-01

    Author's accepted version (post-print). The purpose of this study is to introduce importance performance analysis as a trade show performance evaluation and benchmarking tool. Importance performance analysis considers exhibitors’ performance expectation and perceived performance in unison to evaluate and benchmark trade show performance. The present study uses data obtained from exhibitors of an international trade show to demonstrate how importance performance analysis can be used to eval...

  3. Linkage analysis using co-phenotypes in the BRIGHT study reveals novel potential susceptibility loci for hypertension.

    Wallace, Chris; Xue, Ming-Zhan; Newhouse, Stephen J; Marcano, Ana Carolina B; Onipinla, Abiodun K; Burke, Beverley; Gungadoo, Johannie; Dobson, Richard J; Brown, Morris; Connell, John M; Dominiczak, Anna; Lathrop, G Mark; Webster, John; Farrall, Martin; Mein, Charles; Samani, Nilesh J; Caulfield, Mark J; Clayton, David G; Munroe, Patricia B

    2006-08-01

    Identification of the genetic influences on human essential hypertension and other complex diseases has proved difficult, partly because of genetic heterogeneity. In many complex-trait resources, additional phenotypic data have been collected, allowing comorbid intermediary phenotypes to be used to characterize more genetically homogeneous subsets. The traditional approach to analyzing covariate-defined subsets has typically depended on researchers' previous expectations for definition of a comorbid subset and leads to smaller data sets, with a concomitant attrition in power. An alternative is to test for dependence between genetic sharing and covariates across the entire data set. This approach offers the advantage of exploiting the full data set and could be widely applied to complex-trait genome scans. However, existing maximum-likelihood methods can be prohibitively computationally expensive, especially since permutation is often required to determine significance. We developed a less computationally intensive score test and applied it to biometric and biochemical covariate data, from 2,044 sibling pairs with severe hypertension, collected by the British Genetics of Hypertension (BRIGHT) study. We found genomewide-significant evidence for linkage with hypertension and several related covariates. The strongest signals were with leaner-body-mass measures on chromosome 20q (maximum LOD = 4.24) and with parameters of renal function on chromosome 5p (maximum LOD = 3.71). After correction for the multiple traits and genetic locations studied, our global genomewide P value was .046. This is the first identity-by-descent regression analysis of hypertension to our knowledge, and it demonstrates the value of this approach for the incorporation of additional phenotypic information in genetic studies of complex traits.

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

    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.

  5. 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

    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

  6. Use of linkage mapping and centrality analysis across habitat gradients to conserve connectivity of gray wolf populations in western North America.

    Carroll, Carlos; McRae, Brad H; Brookes, Allen

    2012-02-01

    Centrality metrics evaluate paths between all possible pairwise combinations of sites on a landscape to rank the contribution of each site to facilitating ecological flows across the network of sites. Computational advances now allow application of centrality metrics to landscapes represented as continuous gradients of habitat quality. This avoids the binary classification of landscapes into patch and matrix required by patch-based graph analyses of connectivity. It also avoids the focus on delineating paths between individual pairs of core areas characteristic of most corridor- or linkage-mapping methods of connectivity analysis. Conservation of regional habitat connectivity has the potential to facilitate recovery of the gray wolf (Canis lupus), a species currently recolonizing portions of its historic range in the western United States. We applied 3 contrasting linkage-mapping methods (shortest path, current flow, and minimum-cost-maximum-flow) to spatial data representing wolf habitat to analyze connectivity between wolf populations in central Idaho and Yellowstone National Park (Wyoming). We then applied 3 analogous betweenness centrality metrics to analyze connectivity of wolf habitat throughout the northwestern United States and southwestern Canada to determine where it might be possible to facilitate range expansion and interpopulation dispersal. We developed software to facilitate application of centrality metrics. Shortest-path betweenness centrality identified a minimal network of linkages analogous to those identified by least-cost-path corridor mapping. Current flow and minimum-cost-maximum-flow betweenness centrality identified diffuse networks that included alternative linkages, which will allow greater flexibility in planning. Minimum-cost-maximum-flow betweenness centrality, by integrating both land cost and habitat capacity, allows connectivity to be considered within planning processes that seek to maximize species protection at minimum cost

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

    Gaoyuan Song

    2015-08-01

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

  8. Challenges in administrative data linkage for research

    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.

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

    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...

  10. Probabilistic record linkage.

    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.

  11. Allele-sharing models: LOD scores and accurate linkage tests.

    Kong, A; Cox, N J

    1997-11-01

    Starting with a test statistic for linkage analysis based on allele sharing, we propose an associated one-parameter model. Under general missing-data patterns, this model allows exact calculation of likelihood ratios and LOD scores and has been implemented by a simple modification of existing software. Most important, accurate linkage tests can be performed. Using an example, we show that some previously suggested approaches to handling less than perfectly informative data can be unacceptably conservative. Situations in which this model may not perform well are discussed, and an alternative model that requires additional computations is suggested.

  12. Construction and analysis of a high-density genetic linkage map in cabbage (Brassica oleracea L. var. capitata

    Wang Wanxing

    2012-10-01

    Full Text Available Abstract Background Brassica oleracea encompass a family of vegetables and cabbage that are among the most widely cultivated crops. In 2009, the B. oleracea Genome Sequencing Project was launched using next generation sequencing technology. None of the available maps were detailed enough to anchor the sequence scaffolds for the Genome Sequencing Project. This report describes the development of a large number of SSR and SNP markers from the whole genome shotgun sequence data of B. oleracea, and the construction of a high-density genetic linkage map using a double haploid mapping population. Results The B. oleracea high-density genetic linkage map that was constructed includes 1,227 markers in nine linkage groups spanning a total of 1197.9 cM with an average of 0.98 cM between adjacent loci. There were 602 SSR markers and 625 SNP markers on the map. The chromosome with the highest number of markers (186 was C03, and the chromosome with smallest number of markers (99 was C09. Conclusions This first high-density map allowed the assembled scaffolds to be anchored to pseudochromosomes. The map also provides useful information for positional cloning, molecular breeding, and integration of information of genes and traits in B. oleracea. All the markers on the map will be transferable and could be used for the construction of other genetic maps.

  13. Linkage analysis in nuclear families. 2: Relationship between affected sib-pair tests and lod score analysis.

    Knapp, M; Seuchter, S A; Baur, M P

    1994-01-01

    It is believed that the main advantage of affected sib-pair tests is that their application requires no information about the underlying genetic mechanism of the disease. However, here it is proved that the mean test, which can be considered the most prominent of the affected sib-pair tests, is equivalent to lod score analysis for an assumed recessive mode of inheritance, irrespective of the true mode of the disease. Further relationships of certain sib-pair tests and lod score analysis under specific assumed genetic modes are investigated.

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

    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.

  15. Construction of the model for the Genetic Analysis Workshop 14 simulated data: genotype-phenotype relationships, gene interaction, linkage, association, disequilibrium, and ascertainment effects for a complex phenotype.

    Greenberg, David A; Zhang, Junying; Shmulewitz, Dvora; Strug, Lisa J; Zimmerman, Regina; Singh, Veena; Marathe, Sudhir

    2005-12-30

    The Genetic Analysis Workshop 14 simulated dataset was designed 1) To test the ability to find genes related to a complex disease (such as alcoholism). Such a disease may be given a variety of definitions by different investigators, have associated endophenotypes that are common in the general population, and is likely to be not one disease but a heterogeneous collection of clinically similar, but genetically distinct, entities. 2) To observe the effect on genetic analysis and gene discovery of a complex set of gene x gene interactions. 3) To allow comparison of microsatellite vs. large-scale single-nucleotide polymorphism (SNP) data. 4) To allow testing of association to identify the disease gene and the effect of moderate marker x marker linkage disequilibrium. 5) To observe the effect of different ascertainment/disease definition schemes on the analysis. Data was distributed in two forms. Data distributed to participants contained about 1,000 SNPs and 400 microsatellite markers. Internet-obtainable data consisted of a finer 10,000 SNP map, which also contained data on controls. While disease characteristics and parameters were constant, four "studies" used varying ascertainment schemes based on differing beliefs about disease characteristics. One of the studies contained multiplex two- and three-generation pedigrees with at least four affected members. The simulated disease was a psychiatric condition with many associated behaviors (endophenotypes), almost all of which were genetic in origin. The underlying disease model contained four major genes and two modifier genes. The four major genes interacted with each other to produce three different phenotypes, which were themselves heterogeneous. The population parameters were calibrated so that the major genes could be discovered by linkage analysis in most datasets. The association evidence was more difficult to calibrate but was designed to find statistically significant association in 50% of datasets. We also

  16. A pantograph linkage

    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)

  17. 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

    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.

  18. A study of inter linkage effects on Candu feeder piping

    Li, M.; Aggarwal, M.L.; Meysner, A.

    2005-01-01

    A CANDU (Canadian Deuterium Uranium) reactor core consists of a large number of fuel channels where heat is generated. Two feeder pipes are connected to each fuel channel to transport D 2 O coolant into and out of the reactor core. The feeder piping is designed to the requirements of Class 1 piping of Section III NB of the ASME Boiler and Pressure Vessel and CSA Codes. Feeder piping stress analysis is being performed to demonstrate the code compliance check and the fitness for service of feeders. In the past, stress analyses were conducted for each individual feeder without including interaction effects among connected feeders. Interaction effects occur as a result of linkages that exist between feeders to prevent fretting and impacting damage during normal, abnormal and accident conditions. In this paper, a 'combined' approach is adopted to include all feeders connected by inter linkages into one feeder piping model. MSC/NASTRAN finite element software was used in the stress simulation, which contains up to 127 feeder pipes. The ASME Class 1 piping analysis was conducted to investigate the effects of the linkages between feeders. Both seismic time history and broadened response spectra methods were used in the seismic stress calculation. The results show that the effect of linkages is significant in dynamic stresses for all feeder configurations, as well as in static stresses for certain feeder configurations. The single feeder analysis could either underestimate or overestimate feeder stresses depending on the pipe geometry and bend wall thickness. (authors)

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

    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

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

    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.

  1. Efficient Record Linkage Algorithms Using Complete Linkage Clustering.

    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.

  2. A Unified Discussion on the Concept of Score Functions Used in the Context of Nonparametric Linkage Analysis

    Lars Ängquist

    2008-01-01

    Full Text Available In this article we try to discuss nonparametric linkage (NPL score functions within a broad and quite general framework. The main focus of the paper is the structure, derivation principles and interpretations of the score function entity itself. We define and discuss several families of one-locus score function definitions, i.e. the implicit, explicit and optimal ones. Some generalizations and comments to the two-locus, unconditional and conditional, cases are included as well. Although this article mainly aims at serving as an overview, where the concept of score functions are put into a covering context, we generalize the noncentrality parameter (NCP optimal score functions in Ängquist et al. (2007 to facilitate—through weighting—for incorporation of several plausible distinct genetic models. Since the genetic model itself most oftenly is to some extent unknown this facilitates weaker prior assumptions with respect to plausible true disease models without loosing the property of NCP-optimality. Moreover, we discuss general assumptions and properties of score functions in the above sense. For instance, the concept of identical by descent (IBD sharing structures and score function equivalence are discussed in some detail.

  3. Genome scan for linkage to asthma using a linkage disequilibrium-lod score test.

    Jiang, Y; Slager, S L; Huang, J

    2001-01-01

    We report a genome-wide linkage study of asthma on the German and Collaborative Study on the Genetics of Asthma (CSGA) data. Using a combined linkage and linkage disequilibrium test and the nonparametric linkage score, we identified 13 markers from the German data, 1 marker from the African American (CSGA) data, and 7 markers from the Caucasian (CSGA) data in which the p-values ranged between 0.0001 and 0.0100. From our analysis and taking into account previous published linkage studies of asthma, we suggest that three regions in chromosome 5 (around D5S418, D5S644, and D5S422), one region in chromosome 6 (around three neighboring markers D6S1281, D6S291, and D6S1019), one region in chromosome 11 (around D11S2362), and two regions in chromosome 12 (around D12S351 and D12S324) especially merit further investigation.

  4. Thermally actuated linkage arrangement

    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)

  5. Proteome Analysis of the Plant Pathogenic Fungus Monilinia laxa Showing Host Specificity

    Olja Bregar

    2012-01-01

    Full Text Available Brown rot fungus Monilinia laxa (Aderh. & Ruhl. Honey is an important plant pathogen in stone and pome fruits in Europe. We applied a proteomic approach in a study of M. laxa isolates obtained from apples and apricots in order to show the host specifity of the isolates and to analyse differentially expressed proteins in terms of host specifity, fungal pathogenicity and identification of candidate proteins for diagnostic marker development. Extracted mycelium proteins were separated by 2-D electrophoresis (2-DE and visualized by Coomassie staining in a non-linear pH range of 3–11 and Mr of 14–116 kDa. We set up a 2-DE reference map of M. laxa, resolving up to 800 protein spots, and used it for image analysis. The average technical coefficient of variance (13 % demonstrated a high reproducibility of protein extraction and 2-D polyacrylamide gel electrophoresis (2-DE PAGE, and the average biological coefficient of variance (23 % enabled differential proteomic analysis of the isolates. Multivariate statistical analysis (principal component analysis discriminated isolates from two different hosts, providing new data that support the existence of a M. laxa specialized form f. sp. mali, which infects only apples. A total of 50 differentially expressed proteins were further analyzed by LC-MS/MS, yielding 41 positive identifications. The identified mycelial proteins were functionally classified into 6 groups: amino acid and protein metabolism, energy production, carbohydrate metabolism, stress response, fatty acid metabolism and other proteins. Some proteins expressed only in apple isolates have been described as virulence factors in other fungi. The acetolactate synthase was almost 11-fold more abundant in apple-specific isolates than in apricot isolates and it might be implicated in M. laxa host specificity. Ten proteins identified only in apple isolates are potential candidates for the development of M. laxa host-specific diagnostic markers.

  6. Urine proteome analysis in Dent's disease shows high selective changes potentially involved in chronic renal damage.

    Santucci, Laura; Candiano, Giovanni; Anglani, Franca; Bruschi, Maurizio; Tosetto, Enrica; Cremasco, Daniela; Murer, Luisa; D'Ambrosio, Chiara; Scaloni, Andrea; Petretto, Andrea; Caridi, Gianluca; Rossi, Roberta; Bonanni, Alice; Ghiggeri, Gian Marco

    2016-01-01

    Definition of the urinary protein composition would represent a potential tool for diagnosis in many clinical conditions. The use of new proteomic technologies allows detection of genetic and post-trasductional variants that increase sensitivity of the approach but complicates comparison within a heterogeneous patient population. Overall, this limits research of urinary biomarkers. Studying monogenic diseases are useful models to address this issue since genetic variability is reduced among first- and second-degree relatives of the same family. We applied this concept to Dent's disease, a monogenic condition characterised by low-molecular-weight proteinuria that is inherited following an X-linked trait. Results are presented here on a combined proteomic approach (LC-mass spectrometry, Western blot and zymograms for proteases and inhibitors) to characterise urine proteins in a large family (18 members, 6 hemizygous patients, 6 carrier females, and 6 normals) with Dent's diseases due to the 1070G>T mutation of the CLCN5. Gene ontology analysis on more than 1000 proteins showed that several clusters of proteins characterised urine of affected patients compared to carrier females and normal subjects: proteins involved in extracellular matrix remodelling were the major group. Specific analysis on metalloproteases and their inhibitors underscored unexpected mechanisms potentially involved in renal fibrosis. Studying with new-generation techniques for proteomic analysis of the members of a large family with Dent's disease sharing the same molecular defect allowed highly repetitive results that justify conclusions. Identification in urine of proteins actively involved in interstitial matrix remodelling poses the question of active anti-fibrotic drugs in Dent's patients. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    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.

  8. HIV-1 phylogenetic analysis shows HIV-1 transits through the meninges to brain and peripheral tissues.

    Lamers, Susanna L; Gray, Rebecca R; Salemi, Marco; Huysentruyt, Leanne C; McGrath, Michael S

    2011-01-01

    Brain infection by the human immunodeficiency virus type 1 (HIV-1) has been investigated in many reports with a variety of conclusions concerning the time of entry and degree of viral compartmentalization. To address these diverse findings, we sequenced HIV-1 gp120 clones from a wide range of brain, peripheral and meningeal tissues from five patients who died from several HIV-1 associated disease pathologies. High-resolution phylogenetic analysis confirmed previous studies that showed a significant degree of compartmentalization in brain and peripheral tissue subpopulations. Some intermixing between the HIV-1 subpopulations was evident, especially in patients that died from pathologies other than HIV-associated dementia. Interestingly, the major tissue harboring virus from both the brain and peripheral tissues was the meninges. These results show that (1) HIV-1 is clearly capable of migrating out of the brain, (2) the meninges are the most likely primary transport tissues, and (3) infected brain macrophages comprise an important HIV reservoir during highly active antiretroviral therapy. Copyright © 2010 Elsevier B.V. All rights reserved.

  9. Retrospective Analysis of Patient Presentations at the Sydney (Australia) Royal Easter Show from 2012 to 2014.

    Crabtree, Nathan; Mo, Shirley; Ong, Leon; Jegathees, Thuvarahan; Wei, Daniel; Fahey, David; Liu, Jia Jenny

    2017-04-01

    Introduction Comprehensive studies on the relationship between patient demographics and subsequent treatment and disposition at a single mass-gathering event are lacking. The Sydney Royal Easter Show (SRES; Sydney Olympic Park, New South Wales, Australia) is an annual, 14-day, agricultural mass-gathering event occurring around the Easter weekend, attracting more than 800,000 patrons per year. In this study, patient records from the SRES were analyzed to examine relationships between weather, crowd size, day of week, and demographics on treatment and disposition. This information would help to predict factors affecting patient treatment and disposition to guide ongoing training of first responders and to evaluate the appropriateness of staffing skills mix at future events. Hypothesis Patient demographics, environmental factors, and attendance would influence the nature and severity of presentations at the SRES, which would influence staffing requirements. A retrospective analysis of 4,141 patient record forms was performed for patients who presented to St John Ambulance (Australian Capital Territory, Australia) at the SRES between 2012 and 2014 inclusive. Presentation type was classified using a previously published minimum data set. Data on weather and crowd size were obtained from the Australian Bureau of Meteorology (Melbourne, Victoria, Australia) and the SRES, respectively. Statistical analyses were performed using SPSS v22 (IBM; Armonk, New York USA). Between 2012 to 2014, over 2.5 million people attended the SRES with 4,141 patients treated onsite. As expected, the majority of presentations were injuries (49%) and illnesses (46%). Although patient demographics and presentation types did not change over time, the duration of treatment increased. A higher proportion of patients were discharged to hospital or home compared to the proportion of patients discharged back to the event. Patients from rural/regional locations (accounting for 15% of all patients) were

  10. Clause linkage in Ket

    Nefedov, Andrey

    2015-01-01

    This work provides a typologically oriented description of clause linkage strategies in Ket, a highly endangered language spoken in Central Siberia. It is now the only surviving member of the Yeniseian language family with the last remaining speakers residing in the north of Russia’s Krasnoyarsk

  11. The Identification of Two Head Smut Resistance-Related QTL in Maize by the Joint Approach of Linkage Mapping and Association Analysis.

    Yong-xiang Li

    Full Text Available Head smut, caused by the fungus Sphacelotheca reiliana (Kühn Clint, is a devastating threat to maize production. In this study, QTL mapping of head smut resistance was performed using a recombinant inbred line (RIL population from a cross between a resistant line "QI319" and a susceptible line "Huangzaosi" (HZS with a genetic map constructed from genotyping-by-sequencing (GBS data and composed of 1638 bin markers. Two head smut resistance QTL were identified, located on Chromosome 2 (q2.09HR and Chromosome 5 (q5.03HR, q2.09HR is co-localized with a previously reported QTL for head smut resistance, and the effect of q5.03HR has been validated in backcross populations. It was also observed that pyramiding the resistant alleles of both QTL enhanced the level of resistance to head smut. A genome-wide association study (GWAS using 277 diverse inbred lines was processed to validate the mapped QTL and to identify additional head smut resistance associations. A total of 58 associated SNPs were detected, which were distributed in 31 independent regions. SNPs with significant association to head smut resistance were detected within the q2.09HR and q5.03HR regions, confirming the linkage mapping results. It was also observed that both additive and epistastic effects determine the genetic architecture of head smut resistance in maize. As shown in this study, the combined strategy of linkage mapping and association analysis is a powerful approach in QTL dissection for disease resistance in maize.

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

    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. Dioscorea alata tuber proteome analysis shows over thirty dioscorin isoforms and novel tuber proteins.

    Sharma, Shruti; Gupta, Ravi; Deswal, Renu

    2017-05-01

    In Dioscorea, dioscorin (31 kDa) is the major storage protein constituting 85% of the total tuber proteins. An integrated proteomic and biochemical approach was used to understand the physiological role of dioscorin in the two contrasting growth stages (germinating and mature tuber). HPLC analysis showed 3 fold reduction in mannitol and 12.88 and 1.24 fold increase in sucrose and maltose in the germinating tuber. A 1.8 and 3 fold increase in sucrose phosphate synthase and mannitol dehydrogenase activity respectively was observed in the germinating tuber while a 2 fold higher invertase probably lowers the sucrose accumulation in the mature tuber. SDS-PAGE and 2-D maps of the mature and germinating tubers confirmed depletion (more than 50%) of dioscorin on germination. Dioscorin was purified using ion exchange and gel filtration chromatography with 43.32 fold purification and 38.16 yield. Out of a trail of 35 spots at 31 kDa only 12 spots (identified as dioscorin isoforms) were present in the 2D gel of the purified fraction. To search for other tuber proteins besides dioscorin, the unbound fractions of DEAE column were analysed by 2DGE. DREB 1A, caffeic acid 3-O-methyltransferase and Rab-1 small GTP binding protein were identified perhaps for the first time in the Dioscorea proteome. The interactome analysis revealed these to be involved in oxidative stress, carotenoid synthesis and vesicular transport. This is perhaps the first attempt to identify tuber proteome (although limited) and to understand the physiological significance of these proteins. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. Gut Transcriptome Analysis Shows Different Food Utilization Efficiency by the Grasshopper Oedaleous asiaticus (Orthoptera: Acrididae).

    Huang, Xunbing; McNeill, Mark Richard; Ma, Jingchuan; Qin, Xinghu; Tu, Xiongbing; Cao, Guangchun; Wang, Guangjun; Nong, Xiangqun; Zhang, Zehua

    2017-08-01

    Oedaleus asiaticus B. Bienko is a persistent pest occurring in north Asian grasslands. We found that O. asiaticus feeding on Stipa krylovii Roshev. had higher approximate digestibility (AD), efficiency of conversion of ingested food (ECI), and efficiency of conversion of digested food (ECD), compared with cohorts feeding on Leymus chinensis (Trin.) Tzvel, Artemisia frigida Willd., or Cleistogenes squarrosa (Trin.) Keng. Although this indicated high food utilization efficiency for S. krylovii, the physiological processes and molecular mechanisms underlying these biological observations are not well understood. Transcriptome analysis was used to examine how gene expression levels in O. asiaticus gut are altered by feeding on the four plant species. Nymphs (fifth-instar female) that fed on S. krylovii had the largest variation in gene expression profiles, with a total of 88 genes significantly upregulated compared with those feeding on the other three plants, mainly including nutrition digestive genes of protein, carbohydrate, and lipid digestion. GO and KEGG enrichment also showed that feeding S. krylovii could upregulate the nutrition digestion-related molecular function, biological process, and pathways. These changes in transcripts levels indicate that the physiological processes of activating nutrition digestive enzymes and metabolism pathways can well explain the high food utilization of S. krylovii by O. asiaticus. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Factor analysis shows association between family activity environment and children's health behaviour.

    Hendrie, Gilly A; Coveney, John; Cox, David N

    2011-12-01

    To characterise the family activity environment in a questionnaire format, assess the questionnaire's reliability and describe its predictive ability by examining the relationships between the family activity environment and children's health behaviours - physical activity, screen time and fruit and vegetable intake. This paper describes the creation of a tool, based on previously validated scales, adapted from the food domain. Data are from 106 children and their parents (Adelaide, South Australia). Factor analysis was used to characterise factors within the family activity environment. Pearson-Product Moment correlations between the family environment and child outcomes, controlling for demographic variation, were examined. Three factors described the family activity environment - parental activity involvement, opportunity for role modelling and parental support for physical activity - and explained 37.6% of the variance. Controlling for demographic factors, the scale was significantly correlated with children's health behaviour - physical activity (r=0.27), screen time (r=-0.24) and fruit and vegetable intake (r=0.34). The family activity environment questionnaire shows high internal consistency and moderate predictive ability. This study has built on previous research by taking a more comprehensive approach to measuring the family activity environment. This research suggests the family activity environment should be considered in family-based health promotion interventions. © 2011 The Authors. ANZJPH © 2011 Public Health Association of Australia.

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

    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

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

    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.

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

    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.

  19. Resource linkages and sustainable development

    Anouti, Yahya

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

  20. BIOMETRICAL ANALYSIS OF ARABIAN FOALS AND THEIR LATER SUCCESSES IN SHOWS AND ON RACE TRACK

    M. PIESZKA

    2007-10-01

    Full Text Available Arabian horses are one of the most important products of Polish horse breeding.Many of them are International and World champions in shows; others are very wellknown as courageous race horses. To obtain such champions it is necessary to takeunder consideration many factors affecting the final results. The objective of thisstudy was to evaluate the effect of biometrical measurements of the foals at birthaccording to their future successes in shows and on racetrack. The study was carriedout on 143 horses winning in shows and in races. Body weight, height at withers,girth and canon circumferences taken at birth of these horses were analysed.Additionally coat colour was studied. All studied animals were divided into threegroups according to each measurement and the differences between such groupswere evaluated according points obtained for particular place at shows and place inraces. It was stated that horses heavier at birth and with higher girth circumferencegot more successes both at shows and on racetrack. Horses with higher height atwithers at birth were more successful in shows while animals with higher canoncircumference won oftener at race track. It was observed that the most courageousrace horses were bay while most champions were grey.

  1. Economic impact and market analysis of a special event: The Great New England Air Show

    Rodney B. Warnick; David C. Bojanic; Atul Sheel; Apurv Mather; Deepak Ninan

    2010-01-01

    We conducted a post-event evaluation for the Great New England Air Show to assess its general economic impact and to refine economic estimates where possible. In addition to the standard economic impact variables, we examined travel distance, purchase decision involvement, event satisfaction, and frequency of attendance. Graphic mapping of event visitors' home ZIP...

  2. Radiographic analysis of odontogenic cysts showing displacement of the mandibular canal

    Cho, Bong Hae

    2003-01-01

    To assess the radiographic findings of odontogenic cysts showing displacement of the mandibular canal using computed tomographic (CT) and panoramic images. CT and panoramic images of 63 odontogenic cysts (27 dentigerous, 16 odontogenic keratocysts, and 20 radicular cysts) were analyzed to evaluate the following parameters: the dimension and shape of the cysts, and the effect of the cysts on the mandibular canal and cortical plates. Of the 63 cysts examined in the study, 35 (55.6%) showed inferior displacement of the mandibular canal and 46 (73.0%) showed perforation of the canal. There were statistically significant differenced between CT and panoramic images in depicting displacement and perforation of the mandibular canal. Cortical expansion was seen in 46 cases (73.0%) and cortical perforation in 23 cases (36.5%). The radicular cysts showed cortical expansion and perforation less frequently than the other cyst groups. Large cysts of mandible should be evaluated by multiplanar CT images in order to detect the mandibular canal and cortical bone involvement.

  3. Bayesian estimates of linkage disequilibrium

    Abad-Grau María M

    2007-06-01

    Full Text Available Abstract Background The maximum likelihood estimator of D' – a standard measure of linkage disequilibrium – is biased toward disequilibrium, and the bias is particularly evident in small samples and rare haplotypes. Results This paper proposes a Bayesian estimation of D' to address this problem. The reduction of the bias is achieved by using a prior distribution on the pair-wise associations between single nucleotide polymorphisms (SNPs that increases the likelihood of equilibrium with increasing physical distances between pairs of SNPs. We show how to compute the Bayesian estimate using a stochastic estimation based on MCMC methods, and also propose a numerical approximation to the Bayesian estimates that can be used to estimate patterns of LD in large datasets of SNPs. Conclusion Our Bayesian estimator of D' corrects the bias toward disequilibrium that affects the maximum likelihood estimator. A consequence of this feature is a more objective view about the extent of linkage disequilibrium in the human genome, and a more realistic number of tagging SNPs to fully exploit the power of genome wide association studies.

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

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

    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

  6. Social network analysis shows direct evidence for social transmission of tool use in wild chimpanzees.

    Catherine Hobaiter

    2014-09-01

    Full Text Available Social network analysis methods have made it possible to test whether novel behaviors in animals spread through individual or social learning. To date, however, social network analysis of wild populations has been limited to static models that cannot precisely reflect the dynamics of learning, for instance, the impact of multiple observations across time. Here, we present a novel dynamic version of network analysis that is capable of capturing temporal aspects of acquisition--that is, how successive observations by an individual influence its acquisition of the novel behavior. We apply this model to studying the spread of two novel tool-use variants, "moss-sponging" and "leaf-sponge re-use," in the Sonso chimpanzee community of Budongo Forest, Uganda. Chimpanzees are widely considered the most "cultural" of all animal species, with 39 behaviors suspected as socially acquired, most of them in the domain of tool-use. The cultural hypothesis is supported by experimental data from captive chimpanzees and a range of observational data. However, for wild groups, there is still no direct experimental evidence for social learning, nor has there been any direct observation of social diffusion of behavioral innovations. Here, we tested both a static and a dynamic network model and found strong evidence that diffusion patterns of moss-sponging, but not leaf-sponge re-use, were significantly better explained by social than individual learning. The most conservative estimate of social transmission accounted for 85% of observed events, with an estimated 15-fold increase in learning rate for each time a novice observed an informed individual moss-sponging. We conclude that group-specific behavioral variants in wild chimpanzees can be socially learned, adding to the evidence that this prerequisite for culture originated in a common ancestor of great apes and humans, long before the advent of modern humans.

  7. Social network analysis shows direct evidence for social transmission of tool use in wild chimpanzees.

    Hobaiter, Catherine; Poisot, Timothée; Zuberbühler, Klaus; Hoppitt, William; Gruber, Thibaud

    2014-09-01

    Social network analysis methods have made it possible to test whether novel behaviors in animals spread through individual or social learning. To date, however, social network analysis of wild populations has been limited to static models that cannot precisely reflect the dynamics of learning, for instance, the impact of multiple observations across time. Here, we present a novel dynamic version of network analysis that is capable of capturing temporal aspects of acquisition--that is, how successive observations by an individual influence its acquisition of the novel behavior. We apply this model to studying the spread of two novel tool-use variants, "moss-sponging" and "leaf-sponge re-use," in the Sonso chimpanzee community of Budongo Forest, Uganda. Chimpanzees are widely considered the most "cultural" of all animal species, with 39 behaviors suspected as socially acquired, most of them in the domain of tool-use. The cultural hypothesis is supported by experimental data from captive chimpanzees and a range of observational data. However, for wild groups, there is still no direct experimental evidence for social learning, nor has there been any direct observation of social diffusion of behavioral innovations. Here, we tested both a static and a dynamic network model and found strong evidence that diffusion patterns of moss-sponging, but not leaf-sponge re-use, were significantly better explained by social than individual learning. The most conservative estimate of social transmission accounted for 85% of observed events, with an estimated 15-fold increase in learning rate for each time a novice observed an informed individual moss-sponging. We conclude that group-specific behavioral variants in wild chimpanzees can be socially learned, adding to the evidence that this prerequisite for culture originated in a common ancestor of great apes and humans, long before the advent of modern humans.

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

    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

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

    2013-01-01

    autosomes, especially between autosomes 2 and 5, suggesting that signaling transduction cascades controlled by GPCRs, protein kinase/phosphates and proteases may be involved in the regulation of resistance P450 gene regulation. Conclusion Taken together, our findings suggested that not only is insecticide......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...

  10. Can Automated Facial Expression Analysis Show Differences Between Autism and Typical Functioning?

    Borsos, Zsófia; Gyori, Miklos

    2017-01-01

    Exploratory analyses of emotional expressions using a commercially available facial expression recognition software are reported, from the context of a serious game for screening purposes. Our results are based on a comparative analysis of two matched groups of kindergarten-age children (high-functioning children with autism spectrum condition: n=13; typically developing children: n=13). Results indicate that this technology has the potential to identify autism-specific emotion expression features, and may play a role in affective diagnostic and assistive technologies.

  11. A micro-epidemiological analysis of febrile malaria in Coastal Kenya showing hotspots within hotspots.

    Bejon, Philip; Williams, Thomas N; Nyundo, Christopher; Hay, Simon I; Benz, David; Gething, Peter W; Otiende, Mark; Peshu, Judy; Bashraheil, Mahfudh; Greenhouse, Bryan; Bousema, Teun; Bauni, Evasius; Marsh, Kevin; Smith, David L; Borrmann, Steffen

    2014-04-24

    Malaria transmission is spatially heterogeneous. This reduces the efficacy of control strategies, but focusing control strategies on clusters or 'hotspots' of transmission may be highly effective. Among 1500 homesteads in coastal Kenya we calculated (a) the fraction of febrile children with positive malaria smears per homestead, and (b) the mean age of children with malaria per homestead. These two measures were inversely correlated, indicating that children in homesteads at higher transmission acquire immunity more rapidly. This inverse correlation increased gradually with increasing spatial scale of analysis, and hotspots of febrile malaria were identified at every scale. We found hotspots within hotspots, down to the level of an individual homestead. Febrile malaria hotspots were temporally unstable, but 4 km radius hotspots could be targeted for 1 month following 1 month periods of surveillance.DOI: http://dx.doi.org/10.7554/eLife.02130.001. Copyright © 2014, Bejon et al.

  12. Analysis of allergen immunotherapy studies shows increased clinical efficacy in highly symptomatic patients

    Howarth, P; Malling, Hans-Jørgen; Molimard, M

    2011-01-01

    them. Thus, clinical studies of AIT can neither establish baseline symptom levels nor limit the enrolment of patients to those with the most severe symptoms. Allergen immunotherapy treatment effects are therefore diluted by patients with low symptoms for a particular pollen season. The objective...... tertiles). The difference observed in the average score in each tertile in active vs placebo-treated patients was assessed. This allowed an estimation of the efficacy that could be achieved in patients from sites where symptoms were high during the pollen season. Results:  An increased treatment effect...... of this analysis was to assess the effect possible to achieve with AIT in the groups of patients presenting the most severe allergic symptoms. Methods:  Study centres were grouped into tertiles categorized according to symptom severity scores observed in the placebo patients in each centre (low, middle and high...

  13. Meta-analysis of grain yield QTL identified during agricultural drought in grasses showed consensus.

    Swamy, B P Mallikarjuna; Vikram, Prashant; Dixit, Shalabh; Ahmed, H U; Kumar, Arvind

    2011-06-16

    In the last few years, efforts have been made to identify large effect QTL for grain yield under drought in rice. However, identification of most precise and consistent QTL across the environments and genetics backgrounds is essential for their successful use in Marker-assisted Selection. In this study, an attempt was made to locate consistent QTL regions associated with yield increase under drought by applying a genome-wide QTL meta-analysis approach. The integration of 15 maps resulted in a consensus map with 531 markers and a total map length of 1821 cM. Fifty-three yield QTL reported in 15 studies were projected on a consensus map and meta-analysis was performed. Fourteen meta-QTL were obtained on seven chromosomes. MQTL1.2, MQTL1.3, MQTL1.4, and MQTL12.1 were around 700 kb and corresponded to a reasonably small genetic distance of 1.8 to 5 cM and they are suitable for use in marker-assisted selection (MAS). The meta-QTL for grain yield under drought coincided with at least one of the meta-QTL identified for root and leaf morphology traits under drought in earlier reports. Validation of major-effect QTL on a panel of random drought-tolerant lines revealed the presence of at least one major QTL in each line. DTY12.1 was present in 85% of the lines, followed by DTY4.1 in 79% and DTY1.1 in 64% of the lines. Comparative genomics of meta-QTL with other cereals revealed that the homologous regions of MQTL1.4 and MQTL3.2 had QTL for grain yield under drought in maize, wheat, and barley respectively. The genes in the meta-QTL regions were analyzed by a comparative genomics approach and candidate genes were deduced for grain yield under drought. Three groups of genes such as stress-inducible genes, growth and development-related genes, and sugar transport-related genes were found in clusters in most of the meta-QTL. Meta-QTL with small genetic and physical intervals could be useful in Marker-assisted selection individually and in combinations. Validation and comparative

  14. The effects of dutasteride and finasteride on BPH-related hospitalization, surgery and prostate cancer diagnosis: a record-linkage analysis.

    Cindolo, Luca; Fanizza, Caterina; Romero, Marilena; Pirozzi, Luisella; Autorino, Riccardo; Berardinelli, Francesco; Schips, Luigi

    2013-06-01

    To investigate differences in the risk of benign prostatic hyperplasia (BPH)-related hospitalization, for surgical and non-surgical reasons, and of new prostate cancer (PCa) diagnosis between patients using finasteride or dutasteride. A retrospective cohort study was conducted using data from record linkage of administrative databases (pharmaceutical prescription data, hospital discharge records, Italian population registry). Men aged ≥ 40 years old who had received a prescription for at least 10 packs/year between January 1, 2004 and December 31, 2004 were included and followed for 5 years. The association of the outcomes was assessed using a multiple Cox proportional hazard model. Propensity score-matched analysis and a 5-1, greedy 1:1 matching algorithm were performed. 8,132 patients were identified. Overall incidence rates of BPH hospitalization and BPH-related surgery were 21.05 (95 % CI 19.52-22.71) and 20.97 (95 % CI 19.45-22.61) per 1,000 person-years, respectively. In the dutasteride group compared with finasteride group, the incidence rate of both events was statistically significant lower: 16.07 versus 21.76 for BPH hospitalization and 15.91 versus 21.69 for BPH-related surgery. The incidence rate of new PCa was also lower for the dutasteride group [8.34 (95 % CI 5.96-11.68) vs. 10.25 (95 % CI 9.15-11.49)]. Dutasteride was associated with a reduction in BPH-related hospitalizations (HR 0.75, 95 % CI 0.58-0.98 and 0.58-0.98 for surgical and non-surgical reasons). The matched analysis confirmed the risk reduction with dutasteride for BPH-related surgery. These findings suggest that the clinical effects of dutasteride and finasteride might be different. Patients treated with dutasteride seem to be less likely to experience BPH-related hospitalization. Comparative studies are needed to confirm these results.

  15. Significant linkage to airway responsiveness on chromosome 12q24 in families of children with asthma in Costa Rica.

    Celedón, Juan C; Soto-Quiros, Manuel E; Avila, Lydiana; Lake, Stephen L; Liang, Catherine; Fournier, Eduardo; Spesny, Mitzi; Hersh, Craig P; Sylvia, Jody S; Hudson, Thomas J; Verner, Andrei; Klanderman, Barbara J; Freimer, Nelson B; Silverman, Edwin K; Weiss, Scott T

    2007-01-01

    Although asthma is a major public health problem in certain Hispanic subgroups in the United States and Latin America, only one genome scan for asthma has included Hispanic individuals. Because of small sample size, that study had limited statistical power to detect linkage to asthma and its intermediate phenotypes in Hispanic participants. To identify genomic regions that contain susceptibility genes for asthma and airway responsiveness in an isolated Hispanic population living in the Central Valley of Costa Rica, we conducted a genome-wide linkage analysis of asthma (n = 638) and airway responsiveness (n = 488) in members of eight large pedigrees of Costa Rican children with asthma. Nonparametric multipoint linkage analysis of asthma was conducted by the NPL-PAIR allele-sharing statistic, and variance component models were used for the multipoint linkage analysis of airway responsiveness as a quantitative phenotype. All linkage analyses were repeated after exclusion of the phenotypic data of former and current smokers. Chromosome 12q showed some evidence of linkage to asthma, particularly in nonsmokers (P asthma (airway responsiveness) in Costa Ricans.

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

    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.

  17. Meta-analysis of field experiments shows no change in racial discrimination in hiring over time.

    Quillian, Lincoln; Pager, Devah; Hexel, Ole; Midtbøen, Arnfinn H

    2017-10-10

    This study investigates change over time in the level of hiring discrimination in US labor markets. We perform a meta-analysis of every available field experiment of hiring discrimination against African Americans or Latinos ( n = 28). Together, these studies represent 55,842 applications submitted for 26,326 positions. We focus on trends since 1989 ( n = 24 studies), when field experiments became more common and improved methodologically. Since 1989, whites receive on average 36% more callbacks than African Americans, and 24% more callbacks than Latinos. We observe no change in the level of hiring discrimination against African Americans over the past 25 years, although we find modest evidence of a decline in discrimination against Latinos. Accounting for applicant education, applicant gender, study method, occupational groups, and local labor market conditions does little to alter this result. Contrary to claims of declining discrimination in American society, our estimates suggest that levels of discrimination remain largely unchanged, at least at the point of hire.

  18. Global Trend Analysis of Multi-decade Soil Temperature Records Show Soils Resistant to Warming

    Frey, S. D.; Jennings, K.

    2017-12-01

    Soil temperature is an important determinant of many subterranean ecological processes including plant growth, nutrient cycling, and carbon sequestration. Soils are expected to warm in response to increasing global surface temperatures; however, despite the importance of soil temperature to ecosystem processes, less attention has been given to examining changes in soil temperature over time. We collected long-term (> 20 years) soil temperature records from approximately 50 sites globally, many with multiple depths (5 - 100 cm), and examined temperature trends over the last few decades. For each site and depth we calculated annual summer means and conducted non-parametric Mann Kendall trend and Sen slope analysis to assess changes in summer soil temperature over the length of each time series. The mean summer soil temperature trend across all sites and depths was not significantly different than zero (mean = 0.004 °C year-1 ± 0.033 SD), suggesting that soils have not warmed over the observation period. Of the subset of sites that exhibit significant increases in temperature over time, site location, depth of measurement, time series length, and neither start nor end date seem to be related to trend strength. These results provide evidence that the thermal regime of soils may have a stronger buffering capacity than expected, having important implications for the global carbon cycle and feedbacks to climate change.

  19. Identifying and Mapping Linkages between Actors in the Climate ...

    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 ...

  20. Design of special planar linkages

    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

  1. Analysis of nonlocal phonon thermal conductivity simulations showing the ballistic to diffusive crossover

    Allen, Philip B.

    2018-04-01

    Simulations [e.g., X. W. Zhou et al., Phys. Rev. B 79, 115201 (2009), 10.1103/PhysRevB.79.115201] show nonlocal effects of the ballistic/diffusive crossover. The local temperature has nonlinear spatial variation not contained in the local Fourier law j ⃗(r ⃗) =-κ ∇ ⃗T (r ⃗) . The heat current j ⃗(r ⃗) depends not just on the local temperature gradient ∇ ⃗T (r ⃗) but also on temperatures at points r⃗' within phonon mean free paths, which can be micrometers long. This paper uses the Peierls-Boltzmann transport theory in nonlocal form to analyze the spatial variation Δ T (r ⃗) . The relaxation-time approximation (RTA) is used because the full solution is very challenging. Improved methods of extrapolation to obtain the bulk thermal conductivity κ are proposed. Callaway invented an approximate method of correcting RTA for the q ⃗ (phonon wave vector or crystal momentum) conservation of N (Normal as opposed to Umklapp) anharmonic collisions. This method is generalized to the nonlocal case where κ (k ⃗) depends on the wave vector of the current j ⃗(k ⃗) and temperature gradient i k ⃗Δ T (k ⃗) .

  2. Metachronous metastasis- and survival-analysis show prognostic importance of lymphadenectomy for colon carcinomas

    Laubert Tilman

    2012-03-01

    Full Text Available Abstract Background Lymphadenectomy is performed to assess patient prognosis and to prevent metastasizing. Recently, it was questioned whether lymph node metastases were capable of metastasizing and therefore, if lymphadenectomy was still adequate. We evaluated whether the nodal status impacts on the occurrence of distant metastases by analyzing a highly selected cohort of colon cancer patients. Methods 1,395 patients underwent surgery exclusively for colon cancer at the University of Lübeck between 01/1993 and 12/2008. The following exclusion criteria were applied: synchronous metastasis, R1-resection, prior/synchronous second carcinoma, age Results Five-year survival rates for TM + and TM- were 21% and 73%, respectively (p Conclusions Besides a higher T-category, a positive N-stage independently implies a higher probability to develop distant metastases and correlates with poor survival. Our data thus show a prognostic relevance of lymphadenectomy which should therefore be retained until conclusive studies suggest the unimportance of lmyphadenectomy.

  3. Arctic-midlatitude weather linkages in North America

    Overland, James E.; Wang, Muyin

    2018-06-01

    There is intense public interest in whether major Arctic changes can and will impact midlatitude weather such as cold air outbreaks on the central and east side of continents. Although there is progress in linkage research for eastern Asia, a clear gap is conformation for North America. We show two stationary temperature/geopotential height patterns where warmer Arctic temperatures have reinforced existing tropospheric jet stream wave amplitudes over North America: a Greenland/Baffin Block pattern during December 2010 and an Alaska Ridge pattern during December 2017. Even with continuing Arctic warming over the past decade, other recent eastern US winter months were less susceptible for an Arctic linkage: the jet stream was represented by either zonal flow, progressive weather systems, or unfavorable phasing of the long wave pattern. The present analysis lays the scientific controversy over the validity of linkages to the inherent intermittency of jet stream dynamics, which provides only an occasional bridge between Arctic thermodynamic forcing and extended midlatitude weather events.

  4. Linear models for joint association and linkage QTL mapping

    Fernando Rohan L

    2009-09-01

    Full Text Available Abstract Background Populational linkage disequilibrium and within-family linkage are commonly used for QTL mapping and marker assisted selection. The combination of both results in more robust and accurate locations of the QTL, but models proposed so far have been either single marker, complex in practice or well fit to a particular family structure. Results We herein present linear model theory to come up with additive effects of the QTL alleles in any member of a general pedigree, conditional to observed markers and pedigree, accounting for possible linkage disequilibrium among QTLs and markers. The model is based on association analysis in the founders; further, the additive effect of the QTLs transmitted to the descendants is a weighted (by the probabilities of transmission average of the substitution effects of founders' haplotypes. The model allows for non-complete linkage disequilibrium QTL-markers in the founders. Two submodels are presented: a simple and easy to implement Haley-Knott type regression for half-sib families, and a general mixed (variance component model for general pedigrees. The model can use information from all markers. The performance of the regression method is compared by simulation with a more complex IBD method by Meuwissen and Goddard. Numerical examples are provided. Conclusion The linear model theory provides a useful framework for QTL mapping with dense marker maps. Results show similar accuracies but a bias of the IBD method towards the center of the region. Computations for the linear regression model are extremely simple, in contrast with IBD methods. Extensions of the model to genomic selection and multi-QTL mapping are straightforward.

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

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

    2007-01-01

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

  6. Linkage studies on Gilles de la Tourette syndrome: What is the strategy of choice?

    Heutink, P.; Wetering, J.M. van de; Oostra, B.A. [Erasmus Univ. Rotterdam (Netherlands)] [and others

    1995-08-01

    For a linkage study it is important to ascertain family material that is sufficiently informative. The statistical power of linkage sample can be determined via computer simulation. For complex traits uncertain parameters such as incomplete penetrance, frequency of phenocopies, gene frequency and variable expression have to be taken into account. One can either include only the most severe phenotype in the analysis or apply multiple linkage tests for a gradually broadened disease phenotype. Gilles de la Tourette syndrome (GTS) is a chronic neurological disorder characterized by multiple, intermittent motor and vocal tics. Segregation analyses suggests that GTS and milder phenotypes are caused by a single dominant gene. We report here the results of an extensive simulation study on a large set of families. We compared the effectiveness of linkage tests with only the GTS phenotype versus multiple tests that included various milder phenotypes and different gene frequencies. The scenario of multiple tests yielded superior power. Our results show that computer simulation can indicate the strategy of choice in linkage studies of multiple, complex phenotypes. 33 refs., 2 figs., 3 tabs.

  7. Regional assignment of seven loci to 12p 13. 2-pter by PCR analysis of somatic cell hybrids containing the der(12) or the der(X) chromosome from a mesothelioma showing t(X; 12)(q22; p13)

    Aerssens, J.; Chaffanet, M.; Baens, M.; Matthijs, G.; Van Den Berche, H.; Cassiman, J.J.; Marynen, P. (Arthritis and Metabolic Bone Disease Research Unit, Leuven (Belgium))

    1994-03-01

    Two somatic cell hybrids containing the der(12) or the der(X) from a mesothelioma with a translocation t(X;12) (q22;p13) as the only chromosomal change were generated to characterize the region of 12p12 containing the translocation breakpoint. Fluorescence in situ hybridization analysis showed the breakpoint on chromosome 12 to occur between VWF and D12S158. On the linkage map developed by J. Weissenbach et al., the breakpoints were located between DXS1106 and DCS1001 on chromosome X. PCR analysis based on genomic sequences, with DNA from both somatic cell hybrids, enabled mapping of CACNL1A1, FGF6, D12S370, D12S38OE, D12S381E, and D12S382E distally to the 12p13 breakpoint and to VWF. 11 refs., 2 figs., 1 tab.

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

    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

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

    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

  10. North-South Business Linkages

    Sørensen, Olav Jull; Kuada, John

    2006-01-01

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

  11. Fine mapping quantitative trait loci under selective phenotyping strategies based on linkage and linkage disequilibrium criteria

    Ansari-Mahyari, S; Berg, P; Lund, M S

    2009-01-01

    disequilibrium-based sampling criteria (LDC) for selecting individuals to phenotype are compared to random phenotyping in a quantitative trait loci (QTL) verification experiment using stochastic simulation. Several strategies based on LAC and LDC for selecting the most informative 30%, 40% or 50% of individuals...... for phenotyping to extract maximum power and precision in a QTL fine mapping experiment were developed and assessed. Linkage analyses for the mapping was performed for individuals sampled on LAC within families and combined linkage disequilibrium and linkage analyses was performed for individuals sampled across...... 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...

  12. From Enclave to Linkage Economies?

    Hansen, Michael W.

    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...... as well as foreign multinational corporations (MNCs). MNCs in extractives are increasingly seeking local linkages as part of their efficiency, risk, and asset-seeking strategies, and linkage programmes are becoming integral elements in many MNCs’ corporate social responsibility (CSR) activities....... 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...

  13. Linkage and related analyses of Barrett's esophagus and its associated adenocarcinomas.

    Sun, Xiangqing; Elston, Robert; Falk, Gary W; Grady, William M; Faulx, Ashley; Mittal, Sumeet K; Canto, Marcia I; Shaheen, Nicholas J; Wang, Jean S; Iyer, Prasad G; Abrams, Julian A; Willis, Joseph E; Guda, Kishore; Markowitz, Sanford; Barnholtz-Sloan, Jill S; Chandar, Apoorva; Brock, Wendy; Chak, Amitabh

    2016-07-01

    Familial aggregation and segregation analysis studies have provided evidence of a genetic basis for esophageal adenocarcinoma (EAC) and its premalignant precursor, Barrett's esophagus (BE). We aim to demonstrate the utility of linkage analysis to identify the genomic regions that might contain the genetic variants that predispose individuals to this complex trait (BE and EAC). We genotyped 144 individuals in 42 multiplex pedigrees chosen from 1000 singly ascertained BE/EAC pedigrees, and performed both model-based and model-free linkage analyses, using S.A.G.E. and other software. Segregation models were fitted, from the data on both the 42 pedigrees and the 1000 pedigrees, to determine parameters for performing model-based linkage analysis. Model-based and model-free linkage analyses were conducted in two sets of pedigrees: the 42 pedigrees and a subset of 18 pedigrees with female affected members that are expected to be more genetically homogeneous. Genome-wide associations were also tested in these families. Linkage analyses on the 42 pedigrees identified several regions consistently suggestive of linkage by different linkage analysis methods on chromosomes 2q31, 12q23, and 4p14. A linkage on 15q26 is the only consistent linkage region identified in the 18 female-affected pedigrees, in which the linkage signal is higher than in the 42 pedigrees. Other tentative linkage signals are also reported. Our linkage study of BE/EAC pedigrees identified linkage regions on chromosomes 2, 4, 12, and 15, with some reported associations located within our linkage peaks. Our linkage results can help prioritize association tests to delineate the genetic determinants underlying susceptibility to BE and EAC.

  14. Linkage analysis of candidate genes in autoimmune thyroid disease. II. Selected gender-related genes and the X-chromosome. International Consortium for the Genetics of Autoimmune Thyroid Disease.

    Barbesino, G; Tomer, Y; Concepcion, E S; Davies, T F; Greenberg, D A

    1998-09-01

    Hashimoto's thyroiditis (HT) and Graves' disease (GD) are autoimmune thyroid diseases (AITD) in which multiple genetic factors are suspected to play an important role. Until now, only a few minor risk factors for these diseases have been identified. Susceptibility seems to be stronger in women, pointing toward a possible role for genes related to sex steroid action or mechanisms related to genes on the X-chromosome. We have studied a total of 45 multiplex families, each containing at least 2 members affected with either GD (55 patients) or HT (72 patients), and used linkage analysis to target as candidate susceptibility loci genes involved in estrogen activity, such as the estrogen receptor alpha and beta and the aromatase genes. We then screened the entire X-chromosome using a set of polymorphic microsatellite markers spanning the whole chromosome. We found a region of the X-chromosome (Xq21.33-22) giving positive logarithm of odds (LOD) scores and then reanalyzed this area with dense markers in a multipoint analysis. Our results excluded linkage to the estrogen receptor alpha and aromatase genes when either the patients with GD only, those with HT only, or those with any AITD were considered as affected. Linkage to the estrogen receptor beta could not be totally ruled out, partly due to incomplete mapping information for the gene itself at this time. The X-chromosome data revealed consistently positive LOD scores (maximum of 1.88 for marker DXS8020 and GD patients) when either definition of affectedness was considered. Analysis of the family data using a multipoint analysis with eight closely linked markers generated LOD scores suggestive of linkage to GD in a chromosomal area (Xq21.33-22) extending for about 6 cM and encompassing four markers. The maximum LOD score (2.5) occurred at DXS8020. In conclusion, we ruled out a major role for estrogen receptor alpha and the aromatase genes in the genetic predisposition to AITD. Estrogen receptor beta remains a

  15. Genomic Characterization of DArT Markers Based on High-Density Linkage Analysis and Physical Mapping to the Eucalyptus Genome

    Petroli, César D.; Sansaloni, Carolina P.; Carling, Jason; Steane, Dorothy A.; Vaillancourt, René E.; Myburg, Alexander A.; da Silva, Orzenil Bonfim; Pappas, Georgios Joannis; Kilian, Andrzej; Grattapaglia, Dario

    2012-01-01

    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 which no reference

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

    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

  17. Posterior probability of linkage and maximal lod score.

    Génin, E; Martinez, M; Clerget-Darpoux, F

    1995-01-01

    To detect linkage between a trait and a marker, Morton (1955) proposed to calculate the lod score z(theta 1) at a given value theta 1 of the recombination fraction. If z(theta 1) reaches +3 then linkage is concluded. However, in practice, lod scores are calculated for different values of the recombination fraction between 0 and 0.5 and the test is based on the maximum value of the lod score Zmax. The impact of this deviation of the test on the probability that in fact linkage does not exist, when linkage was concluded, is documented here. This posterior probability of no linkage can be derived by using Bayes' theorem. It is less than 5% when the lod score at a predetermined theta 1 is used for the test. But, for a Zmax of +3, we showed that it can reach 16.4%. Thus, considering a composite alternative hypothesis instead of a single one decreases the reliability of the test. The reliability decreases rapidly when Zmax is less than +3. Given a Zmax of +2.5, there is a 33% chance that linkage does not exist. Moreover, the posterior probability depends not only on the value of Zmax but also jointly on the family structures and on the genetic model. For a given Zmax, the chance that linkage exists may then vary.

  18. Proteomic Analysis Shows Constitutive Secretion of MIF and p53-associated Activity of COX-2−/− Lung Fibroblasts

    Mandar Dave

    2017-12-01

    Full Text Available The differential expression of two closelyassociated cyclooxygenase isozymes, COX-1 and COX-2, exhibited functions beyond eicosanoid metabolism. We hypothesized that COX-1 or COX-2 knockout lung fibroblasts may display altered protein profiles which may allow us to further differentiate the functional roles of these isozymes at the molecular level. Proteomic analysis shows constitutive production of macrophage migration inhibitory factor (MIF in lung fibroblasts derived from COX-2−/− but not wild-type (WT or COX-1−/− mice. MIF was spontaneously released in high levels into the extracellular milieu of COX2−/− fibroblasts seemingly from the preformed intracellular stores, with no change in the basal gene expression of MIF. The secretion and regulation of MIF in COX-2−/− was “prostaglandin-independent.” GO analysis showed that concurrent with upregulation of MIF, there is a significant surge in expression of genes related to fibroblast growth, FK506 binding proteins, and isomerase activity in COX-2−/− cells. Furthermore, COX-2−/− fibroblasts also exhibit a significant increase in transcriptional activity of various regulators, antagonists, and co-modulators of p53, as well as in the expression of oncogenes and related transcripts. Integrative Oncogenomics Cancer Browser (IntroGen analysis shows downregulation of COX-2 and amplification of MIF and/or p53 activity during development of glioblastomas, ependymoma, and colon adenomas. These data indicate the functional role of the MIF-COX-p53 axis in inflammation and cancer at the genomic and proteomic levels in COX-2-ablated cells. This systematic analysis not only shows the proinflammatory state but also unveils a molecular signature of a pro-oncogenic state of COX-1 in COX-2 ablated cells.

  19. Genomic analysis of codon usage shows influence of mutation pressure, natural selection, and host features on Marburg virus evolution.

    Nasrullah, Izza; Butt, Azeem M; Tahir, Shifa; Idrees, Muhammad; Tong, Yigang

    2015-08-26

    The Marburg virus (MARV) has a negative-sense single-stranded RNA genome, belongs to the family Filoviridae, and is responsible for several outbreaks of highly fatal hemorrhagic fever. Codon usage patterns of viruses reflect a series of evolutionary changes that enable viruses to shape their survival rates and fitness toward the external environment and, most importantly, their hosts. To understand the evolution of MARV at the codon level, we report a comprehensive analysis of synonymous codon usage patterns in MARV genomes. Multiple codon analysis approaches and statistical methods were performed to determine overall codon usage patterns, biases in codon usage, and influence of various factors, including mutation pressure, natural selection, and its two hosts, Homo sapiens and Rousettus aegyptiacus. Nucleotide composition and relative synonymous codon usage (RSCU) analysis revealed that MARV shows mutation bias and prefers U- and A-ended codons to code amino acids. Effective number of codons analysis indicated that overall codon usage among MARV genomes is slightly biased. The Parity Rule 2 plot analysis showed that GC and AU nucleotides were not used proportionally which accounts for the presence of natural selection. Codon usage patterns of MARV were also found to be influenced by its hosts. This indicates that MARV have evolved codon usage patterns that are specific to both of its hosts. Moreover, selection pressure from R. aegyptiacus on the MARV RSCU patterns was found to be dominant compared with that from H. sapiens. Overall, mutation pressure was found to be the most important and dominant force that shapes codon usage patterns in MARV. To our knowledge, this is the first detailed codon usage analysis of MARV and extends our understanding of the mechanisms that contribute to codon usage and evolution of MARV.

  20. Recruitment Methods and Show Rates to a Prostate Cancer Early Detection Program for High-Risk Men: A Comprehensive Analysis

    Giri, Veda N.; Coups, Elliot J.; Ruth, Karen; Goplerud, Julia; Raysor, Susan; Kim, Taylor Y.; Bagden, Loretta; Mastalski, Kathleen; Zakrzewski, Debra; Leimkuhler, Suzanne; Watkins-Bruner, Deborah

    2009-01-01

    Purpose Men with a family history (FH) of prostate cancer (PCA) and African American (AA) men are at higher risk for PCA. Recruitment and retention of these high-risk men into early detection programs has been challenging. We report a comprehensive analysis on recruitment methods, show rates, and participant factors from the Prostate Cancer Risk Assessment Program (PRAP), which is a prospective, longitudinal PCA screening study. Materials and Methods Men 35–69 years are eligible if they have a FH of PCA, are AA, or have a BRCA1/2 mutation. Recruitment methods were analyzed with respect to participant demographics and show to the first PRAP appointment using standard statistical methods Results Out of 707 men recruited, 64.9% showed to the initial PRAP appointment. More individuals were recruited via radio than from referral or other methods (χ2 = 298.13, p < .0001). Men recruited via radio were more likely to be AA (p<0.001), less educated (p=0.003), not married or partnered (p=0.007), and have no FH of PCA (p<0.001). Men recruited via referrals had higher incomes (p=0.007). Men recruited via referral were more likely to attend their initial PRAP visit than those recruited by radio or other methods (χ2 = 27.08, p < .0001). Conclusions This comprehensive analysis finds that radio leads to higher recruitment of AA men with lower socioeconomic status. However, these are the high-risk men that have lower show rates for PCA screening. Targeted motivational measures need to be studied to improve show rates for PCA risk assessment for these high-risk men. PMID:19758657

  1. Genome-wide linkage scan for colorectal cancer susceptibility genes supports linkage to chromosome 3q

    Velculescu Victor E

    2008-04-01

    Full Text Available Abstract Background Colorectal cancer is one of the most common causes of cancer-related mortality. The disease is clinically and genetically heterogeneous though a strong hereditary component has been identified. However, only a small proportion of the inherited susceptibility can be ascribed to dominant syndromes, such as Hereditary Non-Polyposis Colorectal Cancer (HNPCC or Familial Adenomatous Polyposis (FAP. In an attempt to identify novel colorectal cancer predisposing genes, we have performed a genome-wide linkage analysis in 30 Swedish non-FAP/non-HNPCC families with a strong family history of colorectal cancer. Methods Statistical analysis was performed using multipoint parametric and nonparametric linkage. Results Parametric analysis under the assumption of locus homogeneity excluded any common susceptibility regions harbouring a predisposing gene for colorectal cancer. However, several loci on chromosomes 2q, 3q, 6q, and 7q with suggestive linkage were detected in the parametric analysis under the assumption of locus heterogeneity as well as in the nonparametric analysis. Among these loci, the locus on chromosome 3q21.1-q26.2 was the most consistent finding providing positive results in both parametric and nonparametric analyses Heterogeneity LOD score (HLOD = 1.90, alpha = 0.45, Non-Parametric LOD score (NPL = 2.1. Conclusion The strongest evidence of linkage was seen for the region on chromosome 3. Interestingly, the same region has recently been reported as the most significant finding in a genome-wide analysis performed with SNP arrays; thus our results independently support the finding on chromosome 3q.

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

    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

  3. Linkage disequilibrium in wild mice.

    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.

  4. From root to fruit: RNA-Seq analysis shows that arbuscular mycorrhizal symbiosis may affect tomato fruit metabolism.

    Zouari, Inès; Salvioli, Alessandra; Chialva, Matteo; Novero, Mara; Miozzi, Laura; Tenore, Gian Carlo; Bagnaresi, Paolo; Bonfante, Paola

    2014-03-21

    Tomato (Solanum lycopersicum) establishes a beneficial symbiosis with arbuscular mycorrhizal (AM) fungi. The formation of the mycorrhizal association in the roots leads to plant-wide modulation of gene expression. To understand the systemic effect of the fungal symbiosis on the tomato fruit, we used RNA-Seq to perform global transcriptome profiling on Moneymaker tomato fruits at the turning ripening stage. Fruits were collected at 55 days after flowering, from plants colonized with Funneliformis mosseae and from control plants, which were fertilized to avoid responses related to nutrient deficiency. Transcriptome analysis identified 712 genes that are differentially expressed in fruits from mycorrhizal and control plants. Gene Ontology (GO) enrichment analysis of these genes showed 81 overrepresented functional GO classes. Up-regulated GO classes include photosynthesis, stress response, transport, amino acid synthesis and carbohydrate metabolism functions, suggesting a general impact of fungal symbiosis on primary metabolisms and, particularly, on mineral nutrition. Down-regulated GO classes include cell wall, metabolism and ethylene response pathways. Quantitative RT-PCR validated the RNA-Seq results for 12 genes out of 14 when tested at three fruit ripening stages, mature green, breaker and turning. Quantification of fruit nutraceutical and mineral contents produced values consistent with the expression changes observed by RNA-Seq analysis. This RNA-Seq profiling produced a novel data set that explores the intersection of mycorrhization and fruit development. We found that the fruits of mycorrhizal plants show two transcriptomic "signatures": genes characteristic of a climacteric fleshy fruit, and genes characteristic of mycorrhizal status, like phosphate and sulphate transporters. Moreover, mycorrhizal plants under low nutrient conditions produce fruits with a nutrient content similar to those from non-mycorrhizal plants under high nutrient conditions

  5. Systems level analysis of systemic sclerosis shows a network of immune and profibrotic pathways connected with genetic polymorphisms.

    J Matthew Mahoney

    2015-01-01

    Full Text Available Systemic sclerosis (SSc is a rare systemic autoimmune disease characterized by skin and organ fibrosis. The pathogenesis of SSc and its progression are poorly understood. The SSc intrinsic gene expression subsets (inflammatory, fibroproliferative, normal-like, and limited are observed in multiple clinical cohorts of patients with SSc. Analysis of longitudinal skin biopsies suggests that a patient's subset assignment is stable over 6-12 months. Genetically, SSc is multi-factorial with many genetic risk loci for SSc generally and for specific clinical manifestations. Here we identify the genes consistently associated with the intrinsic subsets across three independent cohorts, show the relationship between these genes using a gene-gene interaction network, and place the genetic risk loci in the context of the intrinsic subsets. To identify gene expression modules common to three independent datasets from three different clinical centers, we developed a consensus clustering procedure based on mutual information of partitions, an information theory concept, and performed a meta-analysis of these genome-wide gene expression datasets. We created a gene-gene interaction network of the conserved molecular features across the intrinsic subsets and analyzed their connections with SSc-associated genetic polymorphisms. The network is composed of distinct, but interconnected, components related to interferon activation, M2 macrophages, adaptive immunity, extracellular matrix remodeling, and cell proliferation. The network shows extensive connections between the inflammatory- and fibroproliferative-specific genes. The network also shows connections between these subset-specific genes and 30 SSc-associated polymorphic genes including STAT4, BLK, IRF7, NOTCH4, PLAUR, CSK, IRAK1, and several human leukocyte antigen (HLA genes. Our analyses suggest that the gene expression changes underlying the SSc subsets may be long-lived, but mechanistically interconnected

  6. STAKEHOLDER LINKAGES FOR SUSTAINABLE LAND ...

    Osondu

    Key words: Stakeholders; farmer-expert linkages; resource management; Ethiopia. Introduction ... decentralized democratic decision making processes and thus ..... district offices within the given time limits. They were often .... -less willing and less ready to hearing weaker performance reports (expect more success with ...

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

    Scott Ian

    2010-12-01

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

  8. Exploitation of linkage learning in evolutionary algorithms

    Chen, Ying-ping

    2010-01-01

    The exploitation of linkage learning is enhancing the performance of evolutionary algorithms. This monograph examines recent progress in linkage learning, with a series of focused technical chapters that cover developments and trends in the field.

  9. Expression analysis of genes associated with human osteosarcoma tumors shows correlation of RUNX2 overexpression with poor response to chemotherapy

    Sadikovic, Bekim; Thorner, Paul; Chilton-MacNeill, Susan; Martin, Jeff W; Cervigne, Nilva K; Squire, Jeremy; Zielenska, Maria

    2010-01-01

    Human osteosarcoma is the most common pediatric bone tumor. There is limited understanding of the molecular mechanisms underlying osteosarcoma oncogenesis, and a lack of good diagnostic as well as prognostic clinical markers for this disease. Recent discoveries have highlighted a potential role of a number of genes including: RECQL4, DOCK5, SPP1, RUNX2, RB1, CDKN1A, P53, IBSP, LSAMP, MYC, TNFRSF1B, BMP2, HISTH2BE, FOS, CCNB1, and CDC5L. Our objective was to assess relative expression levels of these 16 genes as potential biomarkers of osteosarcoma oncogenesis and chemotherapy response in human tumors. We performed quantitative expression analysis in a panel of 22 human osteosarcoma tumors with differential response to chemotherapy, and 5 normal human osteoblasts. RECQL4, SPP1, RUNX2, and IBSP were significantly overexpressed, and DOCK5, CDKN1A, RB1, P53, and LSAMP showed significant loss of expression relative to normal osteoblasts. In addition to being overexpressed in osteosarcoma tumor samples relative to normal osteoblasts, RUNX2 was the only gene of the 16 to show significant overexpression in tumors that had a poor response to chemotherapy relative to good responders. These data underscore the loss of tumor suppressive pathways and activation of specific oncogenic mechanisms associated with osteosarcoma oncogenesis, while drawing attention to the role of RUNX2 expression as a potential biomarker of chemotherapy failure in osteosarcoma

  10. Global morphological analysis of marine viruses shows minimal regional variation and dominance of non-tailed viruses.

    Brum, Jennifer R; Schenck, Ryan O; Sullivan, Matthew B

    2013-09-01

    Viruses influence oceanic ecosystems by causing mortality of microorganisms, altering nutrient and organic matter flux via lysis and auxiliary metabolic gene expression and changing the trajectory of microbial evolution through horizontal gene transfer. Limited host range and differing genetic potential of individual virus types mean that investigations into the types of viruses that exist in the ocean and their spatial distribution throughout the world's oceans are critical to understanding the global impacts of marine viruses. Here we evaluate viral morphological characteristics (morphotype, capsid diameter and tail length) using a quantitative transmission electron microscopy (qTEM) method across six of the world's oceans and seas sampled through the Tara Oceans Expedition. Extensive experimental validation of the qTEM method shows that neither sample preservation nor preparation significantly alters natural viral morphological characteristics. The global sampling analysis demonstrated that morphological characteristics did not vary consistently with depth (surface versus deep chlorophyll maximum waters) or oceanic region. Instead, temperature, salinity and oxygen concentration, but not chlorophyll a concentration, were more explanatory in evaluating differences in viral assemblage morphological characteristics. Surprisingly, given that the majority of cultivated bacterial viruses are tailed, non-tailed viruses appear to numerically dominate the upper oceans as they comprised 51-92% of the viral particles observed. Together, these results document global marine viral morphological characteristics, show that their minimal variability is more explained by environmental conditions than geography and suggest that non-tailed viruses might represent the most ecologically important targets for future research.

  11. Marmosets, Raree shows and Pulcinelle: an Analysis and Edition of a Hitherto-Unpublished Carnival Play by Antonio de Zamora

    Fernando Plata

    2013-05-01

    Full Text Available This paper is an analyisis, annotation and edition of the Mojiganga del mundinovo (‘The raree show, a carnival play’ by Antonio de Zamora. The play was performed in 1698 Madrid by the troupe of Carlos Vallejo, along with the sacramental one-act play El templo vivo de Dios (‘The living temple of God’. The hitherto unpublished text is based on the only two extant manuscripts, located in archives in Madrid. Despite the play’s title, my analysis argues that the novelty in this play is not so much the raree show, a contraption popularized four decades earlier in Golden Age theater, as the marmosets. The death of two marmosets and the ensuing desolation of their owner, Ms. Estupenda, both trigger the play and provide it with a plot. The marmosets, too, point to a changing mentality in late 17th-century society, regarding the possession among ladies of marmosets and other monkeys as pets.

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

    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...

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

    Douglas Gary Bielenberg

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

  14. Comparative shotgun proteomic analysis of wild and domesticated Opuntia spp. species shows a metabolic adaptation through domestication.

    Pichereaux, Carole; Hernández-Domínguez, Eric E; Santos-Diaz, Maria Del Socorro; Reyes-Agüero, Antonio; Astello-García, Marizel; Guéraud, Françoise; Negre-Salvayre, Anne; Schiltz, Odile; Rossignol, Michel; Barba de la Rosa, Ana Paulina

    2016-06-30

    The Opuntia genus is widely distributed in America, but the highest richness of wild species are found in Mexico, as well as the most domesticated Opuntia ficus-indica, which is the most domesticated species and an important crop in agricultural economies of arid and semiarid areas worldwide. During domestication process, the Opuntia morphological characteristics were favored, such as less and smaller spines in cladodes and less seeds in fruits, but changes at molecular level are almost unknown. To obtain more insights about the Opuntia molecular changes through domestication, a shotgun proteomic analysis and database-dependent searches by homology was carried out. >1000 protein species were identified and by using a label-free quantitation method, the Opuntia proteomes were compared in order to identify differentially accumulated proteins among wild and domesticated species. Most of the changes were observed in glucose, secondary, and 1C metabolism, which correlate with the observed protein, fiber and phenolic compounds accumulation in Opuntia cladodes. Regulatory proteins, ribosomal proteins, and proteins related with response to stress were also observed in differential accumulation. These results provide new valuable data that will help to the understanding of the molecular changes of Opuntia species through domestication. Opuntia species are well adapted to dry and warm conditions in arid and semiarid regions worldwide, and they are highly productive plants showing considerable promises as an alternative food source. However, there is a gap regarding Opuntia molecular mechanisms that enable them to grow in extreme environmental conditions and how the domestication processes has changed them. In the present study, a shotgun analysis was carried out to characterize the proteomes of five Opuntia species selected by its domestication degree. Our results will help to a better understanding of proteomic features underlying the selection and specialization under

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

    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

  16. Heritability and whole genome linkage of pulse pressure in Chinese twin pairs

    Jiang, Wengjie; Zhang, Dongfeng; Pang, Zengchang

    2012-01-01

    with a heritability estimate of 0.45. Genome-wide non-parametric linkage analysis identified three significant linkage peaks on chromosome 11 (lod score 4.06 at 30.5 cM), chromosome 12 (lod score 3.97 at 100.7 cM), and chromosome 18 (lod score 4.01 at 70.7 cM) with the last two peaks closely overlapping with linkage...

  17. Autosomal dominant distal myopathy: Linkage to chromosome 14

    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.

  18. Linkage of PRA models. Phase 1, Results

    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.

  19. Linkage of PRA models. Phase 1, Results

    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

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

    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.

  1. Optimal Monetary Policy with Durable Consumption Goods and Factor Demand Linkages

    Petrella, Ivan; Santoro, Emiliano

    of production in both sectors, according to an input-output matrix calibrated on the US economy. As shown in a number of recent contributions, this roundabout technology allows us to reconcile standard two-sector New Keynesian models with the empirical evidence showing co-movement between durable and non......-durable spending in response to a monetary policy shock. A main result of our monetary policy analysis is that strategic complementarities generated by factor demand linkages amplify social welfare loss. As the degree of interconnection between sectors increases, the cost of misperceiving the correct production......This paper deals with the implications of factor demand linkages for monetary policy design. We develop a dynamic general equilibrium model with two sectors that produce durable and non-durable goods, respectively. Part of the output produced in each sector is used as an intermediate input...

  2. Evolution Analysis of the Aux/IAA Gene Family in Plants Shows Dual Origins and Variable Nuclear Localization Signals

    Wentao Wu

    2017-10-01

    Full Text Available The plant hormone auxin plays pivotal roles in many aspects of plant growth and development. The auxin/indole-3-acetic acid (Aux/IAA gene family encodes short-lived nuclear proteins acting on auxin perception and signaling, but the evolutionary history of this gene family remains to be elucidated. In this study, the Aux/IAA gene family in 17 plant species covering all major lineages of plants is identified and analyzed by using multiple bioinformatics methods. A total of 434 Aux/IAA genes was found among these plant species, and the gene copy number ranges from three (Physcomitrella patens to 63 (Glycine max. The phylogenetic analysis shows that the canonical Aux/IAA proteins can be generally divided into five major clades, and the origin of Aux/IAA proteins could be traced back to the common ancestor of land plants and green algae. Many truncated Aux/IAA proteins were found, and some of these truncated Aux/IAA proteins may be generated from the C-terminal truncation of auxin response factor (ARF proteins. Our results indicate that tandem and segmental duplications play dominant roles for the expansion of the Aux/IAA gene family mainly under purifying selection. The putative nuclear localization signals (NLSs in Aux/IAA proteins are conservative, and two kinds of new primordial bipartite NLSs in P. patens and Selaginella moellendorffii were discovered. Our findings not only give insights into the origin and expansion of the Aux/IAA gene family, but also provide a basis for understanding their functions during the course of evolution.

  3. Evolution Analysis of the Aux/IAA Gene Family in Plants Shows Dual Origins and Variable Nuclear Localization Signals.

    Wu, Wentao; Liu, Yaxue; Wang, Yuqian; Li, Huimin; Liu, Jiaxi; Tan, Jiaxin; He, Jiadai; Bai, Jingwen; Ma, Haoli

    2017-10-08

    The plant hormone auxin plays pivotal roles in many aspects of plant growth and development. The auxin/indole-3-acetic acid (Aux/IAA) gene family encodes short-lived nuclear proteins acting on auxin perception and signaling, but the evolutionary history of this gene family remains to be elucidated. In this study, the Aux/IAA gene family in 17 plant species covering all major lineages of plants is identified and analyzed by using multiple bioinformatics methods. A total of 434 Aux/IAA genes was found among these plant species, and the gene copy number ranges from three ( Physcomitrella patens ) to 63 ( Glycine max ). The phylogenetic analysis shows that the canonical Aux/IAA proteins can be generally divided into five major clades, and the origin of Aux/IAA proteins could be traced back to the common ancestor of land plants and green algae. Many truncated Aux/IAA proteins were found, and some of these truncated Aux/IAA proteins may be generated from the C-terminal truncation of auxin response factor (ARF) proteins. Our results indicate that tandem and segmental duplications play dominant roles for the expansion of the Aux/IAA gene family mainly under purifying selection. The putative nuclear localization signals (NLSs) in Aux/IAA proteins are conservative, and two kinds of new primordial bipartite NLSs in P. patens and Selaginella moellendorffii were discovered. Our findings not only give insights into the origin and expansion of the Aux/IAA gene family, but also provide a basis for understanding their functions during the course of evolution.

  4. Privacy preserving interactive record linkage (PPIRL).

    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.

  5. Construction of an ultrahigh-density genetic linkage map for Jatropha curcas L. and identification of QTL for fruit yield.

    Xia, Zhiqiang; Zhang, Shengkui; Wen, Mingfu; Lu, Cheng; Sun, Yufang; Zou, Meiling; Wang, Wenquan

    2018-01-01

    As an important biofuel plant, the demand for higher yield Jatropha curcas L. is rapidly increasing. However, genetic analysis of Jatropha and molecular breeding for higher yield have been hampered by the limited number of molecular markers available. An ultrahigh-density linkage map for a Jatropha mapping population of 153 individuals was constructed and covered 1380.58 cM of the Jatropha genome, with average marker density of 0.403 cM. The genetic linkage map consisted of 3422 SNP and indel markers, which clustered into 11 linkage groups. With this map, 13 repeatable QTLs (reQTLs) for fruit yield traits were identified. Ten reQTLs, qNF - 1 , qNF - 2a , qNF - 2b , qNF - 2c , qNF - 3 , qNF - 4 , qNF - 6 , qNF - 7a , qNF - 7b and qNF - 8, that control the number of fruits (NF) mapped to LGs 1, 2, 3, 4, 6, 7 and 8, whereas three reQTLs, qTWF - 1 , qTWF - 2 and qTWF - 3, that control the total weight of fruits (TWF) mapped to LGs 1, 2 and 3, respectively. It is interesting that there are two candidate critical genes, which may regulate Jatropha fruit yield. We also identified three pleiotropic reQTL pairs associated with both the NF and TWF traits. This study is the first to report an ultrahigh-density Jatropha genetic linkage map construction, and the markers used in this study showed great potential for QTL mapping. Thirteen fruit-yield reQTLs and two important candidate genes were identified based on this linkage map. This genetic linkage map will be a useful tool for the localization of other economically important QTLs and candidate genes for Jatropha .

  6. Strike-slip tectonics during rift linkage

    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.

  7. insights from a linkage map of the damselfly Ischnura elegans

    tion of achiasmiatic meiosis. Biochem. Genet. 19, 1237–. 1245. Cooper G., Miller P. L. and Holland P. W. H. 1994 Molecular genetic analysis of sperm competition in the damselfly Ischnura elegans (Vander Linden). Proc. R. Soc. London, Ser. B 263,. 1343–1349. Huxley J. S. 1928 Sexual differences in linkage in Gammar-.

  8. Economic Growth, Structural Change and Productive Employment Linkages in India

    Aggarwal, Aradhna

    2018-01-01

    This article presents a quantitative analysis of growth, structural change and employment linkages at the aggregate level and by sector under the state- and market-led regimes in India. The underlying objectives are: (a) to understand how economic liberalization has affected the economic and labour...... intervention to broad base structural change for generating productive employment, which is at the core of poverty reduction....

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

    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

  10. Testing for linkage disequilibrium in the New Zealand radiata pine breeding population

    S. Kumar; Craig Echt; P.L. Wilcox; T.E. Richardson

    2004-01-01

    Linkage analysis is commonly uscd to find marker-trait associations within the full-sib families of forest tree and other species. Study of marker-trait associations at the population level is termed linkage-disequilibrium (LD) mapping. A female-tester design comprising 200 full-sib families generated by crossing 40 pollen parents with five female parents was used to...

  11. An improved recommendation algorithm via weakening indirect linkage effect

    Chen Guang; Qiu Tian; Shen Xiao-Quan

    2015-01-01

    We propose an indirect-link-weakened mass diffusion method (IMD), by considering the indirect linkage and the source object heterogeneity effect in the mass diffusion (MD) recommendation method. Experimental results on the MovieLens, Netflix, and RYM datasets show that, the IMD method greatly improves both the recommendation accuracy and diversity, compared with a heterogeneity-weakened MD method (HMD), which only considers the source object heterogeneity. Moreover, the recommendation accuracy of the cold objects is also better elevated in the IMD than the HMD method. It suggests that eliminating the redundancy induced by the indirect linkages could have a prominent effect on the recommendation efficiency in the MD method. (paper)

  12. Global gene analysis of oocytes from early stages in human folliculogenesis shows high expression of novel genes in reproduction

    Markholt, Sara; Grøndahl, M L; Ernst, Erik

    2012-01-01

    The pool of primordial follicles in humans is laid down during embryonic development and follicles can remain dormant for prolonged intervals, often decades, until individual follicles resume growth. The mechanisms that induce growth and maturation of primordial follicles are poorly understood...... but follicles once activated either continue growth or undergo atresia. We have isolated pure populations of oocytes from human primordial, intermediate and primary follicles using laser capture micro-dissection microscopy and evaluated the global gene expression profiles by whole-genome microarray analysis......) and the mitochondrial-encoded ATPase6 (ATP6). Thus, the present study provides not only a technique to capture and perform transcriptome analysis of the sparse material of human oocytes from the earliest follicle stages but further includes a comprehensive basis for our understanding of the regulatory factors...

  13. Comprehensive Analysis of Oculocutaneous Albinism among Non-Hispanic Caucasians Shows that OCA1 Is the Most Prevalent OCA Type

    Hutton, Saunie M.; Spritz, Richard A.

    2008-01-01

    Oculocutaneous albinism (OCA) is a genetically heterogeneous group of disorders characterized by absent or reduced pigmentation of the skin, hair, and eyes. In humans, four genes have been associated with “classical” OCA and another 12 genes with syndromic forms of OCA. To assess the prevalence of different forms of OCA and different gene mutations among non-Hispanic Caucasian patients, we performed DNA sequence analysis of the four genes associated with “classical” OCA (TYR, OCA2, TYRP1, SLC...

  14. Individual patient data meta-analysis shows no association between the SNP rs1800469 in TGFB and late radiotherapy toxicity

    Barnett, Gillian C.; Elliott, Rebecca M.; Alsner, Jan; Andreassen, Christian N.; Abdelhay, Osama; Burnet, Neil G.; Chang-Claude, Jenny; Coles, Charlotte E.; Gutiérrez-Enríquez, Sara; Fuentes-Raspall, Maria J.; Alonso-Muñoz, Maria C.; Kerns, Sarah; Raabe, Annette; Symonds, R. Paul; Seibold, Petra; Talbot, Chris J.; Wenz, Frederik; Wilkinson, Jennifer; Yarnold, John; Dunning, Alison M.

    2012-01-01

    Background and purpose: Reported associations between risk of radiation-induced normal tissue injury and single nucleotide polymorphisms (SNPs) in TGFB1, encoding the pro-fibrotic cytokine transforming growth factor-beta 1 (TGF-β1), remain controversial. To overcome publication bias, the international Radiogenomics Consortium collected and analysed individual patient level data from both published and unpublished studies. Materials and methods: TGFB1 SNP rs1800469 c.-1347T>C (previously known as C-509T) genotype, treatment-related data, and clinically-assessed fibrosis (measured at least 2 years after therapy) were available in 2782 participants from 11 cohorts. All received adjuvant breast radiotherapy. Associations between late fibrosis or overall toxicity, reported by STAT (Standardised Total Average Toxicity) score, and rs1800469 genotype were assessed. Results: No statistically significant associations between either fibrosis or overall toxicity and rs1800469 genotype were observed with univariate or multivariate regression analysis. The multivariate odds ratio (OR), obtained from meta-analysis, for an increase in late fibrosis grade with each additional rare allele of rs1800469 was 0.98 (95% Confidence Interval (CI) 0.85–1.11). This CI is sufficiently narrow to rule out any clinically relevant effect on toxicity risk in carriers vs. non-carriers with a high probability. Conclusion: This meta-analysis has not confirmed previous reports of association between fibrosis or overall toxicity and rs1800469 genotype in breast cancer patients. It has demonstrated successful collaboration within the Radiogenomics Consortium.

  15. The Dynamics of Linkages and Innovativeness in Publicly and ...

    The study examined how linkages among actors in the cocoa and pineapple value chains relate to the innovativeness of actors in the chains. The study showed that a policy environment that promoted public sector leadership in value chain functions and service provision, tended to offer less incentives for smallholder ...

  16. Linkages over Time between Adolescents' Relationships with Parents and Friends

    De Goede, Irene H. A.; Branje, Susan J. T.; Delsing, Marc J. M. H.; Meeus, Wim H. J.

    2009-01-01

    This 5-wave longitudinal study examines linkages over time between adolescents' perceptions of relationships with parents and friends with respect to support, negative interaction, and power. A total of 575 early adolescents (54.1% boys) and 337 middle adolescents (43.3% boys) participated. Path analyses mainly showed bidirectional associations…

  17. Comparative Analysis of Clinical Samples Showing Weak Serum Reaction on AutoVue System Causing ABO Blood Typing Discrepancies.

    Jo, Su Yeon; Lee, Ju Mi; Kim, Hye Lim; Sin, Kyeong Hwa; Lee, Hyeon Ji; Chang, Chulhun Ludgerus; Kim, Hyung Hoi

    2017-03-01

    ABO blood typing in pre-transfusion testing is a major component of the high workload in blood banks that therefore requires automation. We often experienced discrepant results from an automated system, especially weak serum reactions. We evaluated the discrepant results by the reference manual method to confirm ABO blood typing. In total, 13,113 blood samples were tested with the AutoVue system; all samples were run in parallel with the reference manual method according to the laboratory protocol. The AutoVue system confirmed ABO blood typing of 12,816 samples (97.7%), and these results were concordant with those of the manual method. The remaining 297 samples (2.3%) showed discrepant results in the AutoVue system and were confirmed by the manual method. The discrepant results involved weak serum reactions (serum reactions, samples from patients who had received stem cell transplants, ABO subgroups, and specific system error messages. Among the 98 samples showing ≤1+ reaction grade in the AutoVue system, 70 samples (71.4%) showed a normal serum reaction (≥2+ reaction grade) with the manual method, and 28 samples (28.6%) showed weak serum reaction in both methods. ABO blood tying of 97.7% samples could be confirmed by the AutoVue system and a small proportion (2.3%) needed to be re-evaluated by the manual method. Samples with a 2+ reaction grade in serum typing do not need to be evaluated manually, while those with ≤1+ reaction grade do.

  18. Isolation and expression analysis of EcbZIP17 from different finger millet genotypes shows conserved nature of the gene.

    Chopperla, Ramakrishna; Singh, Sonam; Mohanty, Sasmita; Reddy, Nanja; Padaria, Jasdeep C; Solanke, Amolkumar U

    2017-10-01

    Basic leucine zipper (bZIP) transcription factors comprise one of the largest gene families in plants. They play a key role in almost every aspect of plant growth and development and also in biotic and abiotic stress tolerance. In this study, we report isolation and characterization of EcbZIP17 , a group B bZIP transcription factor from a climate smart cereal, finger millet ( Eleusine coracana L.). The genomic sequence of EcbZIP17 is 2662 bp long encompassing two exons and one intron with ORF of 1722 bp and peptide length of 573 aa. This gene is homologous to AtbZIP17 ( Arabidopsis ), ZmbZIP17 (maize) and OsbZIP60 (rice) which play a key role in endoplasmic reticulum (ER) stress pathway. In silico analysis confirmed the presence of basic leucine zipper (bZIP) and transmembrane (TM) domains in the EcbZIP17 protein. Allele mining of this gene in 16 different genotypes by Sanger sequencing revealed no variation in nucleotide sequence, including the 618 bp long intron. Expression analysis of EcbZIP17 under heat stress exhibited similar pattern of expression in all the genotypes across time intervals with highest upregulation after 4 h. The present study established the conserved nature of EcbZIP17 at nucleotide and expression level.

  19. Feasibility of motion laws for planar one degree of freedom linkage mechanisms at dead point configurations

    Lores García, E.; Veciana Fontanet, J. M.; Jordi Nebot, L.

    2018-01-01

    This paper proposes an analytical solution of the Inverse Kinematics (IK) problem at dead point configurations for any planar one degree of freedom linkage mechanism, with regard to the continuity Cn of the motion law. The systems analyzed are those whose elements are linked with lower pairs and do not present redundancies. The study aims to provide the user with some rules to facilitate the design of feasible motion profiles to be reproduced by conventional electrical actuators at these configurations. During the last decades, several methods and techniques have been developed to study this specific configuration. However, these techniques are mainly focused on solving numerically the IK indeterminacy, rather than analyzing the motion laws that the mechanisms are able to perform at these particular configurations. The analysis presented in this paper has been carried out differentiating and applying l'Hôpital's rule to the system of constraint equations ϕ (q) of the mechanism. The study also considers the feasibility of the time-domain profiles to be reproduced with conventional electrical actuators (i.e. AC/DC motors, linear actuators, etc.). To show the usefulness and effectiveness of the method, the development includes the analytical application and numerical simulations for two common one degree of freedom systems: a slider-crank and a four linkage mechanisms. Finally, experimental results are presented on a four linkage mechanism test bed.

  20. Transcriptomic and metabolomic analysis of Yukon Thellungiella plants grown in cabinets and their natural habitat show phenotypic plasticity

    Guevara David R

    2012-10-01

    Full Text Available Abstract Background Thellungiella salsuginea is an important model plant due to its natural tolerance to abiotic stresses including salt, cold, and water deficits. Microarray and metabolite profiling have shown that Thellungiella undergoes stress-responsive changes in transcript and organic solute abundance when grown under controlled environmental conditions. However, few reports assess the capacity of plants to display stress-responsive traits in natural habitats where concurrent stresses are the norm. Results To determine whether stress-responsive changes observed in cabinet-grown plants are recapitulated in the field, we analyzed leaf transcript and metabolic profiles of Thellungiella growing in its native Yukon habitat during two years of contrasting meteorological conditions. We found 673 genes showing differential expression between field and unstressed, chamber-grown plants. There were comparatively few overlaps between genes expressed under field and cabinet treatment-specific conditions. Only 20 of 99 drought-responsive genes were expressed both in the field during a year of low precipitation and in plants subjected to drought treatments in cabinets. There was also a general pattern of lower abundance among metabolites found in field plants relative to control or stress-treated plants in growth cabinets. Nutrient availability may explain some of the observed differences. For example, proline accumulated to high levels in cold and salt-stressed cabinet-grown plants but proline content was, by comparison, negligible in plants at a saline Yukon field site. We show that proline accumulated in a stress-responsive manner in Thellungiella plants salinized in growth cabinets and in salt-stressed seedlings when nitrogen was provided at 1.0 mM. In seedlings grown on 0.1 mM nitrogen medium, the proline content was low while carbohydrates increased. The relatively higher content of sugar-like compounds in field plants and seedlings on low nitrogen

  1. Transcriptomic and metabolomic analysis of Yukon Thellungiella plants grown in cabinets and their natural habitat show phenotypic plasticity.

    Guevara, David R; Champigny, Marc J; Tattersall, Ashley; Dedrick, Jeff; Wong, Chui E; Li, Yong; Labbe, Aurelie; Ping, Chien-Lu; Wang, Yanxiang; Nuin, Paulo; Golding, G Brian; McCarry, Brian E; Summers, Peter S; Moffatt, Barbara A; Weretilnyk, Elizabeth A

    2012-10-01

    Thellungiella salsuginea is an important model plant due to its natural tolerance to abiotic stresses including salt, cold, and water deficits. Microarray and metabolite profiling have shown that Thellungiella undergoes stress-responsive changes in transcript and organic solute abundance when grown under controlled environmental conditions. However, few reports assess the capacity of plants to display stress-responsive traits in natural habitats where concurrent stresses are the norm. To determine whether stress-responsive changes observed in cabinet-grown plants are recapitulated in the field, we analyzed leaf transcript and metabolic profiles of Thellungiella growing in its native Yukon habitat during two years of contrasting meteorological conditions. We found 673 genes showing differential expression between field and unstressed, chamber-grown plants. There were comparatively few overlaps between genes expressed under field and cabinet treatment-specific conditions. Only 20 of 99 drought-responsive genes were expressed both in the field during a year of low precipitation and in plants subjected to drought treatments in cabinets. There was also a general pattern of lower abundance among metabolites found in field plants relative to control or stress-treated plants in growth cabinets. Nutrient availability may explain some of the observed differences. For example, proline accumulated to high levels in cold and salt-stressed cabinet-grown plants but proline content was, by comparison, negligible in plants at a saline Yukon field site. We show that proline accumulated in a stress-responsive manner in Thellungiella plants salinized in growth cabinets and in salt-stressed seedlings when nitrogen was provided at 1.0 mM. In seedlings grown on 0.1 mM nitrogen medium, the proline content was low while carbohydrates increased. The relatively higher content of sugar-like compounds in field plants and seedlings on low nitrogen media suggests that Thellungiella shows

  2. Transcriptomic and metabolomic analysis of Yukon Thellungiella plants grown in cabinets and their natural habitat show phenotypic plasticity

    2012-01-01

    Background Thellungiella salsuginea is an important model plant due to its natural tolerance to abiotic stresses including salt, cold, and water deficits. Microarray and metabolite profiling have shown that Thellungiella undergoes stress-responsive changes in transcript and organic solute abundance when grown under controlled environmental conditions. However, few reports assess the capacity of plants to display stress-responsive traits in natural habitats where concurrent stresses are the norm. Results To determine whether stress-responsive changes observed in cabinet-grown plants are recapitulated in the field, we analyzed leaf transcript and metabolic profiles of Thellungiella growing in its native Yukon habitat during two years of contrasting meteorological conditions. We found 673 genes showing differential expression between field and unstressed, chamber-grown plants. There were comparatively few overlaps between genes expressed under field and cabinet treatment-specific conditions. Only 20 of 99 drought-responsive genes were expressed both in the field during a year of low precipitation and in plants subjected to drought treatments in cabinets. There was also a general pattern of lower abundance among metabolites found in field plants relative to control or stress-treated plants in growth cabinets. Nutrient availability may explain some of the observed differences. For example, proline accumulated to high levels in cold and salt-stressed cabinet-grown plants but proline content was, by comparison, negligible in plants at a saline Yukon field site. We show that proline accumulated in a stress-responsive manner in Thellungiella plants salinized in growth cabinets and in salt-stressed seedlings when nitrogen was provided at 1.0 mM. In seedlings grown on 0.1 mM nitrogen medium, the proline content was low while carbohydrates increased. The relatively higher content of sugar-like compounds in field plants and seedlings on low nitrogen media suggests that

  3. Quantitative Analysis of the Contributing Factors Affecting Specialty Care No-Show Rates at Brooke Army Medical Center

    2007-03-30

    PHYSICAL THERAPY ,TMC 53 9 14.52% AUDIOLOGY,BAMC 133 22 14.19% OPHTH PEDS,BAMC 28 4 12.50% OCCUPATIONAL THERAPY ,BAMC 135 18 11.76% ALLERGY CLINIC,BAMC...for physical therapy and have a total of 4 appointments set up with that clinic. For this study, only the first referral was counted and not the follow...Nephrology. Some of the other low no-show rate clinics were: Pain Management (1.27%), Endocrinology (1.52%), General Surgery (1.83%), Rheumatology (1.89

  4. Linkage disequilibrium and association mapping.

    Weir, B S

    2008-01-01

    Linkage disequilibrium refers to the association between alleles at different loci. The standard definition applies to two alleles in the same gamete, and it can be regarded as the covariance of indicator variables for the states of those two alleles. The corresponding correlation coefficient rho is the parameter that arises naturally in discussions of tests of association between markers and genetic diseases. A general treatment of association tests makes use of the additive and nonadditive components of variance for the disease gene. In almost all expressions that describe the behavior of association tests, additive variance components are modified by the squared correlation coefficient rho2 and the nonadditive variance components by rho4, suggesting that nonadditive components have less influence than additive components on association tests.

  5. Meta-Analysis of Quantification Methods Shows that Archaea and Bacteria Have Similar Abundances in the Subseafloor

    May, Megan K.; Kevorkian, Richard T.; Steen, Andrew D.

    2013-01-01

    There is no universally accepted method to quantify bacteria and archaea in seawater and marine sediments, and different methods have produced conflicting results with the same samples. To identify best practices, we compiled data from 65 studies, plus our own measurements, in which bacteria and archaea were quantified with fluorescent in situ hybridization (FISH), catalyzed reporter deposition FISH (CARD-FISH), polyribonucleotide FISH, or quantitative PCR (qPCR). To estimate efficiency, we defined “yield” to be the sum of bacteria and archaea counted by these techniques divided by the total number of cells. In seawater, the yield was high (median, 71%) and was similar for FISH, CARD-FISH, and polyribonucleotide FISH. In sediments, only measurements by CARD-FISH in which archaeal cells were permeabilized with proteinase K showed high yields (median, 84%). Therefore, the majority of cells in both environments appear to be alive, since they contain intact ribosomes. In sediments, the sum of bacterial and archaeal 16S rRNA gene qPCR counts was not closely related to cell counts, even after accounting for variations in copy numbers per genome. However, qPCR measurements were precise relative to other qPCR measurements made on the same samples. qPCR is therefore a reliable relative quantification method. Inconsistent results for the relative abundance of bacteria versus archaea in deep subsurface sediments were resolved by the removal of CARD-FISH measurements in which lysozyme was used to permeabilize archaeal cells and qPCR measurements which used ARCH516 as an archaeal primer or TaqMan probe. Data from best-practice methods showed that archaea and bacteria decreased as the depth in seawater and marine sediments increased, although archaea decreased more slowly. PMID:24096423

  6. Comprehensive analysis of oculocutaneous albinism among non-Hispanic caucasians shows that OCA1 is the most prevalent OCA type.

    Hutton, Saunie M; Spritz, Richard A

    2008-10-01

    Oculocutaneous albinism (OCA) is a genetically heterogeneous group of disorders characterized by absent or reduced pigmentation of the skin, hair, and eyes. In humans, four genes have been associated with "classical" OCA and another 12 genes with syndromic forms of OCA. To assess the prevalence of different forms of OCA and different gene mutations among non-Hispanic Caucasian patients, we performed DNA sequence analysis of the four genes associated with "classical" OCA (TYR, OCA2, TYRP1, SLC45A2), the two principal genes associated with syndromic OCA (HPS1, HPS4), and a candidate OCA gene (SILV), in 121 unrelated, unselected non-Hispanic/Latino Caucasian patients carrying the clinical diagnosis of OCA. We identified apparent pathologic TYR gene mutations in 69% of patients, OCA2 mutations in 18%, SLC45A2 mutations in 6%, and no apparent pathological mutations in 7% of patients. We found no mutations of TYRP1, HPS1, HPS4, or SILV in any patients. Although we observed a diversity of mutations for each gene, a relatively small number of different mutant alleles account for a majority of the total. This study demonstrates that, contrary to long-held clinical lore, OCA1, not OCA2, is by far the most frequent cause of OCA among Caucasian patients.

  7. Anatomical Network Analysis Shows Decoupling of Modular Lability and Complexity in the Evolution of the Primate Skull

    Esteve-Altava, Borja; Boughner, Julia C.; Diogo, Rui; Villmoare, Brian A.; Rasskin-Gutman, Diego

    2015-01-01

    Modularity and complexity go hand in hand in the evolution of the skull of primates. Because analyses of these two parameters often use different approaches, we do not know yet how modularity evolves within, or as a consequence of, an also-evolving complex organization. Here we use a novel network theory-based approach (Anatomical Network Analysis) to assess how the organization of skull bones constrains the co-evolution of modularity and complexity among primates. We used the pattern of bone contacts modeled as networks to identify connectivity modules and quantify morphological complexity. We analyzed whether modularity and complexity evolved coordinately in the skull of primates. Specifically, we tested Herbert Simon’s general theory of near-decomposability, which states that modularity promotes the evolution of complexity. We found that the skulls of extant primates divide into one conserved cranial module and up to three labile facial modules, whose composition varies among primates. Despite changes in modularity, statistical analyses reject a positive feedback between modularity and complexity. Our results suggest a decoupling of complexity and modularity that translates to varying levels of constraint on the morphological evolvability of the primate skull. This study has methodological and conceptual implications for grasping the constraints that underlie the developmental and functional integration of the skull of humans and other primates. PMID:25992690

  8. Morphometric analysis of molars in a Middle Pleistocene population shows a mosaic of 'modern' and Neanderthal features.

    Martinón-Torres, María; Spěváčková, Petra; Gracia-Téllez, Ana; Martínez, Ignacio; Bruner, Emiliano; Arsuaga, Juan Luis; Bermúdez de Castro, José María

    2013-10-01

    Previous studies of upper first molar (M1) crown shape have shown significant differences between Homo sapiens and Homo neanderthalensis that were already present in the European Middle Pleistocene populations, including the large dental sample from Atapuerca-Sima de los Huesos (SH). Analysis of other M1 features such as the total crown base area, cusp proportions, cusp angles and occlusal polygon have confirmed the differences between both lineages, becoming a useful tool for the taxonomic assignment of isolated teeth from Late Pleistocene sites. However, until now the pattern of expression of these variables has not been known for the SH sample. This fossil sample, the largest collection from the European Middle Pleistocene, is generally interpreted as being from the direct ancestors of Neanderthals, and thus is a reference sample for assessing the origin of the Neanderthal morphologies. Surprisingly, our study reveals that SH M(1) s present a unique mosaic of H. neanderthalensis and H. sapiens features. Regarding the cusp angles and the relative occlusal polygon area, SH matches the H. neanderthalensis pattern. However, regarding the total crown base area and relative cusps size, SH M(1) s are similar to H. sapiens, with a small crown area, a strong hypocone reduction and a protocone enlargement, although the protocone expansion in SH is significantly larger than in any other group studied. The SH dental sample calls into question the uniqueness of some so-called modern traits. Our study also sounds a note of caution on the use of M(1) occlusal morphology for the alpha taxonomy of isolated M(1) s. © 2013 Anatomical Society.

  9. Morphometric analysis of molars in a Middle Pleistocene population shows a mosaic of ‘modern’ and Neanderthal features

    Martinón-Torres, María; Spěváčková, Petra; Gracia-Téllez, Ana; Martínez, Ignacio; Bruner, Emiliano; Arsuaga, Juan Luis; Bermúdez de Castro, José María

    2013-01-01

    Previous studies of upper first molar (M1) crown shape have shown significant differences between Homo sapiens and Homo neanderthalensis that were already present in the European Middle Pleistocene populations, including the large dental sample from Atapuerca-Sima de los Huesos (SH). Analysis of other M1 features such as the total crown base area, cusp proportions, cusp angles and occlusal polygon have confirmed the differences between both lineages, becoming a useful tool for the taxonomic assignment of isolated teeth from Late Pleistocene sites. However, until now the pattern of expression of these variables has not been known for the SH sample. This fossil sample, the largest collection from the European Middle Pleistocene, is generally interpreted as being from the direct ancestors of Neanderthals, and thus is a reference sample for assessing the origin of the Neanderthal morphologies. Surprisingly, our study reveals that SH M1s present a unique mosaic of H. neanderthalensis and H. sapiens features. Regarding the cusp angles and the relative occlusal polygon area, SH matches the H. neanderthalensis pattern. However, regarding the total crown base area and relative cusps size, SH M1s are similar to H. sapiens, with a small crown area, a strong hypocone reduction and a protocone enlargement, although the protocone expansion in SH is significantly larger than in any other group studied. The SH dental sample calls into question the uniqueness of some so-called modern traits. Our study also sounds a note of caution on the use of M1 occlusal morphology for the alpha taxonomy of isolated M1s. PMID:23914934

  10. Meta-analysis shows similar re-bleeding rates among Western and Eastern populations after index video capsule endoscopy.

    Tziatzios, Georgios; Gkolfakis, Paraskevas; Hassan, Cesare; Toth, Ervin; Zullo, Angelo; Koulaouzidis, Anastasios; Dimitriadis, George D; Triantafyllou, Konstantinos

    2018-03-01

    Video capsule endoscopy (VCE) is the first-line diagnostic procedure for investigating obscure gastrointestinal bleeding (OGIB). Different re-bleeding rates following index VCE have been reported among Western and Eastern studies. We conducted a comprehensive literature search to identify studies examining re-bleeding rates after VCE for OGIB. Meta-analysis assessed the pooled proportion of re-bleeding events after VCE for OGIB according to study's origin (Western vs. Eastern) and according to the length of follow-up (≥24 months vs. Western and 16 Eastern) studies with 5796 patients. Significant heterogeneity was detected among meta-analyzed studies. Overall, the pooled re-bleeding rate was similar between Western (29%; 95% CI: 23-34) and Eastern (21%; 95% CI: 15-27) populations, irrespective of the length of follow-up. The odds of re-bleeding was significantly higher after positive as compared to negative index VCE in Eastern studies (OR: 1.77; 95% CI: 1.07-2.94). Application of specific treatment after positive index VCE was associated with lower re-bleeding odds in both Western (OR: 0.37; 95% CI: 0.16-0.87) and Eastern (OR: 0.39; 95% CI: 0.21-0.72) populations. Patients undergoing VCE for OGIB have similar re-bleeding rates in the East and the West, regardless of the length of follow-up. However, increased re-bleeding odds after positive index VCE is observed in Eastern studies. Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  11. X-ray survival characteristics and genetic analysis for nine saccharomyces deletion mutants that show altered radiation sensitivity

    Game, John C.; Williamson, Marsha S.; Baccari, Clelia

    2004-01-07

    The availability of a genome-wide set of Saccharomyces deletion mutants provides a chance to identify all the yeast genes involved in DNA repair. Using X-rays, we are screening these mutants to identify additional genes that show increased sensitivity to the lethal effects of ionizing radiation. For each mutant identified as sensitive, we are confirming that the sensitivity phenotype co-segregates with the deletion allele and are obtaining multipoint survival-versus-dose assays in at least two haploid and one homozygous diploid strains. We present data for deletion mutants involving the genes DOT1, MDM20, NAT3, SPT7, SPT20, GCN5, HFI1, DCC1 and VID21/EAF1, and discuss their potential roles in repair. Eight of these genes have a clear radiation-sensitive phenotype when deleted, but the ninth, GCN5, has at most a borderline phenotype. None of the deletions confer substantial sensitivity to ultra-violet radiation, although one or two may confer marginal sensitivity. The DOT1 gene is of interest because its only known function is to methylate one lysine residue in the core of the histone H3 protein. We find that histone H3 mutants (supplied by K. Struhl) in which this residue is replaced by other amino-acids are also X-ray sensitive, seeming to confirm that methylation of the lysine-79 residue is required for effective repair of radiation damage.

  12. Comprehensive behavioral analysis of Ox1r-/- mice showed implication of orexin receptor-1 in mood, anxiety and social behavior

    Md Golam Abbas

    2015-12-01

    Full Text Available Neuropeptides orexin A and orexin B, which are exclusively produced by neurons in the lateral hypothalamic area, play an important role in the regulation of a wide range of behaviors and homeostatic processes, including regulation of sleep/wakefulness states and energy homeostasis. The orexin system has close anatomical and functional relationships with systems that regulate the autonomic nervous system, emotion, mood, the reward system and sleep/wakefulness states. Recent pharmacological studies using selective antagonists have suggested that orexin receptor-1 (OX1R is involved in physiological processes that regulate emotion, the reward system and autonomic nervous system. Here, we examined Ox1r-/- mice with a comprehensive behavioral test battery to screen additional OX1R functions. Ox1r-/- mice showed increased anxiety-like behavior, altered depression-like behavior, slightly decreased spontaneous locomotor activity, reduced social interaction, increased startle response and decreased prepulse inhibition. These results suggest that OX1R plays roles in social behaviour and sensory motor gating in addition to roles in mood and anxiety.

  13. An actuarial analysis shows that offering lung cancer screening as an insurance benefit would save lives at relatively low cost.

    Pyenson, Bruce S; Sander, Marcia S; Jiang, Yiding; Kahn, Howard; Mulshine, James L

    2012-04-01

    Lung cancer screening is not established as a public health practice, yet the results of a recent large randomized controlled trial showed that screening with low-dose spiral computed tomography reduces lung cancer mortality. Using actuarial models, this study estimated the costs and benefits of annual lung cancer screening offered as a commercial insurance benefit in the high-risk US population ages 50-64. Assuming current commercial reimbursement rates for treatment, we found that screening would cost about $1 per insured member per month in 2012 dollars. The cost per life-year saved would be below $19,000, an amount that compares favorably with screening for cervical, breast, and colorectal cancers. Our results suggest that commercial insurers should consider lung cancer screening of high-risk individuals to be high-value coverage and provide it as a benefit to people who are at least fifty years old and have a smoking history of thirty pack-years or more. We also believe that payers and patients should demand screening from high-quality, low-cost providers, thus helping set an example of efficient system innovation.

  14. Transcriptome analysis shows activation of the arginine deiminase pathway in Lactococcus lactis as a response to ethanol stress.

    Díez, Lorena; Solopova, Ana; Fernández-Pérez, Rocío; González, Miriam; Tenorio, Carmen; Kuipers, Oscar P; Ruiz-Larrea, Fernanda

    2017-09-18

    This paper describes the molecular response of Lactococcus lactis NZ9700 to ethanol. This strain is a well-known nisin producer and a lactic acid bacteria (LAB) model strain. Global transcriptome profiling using DNA microarrays demonstrated a bacterial adaptive response to the presence of 2% ethanol in the culture broth and differential expression of 67 genes. The highest up-regulation was detected for those genes involved in arginine degradation through the arginine deiminase (ADI) pathway (20-40 fold up-regulation). The metabolic responses to ethanol of wild type L. lactis strains were studied and compared to those of regulator-deletion mutants MG∆argR and MG∆ahrC. The results showed that in the presence of 2% ethanol those strains with an active ADI pathway reached higher growth rates when arginine was available in the culture broth than in absence of arginine. In a chemically defined medium strains with an active ADI pathway consumed arginine and produced ornithine in the presence of 2% ethanol, hence corroborating that arginine catabolism is involved in the bacterial response to ethanol. This is the first study of the L. lactis response to ethanol stress to demonstrate the relevance of arginine catabolism for bacterial adaptation and survival in an ethanol containing medium. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. An estimating function approach to linkage heterogeneity

    Testing linkage heterogeneity between two loci is an important issue in genetics. Currently, there are ... on linkage heterogeneity can help people to better understand complex .... χ2(F − 2) + cχ2 (1), where c is a constant (see Appendix). Here, it can be ..... gin, ancestry, gender, age, etc., for purpose of dividing sub- groups to ...

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

    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

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

    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

  18. Discrimination of candidate subgenome-specific loci by linkage map construction with an S1 population of octoploid strawberry (Fragaria × ananassa).

    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.

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

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

    1997-03-01

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

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

    Dubé, M P; Mlodzienski, M A; Kibar, Z; Farlow, M R; Ebers, G; Harper, P; Kolodny, E H; Rouleau, G A; Figlewicz, D A

    1997-03-01

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

  1. 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

    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.

  2. A Comparative Analysis of Genetic Diversity and Structure in Jaguars (Panthera onca, Pumas (Puma concolor, and Ocelots (Leopardus pardalis in Fragmented Landscapes of a Critical Mesoamerican Linkage Zone.

    Claudia Wultsch

    Full Text Available With increasing anthropogenic impact and landscape change, terrestrial carnivore populations are becoming more fragmented. Thus, it is crucial to genetically monitor wild carnivores and quantify changes in genetic diversity and gene flow in response to these threats. This study combined the use of scat detector dogs and molecular scatology to conduct the first genetic study on wild populations of multiple Neotropical felids coexisting across a fragmented landscape in Belize, Central America. We analyzed data from 14 polymorphic microsatellite loci in 1053 scat samples collected from wild jaguars (Panthera onca, pumas (Puma concolor, and ocelots (Leopardus pardalis. We assessed levels of genetic diversity, defined potential genetic clusters, and examined gene flow for the three target species on a countrywide scale using a combination of individual- and population-based analyses. Wild felids in Belize showed moderate levels of genetic variation, with jaguars having the lowest diversity estimates (HE = 0.57 ± 0.02; AR = 3.36 ± 0.09, followed by pumas (HE = 0.57 ± 0.08; AR = 4.20 ± 0.16, and ocelots (HE = 0.63 ± 0.03; AR = 4.16 ± 0.08. We observed low to moderate levels of genetic differentiation for all three target species, with jaguars showing the lowest degree of genetic subdivision across the country, followed by ocelots and pumas. Although levels of genetic diversity and gene flow were still fairly high, we detected evidence of fine-scale genetic subdivision, indicating that levels of genetic connectivity for wild felids in Belize are likely to decrease if habitat loss and fragmentation continue at the current rate. Our study demonstrates the value of understanding fine-scale patterns of gene flow in multiple co-occurring felid species of conservation concern, which is vital for wildlife movement corridor planning and prioritizing future conservation and management efforts within human-impacted landscapes.

  3. Entrepreneurship And Business Management - Exploring Linkages For Sustainable Development

    Dr Serah K Mbetwa

    2015-08-01

    Full Text Available Entrepreneurs have emerged as market leaders in todays business world amidst the numerous economic turmoil constantly affecting economies on a global scale. This research paper is on entrepreneurship and business management and its linkages to other business stakeholders. The research paper therefore discusses entrepreneurship and business management exploring the linkages to available financing and potential institutions for startup capital by linking entrepreneurs to the government financiers and the public clientele. It is believed that this can bring about achievement of sustainable development goals translating into sustainable development and hence economic growth. The idea of funding is echoed by Robert Rice 2016 An entrepreneur without funding is like a musician with no instruments. Sustainability and entrepreneurship sustainopreneurship is made possible with availability of information on linkages between entrepreneurs and financial lending institutions as well as government policy. It is hoped that the research will add to the existing knowledge and help entrepreneurs with funding options for their business ideas to come to life. Findings show that the government financial lending institutions and the public are the major linkages between entrepreneurship and business management and are critical for attaining sustainable development goals and achieving economic growth.

  4. Linkage Behavior and Practices of Agencies in the Agricultural ...

    The study examined the linkage behaviour and practices of agencies in the ... institutes; while (61.5%,65.5%and 50.0%) indicated that linkages with universities of ... Existing institutional framework for linkages between research and extension ...

  5. Applying Topographic Classification, Based on the Hydrological Process, to Design Habitat Linkages for Climate Change

    Yongwon Mo

    2017-11-01

    Full Text Available The use of biodiversity surrogates has been discussed in the context of designing habitat linkages to support the migration of species affected by climate change. Topography has been proposed as a useful surrogate in the coarse-filter approach, as the hydrological process caused by topography such as erosion and accumulation is the basis of ecological processes. However, some studies that have designed topographic linkages as habitat linkages, so far have focused much on the shape of the topography (morphometric topographic classification with little emphasis on the hydrological processes (generic topographic classification to find such topographic linkages. We aimed to understand whether generic classification was valid for designing these linkages. First, we evaluated whether topographic classification is more appropriate for describing actual (coniferous and deciduous and potential (mammals and amphibians habitat distributions. Second, we analyzed the difference in the linkages between the morphometric and generic topographic classifications. The results showed that the generic classification represented the actual distribution of the trees, but neither the morphometric nor the generic classification could represent the potential animal distributions adequately. Our study demonstrated that the topographic classes, according to the generic classification, were arranged successively according to the flow of water, nutrients, and sediment; therefore, it would be advantageous to secure linkages with a width of 1 km or more. In addition, the edge effect would be smaller than with the morphometric classification. Accordingly, we suggest that topographic characteristics, based on the hydrological process, are required to design topographic linkages for climate change.

  6. Norrie disease: linkage analysis using a 4.2-kb RFLP detected by a human ornithine aminotransferase cDNA probe.

    Ngo, J T; Bateman, J B; Cortessis, V; Sparkes, R S; Mohandas, T; Inana, G; Spence, M A

    1989-05-01

    Previous study has shown that the usual DNA marker for Norrie disease, the L1.28 probe which identifies the DXS7 locus, can recombine with the disease locus. In this study, we used a human ornithine aminotransferase (OAT) cDNA which detects OAT-related DNA sequences mapped to the same region on the X chromosome as that of the L1.28 probe to investigate the family with Norrie disease who exhibited the recombinational event. When genomic DNA from this family was digested with the PvuII restriction endonuclease, we found a restriction fragment length polymorphism (RFLP) of 4.2 kb in size. This fragment was absent in the affected males and cosegregated with the disease locus; we calculated a lod score of 0.602, at theta = 0.00. No deletion could be detected by chromosomal analysis or on Southern blots with other enzymes. These results suggest that one of the OAT-related sequences on the X chromosome may be in close proximity to the Norrie disease locus and represent the first report which indicates that the OAT cDNA may be useful for the identification of carrier status and/or prenatal diagnosis.

  7. Analyzing the Relative Linkages of Land Use and Hydrologic Variables with Urban Surface Water Quality using Multivariate Techniques

    Ahmed, S.; Abdul-Aziz, O. I.

    2015-12-01

    We used a systematic data-analytics approach to analyze and quantify relative linkages of four stream water quality indicators (total nitrogen, TN; total phosphorus, TP; chlorophyll-a, Chla; and dissolved oxygen, DO) with six land use and four hydrologic variables, along with the potential external (upstream in-land and downstream coastal) controls in highly complex coastal urban watersheds of southeast Florida, U.S.A. Multivariate pattern recognition techniques of principle component and factor analyses, in concert with Pearson correlation analysis, were applied to map interrelations and identify latent patterns of the participatory variables. Relative linkages of the in-stream water quality variables with their associated drivers were then quantified by developing dimensionless partial least squares (PLS) regression model based on standardized data. Model fitting efficiency (R2=0.71-0.87) and accuracy (ratio of root-mean-square error to the standard deviation of the observations, RSR=0.35-0.53) suggested good predictions of the water quality variables in both wet and dry seasons. Agricultural land and groundwater exhibited substantial controls on surface water quality. In-stream TN concentration appeared to be mostly contributed by the upstream water entering from Everglades in both wet and dry seasons. In contrast, watershed land uses had stronger linkages with TP and Chla than that of the watershed hydrologic and upstream (Everglades) components for both seasons. Both land use and hydrologic components showed strong linkages with DO in wet season; however, the land use linkage appeared to be less in dry season. The data-analytics method provided a comprehensive empirical framework to achieve crucial mechanistic insights into the urban stream water quality processes. Our study quantitatively identified dominant drivers of water quality, indicating key management targets to maintain healthy stream ecosystems in complex urban-natural environments near the coast.

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

    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....

  9. Fine mapping of multiple QTL using combined linkage and linkage disequilibrium mapping – A comparison of single QTL and multi QTL methods

    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.

  10. Fine mapping of a linkage peak with integration of lipid traits identifies novel coronary artery disease genes on chromosome 5

    Nolan Daniel K

    2012-02-01

    Full Text Available Abstract Background Coronary artery disease (CAD, and one of its intermediate risk factors, dyslipidemia, possess a demonstrable genetic component, although the genetic architecture is incompletely defined. We previously reported a linkage peak on chromosome 5q31-33 for early-onset CAD where the strength of evidence for linkage was increased in families with higher mean low density lipoprotein-cholesterol (LDL-C. Therefore, we sought to fine-map the peak using association mapping of LDL-C as an intermediate disease-related trait to further define the etiology of this linkage peak. The study populations consisted of 1908 individuals from the CATHGEN biorepository of patients undergoing cardiac catheterization; 254 families (N = 827 individuals from the GENECARD familial study of early-onset CAD; and 162 aorta samples harvested from deceased donors. Linkage disequilibrium-tagged SNPs were selected with an average of one SNP per 20 kb for 126.6-160.2 MB (region of highest linkage and less dense spacing (one SNP per 50 kb for the flanking regions (117.7-126.6 and 160.2-167.5 MB and genotyped on all samples using a custom Illumina array. Association analysis of each SNP with LDL-C was performed using multivariable linear regression (CATHGEN and the quantitative trait transmission disequilibrium test (QTDT; GENECARD. SNPs associated with the intermediate quantitative trait, LDL-C, were then assessed for association with CAD (i.e., a qualitative phenotype using linkage and association in the presence of linkage (APL; GENECARD and logistic regression (CATHGEN and aortas. Results We identified four genes with SNPs that showed the strongest and most consistent associations with LDL-C and CAD: EBF1, PPP2R2B, SPOCK1, and PRELID2. The most significant results for association of SNPs with LDL-C were: EBF1, rs6865969, p = 0.01; PPP2R2B, rs2125443, p = 0.005; SPOCK1, rs17600115, p = 0.003; and PRELID2, rs10074645, p = 0.0002. The most significant results for

  11. The importance of including local correlation times in the calculation of inter-proton distances from NMR measurements: ignoring local correlation times leads to significant errors in the conformational analysis of the Glc alpha1-2Glc alpha linkage by NMR spectroscopy.

    Mackeen, Mukram; Almond, Andrew; Cumpstey, Ian; Enis, Seth C; Kupce, Eriks; Butters, Terry D; Fairbanks, Antony J; Dwek, Raymond A; Wormald, Mark R

    2006-06-07

    The experimental determination of oligosaccharide conformations has traditionally used cross-linkage 1H-1H NOE/ROEs. As relatively few NOEs are observed, to provide sufficient conformational constraints this method relies on: accurate quantification of NOE intensities (positive constraints); analysis of absent NOEs (negative constraints); and hence calculation of inter-proton distances using the two-spin approximation. We have compared the results obtained by using 1H 2D NOESY, ROESY and T-ROESY experiments at 500 and 700 MHz to determine the conformation of the terminal Glc alpha1-2Glc alpha linkage in a dodecasaccharide and a related tetrasaccharide. For the tetrasaccharide, the NOESY and ROESY spectra produced the same qualitative pattern of linkage cross-peaks but the quantitative pattern, the relative peak intensities, was different. For the dodecasaccharide, the NOESY and ROESY spectra at 500 MHz produced a different qualitative pattern of linkage cross-peaks, with fewer peaks in the NOESY spectrum. At 700 MHz, the NOESY and ROESY spectra of the dodecasaccharide produced the same qualitative pattern of peaks, but again the relative peak intensities were different. These differences are due to very significant differences in the local correlation times for different proton pairs across this glycosidic linkage. The local correlation time for each proton pair was measured using the ratio of the NOESY and T-ROESY cross-relaxation rates, leaving the NOESY and ROESY as independent data sets for calculating the inter-proton distances. The inter-proton distances calculated including the effects of differences in local correlation times give much more consistent results.

  12. Quantifying sources of bias in longitudinal data linkage studies of child abuse and neglect: measuring impact of outcome specification, linkage error, and partial cohort follow-up.

    Parrish, Jared W; Shanahan, Meghan E; Schnitzer, Patricia G; Lanier, Paul; Daniels, Julie L; Marshall, Stephen W

    2017-12-01

    Health informatics projects combining statewide birth populations with child welfare records have emerged as a valuable approach to conducting longitudinal research of child maltreatment. The potential bias resulting from linkage misspecification, partial cohort follow-up, and outcome misclassification in these studies has been largely unexplored. This study integrated epidemiological survey and novel administrative data sources to establish the Alaska Longitudinal Child Abuse and Neglect Linkage (ALCANLink) project. Using these data we evaluated and quantified the impact of non-linkage misspecification and single source maltreatment ascertainment use on reported maltreatment risk and effect estimates. The ALCANLink project integrates the 2009-2011 Alaska Pregnancy Risk Assessment Monitoring System (PRAMS) sample with multiple administrative databases through 2014, including one novel administrative source to track out-of-state emigration. For this project we limited our analysis to the 2009 PRAMS sample. We report on the impact of linkage quality, cohort follow-up, and multisource outcome ascertainment on the incidence proportion of reported maltreatment before age 6 and hazard ratios of selected characteristics that are often available in birth cohort linkage studies of maltreatment. Failure to account for out-of-state emigration biased the incidence proportion by 12% (from 28.3% w to 25.2% w ), and the hazard ratio (HR) by as much as 33% for some risk factors. Overly restrictive linkage parameters biased the incidence proportion downwards by 43% and the HR by as much as 27% for some factors. Multi-source linkages, on the other hand, were of little benefit for improving reported maltreatment ascertainment. Using the ALCANLink data which included a novel administrative data source, we were able to observe and quantify bias to both the incidence proportion and HR in a birth cohort linkage study of reported child maltreatment. Failure to account for out

  13. Backward linkages from foreign investors to domestic firms

    Apostolov, Mico

    2016-01-01

    The analysis of how to design policies to promote backward linkages would not be complete without introducing sound discovery into the debate. Foreign investors would naturally prefer to avoid creating rivals to their market position, aiming at horizontal positioning. But workers and managers often leave foreign plants to start up their own; local firms learn from watching the operations of foreigners. In the vertical direction, in cont...

  14. Missing Linkages in California's Landscape [ds420

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

  15. Multiobjective optimization of a steering linkage

    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.

  16. EDITORIAL Development Linkages between Tree Breeding ...

    EDITORIAL Development Linkages between Tree Breeding Programmes and National/Regional Tree Seed Centres in Africa. ... Discovery and Innovation. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives.

  17. Missing Linkages in California's Landscape [ds420

    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...

  18. Multiobjective optimization of a steering linkage

    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

  19. Asian Financial Linkages: The Case of Japan

    Fialová, Anežka

    2014-01-01

    This work reviews the topic of international financial linkages, including theoretical definitions and the main methodological approaches of the empirical measurement based on vector autoregressive models. One of the approaches, the Spillover Index methodology based on Diebold & Yilmaz (2009), is then used to analyze the developments of financial linkages of the Japanese stock market in the period from 1995 to 2012. The attention is paid both to the relations with western developed economies ...

  20. Nuclear hazard/fire hazard: an elusive and important linkage

    Mariani, L.P.

    1977-01-01

    The Brown's Ferry Fire signaled a yellow alert for nuclear safety related fire protection and showed that fire protection engineering must be regarded as a bona fide nuclear discipline. A single-failure design criteria violation resulted in fire damage to plant systems and plant instrumentation. Localized damage lead to significant consequences. Although the linkage between fire and nuclear hazard is termed subtle, effective standards and criteria development must be aimed to future plants. Combined fire protection and nuclear engineering inspections are planned

  1. Linkages at Tourism Destinations: Challenges in Zanzibar

    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.

  2. A High-Density SNP Genetic Linkage Map and QTL Analysis of Growth-Related Traits in a Hybrid Family of Oysters (Crassostrea gigas × Crassostrea angulata Using Genotyping-by-Sequencing

    Jinpeng Wang

    2016-05-01

    Full Text Available Oysters are among the most important species in global aquaculture. Crassostrea gigas, and its subspecies C. angulata, are the major cultured species. To determine the genetic basis of growth-related traits in oysters, we constructed a second-generation linkage map from 3367 single-nucleotide polymorphisms (SNPs based on genotyping-by-sequencing, genotyped from a C. gigas × C. angulata hybrid family. These 3367 SNPs were distributed on 1695 markers, which were assigned to 10 linkage groups. The genetic linkage map had a total length of 1084.3 cM, with an average of 0.8 cM between markers; it thus represents the densest genetic map constructed for oysters to date. Twenty-seven quantitative trait loci (QTL for five growth-related traits were detected. These QTL could explain 4.2–7.7% (mean = 5.4% of the phenotypic variation. In total, 50.8% of phenotypic variance for shell width, 7.7% for mass weight, and 34.1% for soft tissue weight were explained. The detected QTL were distributed among eight linkage groups, and more than half (16 were concentrated within narrow regions in their respective linkage groups. Thirty-eight annotated genes were identified within the QTL regions, two of which are key genes for carbohydrate metabolism. Other genes were found to participate in assembly and regulation of the actin cytoskeleton, signal transduction, and regulation of cell differentiation and development. The newly developed high-density genetic map, and the QTL and candidate genes identified provide a valuable genetic resource and a basis for marker-assisted selection for C. gigas and C. angulata.

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

    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...... represents one of the biggest genome scans so far reported for asthma related phenotypes. This study also demonstrates the utility of increased sample sizes and quantitative phenotypes in linkage analysis of complex disorders....

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

    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

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

    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.

  6. Genome scan for linkage to Gilles de la Tourette syndrome

    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.

  7. Phase-Division-Based Dynamic Optimization of Linkages for Drawing Servo Presses

    Zhang, Zhi-Gang; Wang, Li-Ping; Cao, Yan-Ke

    2017-11-01

    Existing linkage-optimization methods are designed for mechanical presses; few can be directly used for servo presses, so development of the servo press is limited. Based on the complementarity of linkage optimization and motion planning, a phase-division-based linkage-optimization model for a drawing servo press is established. Considering the motion-planning principles of a drawing servo press, and taking account of work rating and efficiency, the constraints of the optimization model are constructed. Linkage is optimized in two modes: use of either constant eccentric speed or constant slide speed in the work segments. The performances of optimized linkages are compared with those of a mature linkage SL4-2000A, which is optimized by a traditional method. The results show that the work rating of a drawing servo press equipped with linkages optimized by this new method improved and the root-mean-square torque of the servo motors is reduced by more than 10%. This research provides a promising method for designing energy-saving drawing servo presses with high work ratings.

  8. An improved recommendation algorithm via weakening indirect linkage effect

    Chen, Guang; Qiu, Tian; Shen, Xiao-Quan

    2015-07-01

    We propose an indirect-link-weakened mass diffusion method (IMD), by considering the indirect linkage and the source object heterogeneity effect in the mass diffusion (MD) recommendation method. Experimental results on the MovieLens, Netflix, and RYM datasets show that, the IMD method greatly improves both the recommendation accuracy and diversity, compared with a heterogeneity-weakened MD method (HMD), which only considers the source object heterogeneity. Moreover, the recommendation accuracy of the cold objects is also better elevated in the IMD than the HMD method. It suggests that eliminating the redundancy induced by the indirect linkages could have a prominent effect on the recommendation efficiency in the MD method. Project supported by the National Natural Science Foundation of China (Grant No. 11175079) and the Young Scientist Training Project of Jiangxi Province, China (Grant No. 20133BCB23017).

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

    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.

  10. Dimensional threshold for fracture linkage and hooking

    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°.

  11. #13ReasonsWhy Health Professionals and Educators are Tweeting: A Systematic Analysis of Uses and Perceptions of Show Content and Learning Outcomes.

    Walker, Kimberly K; Burns, Kelli

    2018-04-27

    This study is a content analysis of health professionals' and educators' tweets about a popular Netflix show that depicts teen suicide: 13 Reasons Why. A content analysis of 740 tweets was conducted to determine the main themes associated with professionals' and educators' tweets about the show, as well as the valence of the tweets. Additionally, a thematic analysis of linked content in tweets (n = 178) was conducted to explore additional content shared about the show and modeling outcomes. Results indicated the largest percentage of tweets was related to social learning, particularly about outcomes that could occur from viewing the show. The valence of the tweets about outcomes was more positive than negative. However, linked materials commonly circulated in tweets signified greater concern with unintended learning outcomes. Some of the linked content included media guidelines for reporting on suicide with recommendations that entertainment producers follow the guidelines. This study emphasizes the importance of including social learning objectives in future typologies of Twitter uses and demonstrates the importance of examining linked content in Twitter studies.

  12. Genetic linkage map and QTL identification for adventitious rooting traits in red gum eucalypts.

    Sumathi, Murugan; Bachpai, Vijaya Kumar Waman; Mayavel, A; Dasgupta, Modhumita Ghosh; Nagarajan, Binai; Rajasugunasekar, D; Sivakumar, Veerasamy; Yasodha, Ramasamy

    2018-05-01

    The eucalypt species, Eucalyptus tereticornis and Eucalyptus camaldulensis , show tolerance to drought and salinity conditions, respectively, and are widely cultivated in arid and semiarid regions of tropical countries. In this study, genetic linkage map was developed for interspecific cross E. tereticornis  ×  E. camaldulensis using pseudo-testcross strategy with simple sequence repeats (SSRs), intersimple sequence repeats (ISSRs), and sequence-related amplified polymorphism (SRAP) markers. The consensus genetic map comprised totally 283 markers with 84 SSRs, 94 ISSRs, and 105 SRAP markers on 11 linkage groups spanning 1163.4 cM genetic distance. Blasting the SSR sequences against E. grandis sequences allowed an alignment of 64% and the average ratio of genetic-to-physical distance was 1.7 Mbp/cM, which strengths the evidence that high amount of synteny and colinearity exists among eucalypts genome. Blast searches also revealed that 37% of SSRs had homologies with genes, which could potentially be used in the variety of downstream applications including candidate gene polymorphism. Quantitative trait loci (QTL) analysis for adventitious rooting traits revealed six QTL for rooting percent and root length on five chromosomes with interval and composite interval mapping. All the QTL explained 12.0-14.7% of the phenotypic variance, showing the involvement of major effect QTL on adventitious rooting traits. Increasing the density of markers would facilitate the detection of more number of small-effect QTL and also underpinning the genes involved in rooting process.

  13. A novel syndrome of abnormal striatum and congenital cataract: evidence for linkage to chromosomes 11.

    Al-Owain, M; Al-Zahrani, J; Al-Bakheet, A; Abudheim, N; Al-Younes, B; Aldhalaan, H; Al-Zaidan, H; Colak, D; Almohaileb, F; Abouzied, M E; Al-Fadhli, F; Meyer, B; Kaya, N

    2013-09-01

    We report a consanguineous family of three girls and one boy affected with a novel syndrome involving the lens and the basal ganglia. The phenotype is strikingly similar between affected siblings with cognitive impairment, attention deficit hyperactivity disorder (ADHD), microcephaly, growth retardation, congenital cataract, and dystonia. The magnetic resonance imaging showed unusual pattern of swelling of the caudate heads and thinning of the putamina with severe degree of hypometabolism on the [18F] deoxyglucose positron emission tomography. Furthermore, the clinical assessment provides the evidence that the neurological phenotype is very slowly progressive. We utilized the 10K single-nucleotide polymorphism (SNP) microarray genotyping for linkage analysis. Genome-wide scan indicated a 45.9-Mb region with a 4.2353 logarithm of the odds score on chromosome 11. Affymetrix genome-wide human SNP array 6.0 assay did not show any gross chromosomal abnormality. Targeted sequencing of two candidate genes within the linkage interval (PAX6 and B3GALTL) as well as mtDNA genome sequencing did not reveal any putative mutations. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Evolution of zygotic linkage disequilibrium in a finite local population.

    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.

  15. Intragroup emotions: physiological linkage and social presence

    Simo eJärvelä

    2016-02-01

    Full Text Available We investigated how technologically mediating two different components of emotion – communicative expression and physiological state – to group members affects physiological linkage and self-reported feelings in a small group during video viewing. In different conditions the availability of second screen text chat (communicative expression and visualization of group level physiological heart rates and their dyadic linkage (physiology was varied. Within this four person group two participants formed a physically co-located dyad and the other two were individually situated in two separate rooms. We found that text chat always increased heart rate synchrony but HR visualization only with non-co-located dyads. We also found that physiological linkage was strongly connected to self-reported social presence. The results encourage further exploration of the possibilities of sharing group member’s physiological components of emotion by technological means to enhance mediated communication and strengthen social presence.

  16. Intragroup Emotions: Physiological Linkage and Social Presence.

    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.

  17. A microsatellite linkage map of Drosophila mojavensis

    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

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

    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...

  20. Some methods for blindfolded record linkage

    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

  1. The Barley Chromosome 5 Linkage Map

    Jensen, J.; Jørgensen, Jørgen Helms

    1975-01-01

    The distances between nine loci on barley chromosome 5 have been studied in five two-point tests, three three-point tests, and one four-point test. Our previous chromosome 5 linkage map, which contained eleven loci mapped from literature data (Jensen and Jørgensen 1975), is extended with four loci......-position is fixed on the map by a locus (necl), which has a good marker gene located centrally in the linkage group. The positions of the other loci are their distances in centimorgans from the 0-position; loci in the direction of the short chromosome arm are assigned positive values and those...

  2. Predicting the number and sizes of IBD regions among family members and evaluating the family size requirement for linkage studies.

    Yang, Wanling; Wang, Zhanyong; Wang, Lusheng; Sham, Pak-Chung; Huang, Peng; Lau, Yu Lung

    2008-12-01

    With genotyping of high-density single nucleotide polymorphisms (SNPs) replacing that of microsatellite markers in linkage studies, it becomes possible to accurately determine the genomic regions shared identity by descent (IBD) by family members. In addition to evaluating the likelihood of linkage for a region with the underlining disease (the LOD score approach), an appropriate question to ask is what would be the expected number and sizes of IBD regions among the affecteds, as there could be more than one region reaching the maximum achievable LOD score for a given family. Here, we introduce a computer program to allow the prediction of the total number of IBD regions among family members and their sizes. Reversely, it can be used to predict the portion of the genome that can be excluded from consideration according to the family size and user-defined inheritance mode and penetrance. Such information has implications on the feasibility of conducting linkage analysis on a given family of certain size and structure or on a few small families when interfamily homogeneity can be assumed. It can also help determine the most relevant members to be genotyped for such a study. Simulation results showed that the IBD regions containing true mutations are usually larger than regions IBD due to random chance. We have made use of this feature in our program to allow evaluation of the identified IBD regions based on Bayesian probability calculation and simulation results.

  3. Systematic analysis of DEMETER-like DNA glycosylase genes shows lineage-specific Smi-miR7972 involved in SmDML1 regulation in Salvia miltiorrhiza.

    Li, Jiang; Li, Caili; Lu, Shanfa

    2018-05-08

    DEMETER-like DNA glycosylases (DMLs) initiate the base excision repair-dependent DNA demethylation to regulate a wide range of biological processes in plants. Six putative SmDML genes, termed SmDML1-SmDML6, were identified from the genome of S. miltiorrhiza, an emerging model plant for Traditional Chinese Medicine (TCM) studies. Integrated analysis of gene structures, sequence features, conserved domains and motifs, phylogenetic analysis and differential expression showed the conservation and divergence of SmDMLs. SmDML1, SmDML2 and SmDML4 were significantly down-regulated by the treatment of 5Aza-dC, a general DNA methylation inhibitor, suggesting involvement of SmDMLs in genome DNA methylation change. SmDML1 was predicted and experimentally validated to be target of Smi-miR7972. Computational analysis of forty whole genome sequences and almost all of RNA-seq data from Lamiids revealed that MIR7972s were only distributed in some plants of the three orders, including Lamiales, Solanales and Boraginales, and the number of MIR7972 genes varied among species. It suggests that MIR7972 genes underwent expansion and loss during the evolution of some Lamiids species. Phylogenetic analysis of MIR7972s showed closer evolutionary relationships between MIR7972s in Boraginales and Solanales in comparison with Lamiales. These results provide a valuable resource for elucidating DNA demethylation mechanism in S. miltiorrhiza.

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

    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.

  5. A procedure for the detection of linkage with high density SNP arrays in a large pedigree with colorectal cancer

    Middeldorp, Anneke; Wijnen, Juul T; Wezel, Tom van; Jagmohan-Changur, Shantie; Helmer, Quinta; Klift, Heleen M van der; Tops, Carli MJ; Vasen, Hans FA; Devilee, Peter; Morreau, Hans; Houwing-Duistermaat, Jeanine J

    2007-01-01

    The apparent dominant model of colorectal cancer (CRC) inheritance in several large families, without mutations in known CRC susceptibility genes, suggests the presence of so far unidentified genes with strong or moderate effect on the development of CRC. Linkage analysis could lead to identification of susceptibility genes in such families. In comparison to classical linkage analysis with multi-allelic markers, single nucleotide polymorphism (SNP) arrays have increased information content and can be processed with higher throughput. Therefore, SNP arrays can be excellent tools for linkage analysis. However, the vast number of SNPs on the SNP arrays, combined with large informative pedigrees (e.g. >35–40 bits), presents us with a computational complexity that is challenging for existing statistical packages or even exceeds their capacity. We therefore setup a procedure for linkage analysis in large pedigrees and validated the method by genotyping using SNP arrays of a colorectal cancer family with a known MLH1 germ line mutation. Quality control of the genotype data was performed in Alohomora, Mega2 and SimWalk2, with removal of uninformative SNPs, Mendelian inconsistencies and Mendelian consistent errors, respectively. Linkage disequilibrium was measured by SNPLINK and Merlin. Parametric linkage analysis using two flanking markers was performed using MENDEL. For multipoint parametric linkage analysis and haplotype analysis, SimWalk2 was used. On chromosome 3, in the MLH1-region, a LOD score of 1.9 was found by parametric linkage analysis using two flanking markers. On chromosome 11 a small region with LOD 1.1 was also detected. Upon linkage disequilibrium removal, multipoint linkage analysis yielded a LOD score of 2.1 in the MLH1 region, whereas the LOD score dropped to negative values in the region on chromosome 11. Subsequent haplotype analysis in the MLH1 region perfectly matched the mutation status of the family members. We developed a workflow for linkage

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

    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 ...

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

    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.

  8. Aquaculture disturbance impacts the diet but not ecological linkages of a ubiquitous predatory fish

    McPeek, Kathleen C.; McDonald, P. Sean; VanBlaricom, Glenn

    2015-01-01

    Aquaculture operations are a frequent and prominent cause of anthropogenic disturbance to marine and estuarine communities and may alter species composition and abundance. However, little is known about how such disturbances affect trophic linkages or ecosystem functions. In Puget Sound, Washington, aquaculture of the Pacific geoduck clam (Panopea generosa) is increasing and involves placing nets and polyvinyl chloride (PVC) tubes in intertidal areas to protect juvenile geoducks from predators. Initial studies of the structured phase of the farming cycle have documented limited impacts on the abundance of some species. To examine the effect of geoduck aquaculture on ecological linkages, the trophic relationships of a local ubiquitous consumer, Pacific staghorn sculpin (Leptocottus armatus), to its invertebrate prey were compared between geoduck aquaculture sites and nearby reference areas with no aquaculture. Mark-recapture data indicated that sculpin exhibit local site fidelity to cultured and reference areas. The stomach contents of sculpin and stable isotope signatures of sculpin and their prey were examined to study the trophic ecology of cultured and reference areas. Results showed that the structured phase of geoduck aquaculture initiated some changes to staghorn sculpin ecology, as reflected in sculpin diet through stomach content analysis. However, carbon and nitrogen stable isotopes revealed that the general food web function of sculpin remained unchanged. The source of carbon at the base of the food web and the trophic position of sculpin were not impacted by geoduck aquaculture. The study has important implications for geoduck aquaculture management and will inform regulatory decisions related to shellfish aquaculture policy.

  9. Development of a humanoid robot hand with coupling four-bar linkage

    Xinhua Liu

    2017-01-01

    Full Text Available To improve the operating performance of robots’ end-effector, a humanoid robot hand based on coupling four-bar linkage was designed. An improved transmission system was proposed for the base joint of the thumb. Thus, a far greater motion range and more reasonable layout of the palm were obtained. Moreover, the mathematical model for kinematics simulation was presented based on the Assur linkage group theory to verify and optimize the proposed structure. To research the motion relationships between the fingers and the object in the process of grasping object, the grasping analysis of multi-finger manipulation was presented based on contact kinematics. Finally, a prototype of the humanoid robot hand was produced by a three-dimensional printer, and a kinematics simulation example and the workspace solving of the humanoid robot hand were carried out. The results showed that the velocities of finger joints approximately met the proportion relationship 1:1:1, which accorded with the grasping law of the human hand. In addition, the large workspace, reasonable layout, and good manipulability of the humanoid robot hand were verified.

  10. Construction of an almond linkage map in an Australian population Nonpareil × Lauranne

    2010-01-01

    Background Despite a high genetic similarity to peach, almonds (Prunus dulcis) have a fleshless fruit and edible kernel, produced as a crop for human consumption. While the release of peach genome v1.0 provides an excellent opportunity for almond genetic and genomic studies, well-assessed segregating populations and the respective saturated genetic linkage maps lay the foundation for such studies to be completed in almond. Results Using an almond intraspecific cross between 'Nonpareil' and 'Lauranne' (N × L), we constructed a moderately saturated map with SSRs, SNPs, ISSRs and RAPDs. The N × L map covered 591.4 cM of the genome with 157 loci. The average marker distance of the map was 4.0 cM. The map displayed high synteny and colinearity with the Prunus T × E reference map in all eight linkage groups (G1-G8). The positions of 14 mapped gene-anchored SNPs corresponded approximately with the positions of homologous sequences in the peach genome v1.0. Analysis of Mendelian segregation ratios showed that 17.9% of markers had significantly skewed genotype ratios at the level of P almond map, which is highly syntenic and collinear with the Prunus reference map and peach genome V1.0. Therefore, the well-assessed almond population reported here can be used to investigate the traits of interest under Australian growing conditions, and provides more information on the almond genome for the international community. PMID:20932335

  11. Meta-analysis of diffusion tensor imaging (DTI) studies shows altered fractional anisotropy occurring in distinct brain areas in association with depression

    Murphy, Melissa L

    2011-09-27

    Abstract Fractional anisotropy anomalies occurring in the white matter tracts in the brains of depressed patients may reflect microstructural changes underlying the pathophysiology of this disorder. We conducted a meta-analysis of fractional anisotropy abnormalities occurring in major depressive disorder using voxel-based diffusion tensor imaging studies. Using the Embase, PubMed and Google Scholar databases, 89 relevant data sets were identified, of which 7 (including 188 patients with major depressive disorder and 221 healthy controls) met our inclusion criteria. Authors were contacted to retrieve any additional data required. Coordinates were extracted from clusters of significant white matter fractional anisotropy differences between patients and controls. Relevant demographic, clinical and methodological variables were extracted from each study or obtained directly from authors. The meta-analysis was carried out using Signed Differential Mapping. Patients with depression showed decreased white matter fractional anisotropy values in the superior longitudinal fasciculus and increased fractional anisotropy values in the fronto-occipital fasciculus compared to controls. Using quartile and jackknife sensitivity analysis, we found that reduced fractional anisotropy in the left superior longitudinal fasciculus was very stable, with increases in the right fronto-occipital fasciculus driven by just one study. In conclusion, our meta-analysis revealed a significant reduction in fractional anisotropy values in the left superior longitudinal fasciculus, which may ultimately play an important role in the pathology of depression.

  12. Meta-analysis of diffusion tensor imaging studies shows altered fractional anisotropy occurring in distinct brain areas in association with depression.

    Murphy, Melissa L

    2011-09-01

    Fractional anisotropy anomalies occurring in the white matter tracts in the brains of depressed patients may reflect microstructural changes underlying the pathophysiology of this disorder. We conducted a meta-analysis of fractional anisotropy abnormalities occurring in major depressive disorder using voxel-based diffusion tensor imaging studies. Using the Embase, PubMed and Google Scholar databases, 89 relevant data sets were identified, of which 7 (including 188 patients with major depressive disorder and 221 healthy controls) met our inclusion criteria. Authors were contacted to retrieve any additional data required. Coordinates were extracted from clusters of significant white matter fractional anisotropy differences between patients and controls. Relevant demographic, clinical and methodological variables were extracted from each study or obtained directly from authors. The meta-analysis was carried out using Signed Differential Mapping. Patients with depression showed decreased white matter fractional anisotropy values in the superior longitudinal fasciculus and increased fractional anisotropy values in the fronto-occipital fasciculus compared to controls. Using quartile and jackknife sensitivity analysis, we found that reduced fractional anisotropy in the left superior longitudinal fasciculus was very stable, with increases in the right fronto-occipital fasciculus driven by just one study. In conclusion, our meta-analysis revealed a significant reduction in fractional anisotropy values in the left superior longitudinal fasciculus, which may ultimately play an important role in the pathology of depression.

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

    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.

  14. A Targeted Capture Linkage Map Anchors the Genome of the Schistosomiasis Vector Snail, Biomphalaria glabrata.

    Tennessen, Jacob A; Bollmann, Stephanie R; Blouin, Michael S

    2017-07-05

    The aquatic planorbid snail Biomphalaria glabrata is one of the most intensively-studied mollusks due to its role in the transmission of schistosomiasis. Its 916 Mb genome has recently been sequenced and annotated, but it remains poorly assembled. Here, we used targeted capture markers to map over 10,000 B. glabrata scaffolds in a linkage cross of 94 F1 offspring, generating 24 linkage groups (LGs). We added additional scaffolds to these LGs based on linkage disequilibrium (LD) analysis of targeted capture and whole-genome sequences of 96 unrelated snails. Our final linkage map consists of 18,613 scaffolds comprising 515 Mb, representing 56% of the genome and 75% of genic and nonrepetitive regions. There are 18 large (> 10 Mb) LGs, likely representing the expected 18 haploid chromosomes, and > 50% of the genome has been assigned to LGs of at least 17 Mb. Comparisons with other gastropod genomes reveal patterns of synteny and chromosomal rearrangements. Linkage relationships of key immune-relevant genes may help clarify snail-schistosome interactions. By focusing on linkage among genic and nonrepetitive regions, we have generated a useful resource for associating snail phenotypes with causal genes, even in the absence of a complete genome assembly. A similar approach could potentially improve numerous poorly-assembled genomes in other taxa. This map will facilitate future work on this host of a serious human parasite. Copyright © 2017 Tennessen et al.

  15. Construction of a reference genetic linkage map for carnation (Dianthus caryophyllus L.).

    Yagi, Masafumi; Yamamoto, Toshiya; Isobe, Sachiko; Hirakawa, Hideki; Tabata, Satoshi; Tanase, Koji; Yamaguchi, Hiroyasu; Onozaki, Takashi

    2013-10-26

    Genetic linkage maps are important tools for many genetic applications including mapping of quantitative trait loci (QTLs), identifying DNA markers for fingerprinting, and map-based gene cloning. Carnation (Dianthus caryophyllus L.) is an important ornamental flower worldwide. We previously reported a random amplified polymorphic DNA (RAPD)-based genetic linkage map derived from Dianthus capitatus ssp. andrezejowskianus and a simple sequence repeat (SSR)-based genetic linkage map constructed using data from intraspecific F2 populations; however, the number of markers was insufficient, and so the number of linkage groups (LGs) did not coincide with the number of chromosomes (x = 15). Therefore, we aimed to produce a high-density genetic map to improve its usefulness for breeding purposes and genetic research. We improved the SSR-based genetic linkage map using SSR markers derived from a genomic library, expression sequence tags, and RNA-seq data. Linkage analysis revealed that 412 SSR loci (including 234 newly developed SSR loci) could be mapped to 17 linkage groups (LGs) covering 969.6 cM. Comparison of five minor LGs covering less than 50 cM with LGs in our previous RAPD-based genetic map suggested that four LGs could be integrated into two LGs by anchoring common SSR loci. Consequently, the number of LGs corresponded to the number of chromosomes (x = 15). We added 192 new SSRs, eight RAPD, and two sequence-tagged site loci to refine the RAPD-based genetic linkage map, which comprised 15 LGs consisting of 348 loci covering 978.3 cM. The two maps had 125 SSR loci in common, and most of the positions of markers were conserved between them. We identified 635 loci in carnation using the two linkage maps. We also mapped QTLs for two traits (bacterial wilt resistance and anthocyanin pigmentation in the flower) and a phenotypic locus for flower-type by analyzing previously reported genotype and phenotype data. The improved genetic linkage maps and SSR markers developed

  16. A high-density SNP linkage scan with 142 combined subtype ADHD sib pairs identifies linkage regions on chromosomes 9 and 16.

    Asherson, P; Zhou, K; Anney, R J L; Franke, B; Buitelaar, J; Ebstein, R; Gill, M; Altink, M; Arnold, R; Boer, F; Brookes, K; Buschgens, C; Butler, L; Cambell, D; Chen, W; Christiansen, H; Feldman, L; Fleischman, K; Fliers, E; Howe-Forbes, R; Goldfarb, A; Heise, A; Gabriëls, I; Johansson, L; Lubetzki, I; Marco, R; Medad, S; Minderaa, R; Mulas, F; Müller, U; Mulligan, A; Neale, B; Rijsdijk, F; Rabin, K; Rommelse, N; Sethna, V; Sorohan, J; Uebel, H; Psychogiou, L; Weeks, A; Barrett, R; Xu, X; Banaschewski, T; Sonuga-Barke, E; Eisenberg, J; Manor, I; Miranda, A; Oades, R D; Roeyers, H; Rothenberger, A; Sergeant, J; Steinhausen, H-C; Taylor, E; Thompson, M; Faraone, S V

    2008-05-01

    As part of the International Multi-centre ADHD Genetics project we completed an affected sibling pair study of 142 narrowly defined Diagnostic and Statistical Manual of Mental Disorders, fourth edition combined type attention deficit hyperactivity disorder (ADHD) proband-sibling pairs. No linkage was observed on the most established ADHD-linked genomic regions of 5p and 17p. We found suggestive linkage signals on chromosomes 9 and 16, respectively, with the highest multipoint nonparametric linkage signal on chromosome 16q23 at 99 cM (log of the odds, LOD=3.1) overlapping data published from the previous UCLA (University of California, Los Angeles) (LOD>1, approximately 95 cM) and Dutch (LOD>1, approximately 100 cM) studies. The second highest peak in this study was on chromosome 9q22 at 90 cM (LOD=2.13); both the previous UCLA and German studies also found some evidence of linkage at almost the same location (UCLA LOD=1.45 at 93 cM; German LOD=0.68 at 100 cM). The overlap of these two main peaks with previous findings suggests that loci linked to ADHD may lie within these regions. Meta-analysis or reanalysis of the raw data of all the available ADHD linkage scan data may help to clarify whether these represent true linked loci.

  17. Quality of record linkage in a highly automated cancer registry that relies on encrypted identity data

    Schmidtmann, Irene

    2016-06-01

    Full Text Available Objectives: In the absence of unique ID numbers, cancer and other registries in Germany and elsewhere rely on identity data to link records pertaining to the same patient. These data are often encrypted to ensure privacy. Some record linkage errors unavoidably occur. These errors were quantified for the cancer registry of North Rhine Westphalia which uses encrypted identity data. Methods: A sample of records was drawn from the registry, record linkage information was included. In parallel, plain text data for these records were retrieved to generate a gold standard. Record linkage error frequencies in the cancer registry were determined by comparison of the results of the routine linkage with the gold standard. Error rates were projected to larger registries.Results: In the sample studied, the homonym error rate was 0.015%; the synonym error rate was 0.2%. The F-measure was 0.9921. Projection to larger databases indicated that for a realistic development the homonym error rate will be around 1%, the synonym error rate around 2%.Conclusion: Observed error rates are low. This shows that effective methods to standardize and improve the quality of the input data have been implemented. This is crucial to keep error rates low when the registry’s database grows. The planned inclusion of unique health insurance numbers is likely to further improve record linkage quality. Cancer registration entirely based on electronic notification of records can process large amounts of data with high quality of record linkage.

  18. Association between cancer and contact allergy: a linkage study

    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...... 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...

  19. A RAD-based linkage map and comparative genomics in the gudgeons (genus Gnathopogon, Cyprinidae

    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. Gene network analysis shows immune-signaling and ERK1/2 as novel genetic markers for multiple addiction phenotypes: alcohol, smoking and opioid addiction.

    Reyes-Gibby, Cielito C; Yuan, Christine; Wang, Jian; Yeung, Sai-Ching J; Shete, Sanjay

    2015-06-05

    Addictions to alcohol and tobacco, known risk factors for cancer, are complex heritable disorders. Addictive behaviors have a bidirectional relationship with pain. We hypothesize that the associations between alcohol, smoking, and opioid addiction observed in cancer patients have a genetic basis. Therefore, using bioinformatics tools, we explored the underlying genetic basis and identified new candidate genes and common biological pathways for smoking, alcohol, and opioid addiction. Literature search showed 56 genes associated with alcohol, smoking and opioid addiction. Using Core Analysis function in Ingenuity Pathway Analysis software, we found that ERK1/2 was strongly interconnected across all three addiction networks. Genes involved in immune signaling pathways were shown across all three networks. Connect function from IPA My Pathway toolbox showed that DRD2 is the gene common to both the list of genetic variations associated with all three addiction phenotypes and the components of the brain neuronal signaling network involved in substance addiction. The top canonical pathways associated with the 56 genes were: 1) calcium signaling, 2) GPCR signaling, 3) cAMP-mediated signaling, 4) GABA receptor signaling, and 5) G-alpha i signaling. Cancer patients are often prescribed opioids for cancer pain thus increasing their risk for opioid abuse and addiction. Our findings provide candidate genes and biological pathways underlying addiction phenotypes, which may be future targets for treatment of addiction. Further study of the variations of the candidate genes could allow physicians to make more informed decisions when treating cancer pain with opioid analgesics.

  1. The fading affect bias shows positive outcomes at the general but not the individual level of analysis in the context of social media.

    Gibbons, Jeffrey A; Horowitz, Kyle A; Dunlap, Spencer M

    2017-08-01

    Unpleasant affect fades faster than pleasant affect (e.g., Walker, Vogl, & Thompson, 1997); this effect is referred to as the Fading Affect Bias (FAB; Walker, Skowronski, Gibbons, Vogl, & Thompson, 2003a). Research shows that the FAB is consistently related to positive/healthy outcomes at a general but not at a specific level of analysis based on event types and individual differences (e.g., Gibbons et al., 2013). Based on the positive outcomes for FAB and negative outcomes for social media (Bolton et al., 2013; Huang, 2010), the current study examined FAB in the context of social media events along with related individual differences. General positive outcomes were shown in the form of robust FAB effects across social media and non-social media events, a larger FAB for non-social media events than for social media events, negative correlations of FAB with depression, anxiety, and stress as well as a positive correlation of FAB with self-esteem. However, the lack of a negative correlation between FAB and anxiety for social media events in a 3-way interaction did not show positive outcomes at a specific level of analysis. Rehearsal ratings mediated the 3-way interaction. Implications are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. A comparison of genotyping-by-sequencing analysis methods on low-coverage crop datasets shows advantages of a new workflow, GB-eaSy.

    Wickland, Daniel P; Battu, Gopal; Hudson, Karen A; Diers, Brian W; Hudson, Matthew E

    2017-12-28

    Genotyping-by-sequencing (GBS), a method to identify genetic variants and quickly genotype samples, reduces genome complexity by using restriction enzymes to divide the genome into fragments whose ends are sequenced on short-read sequencing platforms. While cost-effective, this method produces extensive missing data and requires complex bioinformatics analysis. GBS is most commonly used on crop plant genomes, and because crop plants have highly variable ploidy and repeat content, the performance of GBS analysis software can vary by target organism. Here we focus our analysis on soybean, a polyploid crop with a highly duplicated genome, relatively little public GBS data and few dedicated tools. We compared the performance of five GBS pipelines using low-coverage Illumina sequence data from three soybean populations. To address issues identified with existing methods, we developed GB-eaSy, a GBS bioinformatics workflow that incorporates widely used genomics tools, parallelization and automation to increase the accuracy and accessibility of GBS data analysis. Compared to other GBS pipelines, GB-eaSy rapidly and accurately identified the greatest number of SNPs, with SNP calls closely concordant with whole-genome sequencing of selected lines. Across all five GBS analysis platforms, SNP calls showed unexpectedly low convergence but generally high accuracy, indicating that the workflows arrived at largely complementary sets of valid SNP calls on the low-coverage data analyzed. We show that GB-eaSy is approximately as good as, or better than, other leading software solutions in the accuracy, yield and missing data fraction of variant calling, as tested on low-coverage genomic data from soybean. It also performs well relative to other solutions in terms of the run time and disk space required. In addition, GB-eaSy is built from existing open-source, modular software packages that are regularly updated and commonly used, making it straightforward to install and maintain

  3. A Content Analysis of How Sexual Behavior and Reproductive Health are Being Portrayed on Primetime Television Shows Being Watched by Teens and Young Adults.

    Kinsler, Janni J; Glik, Deborah; de Castro Buffington, Sandra; Malan, Hannah; Nadjat-Haiem, Carsten; Wainwright, Nicole; Papp-Green, Melissa

    2018-02-01

    Television is a leading source of sexual education for teens and young adults, thus it is important to understand how sexual behavior and reproductive health are portrayed in popular primetime programming. This study is a media content analysis of the 19 top-rated scripted English-language primetime television shows aired between January 1, 2015 and May 31, 2015, and viewed by American youth audiences 12-24 years of age. The purpose of this study is to assess how sex/sexuality and reproductive health are being portrayed in a popular medium that reaches many adolescent and young adult audiences. Themes used for this analysis include youth pregnancy/parenting, mentoring/guidance of youth regarding sexual behavior, sex/sexuality, body image/identity, sexual violence/abuse/harassment, gender identity/sexual orientation, and reproductive health. Themes have been classified in one of the following six categories: visual cues, brief mentions, dialogue, minor storylines, major storylines, and multi-episode storylines. Our findings indicate that narratives providing educational information regarding the risks and consequences of sexual behavior were missing from the television shows we analyzed and that storylines promoting low risk sexual behavior were rare. Sexual violence and abuse, casual sex among adults, lack of contraception use, or no portrayal of consequences of risky behaviors were common. Compared to prior research, we found an emergent theme normalizing non-heterosexual gender identity and sexual orientation. Our findings have important implications as exposure to popular media shapes the perceptions and behaviors of teens and young adults. This study has the potential to shed light on the need to create stories and narratives in television shows watched by American teens and young adults with educational messages regarding the risks and consequences of sexual behavior.

  4. Availability of Insurance Linkage Programs in U.S. Emergency Departments

    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

  5. Semantic Linkage of Control Systems

    Rolf Andreas Rasenack

    2006-01-01

    Full Text Available Control systems are sets of interconnected hardware and software components which regulate the behaviour of processes. The software of modern control systems rises for some years by requirements regarding the flexibility and functionality. Thus the force of innovation grows on enterprises, since ever newer products in ever shorter time intervals must be made available. Associated hereby is the crucial shortening of the product life cycle, whose effects show up in reduced care of the software and the spares inventory. The aim, the concept presented here and developed in a modeling environment, is proved and ensures a minimum functionality of software components. Replacing software components of a control system verified for functionality by a framework at run-time and if necessary the software conditions will become adapted. Quintessential point of this implementation is the usage of an abstract syntax tree. Within its hierarchical structure meta information is attached to nodes and processed by the framework. With the development of the concept for semantic proving of software components the lifetime of software-based products is increased.

  6. Analysis of genetic distance between Peruvian Alpaca (Vicugna Pacos showing two distinct fleece phenotypes, Suri and Huacaya, by means of microsatellite markers

    Carlo Renieri

    2011-10-01

    Full Text Available Two coat phenotypes exist in Alpaca, Huacaya and Suri. The two coats show different fleece structure, textile characteristics and prices on the market. Although present scientific knowledge suggests a simple genetic model of inheritance, there is a tendency to manage and consider the two phenotypes as two different breeds. A 13 microsatellite panel was used in this study to assess genetic distance between Suri and Huacaya alpacas in a sample of non-related animals from two phenotypically pure flocks at the Illpa-Puno experimental station in Quimsachata, Peru. The animals are part of a germplasm established approximately 20 years ago and have been bred separately according to their coat type since then. Genetic variability parameters were also calculated. The data were statistically analyzed using the software Genalex 6.3, Phylip 3.69 and Fstat 2.9.3.2. The sample was tested for Hardy-Weinberg equilibrium (HWE and after strict Bonferroni correction only one locus (LCA37 showed deviation from equilibrium (Ploci associations showed significant disequilibrium. Observed heterozygosis (Ho= 0.766; SE=0.044, expected heterozygosis (He=0.769; SE=0.033, number of alleles (Na=9.667, SE=0.772 and Fixation index (F=0.004; SE=0.036 are comparable to data from previous studies. Measures of genetic distance were 0.06 for Nei’s and 0.03 for Cavalli-Sforza’s. The analysis of molecular variance reported no existing variance between populations. Considering the origin of the animals, their post domestication evolution and the reproductive practices in place, the results do not show genetic differentiation between the two populations for the studied loci.

  7. Gc, gc-ms analysis of lipophilic fractions of aerial parts of fagonia indica burm.f. showing growth inhibitory effect on ht 29 colorectal cancer cells

    Farheen, R.; Mahmood, I.

    2016-01-01

    Fagonia indica Burm.f. is a small genus of herbs and under shrubs. The plant contains potentially active substances and has been used traditionally for the treatment of many illnesses including cancer. Many polar compounds have been reported from this plant but its non-polar constituents have only been rarely studied. In the present studies these constituents of aerial parts of Fagonia indica Burm.f. and its sub fractions showing growth inhibitory effect on HT 29 colorectal cancer cells were analyzed using flame ionization detector (GC-FID) and GC-EIMS analysis. The present studies exhibited the presence of free fatty acids and their esters along with structurally diverse constituents including triterpene, heterocyclic organic compound, aromatics, hydrocarbons, alcohols, lactone and sterols which may be responsible for this activity. The results suggest that the non-polar constituents of F. indica bear a potential of further studies. (author)

  8. Show-Bix &

    2014-01-01

    The anti-reenactment 'Show-Bix &' consists of 5 dias projectors, a dial phone, quintophonic sound, and interactive elements. A responsive interface will enable the Dias projectors to show copies of original dias slides from the Show-Bix piece ”March på Stedet”, 265 images in total. The copies are...

  9. CITY HOTSPOT: LINKAGES BETWEEN ECOSYSTEM SERVICES AND BIODIVERSITY OF URBAN GREEN AREAS

    Špela Železnikar

    2017-01-01

    Full Text Available Green areas in cities and their ecosystem services (ES offer residents various benefits. The range of services depends on biodiversity of a green space. The aim was to determine the relationship between biodiversity in different categories of green areas in the city and the ecosystem services, which appear in it. We made 108 relevés in the autumn and spring time, within nine categories of green areas in the Municipality of Ljubljana. In each category the range of ES was assessed based on field analysis and compared with literature assessed ecosystem services. Results showed that the category of forests differ from others. Other categories were similar to each other, in particular grassland categories. Also, a positive relationship linkage was found - more plant species mean more assessed ecosystem services in a specific green infrastructure category.

  10. Large Scale Genome Analysis Shows that the Epitopes for Broadly Cross-Reactive Antibodies Are Predominant in the Pandemic 2009 Influenza Virus A H1N1 Strain

    Edgar E. Lara-Ramírez

    2013-11-01

    Full Text Available The past pandemic strain H1N1 (A (H1N1pdm09 has now become a common component of current seasonal influenza viruses. It has changed the pre-existing immunity of the human population to succeeding infections. In the present study, a total of 14,210 distinct sequences downloaded from National Center for Biotechnology Information (NCBI database were used for the analysis. The epitope compositions in A (H1N1pdm09, classic seasonal strains, swine strains as well as highly virulent avian strain H5N1, identified with the aid of the Immune Epitope DataBase (IEDB, were compared at genomic level. The result showed that A (H1N1 pdm09 contains the 90% of B-cell epitopes for broadly cross-reactive antibodies (EBCA, which is in consonance with the recent reports on the experimental identification of new epitopes or antibodies for this virus and the binding tests with influenza virus protein HA of different subtypes. Our analysis supports that high proportional EBCA depends on the epitope pattern of A (H1N1pdm09 virus. This study may be helpful for better understanding of A (H1N1pdm09 and the production of new influenza vaccines.

  11. Kempe's Linkages and the Universality Theorem

    sriranga

    that between BO and OA (i.e., \\BOA). Let these two angles be denoted by µ. Thus, if link OA makes an angle. µ with link OB, OE makes the same angle on the other side of OB. Kempe therefore referred to this linkage as the (angle) reversor. This is true irrespective of how OA and OB are placed relative to each other. Also ...

  12. Hidden linkages between urbanization and food systems.

    Seto, Karen C; Ramankutty, Navin

    2016-05-20

    Global societies are becoming increasingly urban. This shift toward urban living is changing our relationship with food, including how we shop and what we buy, as well as ideas about sanitation and freshness. Achieving food security in an era of rapid urbanization will require considerably more understanding about how urban and food systems are intertwined. Here we discuss some potential understudied linkages that are ripe for further examination. Copyright © 2016, American Association for the Advancement of Science.

  13. Robotic Assisted Radical Cystectomy with Extracorporeal Urinary Diversion Does Not Show a Benefit over Open Radical Cystectomy: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

    Wei Shen Tan

    Full Text Available The number of robotic assisted radical cystectomy (RARC procedures is increasing despite the lack of Level I evidence showing any advantages over open radical cystectomy (ORC. However, several systematic reviews with meta-analyses including non-randomised studies, suggest an overall benefit for RARC compared to ORC. We performed a systematic review with meta-analysis of randomised controlled trials (RCTs to evaluate the perioperative morbidity and efficacy of RARC compared to ORC in patients with bladder cancer.Literature searches of Medline/Pubmed, Embase, Web of Science and clinicaltrials.gov databases up to 10th March 2016 were performed. The inclusion criteria for eligible studies were RCTs which compared perioperative outcomes of ORC and RARC for bladder cancer. Primary objective was perioperative and histopathological outcomes of RARC versus ORC while the secondary objective was quality of life assessment (QoL, oncological outcomes and cost analysis.Four RCTs (from 5 articles met the inclusion criteria, with a total of 239 patients all with extracorporeal urinary diversion. Patient demographics and clinical characteristics of RARC and ORC patients were evenly matched. There was no significant difference between groups in perioperative morbidity, length of stay, positive surgical margin, lymph node yield and positive lymph node status. RARC group had significantly lower estimated blood loss (p<0.001 and wound complications (p = 0.03 but required significantly longer operating time (p<0.001. QoL was not measured uniformly across trials and cost analysis was reported in one RCTs. A test for heterogeneity did highlight differences across operating time of trials suggesting that surgeon experience may influence outcomes.This study does not provide evidence to support a benefit for RARC compared to ORC. These results may not have inference for RARC with intracorporeal urinary diversion. Well-designed trials with appropriate endpoints conducted

  14. Gene expression analysis of two extensively drug-resistant tuberculosis isolates show that two-component response systems enhance drug resistance.

    Yu, Guohua; Cui, Zhenling; Sun, Xian; Peng, Jinfu; Jiang, Jun; Wu, Wei; Huang, Wenhua; Chu, Kaili; Zhang, Lu; Ge, Baoxue; Li, Yao

    2015-05-01

    Global analysis of expression profiles using DNA microarrays was performed between a reference strain H37Rv and two clinical extensively drug-resistant isolates in response to three anti-tuberculosis drug exposures (isoniazid, capreomycin, and rifampicin). A deep analysis was then conducted using a combination of genome sequences of the resistant isolates, resistance information, and related public microarray data. Certain known resistance-associated gene sets were significantly overrepresented in upregulated genes in the resistant isolates relative to that observed in H37Rv, which suggested a link between resistance and expression levels of particular genes. In addition, isoniazid and capreomycin response genes, but not rifampicin, either obtained from published works or our data, were highly consistent with the differentially expressed genes of resistant isolates compared to those of H37Rv, indicating a strong association between drug resistance of the isolates and genes differentially regulated by isoniazid and capreomycin exposures. Based on these results, 92 genes of the studied isolates were identified as candidate resistance genes, 10 of which are known resistance-related genes. Regulatory network analysis of candidate resistance genes using published networks and literature mining showed that three two-component regulatory systems and regulator CRP play significant roles in the resistance of the isolates by mediating the production of essential envelope components. Finally, drug sensitivity testing indicated strong correlations between expression levels of these regulatory genes and sensitivity to multiple anti-tuberculosis drugs in Mycobacterium tuberculosis. These findings may provide novel insights into the mechanism underlying the emergence and development of drug resistance in resistant tuberculosis isolates and useful clues for further studies on this issue. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. 'Linkage' pharmaceutical evergreening in Canada and Australia

    Faunce, Thomas A; Lexchin, Joel

    2007-01-01

    'Evergreening' is not a formal concept of patent law. It is best understood as a social idea used to refer to the myriad ways in which pharmaceutical patent owners utilise the law and related regulatory processes to extend their high rent-earning intellectual monopoly privileges, particularly over highly profitable (either in total sales volume or price per unit) 'blockbuster' drugs. Thus, while the courts are an instrument frequently used by pharmaceutical brand name manufacturers to prolong their patent royalties, 'evergreening' is rarely mentioned explicitly by judges in patent protection cases. The term usually refers to threats made to competitors about a brand-name manufacturer's tactical use of pharmaceutical patents (including over uses, delivery systems and even packaging), not to extension of any particular patent over an active product ingredient. This article focuses in particular on the 'evergreening' potential of so-called 'linkage' provisions, imposed on the regulatory (safety, quality and efficacy) approval systems for generic pharmaceuticals of Canada and Australia, by specific articles in trade agreements with the US. These 'linkage' provisions have also recently appeared in the Korea-US Free Trade Agreement (KORUSFTA). They require such drug regulators to facilitate notification of, or even prevent, any potential patent infringement by a generic pharmaceutical manufacturer. This article explores the regulatory lessons to be learnt from Canada's and Australia's shared experience in terms of minimizing potential adverse impacts of such 'linkage evergreening' provisions on drug costs and thereby potentially on citizen's access to affordable, essential medicines. PMID:17543113

  16. An Analysis of Trafficking Receptors Shows that CD44 and P-Selectin Glycoprotein Ligand-1 Collectively Control the Migration of Activated Human T-Cells

    Ali, Amal J.

    2017-05-03

    Selectins guide the traffic of activated T-cells through the blood stream by mediating their tethering and rolling onto inflamed endothelium, in this way acting as beacons to help navigate them to sites of inflammation. Here, we present a comprehensive analysis of E-selectin ligands expressed on activated human T-cells. We identified several novel glycoproteins that function as E-selectin ligands. Specifically, we compared the role of P-selectin glycoprotein ligand-1 (PSGL-1) and CD43, known E-selectin ligands, to CD44, a ligand that has not previously been characterized as an E-selectin ligand on activated human T-cells. We showed that CD44 acts as a functional E-selectin ligand when expressed on both CD4+ and CD8+ T-cells. Moreover, the CD44 protein carries a binding epitope identifying it as hematopoietic cell E- and/or L-selectin ligand (HCELL). Furthermore, by knocking down these ligands individually or together in primary activated human T-cells, we demonstrated that CD44/HCELL, and not CD43, cooperates with PSGL-1 as a major E-selectin ligand. Additionally, we demonstrated the relevance of our findings to chronic autoimmune disease, by showing that CD44/HCELL and PSGL-1, but not CD43, from T-cells isolated from psoriasis patients, bind E-selectin.

  17. Estimating effective population size from linkage disequilibrium between unlinked loci: theory and application to fruit fly outbreak populations.

    John A Sved

    Full Text Available There is a substantial literature on the use of linkage disequilibrium (LD to estimate effective population size using unlinked loci. The Ne estimates are extremely sensitive to the sampling process, and there is currently no theory to cope with the possible biases. We derive formulae for the analysis of idealised populations mating at random with multi-allelic (microsatellite loci. The 'Burrows composite index' is introduced in a novel way with a 'composite haplotype table'. We show that in a sample of diploid size S, the mean value of x2 or r2 from the composite haplotype table is biased by a factor of 1-1/(2S-12, rather than the usual factor 1+1/(2S-1 for a conventional haplotype table. But analysis of population data using these formulae leads to Ne estimates that are unrealistically low. We provide theory and simulation to show that this bias towards low Ne estimates is due to null alleles, and introduce a randomised permutation correction to compensate for the bias. We also consider the effect of introducing a within-locus disequilibrium factor to r2, and find that this factor leads to a bias in the Ne estimate. However this bias can be overcome using the same randomised permutation correction, to yield an altered r2 with lower variance than the original r2, and one that is also insensitive to null alleles. The resulting formulae are used to provide Ne estimates on 40 samples of the Queensland fruit fly, Bactrocera tryoni, from populations with widely divergent Ne expectations. Linkage relationships are known for most of the microsatellite loci in this species. We find that there is little difference in the estimated Ne values from using known unlinked loci as compared to using all loci, which is important for conservation studies where linkage relationships are unknown.

  18. Estimating effective population size from linkage disequilibrium between unlinked loci: theory and application to fruit fly outbreak populations.

    Sved, John A; Cameron, Emilie C; Gilchrist, A Stuart

    2013-01-01

    There is a substantial literature on the use of linkage disequilibrium (LD) to estimate effective population size using unlinked loci. The Ne estimates are extremely sensitive to the sampling process, and there is currently no theory to cope with the possible biases. We derive formulae for the analysis of idealised populations mating at random with multi-allelic (microsatellite) loci. The 'Burrows composite index' is introduced in a novel way with a 'composite haplotype table'. We show that in a sample of diploid size S, the mean value of x2 or r2 from the composite haplotype table is biased by a factor of 1-1/(2S-1)2, rather than the usual factor 1+1/(2S-1) for a conventional haplotype table. But analysis of population data using these formulae leads to Ne estimates that are unrealistically low. We provide theory and simulation to show that this bias towards low Ne estimates is due to null alleles, and introduce a randomised permutation correction to compensate for the bias. We also consider the effect of introducing a within-locus disequilibrium factor to r2, and find that this factor leads to a bias in the Ne estimate. However this bias can be overcome using the same randomised permutation correction, to yield an altered r2 with lower variance than the original r2, and one that is also insensitive to null alleles. The resulting formulae are used to provide Ne estimates on 40 samples of the Queensland fruit fly, Bactrocera tryoni, from populations with widely divergent Ne expectations. Linkage relationships are known for most of the microsatellite loci in this species. We find that there is little difference in the estimated Ne values from using known unlinked loci as compared to using all loci, which is important for conservation studies where linkage relationships are unknown.

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

    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

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

    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

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

    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.

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

    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.

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

    de Miguel, Marina; de Maria, Nuria; Guevara, M Angeles; Diaz, Luis; Sáez-Laguna, Enrique; Sánchez-Gómez, David; Chancerel, Emilie; Aranda, Ismael; Collada, Carmen; Plomion, Christophe; Cabezas, José-Antonio; Cervera, María-Teresa

    2012-10-04

    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. 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. 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.

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

    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.

  5. T-cell receptor variable genes and genetic susceptibility to celiac disease: an association and linkage study.

    Roschmann, E; Wienker, T F; Gerok, W; Volk, B A

    1993-12-01

    Genetic susceptibility of celiac disease is primarily associated with a particular combination of and HLA-DQA1/DQB1 gene; however, this does not fully account for the genetic predisposition. Therefore, the aim of this study was to examine whether T-cell receptor (TCR) genes may be susceptibility genes in celiac disease. HLA class II typing was performed by polymerase chain reaction amplification in combination with sequence-specific oligonucleotide hybridization. TCR alpha (TCRA), TCR gamma (TCRG), and TCR beta (TCRB) loci were investigated by restriction fragment length polymorphism analysis. Allelic frequencies of TCRA, TCRG, and TCRB variable genes were compared between patients with celiac disease (n = 53) and control patients (n = 67), and relative risk (RR) estimates were calculated. The RR was 1.67 for allele C1 at TCRA1, 3.35 for allele D2 at TCRA2, 1.66 for allele B2 at TCRG, and 1.35 for allele B at TCRB, showing no significant association. Additionally, linkage analysis was performed in 23 families. The logarithm of odd scores for celiac disease vs. the TCR variable genes at TCRA, TCRG, and TCRB showed no significant linkage. These data suggest that the analyzed TCR variable gene segments V alpha 1.2, V gamma 11, and V beta 8 do not play a major role in susceptibility to celiac disease.

  6. Revealing the fate of the phenylcoumaran linkage during lignin oxidation reactions.

    Lahive, Ciaran W; Lancefield, Christopher S; Codina, Anna; Kamer, Paul C J; Westwood, Nicholas J

    2018-03-14

    The fate of most lignin linkages, other than the β-O-4, under selective oxidation conditions is largely unknown. In this work we use advanced β-5 lignin model compounds to identify the fate of phenylcoumaran units in a softwood lignin during oxidation with DDQ. By using model compounds combined with detailed characterisation of the oxidised lignin polymer using HSQC and HMBC NMR we show that phenylcoumarones are a major product, and therefore constitute a novel non-native β-5 linkage in oxidised lignins. Additionally, the reactivity of these units in lignin led us to further investigate their connectivity in lignin, showing that they are found as both phenolic and etherified units. The findings and approach developed here will help improve the efficiency of selective oxidative lignin depolymerisation processes, particularly those aimed at the upgrading of softwood lignin in which phenylcoumarans are a major linkage.

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

    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.

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

    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

  9. Talking with TV shows

    Sandvik, Kjetil; Laursen, Ditte

    2014-01-01

    User interaction with radio and television programmes is not a new thing. However, with new cross-media production concepts such as X Factor and Voice, this is changing dramatically. The second-screen logic of these productions encourages viewers, along with TV’s traditional one-way communication...... mode, to communicate on interactive (dialogue-enabling) devices such as laptops, smartphones and tablets. Using the TV show Voice as our example, this article shows how the technological and situational set-up of the production invites viewers to engage in new ways of interaction and communication...

  10. Construction of a reference molecular linkage map of globe artichoke (Cynara cardunculus var. scolymus).

    Portis, E; Mauromicale, G; Mauro, R; Acquadro, A; Scaglione, D; Lanteri, S

    2009-12-01

    The genome organization of globe artichoke (Cynara cardunculus var. scolymus), unlike other species belonging to Asteraceae (=Compositae) family (i.e. sunflower, lettuce and chicory), remains largely unexplored. The species is highly heterozygous and suffers marked inbreeding depression when forced to self-fertilize. Thus a two-way pseudo-testcross represents the optimal strategy for linkage analysis. Here, we report linkage maps based on the progeny of a cross between globe artichoke (C. cardunculus var. scolymus) and cultivated cardoon (C. cardunculus var. altilis). The population was genotyped using a variety of PCR-based marker platforms, resulting in the identification of 708 testcross markers suitable for map construction. The male map consisted of 177 loci arranged in 17 major linkage groups, spanning 1,015.5 cM, while female map was built with 326 loci arranged into 20 major linkage groups, spanning 1,486.8 cM. The presence of 84 loci shared between these maps and those previously developed from a cross within globe artichoke allowed for map alignment and the definition of 17 homologous linkage groups, corresponding to the haploid number of the species. This will provide a favourable property for QTL scanning; furthermore, as 25 mapped markers (8%) correspond to coding regions, it has an additional value as functional map and might represent an important genetic tool for candidate gene studies in globe artichoke.

  11. Genomewide Linkage Scan for Diabetic Renal Failure and Albuminuria: The FIND Study

    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

    Background 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. Methods 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. Results 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. Conclusion These results strengthen the evidence for previously identified genomic regions and implicate several novel loci potentially involved in the pathogenesis of DN. PMID:21454968

  12. Irish study of high-density Schizophrenia families: Field methods and power to detect linkage

    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.

  13. Talk Show Science.

    Moore, Mitzi Ruth

    1992-01-01

    Proposes having students perform skits in which they play the roles of the science concepts they are trying to understand. Provides the dialog for a skit in which hot and cold gas molecules are interviewed on a talk show to study how these properties affect wind, rain, and other weather phenomena. (MDH)

  14. Obesity in show cats.

    Corbee, R J

    2014-12-01

    Obesity is an important disease with a high prevalence in cats. Because obesity is related to several other diseases, it is important to identify the population at risk. Several risk factors for obesity have been described in the literature. A higher incidence of obesity in certain cat breeds has been suggested. The aim of this study was to determine whether obesity occurs more often in certain breeds. The second aim was to relate the increased prevalence of obesity in certain breeds to the official standards of that breed. To this end, 268 cats of 22 different breeds investigated by determining their body condition score (BCS) on a nine-point scale by inspection and palpation, at two different cat shows. Overall, 45.5% of the show cats had a BCS > 5, and 4.5% of the show cats had a BCS > 7. There were significant differences between breeds, which could be related to the breed standards. Most overweight and obese cats were in the neutered group. It warrants firm discussions with breeders and cat show judges to come to different interpretations of the standards in order to prevent overweight conditions in certain breeds from being the standard of beauty. Neutering predisposes for obesity and requires early nutritional intervention to prevent obese conditions. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

  15. Honored Teacher Shows Commitment.

    Ratte, Kathy

    1987-01-01

    Part of the acceptance speech of the 1985 National Council for the Social Studies Teacher of the Year, this article describes the censorship experience of this honored social studies teacher. The incident involved the showing of a videotape version of the feature film entitled "The Seduction of Joe Tynan." (JDH)

  16. Close linkage of the locus for X chromosome-linked severe combined immunodeficiency to polymorphic DNA markers in Xq11-q13

    de Saint Basile, G.; Arveiler, B.; Oberle, I.

    1987-01-01

    The gene for X chromosome-linked severe combined immunodeficiency (SCID), a disease characterized by a block in early T-cell differentiation, has been mapped to the region Xq11-q13 by linkage analysis with restriction fragment length polymorphisms. High logarithm of odds (lod) scores were obtained with the marker 19.2 (DXS3) and with the marker cpX73 (DXS159) that showed complete cosegregation with the disease locus in the informative families analyzed. Other significant linkages were obtained with several markers from Xq11 to q22. With the help of a recently developed genetic map of the region, it was possible to perform multipoint linkage analysis, and the most likely genetic order is DXS1-(SCID, DXS159)-DXYS1-DXYS12-DXS3, with a maximum multipoint logarithm of odds score of 11.0. The results demonstrate that the SCID locus (gene symbol IMD4) is not closely linked to the locus of Bruton's agammaglobulinemia (a defect in B-cell maturation). They also provide a way for a better estimation of risk for carrier and antenatal diagnosis

  17. A node linkage approach for sequential pattern mining.

    Osvaldo Navarro

    Full Text Available Sequential Pattern Mining is a widely addressed problem in data mining, with applications such as analyzing Web usage, examining purchase behavior, and text mining, among others. Nevertheless, with the dramatic increase in data volume, the current approaches prove inefficient when dealing with large input datasets, a large number of different symbols and low minimum supports. In this paper, we propose a new sequential pattern mining algorithm, which follows a pattern-growth scheme to discover sequential patterns. Unlike most pattern growth algorithms, our approach does not build a data structure to represent the input dataset, but instead accesses the required sequences through pseudo-projection databases, achieving better runtime and reducing memory requirements. Our algorithm traverses the search space in a depth-first fashion and only preserves in memory a pattern node linkage and the pseudo-projections required for the branch being explored at the time. Experimental results show that our new approach, the Node Linkage Depth-First Traversal algorithm (NLDFT, has better performance and scalability in comparison with state of the art algorithms.

  18. Optimizing Opt-Out Consent for Record Linkage

    Das Marcel

    2014-09-01

    Full Text Available This article reports on a study testing the effects of different ways of administering an opt-out consent for record linkage in a probability-based Internet panel. First, we conducted cognitive interviews to explore reactions to a draft version of the opt-out consent text. Second, we conducted a two-factor experiment to test the effects of content manipulations and mode. The results indicate that the way in which respondents were informed did not have much effect on opting out. Results from a follow-up survey on attitudes regarding privacy, confidentiality, and trust, along with knowledge questions about the process of linking, showed no evidence that presenting the opt-out consent statement makes respondents more concerned about privacy. Knowledge about the aspects of record linkage is generally not high. When looking at long-term effects of sending an opt-out consent statement, we found no evidence that this leads to higher attrition or lower participation rates.

  19. Ethnicity and the ethics of data linkage

    Boyd Kenneth M

    2007-11-01

    Full Text Available Abstract Linking health data with census data on ethnicity has potential benefits for the health of ethnic minority groups. Ethical objections to linking these data however include concerns about informed consent and the possibility of the findings being misused against the interests of ethnic minority groups. While consent concerns may be allayed by procedures to safeguard anonymity and respect privacy, robust procedures to demonstrate public approval of data linkage also need to be devised. The possibility of findings being misused against the interests of ethnic minority groups may be diminished by informed and open public discussion in mature democracies, but remain a concern in the international context.

  20. The energy show

    1988-01-01

    The Energy Show is a new look at the problems of world energy, where our supplies come from, now and in the future. The programme looks at how we need energy to maintain our standards of living. Energy supply is shown as the complicated set of problems it is - that Fossil Fuels are both raw materials and energy sources, that some 'alternatives' so readily suggested as practical options are in reality a long way from being effective. (author)

  1. Influence of Ti–O–Si hetero-linkages in the photocatalytic degradation of Rhodamine B

    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

  2. Linkage and mapping analyses of the no glue egg gene Ng in the ...

    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 ...

  3. Transformational leadership climate : Performance linkages, mechanisms, and boundary conditions at the organizational level

    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

  4. Indian migrants in britain: mirror image of social linkages between Gujarat and London

    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

  5. Linkages to Public Land Framework: toward embedding humans in ecosystem analyses by using “inside-out social assessment.”

    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...

  6. HIV-1 transmission linkage in an HIV-1 prevention clinical trial

    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

  7. Viral linkage in HIV-1 seroconverters and their partners in an HIV-1 prevention clinical trial.

    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

  8. Initial Reactivity of Linkages and Monomer Rings in Lignin Pyrolysis Revealed by ReaxFF Molecular Dynamics.

    Zhang, Tingting; Li, Xiaoxia; Guo, Li

    2017-10-24

    The initial conversion pathways of linkages and their linked monomer units in lignin pyrolysis were investigated comprehensively by ReaxFF MD simulations facilitated by the unique VARxMD for reaction analysis. The simulated molecular model contains 15 920 atoms and was constructed on the basis of Adler's softwood lignin model. The simulations uncover the initial conversion ratio of various linkages and their linked aryl monomers. For linkages and their linked monomer aryl rings of α-O-4, β-O-4 and α-O-4 & β-5, the C α /C β ether bond cracking dominates the initial pathway accounting for at least up to 80% of their consumption. For the linkage of β-β & γ-O-α, both the C α -O ether bond cracking and its linked monomer aryl ring opening are equally important. Ring-opening reactions dominate the initial consumption of other 4-O-5, 5-5, β-1, β-2, and β-5 linkages and their linked monomers. The ether bond cracking of C α -O and C β -O occurs at low temperature, and the aryl ring-opening reactions take place at relatively high temperature. The important intermediates leading to the stable aryl ring opening are the phenoxy radicals, the bridged five-membered and three-membered rings and the bridged six-membered and three-membered rings. In addition, the reactivity of a linkage and its monomer aryl ring may be affected by other linkages. The ether bond cracking of α-O-4 and β-O-4 linkages can activate its neighboring linkage or monomer ring through the formed phenoxy radicals as intermediates. The important intermediates revealed in this article should be of help in deepening the understanding of the controlling mechanism for producing aromatic chemicals from lignin pyrolysis.

  9. Conformation analysis of trehalose. Molecular dynamics simulation and molecular mechanics

    Donnamaira, M.C.; Howard, E.I.; Grigera, J.R.

    1992-09-01

    Conformational analysis of the disaccharide trehalose is done by molecular dynamics and molecular mechanics. In spite of the different force fields used in each case, comparison between the molecular dynamics trajectories of the torsional angles of glycosidic linkage and energy conformational map shows a good agreement between both methods. By molecular dynamics it is observed a moderate mobility of the glycosidic linkage. The demands of computer time is comparable in both cases. (author). 6 refs, 4 figs

  10. Showing Value (Editorial

    Denise Koufogiannakis

    2009-06-01

    Full Text Available When Su Cleyle and I first decided to start Evidence Based Library and Information Practice, one of the things we agreed upon immediately was that the journal be open access. We knew that a major obstacle to librarians using the research literature was that they did not have access to the research literature. Although Su and I are both academic librarians who can access a wide variety of library and information literature from our institutions, we belong to a profession where not everyone has equal access to the research in our field. Without such access to our own body of literature, how can we ever hope for practitioners to use research evidence in their decision making? It would have been contradictory to the principles of evidence based library and information practice to do otherwise.One of the specific groups we thought could use such an open access venue for discovering research literature was school librarians. School librarians are often isolated and lacking access to the research literature that may help them prove to stakeholders the importance of their libraries and their role within schools. Certainly, school libraries have been in decline and the use of evidence to show value is needed. As Ken Haycock noted in his 2003 report, The Crisis in Canada’s School Libraries: The Case for Reform and Reinvestment, “Across the country, teacher-librarians are losing their jobs or being reassigned. Collections are becoming depleted owing to budget cuts. Some principals believe that in the age of the Internet and the classroom workstation, the school library is an artifact” (9. Within this context, school librarians are looking to our research literature for evidence of the impact that school library programs have on learning outcomes and student success. They are integrating that evidence into their practice, and reflecting upon what can be improved locally. They are focusing on students and showing the impact of school libraries and

  11. Effects of Worldwide Population Subdivision on ALDH2 Linkage Disequilibrium

    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...

  12. Species discrimination, population structure and linkage disequilibrium in Eucalyptus camaldulensis and Eucalyptus tereticornis using SSR markers.

    Shanmugapriya Arumugasundaram

    Full Text Available Eucalyptus camaldulensis and E. tereticornis are closely related species commonly cultivated for pulp wood in many tropical countries including India. Understanding the genetic structure and linkage disequilibrium (LD existing in these species is essential for the improvement of industrially important traits. Our goal was to evaluate the use of simple sequence repeat (SSR loci for species discrimination, population structure and LD analysis in these species. Investigations were carried out with the most common alleles in 93 accessions belonging to these two species using 62 SSR markers through cross amplification. The polymorphic information content (PIC ranged from 0.44 to 0.93 and 0.36 to 0.93 in E. camaldulensis and E. tereticornis respectively. A clear delineation between the two species was evident based on the analysis of population structure and species-specific alleles. Significant genotypic LD was found in E. camaldulensis, wherein out of 135 significant pairs, 17 pairs showed r(2≥0.1. Similarly, in E. tereticornis, out of 136 significant pairs, 18 pairs showed r(2≥0.1. The extent of LD decayed rapidly showing the significance of association analyses in eucalypts with higher resolution markers. The availability of whole genome sequence for E. grandis and the synteny and co-linearity in the genome of eucalypts, will allow genome-wide genotyping using microsatellites or single nucleotide polymorphims.

  13. Linkages among Adolescent Girls' Romantic Relationships, Best Friendships, and Peer Networks

    Kuttler, Ami Flam; La Greca, Annette M.

    2004-01-01

    This study examined the linkages among girls' best friendships and romantic relationships and accounted for the level of dating involvement as a moderating variable. Social exchange and Sullivan's socioemotional theories served as guides in this process. Questionnaires were administered to 446 girls aged 15-19 years. Results showed that: (a)…

  14. Construction of an almond linkage map in an Australian population Nonpareil × Lauranne

    Gibson John P

    2010-10-01

    Full Text Available Abstract Background Despite a high genetic similarity to peach, almonds (Prunus dulcis have a fleshless fruit and edible kernel, produced as a crop for human consumption. While the release of peach genome v1.0 provides an excellent opportunity for almond genetic and genomic studies, well-assessed segregating populations and the respective saturated genetic linkage maps lay the foundation for such studies to be completed in almond. Results Using an almond intraspecific cross between 'Nonpareil' and 'Lauranne' (N × L, we constructed a moderately saturated map with SSRs, SNPs, ISSRs and RAPDs. The N × L map covered 591.4 cM of the genome with 157 loci. The average marker distance of the map was 4.0 cM. The map displayed high synteny and colinearity with the Prunus T × E reference map in all eight linkage groups (G1-G8. The positions of 14 mapped gene-anchored SNPs corresponded approximately with the positions of homologous sequences in the peach genome v1.0. Analysis of Mendelian segregation ratios showed that 17.9% of markers had significantly skewed genotype ratios at the level of P ® 3 were compared, and their high degree of similarity was evident despite the positional inconsistency of a few markers. Conclusions We presented a moderately saturated Australian almond map, which is highly syntenic and collinear with the Prunus reference map and peach genome V1.0. Therefore, the well-assessed almond population reported here can be used to investigate the traits of interest under Australian growing conditions, and provides more information on the almond genome for the international community.

  15. Keep your opponents close: social context affects EEG and fEMG linkage in a turn-based computer game.

    Spapé, Michiel M; Kivikangas, J Matias; Järvelä, Simo; Kosunen, Ilkka; Jacucci, Giulio; Ravaja, Niklas

    2013-01-01

    In daily life, we often copy the gestures and expressions of those we communicate with, but recent evidence shows that such mimicry has a physiological counterpart: interaction elicits linkage, which is a concordance between the biological signals of those involved. To find out how the type of social interaction affects linkage, pairs of participants played a turn-based computer game in which the level of competition was systematically varied between cooperation and competition. Linkage in the beta and gamma frequency bands was observed in the EEG, especially when the participants played directly against each other. Emotional expression, measured using facial EMG, reflected this pattern, with the most competitive condition showing enhanced linkage over the facial muscle-regions involved in smiling. These effects were found to be related to self-reported social presence: linkage in positive emotional expression was associated with self-reported shared negative feelings. The observed effects confirmed the hypothesis that the social context affected the degree to which participants had similar reactions to their environment and consequently showed similar patterns of brain activity. We discuss the functional resemblance between linkage, as an indicator of a shared physiology and affect, and the well-known mirror neuron system, and how they relate to social functions like empathy.

  16. Keep your opponents close: social context affects EEG and fEMG linkage in a turn-based computer game.

    Michiel M Spapé

    Full Text Available In daily life, we often copy the gestures and expressions of those we communicate with, but recent evidence shows that such mimicry has a physiological counterpart: interaction elicits linkage, which is a concordance between the biological signals of those involved. To find out how the type of social interaction affects linkage, pairs of participants played a turn-based computer game in which the level of competition was systematically varied between cooperation and competition. Linkage in the beta and gamma frequency bands was observed in the EEG, especially when the participants played directly against each other. Emotional expression, measured using facial EMG, reflected this pattern, with the most competitive condition showing enhanced linkage over the facial muscle-regions involved in smiling. These effects were found to be related to self-reported social presence: linkage in positive emotional expression was associated with self-reported shared negative feelings. The observed effects confirmed the hypothesis that the social context affected the degree to which participants had similar reactions to their environment and consequently showed similar patterns of brain activity. We discuss the functional resemblance between linkage, as an indicator of a shared physiology and affect, and the well-known mirror neuron system, and how they relate to social functions like empathy.

  17. Spin Transfer in Polymer Degradation of Abnormal Linkage

    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.

  18. Dense genetic linkage maps of three Populus species (Populus deltoides, P. nigra and P. trichocarpa) based on AFLP and microsatellite markers.

    Cervera, M T; Storme, V; Ivens, B; Gusmão, J; Liu, B H; Hostyn, V; Van Slycken, J; Van Montagu, M; Boerjan, W

    2001-06-01

    Populus deltoides, P. nigra, and P. trichocarpa are the most important species for poplar breeding programs worldwide. In addition, Populus has become a model for fundamental research on trees. Linkage maps were constructed for these three species by analyzing progeny of two controlled crosses sharing the same female parent, Populus deltoides cv. S9-2 x P. nigra cv. Ghoy and P. deltoides cv. S9-2 x P. trichocarpa cv. V24. The two-way pseudotestcross mapping strategy was used to construct the maps. Amplified fragment length polymorphism (AFLP) markers that segregated 1:1 were used to form the four parental maps. Microsatellites and sequence-tagged sites were used to align homoeologous groups between the maps and to merge linkage groups within the individual maps. Linkage analysis and alignment of the homoeologous groups resulted in 566 markers distributed over 19 groups for P. deltoides covering 86% of the genome, 339 markers distributed over 19 groups for P. trichocarpa covering 73%, and 369 markers distributed over 28 groups for P. nigra covering 61%. Several tests for randomness showed that the AFLP markers were randomly distributed over the genome.

  19. The linkage between geopotential height and monthly precipitation in Iran

    Shirvani, Amin; Fadaei, Amir Sabetan; Landman, Willem A.

    2018-04-01

    This paper investigates the linkage between large-scale atmospheric circulation and monthly precipitation during November to April over Iran. Canonical correlation analysis (CCA) is used to set up the statistical linkage between the 850 hPa geopotential height large-scale circulation and monthly precipitation over Iran for the period 1968-2010. The monthly precipitation dataset for 50 synoptic stations distributed in different climate regions of Iran is considered as the response variable in the CCA. The monthly geopotential height reanalysis dataset over an area between 10° N and 60° N and from 20° E to 80° E is utilized as the explanatory variable in the CCA. Principal component analysis (PCA) as a pre-filter is used for data reduction for both explanatory and response variables before applying CCA. The optimal number of principal components and canonical variables to be retained in the CCA equations is determined using the highest average cross-validated Kendall's tau value. The 850 hPa geopotential height pattern over the Red Sea, Saudi Arabia, and Persian Gulf is found to be the major pattern related to Iranian monthly precipitation. The Pearson correlation between the area averaged of the observed and predicted precipitation over the study area for Jan, Feb, March, April, November, and December months are statistically significant at the 5% significance level and are 0.78, 0.80, 0.82, 0.74, 0.79, and 0.61, respectively. The relative operating characteristic (ROC) indicates that the highest scores for the above- and below-normal precipitation categories are, respectively, for February and April and the lowest scores found for December.

  20. Individual patient data meta-analysis shows a significant association between the ATM rs1801516 SNP and toxicity after radiotherapy in 5456 breast and prostate cancer patients

    Andreassen, Christian Nicolaj; Rosenstein, Barry S; Kerns, Sarah L

    2016-01-01

    PURPOSE: Several small studies have indicated that the ATM rs1801516 SNP is associated with risk of normal tissue toxicity after radiotherapy. However, the findings have not been consistent. In order to test this SNP in a well-powered study, an individual patient data meta-analysis was carried ou...

  1. An Analysis of Trafficking Receptors Shows that CD44 and P-Selectin Glycoprotein Ligand-1 Collectively Control the Migration of Activated Human T-Cells

    Ali, Amal J.; AbuElela, Ayman; Merzaban, Jasmeen

    2017-01-01

    -selectin ligands, to CD44, a ligand that has not previously been characterized as an E-selectin ligand on activated human T-cells. We showed that CD44 acts as a functional E-selectin ligand when expressed on both CD4+ and CD8+ T-cells. Moreover, the CD44 protein

  2. Spatial Heterodyne Observations of Water (SHOW) vapour in the upper troposphere and lower stratosphere from a high altitude aircraft: Modelling and sensitivity analysis

    Langille, J. A.; Letros, D.; Zawada, D.; Bourassa, A.; Degenstein, D.; Solheim, B.

    2018-04-01

    A spatial heterodyne spectrometer (SHS) has been developed to measure the vertical distribution of water vapour in the upper troposphere and the lower stratosphere with a high vertical resolution (∼500 m). The Spatial Heterodyne Observations of Water (SHOW) instrument combines an imaging system with a monolithic field-widened SHS to observe limb scattered sunlight in a vibrational band of water (1363 nm-1366 nm). The instrument has been optimized for observations from NASA's ER-2 aircraft as a proof-of-concept for a future low earth orbit satellite deployment. A robust model has been developed to simulate SHOW ER-2 limb measurements and retrievals. This paper presents the simulation of the SHOW ER-2 limb measurements along a hypothetical flight track and examines the sensitivity of the measurement and retrieval approach. Water vapour fields from an Environment and Climate Change Canada forecast model are used to represent realistic spatial variability along the flight path. High spectral resolution limb scattered radiances are simulated using the SASKTRAN radiative transfer model. It is shown that the SHOW instrument onboard the ER-2 is capable of resolving the water vapour variability in the UTLS from approximately 12 km - 18 km with ±1 ppm accuracy. Vertical resolutions between 500 m and 1 km are feasible. The along track sampling capability of the instrument is also discussed.

  3. A first linkage map of globe artichoke (Cynara cardunculus var. scolymus L.) based on AFLP, S-SAP, M-AFLP and microsatellite markers.

    Lanteri, S; Acquadro, A; Comino, C; Mauro, R; Mauromicale, G; Portis, E

    2006-05-01

    We present the first genetic maps of globe artichoke (Cynara cardunculus var. scolymus L. 2n=2x=34), constructed with a two-way pseudo-testcross strategy. A F1 mapping population of 94 individuals was generated between a late-maturing, non-spiny type and an early-maturing spiny type. The 30 AFLP, 13 M-AFLP and 9 S-SAP primer combinations chosen identified, respectively, 352, 38 and 41 polymorphic markers. Of 32 microsatellite primer pairs tested, 12 identified heterozygous loci in one or other parent, and 7 were fully informative as they segregated in both parents. The female parent map comprised 204 loci, spread over 18 linkage groups and spanned 1330.5 cM with a mean marker density of 6.5 cM. The equivalent figures for the male parent map were 180 loci, 17 linkage groups, 1239.4 and 6.9 cM. About 3% of the AFLP and AFLP-derived markers displayed segregation distortion with a P value below 0.01, and were not used for map construction. All the SSR loci were included in the linkage analysis, although one locus did show some segregation distortion. The presence of 78 markers in common to both maps allowed the alignment of 16 linkage groups. The maps generated provide a firm basis for the mapping of agriculturally relevant traits, which will then open the way for the application of a marker-assisted selection breeding strategy in this species.

  4. Conservation of gene linkage in dispersed vertebrate NK homeobox clusters.

    Wotton, Karl R; Weierud, Frida K; Juárez-Morales, José L; Alvares, Lúcia E; Dietrich, Susanne; Lewis, Katharine E

    2009-10-01

    Nk homeobox genes are important regulators of many different developmental processes including muscle, heart, central nervous system and sensory organ development. They are thought to have arisen as part of the ANTP megacluster, which also gave rise to Hox and ParaHox genes, and at least some NK genes remain tightly linked in all animals examined so far. The protostome-deuterostome ancestor probably contained a cluster of nine Nk genes: (Msx)-(Nk4/tinman)-(Nk3/bagpipe)-(Lbx/ladybird)-(Tlx/c15)-(Nk7)-(Nk6/hgtx)-(Nk1/slouch)-(Nk5/Hmx). Of these genes, only NKX2.6-NKX3.1, LBX1-TLX1 and LBX2-TLX2 remain tightly linked in humans. However, it is currently unclear whether this is unique to the human genome as we do not know which of these Nk genes are clustered in other vertebrates. This makes it difficult to assess whether the remaining linkages are due to selective pressures or because chance rearrangements have "missed" certain genes. In this paper, we identify all of the paralogs of these ancestrally clustered NK genes in several distinct vertebrates. We demonstrate that tight linkages of Lbx1-Tlx1, Lbx2-Tlx2 and Nkx3.1-Nkx2.6 have been widely maintained in both the ray-finned and lobe-finned fish lineages. Moreover, the recently duplicated Hmx2-Hmx3 genes are also tightly linked. Finally, we show that Lbx1-Tlx1 and Hmx2-Hmx3 are flanked by highly conserved noncoding elements, suggesting that shared regulatory regions may have resulted in evolutionary pressure to maintain these linkages. Consistent with this, these pairs of genes have overlapping expression domains. In contrast, Lbx2-Tlx2 and Nkx3.1-Nkx2.6, which do not seem to be coexpressed, are also not associated with conserved noncoding sequences, suggesting that an alternative mechanism may be responsible for the continued clustering of these genes.

  5. Evidence for bivariate linkage of obesity and HDL-C levels in the Framingham Heart Study.

    Arya, Rector; Lehman, Donna; Hunt, Kelly J; Schneider, Jennifer; Almasy, Laura; Blangero, John; Stern, Michael P; Duggirala, Ravindranath

    2003-12-31

    Epidemiological studies have indicated that obesity and low high-density lipoprotein (HDL) levels are strong cardiovascular risk factors, and that these traits are inversely correlated. Despite the belief that these traits are correlated in part due to pleiotropy, knowledge on specific genes commonly affecting obesity and dyslipidemia is very limited. To address this issue, we first conducted univariate multipoint linkage analysis for body mass index (BMI) and HDL-C to identify loci influencing variation in these phenotypes using Framingham Heart Study data relating to 1702 subjects distributed across 330 pedigrees. Subsequently, we performed bivariate multipoint linkage analysis to detect common loci influencing covariation between these two traits. We scanned the genome and identified a major locus near marker D6S1009 influencing variation in BMI (LOD = 3.9) using the program SOLAR. We also identified a major locus for HDL-C near marker D2S1334 on chromosome 2 (LOD = 3.5) and another region near marker D6S1009 on chromosome 6 with suggestive evidence for linkage (LOD = 2.7). Since these two phenotypes have been independently mapped to the same region on chromosome 6q, we used the bivariate multipoint linkage approach using SOLAR. The bivariate linkage analysis of BMI and HDL-C implicated the genetic region near marker D6S1009 as harboring a major gene commonly influencing these phenotypes (bivariate LOD = 6.2; LODeq = 5.5) and appears to improve power to map the correlated traits to a region, precisely. We found substantial evidence for a quantitative trait locus with pleiotropic effects, which appears to influence both BMI and HDL-C phenotypes in the Framingham data.

  6. Effects of aquaculture researchers' job characteristics on linkage ...

    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. Electrostatic microactuators with integrated gear linkages for mechanical power transmission

    Legtenberg, R.; Legtenberg, Rob; Berenschot, Johan W.; Elwenspoek, Michael Curt; Fluitman, J.H.J.

    1996-01-01

    In this paper a surface micromachining process is presented which has been used to fabricate electrostatic microactuators that are interconnected with each other and linked to other movable microstructures by integrated gear linkages. The gear linkages consist of rotational and linear gear

  8. Privacy-preserving record linkage on large real world datasets.

    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.

  9. Agriculture–Tourism Linkages in Botswana: Evidence from the ...

    Tourism researchers are increasingly recognising that strengthened linkages between the sectors of tourism and agriculture are significant for maximising local multipliers and especially for pro-poor impacts. This article examines the linkages between the tourism and agriculture sectors in Botswana using evidence ...

  10. Diffusion tensor MRI shows progressive changes in the hippocampus and dentate gyrus after status epilepticus in rat - histological validation with Fourier-based analysis.

    Salo, Raimo A; Miettinen, Tuukka; Laitinen, Teemu; Gröhn, Olli; Sierra, Alejandra

    2017-05-15

    Imaging markers for monitoring disease progression, recovery, and treatment efficacy are a major unmet need for many neurological diseases, including epilepsy. Recent evidence suggests that diffusion tensor imaging (DTI) provides high microstructural contrast even outside major white matter tracts. We hypothesized that in vivo DTI could detect progressive microstructural changes in the dentate gyrus and the hippocampal CA3bc in the rat brain after status epilepticus (SE). To test this hypothesis, we induced SE with systemic kainic acid or pilocarpine in adult male Wistar rats and subsequently scanned them using in vivo DTI at five time-points: prior to SE, and 10, 20, 34, and 79 days post SE. In order to tie the DTI findings to changes in the tissue microstructure, myelin- and glial fibrillary acidic protein (GFAP)-stained sections from the same animals underwent Fourier analysis. We compared the Fourier analysis parameters, anisotropy index and angle of myelinated axons or astrocyte processes, to corresponding DTI parameters, fractional anisotropy (FA) and the orientation angle of the principal eigenvector. We found progressive detectable changes in DTI parameters in both the dentate gyrus (FA, axial diffusivity [D || ], linear anisotropy [CL] and spherical anisotropy [CS], pFourier analysis revealed that both myelinated axons and astrocyte processes played a role in the water diffusion anisotropy changes detected by DTI in individual portions of the dentate gyrus (suprapyramidal blade, mid-portion, and infrapyramidal blade). In the whole dentate gyrus, myelinated axons markedly contributed to the water diffusion changes. In CA3bc as well as in CA3b and CA3c, both myelinated axons and astrocyte processes contributed to water diffusion anisotropy and orientation. Our study revealed that DTI is a promising method for noninvasive detection of microstructural alterations in the hippocampus proper. These alterations may be potential imaging markers for epileptogenesis

  11. A novel approach for soil contamination assessment from heavy metal pollution: a linkage between discharge and adsorption.

    Dong, Xiaoqing; Li, Chaolin; Li, Ji; Wang, Jiaxin; Liu, Suting; Ye, Bin

    2010-03-15

    Soil protection from heavy metal contamination requires scientific assessment on the linkage between site-specific pollutant discharge and environmental effects. However, this kind of linkage is usually disregarded due to the lack of assessment tools in environmental policies, e.g., some developed coastal cities in China have forced their highly polluting industries out to less developed interior areas without consideration of the impacts from pollution transfer. This paper developed a soil adsorption fraction (SAF) model to characterize the emissions-to-adsorption relationship between heavy metal emission and the adsorption by soil. Case studies were carried out for two adjacent southern cities in China, i.e., Guangzhou and Shaoguan. The results indicated that the average SAF of cadmium was 5.38 x 10(-3) for Shaoguan and 1.28 x 10(-3) for Guangzhou, i.e., cadmium released from Shaoguan threatened the soil environment 4.2 times of that from Guangzhou. Further analysis showed the polluting pathway and abundance of water resources were the main influencing factors on SAF. Soil contamination will be exaggerated by relocating heavy metal polluting industries from coastal areas to interior areas. The results should be useful to prompt site-specific policies on heavy metal pollution control. (c) 2009 Elsevier B.V. All rights reserved.

  12. A novel approach for soil contamination assessment from heavy metal pollution: A linkage between discharge and adsorption

    Dong Xiaoqing; Li Chaolin; Li Ji; Wang Jiaxin; Liu Suting; Ye Bin

    2010-01-01

    Soil protection from heavy metal contamination requires scientific assessment on the linkage between site-specific pollutant discharge and environmental effects. However, this kind of linkage is usually disregarded due to the lack of assessment tools in environmental policies, e.g., some developed coastal cities in China have forced their highly polluting industries out to less developed interior areas without consideration of the impacts from pollution transfer. This paper developed a soil adsorption fraction (SAF) model to characterize the emissions-to-adsorption relationship between heavy metal emission and the adsorption by soil. Case studies were carried out for two adjacent southern cities in China, i.e., Guangzhou and Shaoguan. The results indicated that the average SAF of cadmium was 5.38 x 10 -3 for Shaoguan and 1.28 x 10 -3 for Guangzhou, i.e., cadmium released from Shaoguan threatened the soil environment 4.2 times of that from Guangzhou. Further analysis showed the polluting pathway and abundance of water resources were the main influencing factors on SAF. Soil contamination will be exaggerated by relocating heavy metal polluting industries from coastal areas to interior areas. The results should be useful to prompt site-specific policies on heavy metal pollution control.

  13. 'You want to show you're a valuable employee': A critical discourse analysis of multi-perspective portrayals of employed women with fibromyalgia.

    Oldfield, Margaret; MacEachen, Ellen; MacNeill, Margaret; Kirsh, Bonnie

    2018-06-01

    Background Advice on fibromyalgia, a chronic illness primarily affecting women, often presents it as incompatible with work and rarely covers how to remain employed. Yet many women do. Objectives We aimed to understand how these women, their family members, and workmates portrayed employees with fibromyalgia, and how these portrayals helped women retain employment. Methods We interviewed 22 participants, comprising five triads and three dyads of people who knew each other. Using the methodology of critical discourse analysis, we analysed the interview data within and across the triads/dyads through coding, narrative summaries, and relational mapping. Results Participants reported stereotypes that employees with fibromyalgia are lazy, malingering, and less productive than healthy workers. Countering these assumptions, participants portrayed the women as normal, valuable employees who did not 'give in' to their illness. The portrayals drew on two discourses, normalcy and mind-controlling-the-body, and a related narrative, overcoming disability. We propose that participants' portrayals helped women manage their identities in competitive workplaces and thereby remain employed. Discussion Our findings augment the very sparse literature on employment with fibromyalgia. Using a new approach, critical discourse analysis, we expand on known job-retention strategies and add the perspectives of two key stakeholders: family members and workmates.

  14. Extreme drought decouples silicon and carbon geochemical linkages in lakes.

    Li, Tianyang; Li, Siyue; Bush, Richard T; Liang, Chuan

    2018-09-01

    Silicon and carbon geochemical linkages were usually regulated by chemical weathering and organism activity, but had not been investigated under the drought condition, and the magnitude and extent of drought effects remain poorly understood. We collected a comprehensive data set from a total of 13 sampling sites covering the main water body of the largest freshwater lake system in Australia, the Lower Lakes. Changes to water quality during drought (April 2008-September 2010) and post-drought (October 2010-October 2013) were compared to reveal the effects of drought on dissolved silica (DSi) and bicarbonate (HCO 3 - ) and other environmental factors, including sodium (Na + ), pH, electrical conductivity (EC), chlorophyll a (Chl-a), total dissolved solids (TDS), dissolved inorganic nitrogen (DIN), total nitrogen (TN), total phosphorus (TP) and water levels. Among the key observations, concentrations of DSi and DIN were markedly lower in drought than in post-drought period while pH, EC and concentrations of HCO 3 - , Na + , Chl-a, TDS, TN, TP and the ratio TN:TP had inverse trends. Stoichiometric ratios of DSi:HCO 3 - , DSi:Na + and HCO 3 - :Na + were significantly lower in the drought period. DSi exhibited significantly negative relationships with HCO 3 - , and DSi:Na + was strongly correlated with HCO 3 - :Na + in both drought and post-drought periods. The backward stepwise regression analysis that could avoid multicollinearity suggested that DSi:HCO 3 - ratio in drought period had significant relationships with fewer variables when compared to the post-drought, and was better predictable using nutrient variables during post-drought. Our results highlight the drought effects on variations of water constituents and point to the decoupling of silicon and carbon geochemical linkages in the Lower Lakes under drought conditions. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Analysis of S gene mutation of the hepatitis B virus in adult liver transplant recipients showing resistance to hepatitis B immunoglobulin therapy.

    Park, G-C; Hwang, S; Ahn, C-S; Kim, K-H; Moon, D-B; Ha, T-Y; Song, G-W; Jung, D-H; Shin, Y W; Kim, S-H; Chang, K-H; Namgoong, J-M; Park, C-S; Park, H-W; Park, Y-H; Kang, S-H; Jung, B-H; Lee, S-G

    2013-10-01

    A considerable proportion of recipients of liver transplantations who are presented hepatitis B immunoglobulin (HBIG) monotherapy for hepatitis B virus (HBV) prophylaxis develop HBIG resistance. In this study, we investigated the mutation patterns in the major hydrophilic region (MHR) of amino acid sequences 100 to 160. Using the gene sequence analyzer for amino acid sequences 0 to 226 in the S/pre-S region we analyzed blood samples of 15 patients showing HBIG resistance after high-dose HBIG prophylaxis. Various mutations in the MHR were observed in 14/15 samples: Gly145Arg mutation in 8/13 Adr subtype and 1/2 Ayw subtype samples (60%). The next most common mutation was Gly165Trp in 8/13 Adr subtype but neither of 2 Ayw subtype samples (53.3%). Concurrent antiviral resistance was noted in 5 patients: lamivudine (n = 5), or entecavir (n = 3), but not adefovir, suggesting the occurrence of simultaneous, antiviral cross-resistances. Two patients underwent retransplantation due to the progression of HBV infection despite vigorous antiviral therapy. At diagnosis of HBV recurrence, the mean HBV DNA load was 6.5 × 10(6) copies/mL; 4 patients showed paradoxical coexistence of anti-HBs and HBsAg. Currently, 2 subjects show low-level HBV DNA replication in peripheral blood, although the other 12 had no DNA replication after prolonged antiviral therapy. This study suggested that various mutations in the "a" determinant were associated with HBIG resistance. Since treatment failure to rescue antiviral therapy was often associated with delayed detection of HBV recurrence rather than concurrent antiviral resistance, frequent HBV surveillance using more sensitive screening tests, such as HBeAg and HBV DNA polymerase chain reaction assay, seems to be mandatory. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Linkages between Income Inequality, International Remittances and Economic Growth in Pakistan

    Shahbaz, Muhammad; Ur Rehman, Ijaz; Ahmad Mahdzan, Nurul Shahnaz

    2013-01-01

    This paper explores the dynamic linkages between income inequality, international remittances and economic growth using time series data over the period of 1976-2006 in case of Pakistan. The cointegration analysis based on the bounds test confirms the existence of a long-run relationship between income inequality, international remittances and economic growth. Our results reveal that income inequality and international remittances enhance economic growth. The causality analysis based on innov...

  17. Combined analysis of 19 common validated type 2 diabetes susceptibility gene variants shows moderate discriminative value and no evidence of gene-gene interaction

    Sparsø, T; Grarup, N; Andreasen, C.

    2009-01-01

    study; and additional type 2 diabetic patients and glucose-tolerant individuals. The case-control studies involved 4,093 type 2 diabetic patients and 5,302 glucose-tolerant individuals. RESULTS: Single-variant analyses demonstrated allelic odds ratios ranging from 1.04 (95% CI 0.98-1.11) to 1.33 (95% CI...... analysis of the 19 validated variants enables detection of subgroups at substantially increased risk of type 2 diabetes; however, the discrimination between glucose-tolerant and type 2 diabetes individuals is still too inaccurate to achieve clinical value.......AIMS/HYPOTHESIS: The list of validated type 2 diabetes susceptibility variants has recently been expanded from three to 19. The variants identified are common and have low penetrance in the general population. The aim of the study is to investigate the combined effect of the 19 variants by applying...

  18. Rethinking health sector procurement as developmental linkages in East Africa.

    Mackintosh, Maureen; Tibandebage, Paula; Karimi Njeru, Mercy; Kariuki Kungu, Joan; Israel, Caroline; Mujinja, Phares G M

    2018-03-01

    Health care forms a large economic sector in all countries, and procurement of medicines and other essential commodities necessarily creates economic linkages between a country's health sector and local and international industrial development. These procurement processes may be positive or negative in their effects on populations' access to appropriate treatment and on local industrial development, yet procurement in low and middle income countries (LMICs) remains under-studied: generally analysed, when addressed at all, as a public sector technical and organisational challenge rather than a social and economic element of health system governance shaping its links to the wider economy. This article uses fieldwork in Tanzania and Kenya in 2012-15 to analyse procurement of essential medicines and supplies as a governance process for the health system and its industrial links, drawing on aspects of global value chain theory. We describe procurement work processes as experienced by front line staff in public, faith-based and private sectors, linking these experiences to wholesale funding sources and purchasing practices, and examining their implications for medicines access and for local industrial development within these East African countries. We show that in a context of poor access to reliable medicines, extensive reliance on private medicines purchase, and increasing globalisation of procurement systems, domestic linkages between health and industrial sectors have been weakened, especially in Tanzania. We argue in consequence for a more developmental perspective on health sector procurement design, including closer policy attention to strengthening vertical and horizontal relational working within local health-industry value chains, in the interests of both wider access to treatment and improved industrial development in Africa. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Exploiting semantic linkages among multiple sources for semantic information retrieval

    Li, JianQiang; Yang, Ji-Jiang; Liu, Chunchen; Zhao, Yu; Liu, Bo; Shi, Yuliang

    2014-07-01

    The vision of the Semantic Web is to build a global Web of machine-readable data to be consumed by intelligent applications. As the first step to make this vision come true, the initiative of linked open data has fostered many novel applications aimed at improving data accessibility in the public Web. Comparably, the enterprise environment is so different from the public Web that most potentially usable business information originates in an unstructured form (typically in free text), which poses a challenge for the adoption of semantic technologies in the enterprise environment. Considering that the business information in a company is highly specific and centred around a set of commonly used concepts, this paper describes a pilot study to migrate the concept of linked data into the development of a domain-specific application, i.e. the vehicle repair support system. The set of commonly used concepts, including the part name of a car and the phenomenon term on the car repairing, are employed to build the linkage between data and documents distributed among different sources, leading to the fusion of documents and data across source boundaries. Then, we describe the approaches of semantic information retrieval to consume these linkages for value creation for companies. The experiments on two real-world data sets show that the proposed approaches outperform the best baseline 6.3-10.8% and 6.4-11.1% in terms of top five and top 10 precisions, respectively. We believe that our pilot study can serve as an important reference for the development of similar semantic applications in an enterprise environment.

  20. [MapDraw: a microsoft excel macro for drawing genetic linkage maps based on given genetic linkage data].

    Liu, Ren-Hu; Meng, Jin-Ling

    2003-05-01

    MAPMAKER is one of the most widely used computer software package for constructing genetic linkage maps.However, the PC version, MAPMAKER 3.0 for PC, could not draw the genetic linkage maps that its Macintosh version, MAPMAKER 3.0 for Macintosh,was able to do. Especially in recent years, Macintosh computer is much less popular than PC. Most of the geneticists use PC to analyze their genetic linkage data. So a new computer software to draw the same genetic linkage maps on PC as the MAPMAKER for Macintosh to do on Macintosh has been crying for. Microsoft Excel,one component of Microsoft Office package, is one of the most popular software in laboratory data processing. Microsoft Visual Basic for Applications (VBA) is one of the most powerful functions of Microsoft Excel. Using this program language, we can take creative control of Excel, including genetic linkage map construction, automatic data processing and more. In this paper, a Microsoft Excel macro called MapDraw is constructed to draw genetic linkage maps on PC computer based on given genetic linkage data. Use this software,you can freely construct beautiful genetic linkage map in Excel and freely edit and copy it to Word or other application. This software is just an Excel format file. You can freely copy it from ftp://211.69.140.177 or ftp://brassica.hzau.edu.cn and the source code can be found in Excel's Visual Basic Editor.

  1. Nonsyndromic cleft lip with or without cleft palate: Evidence of linkage to BCL3 in 17 multigenerational families

    Stein, J.; Hecht, T. [Univ. of Texas, Houston, TX (United States); Stal, S. [Texas Children`s Hospital, Houston, TX (United States)] [and others

    1995-08-01

    Nonsyndromic cleft lip with or without cleft palate (CL/P) is a common craniofacial developmental defect. Recent segregation analyses have suggested that major genes play a role in the etiology of CL/P. Linkage to 22 candidate genes was tested in 11 multigenerational families with CL/P, and 21 of these candidates were excluded. APOC2, 19q13.1, which is linked to the proto-oncogene BCL3, gave suggestive evidence for linkage to CL/P. The study was expanded to include a total of 39 multigenerational CL/P families. Linkage was tested in all families, using anonymous marker, D19S178, and intragenic markers in BCL3 and APOC2. Linkage was tested under two models, autosomal dominant with reduced penetrance and affecteds-only model. Both models showed evidence of heterogeneity, with 43% of families linked at zero recombination to BCL3 when marker data from BCL3 and APOC2 were included. A maximum multipoint LOD score of 7.00 at BCL3 was found among the 17 families that had posterior probabilities {ge}50% in favor of linkage. The transmission disequilibrium test provided additional evidence for linkage with the 3 allele of BCL3 more often transmitted to affected children. These results suggest that BCL3, or a nearby gene, plays a role in the etiology of CL/P in some families. 39 refs., 8 figs., 4 tabs.

  2. Analysis of Static and Dynamic E-Reference Content at a Multi-Campus University Shows, that Updated Content is Associated with Greater Annual Usage

    Laura Costello

    2016-03-01

    Full Text Available Objective – To discover whether there is a difference in use over time between dynamically updated and changing subscription e-reference titles and collections, and static purchased e-reference titles and collections. Design – Case study. Setting – A multi-campus Canadian university with 9,200 students enrolled in both graduate and undergraduate programs. Subjects – E-reference book packages and individual e-reference titles. Methods – The author compared data from individual e-reference books and packages. First, individual subscription e-reference books that periodically added updated content were compared to individually purchased e-reference books that remained static after purchase. The author then compared two e-reference book packages that provided new and updated content to two static e-reference book packages. The author compared data from patron usage to new content added over time using regression analysis. Main Results – As the library acquired e-reference titles, dynamic title subscriptions added to the collection were associated with 2,246 to 4,635 views per subscription while static title additions were associated with 8 to 123 views per purchase. The author also found that there was a strong linear relationship between views and dynamic titles added to the collection (R2=0.79 and a very weak linear relationship (R2=0.18 with views when static titles are added to the collection. Regression analysis of dynamic e-reference collections revealed that the number of titles added to each collection was strongly associated with views of the material (R2=0.99, while static e-reference collections were less strongly linked (R2=0.43. Conclusion – Dynamic e-reference titles and collections experienced increases in usage each year while static titles and collections experienced decreases in usage. This indicates that collections and titles that offer new content to users each year will continue to see growth in usage while static

  3. The ties that bind: interorganizational linkages and physician-system alignment.

    Alexander, J A; Waters, T M; Burns, L R; Shortell, S M; Gillies, R R; Budetti, P P; Zuckerman, H S

    2001-07-01

    To examine the association between the degree of alignment between physicians and health care systems, and interorganizational linkages between physician groups and health care systems. The study used a cross sectional, comparative analysis using a sample of 1,279 physicians practicing in loosely affiliated arrangements and 1,781 physicians in 61 groups closely affiliated with 14 vertically integrated health systems. Measures of physician alignment were based on multiitem scales validated in previous studies and derived from surveys sent to individual physicians. Measures of interorganizational linkages were specified at the institutional, administrative, and technical core levels of the physician group and were developed from surveys sent to the administrator of each of the 61 physician groups in the sample. Two stage Heckman models with fixed effects adjustments in the second stage were used to correct for sample selection and clustering respectively. After accounting for sample selection, fixed effects, and group and individual controls, physicians in groups with more valued practice service linkages display consistently higher alignment with systems than physicians in groups that have fewer such linkages. Results also suggest that centralized administrative control lowers physician-system alignment for selected measures of alignment. Governance interlocks exhibited only weak associations with alignment. Our findings suggest that alignment generally follows resource exchanges that promote value-added contributions to physicians and physician groups while preserving control and authority within the group.

  4. High-density Integrated Linkage Map Based on SSR Markers in Soybean

    Hwang, Tae-Young; Sayama, Takashi; Takahashi, Masakazu; Takada, Yoshitake; Nakamoto, Yumi; Funatsuki, Hideyuki; Hisano, Hiroshi; Sasamoto, Shigemi; Sato, Shusei; Tabata, Satoshi; Kono, Izumi; Hoshi, Masako; Hanawa, Masayoshi; Yano, Chizuru; Xia, Zhengjun; Harada, Kyuya; Kitamura, Keisuke; Ishimoto, Masao

    2009-01-01

    A well-saturated molecular linkage map is a prerequisite for modern plant breeding. Several genetic maps have been developed for soybean with various types of molecular markers. Simple sequence repeats (SSRs) are single-locus markers with high allelic variation and are widely applicable to different genotypes. We have now mapped 1810 SSR or sequence-tagged site markers in one or more of three recombinant inbred populations of soybean (the US cultivar ‘Jack’ × the Japanese cultivar ‘Fukuyutaka’, the Chinese cultivar ‘Peking’ × the Japanese cultivar ‘Akita’, and the Japanese cultivar ‘Misuzudaizu’ × the Chinese breeding line ‘Moshidou Gong 503’) and have aligned these markers with the 20 consensus linkage groups (LGs). The total length of the integrated linkage map was 2442.9 cM, and the average number of molecular markers was 90.5 (range of 70–114) for the 20 LGs. We examined allelic diversity for 1238 of the SSR markers among 23 soybean cultivars or lines and a wild accession. The number of alleles per locus ranged from 2 to 7, with an average of 2.8. Our high-density linkage map should facilitate ongoing and future genomic research such as analysis of quantitative trait loci and positional cloning in addition to marker-assisted selection in soybean breeding. PMID:19531560

  5. Genotypic and phenotypic analysis of familial male breast cancer shows under representation of the HER2 and basal subtypes in BRCA-associated carcinomas

    Deb, Siddhartha; Jene, Nicholas; Fox, Stephen B

    2012-01-01

    Male breast cancer (MBC) is an uncommon and relatively uncharacterised disease accounting for <1% of all breast cancers. A significant proportion occurs in families with a history of breast cancer and in particular those carrying BRCA2 mutations. Here we describe clinicopathological features and genomic BRCA1 and BRCA2 mutation status in a large cohort of familial MBCs. Cases (n=60) included 3 BRCA1 and 25 BRCA2 mutation carries, and 32 non-BRCA1/2 (BRCAX) carriers with strong family histories of breast cancer. The cohort was examined with respect to mutation status, clinicopathological parameters including TNM staging, grade, histological subtype and intrinsic phenotype. Compared to the general population, MBC incidence was higher in all subgroups. In contrast to female breast cancer (FBC) there was greater representation of BRCA2 tumours (41.7% vs 8.3%, p=0.0008) and underrepresentation of BRCA1 tumours (5.0% vs 14.4%, p=0.0001). There was no correlation between mutation status and age of onset, disease specific survival (DSS) or other clincopathological factors. Comparison with sporadic MBC studies showed similar clinicopathological features. Prognostic variables affecting DSS included primary tumour size (p=0.003, HR:4.26 95%CI 1.63-11.11), age (p=0.002, HR:4.09 95%CI 1.65-10.12), lymphovascular (p=0.019, HR:3.25 95%CI 1.21-8.74) and perineural invasion (p=0.027, HR:2.82 95%CI 1.13-7.06). Unlike familial FBC, the histological subtypes seen in familial MBC were more similar to those seen in sporadic MBC with 46 (76.7%) pure invasive ductal carcinoma of no special type (IDC-NST), 2 (3.3%) invasive lobular carcinomas and 4 (6.7%) invasive papillary carcinoma. A further 8 (13.3%) IDC-NST had foci of micropapillary differentiation, with a strong trend for co-occurrence in BRCA2 carriers (p=0.058). Most tumours were of the luminal phenotype (89.7%), with infrequent HER2 (8.6%) and basal (1.7%) phenotype tumours seen. MBC in BRCA1/2 carriers and BRCAX families is

  6. Surface plasmon resonance analysis shows an IgG-isotype-specific defect in ABO blood group antibody formation in patients with common variable immunodeficiency

    Michael Bernhard Fischer

    2015-05-01

    Full Text Available Background: Common variable immunodeficiency (CVID is the most common clinically severe primary immunodeficiency and comprises a heterogeneous group of patients with recurrent severe bacterial infections due to the failure to produce IgG antibodies after exposure to infectious agents and immunization. Diagnostic recommendations for antibody failure include assessment of isoagglutinins. We have readdressed this four decades old but still accepted recommendation with up to date methodology.Methods: Anti-A/B IgM- and IgG-antibodies were measured by Diamed-ID Micro Typing, surface plasmon resonance (SPR using the Biacore® device and flow cytometry.Results: When Diamed-ID Micro Typing was used, CVID patients (n=34 showed IgG- and IgM-isoagglutinins that were comparable to healthy volunteers (n=28, while all XLA patients (n=8 had none. Anti-A/B IgM-antibodies were present in more than 2/3 of the CVID patients and showed binding kinetics comparable to anti-A/B IgM-antibodies from healthy individuals. A correlation could be found in CVID patients between levels of anti-A/B IgM-antibodies and levels of serum IgM and PnP-IgM-antibodies. In contrast in CVID patients as a group ABO antibodies were significantly decreased when assessed by SPR, which correlated with levels of switched memory, non-switched memory and naïve B cells, but all CVID patients had low/undetectable anti-A/B IgG-antibodies.Conclusion: These results indicate that conventional isoagglutinin assessment and assessment of anti-A/B IgM antibodies are not suited for the diagnosis of impaired antibody production in CVID. Examination of anti-A/B IgG antibodies by SPR provides a useful method for the diagnosis of IgG antibody failure in all CVID patients studied, thus indicating an important additional rationale to start immunoglobulin replacement therapy early in these patients, before post-infectious sequelae develop.

  7. Program impact pathway analysis of a social franchise model shows potential to improve infant and young child feeding practices in Vietnam.

    Nguyen, Phuong H; Menon, Purnima; Keithly, Sarah C; Kim, Sunny S; Hajeebhoy, Nemat; Tran, Lan M; Ruel, Marie T; Rawat, Rahul

    2014-10-01

    By mapping the mechanisms through which interventions are expected to achieve impact, program impact pathway (PIP) analysis lays out the theoretical causal links between program activities, outcomes, and impacts. This study examines the pathways through which the Alive & Thrive (A&T) social franchise model is intended to improve infant and young child feeding (IYCF) practices in Vietnam. Mixed methods were used, including qualitative interviews with franchise management board members (n = 12), surveys with health providers (n = 120), counseling observations (n = 160), and household surveys (n = 2045). Six PIP components were assessed: 1) franchise management, 2) training and IYCF knowledge of health providers, 3) service delivery, 4) program exposure and utilization, 5) maternal behavioral determinants (knowledge, beliefs, and intentions) toward optimal IYCF practices, and 6) IYCF practices. Data were collected from A&T-intensive areas (A&T-I; mass media + social franchise) and A&T-nonintensive areas (A&T-NI; mass media only) by using a cluster-randomized controlled trial design. Data from 2013 were compared with baseline where similar measures were available. Results indicate that mechanisms are in place for effective management of the franchise system, despite challenges to routine monitoring. A&T training was associated with increased capacity of providers, resulting in higher-quality IYCF counseling (greater technical knowledge and communication skills during counseling) in A&T-I areas. Franchise utilization increased from 10% in 2012 to 45% in 2013 but fell below the expected frequency of 9-15 contacts per mother-child dyad. Improvements in breastfeeding knowledge, beliefs, intentions, and practices were greater among mothers in A&T-I areas than among those in A&T-NI areas. In conclusion, there are many positive changes along the impact pathway of the franchise services, but challenges in utilization and demand creation should be addressed to achieve the full

  8. Seasonality shows evidence for polygenic architecture and genetic correlation with schizophrenia and bipolar disorder – a meta-analysis of genetic studies

    Byrne, Enda M; Raheja, Uttam; Stephens, Sarah H.; Heath, Andrew C; Madden, Pamela AF; Vaswani, Dipika; Nijjar, Gagan V.; Ryan, Kathleen A.; Youssufi, Hassaan; Gehrman, Philip R; Shuldiner, Alan R; Martin, Nicholas G; Montgomery, Grant W; Wray, Naomi R; Nelson, Elliot C; Mitchell, Braxton D; Postolache, Teodor T

    2015-01-01

    Objective To test common genetic variants for association with seasonality (seasonal changes in mood and behavior) and to investigate whether there are shared genetic risk factors between psychiatric disorders and seasonality. Methods A meta-analysis of genome-wide association studies (GWAS) conducted in Australian and Amish populations in whom the Seasonal Pattern Assessment Questionnaire (SPAQ) had been administered. The total sample size was 4,156 individuals. Genetic risk scores based on results from prior large GWAS studies of bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ) were calculated to test for overlap in risk between psychiatric disorders and seasonality. Results The most significant association was with rs11825064 (p = 1.7 × 10−6, β = 0.64, S.E = 0.13), an intergenic SNP found on chromosome 11. The evidence for overlap in risk factors was strongest for SCZ and seasonality, with the SCZ genetic profile scores explaining 3% of the variance in log-transformed GSS. BD genetic profile scores were also significantly associated with seasonality, although at much weaker levels, and no evidence for overlap in risk was detected between MDD and seasonality. Conclusions Common SNPs of very large effect likely do not exist for seasonality in the populations examined. As expected, there was overlapping genetic risk factors for BD (but not MDD) with seasonality. Unexpectedly, the risk for SCZ and seasonality had the largest overlap, an unprecedented finding that requires replication in other populations, and has potential clinical implications considering overlapping cognitive deficits in seasonal affective disorders and SCZ PMID:25562672

  9. PIXE analysis showed that the preirradiation enhanced recovery of bone marrow elements after challenging irradiation in C57BL/6N Mice

    Matsuda, Y.; Yonezawa, M.; Nishiyama, F.

    2000-01-01

    Priming X-irradiation with 0.3-0.5 Gy induces radio-resistance in C57BL/6 strain of mice 2 weeks afterward. Elements in the bone marrow, sampled 11 days after challenging exposure to 5.0 Gy, were determined by PIXE. The challenging irradiation decreased Mg, P, S, K, Ca and Zn as well as dried bone marrow weight. The pre-irradiation enhanced recovery of these levels, indicating stimulated recovery of the metabolism int he tissue. Fe in both control (without pre-irradiation) and experimental groups increased to about twice the original value, showing elevated hemoglobin synthesis after challenging exposure. In previous studies we have reported that recovery of peripheral blood cell counts after sub-lethal irradiation was enhanced by the pre-irradiation. Further, study on accumulation of p53 and Bax proteins, which lead to apoptotic cell death, revealed that the pre-irradiation significantly suppressed accumulation of these proteins in the spleen after challenging irradiation with 3 Gy. These results and our present study suggest that the pre-irradiation decreased the spleen cell death, and favored re-growth of the spleen cells, resulting in stimulated recovery of metabolism for hematopoiesis in the bone marrow as well as in the spleen after challenging high dose irradiation. Stimulated recovery of Mg, P, S, K, Ca and Zn levels might indicate the importance of these elements in hematopoiesis. (author)

  10. Comprehensive Behavioral Analysis of Male Ox1r−/− Mice Showed Implication of Orexin Receptor-1 in Mood, Anxiety, and Social Behavior

    Abbas, Md. G.; Shoji, Hirotaka; Soya, Shingo; Hondo, Mari; Miyakawa, Tsuyoshi; Sakurai, Takeshi

    2015-01-01

    Neuropeptides orexin A and orexin B, which are exclusively produced by neurons in the lateral hypothalamic area, play an important role in the regulation of a wide range of behaviors and homeostatic processes, including regulation of sleep/wakefulness states and energy homeostasis. The orexin system has close anatomical and functional relationships with systems that regulate the autonomic nervous system, emotion, mood, the reward system, and sleep/wakefulness states. Recent pharmacological studies using selective antagonists have suggested that orexin receptor-1 (OX1R) is involved in physiological processes that regulate emotion, the reward system, and autonomic nervous system. Here, we examined Ox1r−/− mice with a comprehensive behavioral test battery to screen additional OX1R functions. Ox1r−/− mice showed increased anxiety-like behavior, altered depression-like behavior, slightly decreased spontaneous locomotor activity, reduced social interaction, increased startle response, and decreased prepulse inhibition. These results suggest that OX1R plays roles in social behavior and sensory motor gating in addition to roles in mood and anxiety. PMID:26696848

  11. High Content Analysis of Hippocampal Neuron-Astrocyte Co-cultures Shows a Positive Effect of Fortasyn Connect on Neuronal Survival and Postsynaptic Maturation.

    van Deijk, Anne-Lieke F; Broersen, Laus M; Verkuyl, J Martin; Smit, August B; Verheijen, Mark H G

    2017-01-01

    Neuronal and synaptic membranes are composed of a phospholipid bilayer. Supplementation with dietary precursors for phospholipid synthesis -docosahexaenoic acid (DHA), uridine and choline- has been shown to increase neurite outgrowth and synaptogenesis both in vivo and in vitro . A role for multi-nutrient intervention with specific precursors and cofactors has recently emerged in early Alzheimer's disease, which is characterized by decreased synapse numbers in the hippocampus. Moreover, the medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect (FC), improves memory performance in early Alzheimer's disease patients, possibly via maintaining brain connectivity. This suggests an effect of FC on synapses, but the underlying cellular mechanism is not fully understood. Therefore, we investigated the effect of FC (consisting of DHA, eicosapentaenoic acid (EPA), uridine, choline, phospholipids, folic acid, vitamins B12, B6, C and E, and selenium), on synaptogenesis by supplementing it to primary neuron-astrocyte co-cultures, a cellular model that mimics metabolic dependencies in the brain. We measured neuronal developmental processes using high content screening in an automated manner, including neuronal survival, neurite morphology, as well as the formation and maturation of synapses. Here, we show that FC supplementation resulted in increased numbers of neurons without affecting astrocyte number. Furthermore, FC increased postsynaptic PSD95 levels in both immature and mature synapses. These findings suggest that supplementation with FC to neuron-astrocyte co-cultures increased both neuronal survival and the maturation of postsynaptic terminals, which might aid the functional interpretation of FC-based intervention strategies in neurological diseases characterized by neuronal loss and impaired synaptic functioning.

  12. High Content Analysis of Hippocampal Neuron-Astrocyte Co-cultures Shows a Positive Effect of Fortasyn Connect on Neuronal Survival and Postsynaptic Maturation

    Anne-Lieke F. van Deijk

    2017-08-01

    Full Text Available Neuronal and synaptic membranes are composed of a phospholipid bilayer. Supplementation with dietary precursors for phospholipid synthesis –docosahexaenoic acid (DHA, uridine and choline– has been shown to increase neurite outgrowth and synaptogenesis both in vivo and in vitro. A role for multi-nutrient intervention with specific precursors and cofactors has recently emerged in early Alzheimer's disease, which is characterized by decreased synapse numbers in the hippocampus. Moreover, the medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect (FC, improves memory performance in early Alzheimer's disease patients, possibly via maintaining brain connectivity. This suggests an effect of FC on synapses, but the underlying cellular mechanism is not fully understood. Therefore, we investigated the effect of FC (consisting of DHA, eicosapentaenoic acid (EPA, uridine, choline, phospholipids, folic acid, vitamins B12, B6, C and E, and selenium, on synaptogenesis by supplementing it to primary neuron-astrocyte co-cultures, a cellular model that mimics metabolic dependencies in the brain. We measured neuronal developmental processes using high content screening in an automated manner, including neuronal survival, neurite morphology, as well as the formation and maturation of synapses. Here, we show that FC supplementation resulted in increased numbers of neurons without affecting astrocyte number. Furthermore, FC increased postsynaptic PSD95 levels in both immature and mature synapses. These findings suggest that supplementation with FC to neuron-astrocyte co-cultures increased both neuronal survival and the maturation of postsynaptic terminals, which might aid the functional interpretation of FC-based intervention strategies in neurological diseases characterized by neuronal loss and impaired synaptic functioning.

  13. Tyrosine kinase inhibitors show different anti-brain metastases efficacy in NSCLC: A direct comparative analysis of icotinib, gefitinib, and erlotinib in a nude mouse model.

    Tan, Jianlong; Li, Min; Zhong, Wen; Hu, Chengping; Gu, Qihua; Xie, Yali

    2017-11-17

    Brain metastasis is an increasing problem in non-small cell lung cancer (NSCLC) patients. Tyrosine kinase inhibitors (TKIs), including gefitinib, erlotinib, and icotinib, are reported to be effective in patients with brain metastases. However, direct comparative studies of the pharmacokinetics and efficacy of these three drugs in treating brain metastases are lacking. In the present investigation, we found that gefitinib penetrated the blood-tumor barrier and was distributed to brain metastases more effectively than erlotinib or icotinib in a nude mouse model. The 1-h ratio of brain metastases to plasma concentration for gefitinib, erlotinib, and icotinib was 9.82±1.03%, 4.83±0.25%, and 2.62±0.21%, respectively. The 2-h ratio of brain metastases to plasma concentration for gefitinib, erlotinib, and icotinib was 15.11±2.00%, 5.73±1.31%, and 2.69±0.31%, respectively. Gefitinib exhibited the strongest antitumor activity ( p gefitinib vs. erlotinib =0.005; p gefitinib vs. icotinib =0.002). Notably, erlotinib exhibited a better treatment efficacy than icotinib ( p =0.037). Consistently, immunohistochemical data showed that TKIs differentially inhibit the proliferation of metastatical tumor cells. Gefitinib and erlotinib markedly inhibited the proliferation of tumor cells, while there were more ki-67-positive tumor cells in the icotinib group. Additionally, gefitinib inhibited the phosphorylation of EGFR better than the other drugs, whereas pEGFR expression levels in erlotinib groups were lower than levels in the icotinib group ( p gefitinib vs. erlotinib =0.995; p gefitinib vs. icotinib =0.028; p erlotinib vs. icotinib =0.042).Altogether, our findings suggest that gefitinib and erlotinib can inhibit the growth of PC-9-luc brain tumors. Gefitinib demonstrated better antitumor activity and penetration rate in brain metastases than erlotinib or icotinib.

  14. Retrotransposon-centered analysis of piRNA targeting shows a shift from active to passive retrotransposon transcription in developing mouse testes

    Mourier Tobias

    2011-09-01

    Full Text Available Abstract Background Piwi-associated RNAs (piRNAs bind transcripts from retrotransposable elements (RTE in mouse germline cells and seemingly act as guides for genomic methylation, thereby repressing the activity of RTEs. It is currently unknown if and how Piwi proteins distinguish RTE transcripts from other cellular RNAs. During germline development, the main target of piRNAs switch between different types of RTEs. Using the piRNA targeting of RTEs as an indicator of RTE activity, and considering the entire population of genomic RTE loci along with their age and location, this study aims at further elucidating the dynamics of RTE activity during mouse germline development. Results Due to the inherent sequence redundancy between RTE loci, assigning piRNA targeting to specific loci is problematic. This limits the analysis, although certain features of piRNA targeting of RTE loci are apparent. As expected, young RTEs display a much higher level of piRNA targeting than old RTEs. Further, irrespective of age, RTE loci near protein-coding coding genes are targeted to a greater extent than RTE loci far from genes. During development, a shift in piRNA targeting is observed, with a clear increase in the relative piRNA targeting of RTEs residing within boundaries of protein-coding gene transcripts. Conclusions Reanalyzing published piRNA sequences and taking into account the features of individual RTE loci provide novel insight into the activity of RTEs during development. The obtained results are consistent with some degree of proportionality between what transcripts become substrates for Piwi protein complexes and the level by which the transcripts are present in the cell. A transition from active transcription of RTEs to passive co-transcription of RTE sequences residing within protein-coding transcripts appears to take place in postnatal development. Hence, the previously reported increase in piRNA targeting of SINEs in postnatal testis development

  15. Post-mortem analysis of suicide victims shows ABCB1 haplotype 1236T-2677T-3435T as a candidate predisposing factor behind adverse drug reactions in females.

    Rahikainen, Anna-Liina; Palo, Jukka U; Haukka, Jari; Sajantila, Antti

    2018-04-01

    Genetic variation in efflux transporter, permeability glycoprotein (P-gp), has recently been associated with completed violent suicides and also violent suicide attempts. As depression is known to be a risk factor for suicide and many antidepressants are P-gp substrates, it has been speculated that inadequate antidepressant treatment response or adverse side effects could be involved. The aim of this study was to investigate whether there is an association between the P-gp coding ABCB1 gene and completed suicides in citalopram users. Also, the effect of sex and suicide method used (violent vs. non-violent) was evaluated. All cases included in the study population, 349 completed suicide victims and 284 controls, were shown to be positive for antidepressant citalopram in a post-mortem toxicological drug screen. ABCB1 1236C>T, 2677G>T/A and 3435C>T polymorphisms were determined by TaqMan genotyping assays. Haplotypes were constructed from genotype data using the PHASE software. The association between the manner of death and the ABCB1 haplotype was tested with logistic regression analysis. No statistically significant differences were observed in the ABCB1 allele or genotype frequencies between the suicide and control groups. However, the ABCB1 1236T-2677T-3435T haplotype was associated with completed suicides of female citalopram users (odds ratio: 2.23; 95% confidence interval: 1.22-4.07; P=0.009). After stratification by the method used for suicide, the association emerged in fatal intoxications (odds ratio: 2.51; 95% confidence interval: 1.29-4.87; P=0.007). In other groups, no statistically significant associations were observed. Our results suggest that female citalopram users with ABCB1 1236T-2677T-3435T are more vulnerable to adverse effects of the drugs as this haplotype was enriched in non-violent suicides of female citalopram users. Even though the biological mechanism behind this observation is unknown, the results provide another example of the importance

  16. Polarization-induced interference within electromagnetically induced transparency for atoms of double-V linkage

    Sun, Yuan; Liu, Chang; Chen, Ping-Xing; Liu, Liang

    2018-02-01

    People have been paying attention to the role of atoms' complex internal level structures in the research of electromagnetically induced transparency (EIT) for a long time, where the various degenerate Zeeman levels usually generate complex linkage patterns for the atomic transitions. It turns out, with special choices of the atomic states and the atomic transitions' linkage structure, clear signatures of quantum interference induced by the probe and coupling light's polarizations can emerge from a typical EIT phenomena. We propose to study a four-state system with double-V linkage pattern for the transitions and analyze the polarization-induced interference under the EIT condition. We show that such interference arises naturally under mild conditions on the optical field and atom manipulation techniques. Moreover, we construct a variation form of double-M linkage pattern where the polarization-induced interference enables polarization-dependent cross modulation between incident weak lights that can be effective even at the few-photon level. The theme is to gain more insight into the essential question: how can we build a nontrivial optical medium where incident lights experience polarization-dependent nonlinear optical interactions, valid for a wide range of incidence intensities down to the few-photon level?

  17. Method to eliminate flux linkage DC component in load transformer for static transfer switch.

    He, Yu; Mao, Chengxiong; Lu, Jiming; Wang, Dan; Tian, Bing

    2014-01-01

    Many industrial and commercial sensitive loads are subject to the voltage sags and interruptions. The static transfer switch (STS) based on the thyristors is applied to improve the power quality and reliability. However, the transfer will result in severe inrush current in the load transformer, because of the DC component in the magnetic flux generated in the transfer process. The inrush current which is always 2 ~ 30 p.u. can cause the disoperation of relay protective devices and bring potential damage to the transformer. The way to eliminate the DC component is to transfer the related phases when the residual flux linkage of the load transformer and the prospective flux linkage of the alternate source are equal. This paper analyzes how the flux linkage of each winding in the load transformer changes in the transfer process. Based on the residual flux linkage when the preferred source is completely disconnected, the method to calculate the proper time point to close each phase of the alternate source is developed. Simulation and laboratory experiments results are presented to show the effectiveness of the transfer method.

  18. Amides are excellent mimics of phosphate internucleoside linkages and are well tolerated in short interfering RNAs.

    Mutisya, Daniel; Selvam, Chelliah; Lunstad, Benjamin D; Pallan, Pradeep S; Haas, Amanda; Leake, Devin; Egli, Martin; Rozners, Eriks

    2014-06-01

    RNA interference (RNAi) has become an important tool in functional genomics and has an intriguing therapeutic potential. However, the current design of short interfering RNAs (siRNAs) is not optimal for in vivo applications. Non-ionic phosphate backbone modifications may have the potential to improve the properties of siRNAs, but are little explored in RNAi technologies. Using X-ray crystallography and RNAi activity assays, the present study demonstrates that 3'-CH2-CO-NH-5' amides are excellent replacements for phosphodiester internucleoside linkages in RNA. The crystal structure shows that amide-modified RNA forms a typical A-form duplex. The amide carbonyl group points into the major groove and assumes an orientation that is similar to the P-OP2 bond in the phosphate linkage. Amide linkages are well hydrated by tandem waters linking the carbonyl group and adjacent phosphate oxygens. Amides are tolerated at internal positions of both the guide and passenger strand of siRNAs and may increase the silencing activity when placed near the 5'-end of the passenger strand. As a result, an siRNA containing eight amide linkages is more active than the unmodified control. The results suggest that RNAi may tolerate even more extensive amide modification, which may be useful for optimization of siRNAs for in vivo applications. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  19. Amides are excellent mimics of phosphate internucleoside linkages and are well tolerated in short interfering RNAs

    Mutisya, Daniel; Selvam, Chelliah; Lunstad, Benjamin D.; Pallan, Pradeep S.; Haas, Amanda; Leake, Devin; Egli, Martin; Rozners, Eriks

    2014-01-01

    RNA interference (RNAi) has become an important tool in functional genomics and has an intriguing therapeutic potential. However, the current design of short interfering RNAs (siRNAs) is not optimal for in vivo applications. Non-ionic phosphate backbone modifications may have the potential to improve the properties of siRNAs, but are little explored in RNAi technologies. Using X-ray crystallography and RNAi activity assays, the present study demonstrates that 3′-CH2-CO-NH-5′ amides are excellent replacements for phosphodiester internucleoside linkages in RNA. The crystal structure shows that amide-modified RNA forms a typical A-form duplex. The amide carbonyl group points into the major groove and assumes an orientation that is similar to the P–OP2 bond in the phosphate linkage. Amide linkages are well hydrated by tandem waters linking the carbonyl group and adjacent phosphate oxygens. Amides are tolerated at internal positions of both the guide and passenger strand of siRNAs and may increase the silencing activity when placed near the 5′-end of the passenger strand. As a result, an siRNA containing eight amide linkages is more active than the unmodified control. The results suggest that RNAi may tolerate even more extensive amide modification, which may be useful for optimization of siRNAs for in vivo applications. PMID:24813446

  20. Photoactive Zn(II)Porphyrin–multi-walled carbon nanotubes nanohybrids through covalent β-linkages

    Lipińska, Monika E.; Rebelo, Susana L.H.; Pereira, M. Fernando R.; Figueiredo, José L.; Freire, Cristina

    2013-01-01

    Donor–acceptor nanohybrids by a covalent linkage between the β-position of a Zn(II)Porphyrin and multi-walled carbon nanotubes are reported for the first time, in a closer analogy to the natural light harvesting systems, which are based on β-substituted porphyrinoid structures, the chlorophylls. An unique and direct connection was established through the immobilization of the Zn(II)(β-NH 2 -tetraphenylporphyrin), using diazonium chemistry, in order to afford i) a short and conjugated linkage between the two aromatic systems and ii) an amide bond resulting from a three-step functionalization synthesis. Electronic and steady-state fluorescence spectroscopies confirmed high photoinduced electron communication through the β-linkage when compared to analogous meso-phenyl linkers, stating its positive effect. The procedure involving the amide linkage allowed higher chromophore loadings; however, the direct conjugated bond showed improved photoinduced activity and a different emission pattern that can be associated with intense communication within the expanded π-system MWCNT–metalloporphyrin. - Graphical abstract: Preparation and photo-induced activity of two donor–acceptor nanohybrids is reported based on different linkages through β-position of porphyrin core to MWCNT, direct conjugation and amide bond. - Highlights: • β-linked Zn(II)Porphyrin–MWCNT nanohybrids were prepared through direct or amide bond. • Efficient and mild functionalizations were achieved using diazonium chemistry. • Good nanohybrid dispersibility was obtained in low boiling point solvent. • Nanohybrids showed strong photoinduced electronic transfer. • The emission quenching was higher for the π-expanded system

  1. Photoactive Zn(II)Porphyrin–multi-walled carbon nanotubes nanohybrids through covalent β-linkages

    Lipińska, Monika E., E-mail: m.e.lipinska@gmail.com [REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre s/n, 4169-007 Porto (Portugal); Rebelo, Susana L.H., E-mail: susana.rebelo@fc.up.pt [REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre s/n, 4169-007 Porto (Portugal); Pereira, M. Fernando R., E-mail: fpereira@fe.up.pt [Laboratório de Catálise e Materiais (LCM), Laboratório Associado LSRE/LCM, Departamento de Engenharia Química, Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto (Portugal); Figueiredo, José L., E-mail: jlfig@fe.up.pt [Laboratório de Catálise e Materiais (LCM), Laboratório Associado LSRE/LCM, Departamento de Engenharia Química, Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto (Portugal); Freire, Cristina, E-mail: acfreire@fc.up.pt [REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre s/n, 4169-007 Porto (Portugal)

    2013-12-16

    Donor–acceptor nanohybrids by a covalent linkage between the β-position of a Zn(II)Porphyrin and multi-walled carbon nanotubes are reported for the first time, in a closer analogy to the natural light harvesting systems, which are based on β-substituted porphyrinoid structures, the chlorophylls. An unique and direct connection was established through the immobilization of the Zn(II)(β-NH{sub 2}-tetraphenylporphyrin), using diazonium chemistry, in order to afford i) a short and conjugated linkage between the two aromatic systems and ii) an amide bond resulting from a three-step functionalization synthesis. Electronic and steady-state fluorescence spectroscopies confirmed high photoinduced electron communication through the β-linkage when compared to analogous meso-phenyl linkers, stating its positive effect. The procedure involving the amide linkage allowed higher chromophore loadings; however, the direct conjugated bond showed improved photoinduced activity and a different emission pattern that can be associated with intense communication within the expanded π-system MWCNT–metalloporphyrin. - Graphical abstract: Preparation and photo-induced activity of two donor–acceptor nanohybrids is reported based on different linkages through β-position of porphyrin core to MWCNT, direct conjugation and amide bond. - Highlights: • β-linked Zn(II)Porphyrin–MWCNT nanohybrids were prepared through direct or amide bond. • Efficient and mild functionalizations were achieved using diazonium chemistry. • Good nanohybrid dispersibility was obtained in low boiling point solvent. • Nanohybrids showed strong photoinduced electronic transfer. • The emission quenching was higher for the π-expanded system.

  2. The Structure-Function Linkage Database.

    Akiva, Eyal; Brown, Shoshana; Almonacid, Daniel E; Barber, Alan E; Custer, Ashley F; Hicks, Michael A; Huang, Conrad C; Lauck, Florian; Mashiyama, Susan T; Meng, Elaine C; Mischel, David; Morris, John H; Ojha, Sunil; Schnoes, Alexandra M; Stryke, Doug; Yunes, Jeffrey M; Ferrin, Thomas E; Holliday, Gemma L; Babbitt, Patricia C

    2014-01-01

    The Structure-Function Linkage Database (SFLD, http://sfld.rbvi.ucsf.edu/) is a manually curated classification resource describing structure-function relationships for functionally diverse enzyme superfamilies. Members of such superfamilies are diverse in their overall reactions yet share a common ancestor and some conserved active site features associated with conserved functional attributes such as a partial reaction. Thus, despite their different functions, members of these superfamilies 'look alike', making them easy to misannotate. To address this complexity and enable rational transfer of functional features to unknowns only for those members for which we have sufficient functional information, we subdivide superfamily members into subgroups using sequence information, and lastly into families, sets of enzymes known to catalyze the same reaction using the same mechanistic strategy. Browsing and searching options in the SFLD provide access to all of these levels. The SFLD offers manually curated as well as automatically classified superfamily sets, both accompanied by search and download options for all hierarchical levels. Additional information includes multiple sequence alignments, tab-separated files of functional and other attributes, and sequence similarity networks. The latter provide a new and intuitively powerful way to visualize functional trends mapped to the context of sequence similarity.

  3. The Structure–Function Linkage Database

    Akiva, Eyal; Brown, Shoshana; Almonacid, Daniel E.; Barber, Alan E.; Custer, Ashley F.; Hicks, Michael A.; Huang, Conrad C.; Lauck, Florian; Mashiyama, Susan T.; Meng, Elaine C.; Mischel, David; Morris, John H.; Ojha, Sunil; Schnoes, Alexandra M.; Stryke, Doug; Yunes, Jeffrey M.; Ferrin, Thomas E.; Holliday, Gemma L.; Babbitt, Patricia C.

    2014-01-01

    The Structure–Function Linkage Database (SFLD, http://sfld.rbvi.ucsf.edu/) is a manually curated classification resource describing structure–function relationships for functionally diverse enzyme superfamilies. Members of such superfamilies are diverse in their overall reactions yet share a common ancestor and some conserved active site features associated with conserved functional attributes such as a partial reaction. Thus, despite their different functions, members of these superfamilies ‘look alike’, making them easy to misannotate. To address this complexity and enable rational transfer of functional features to unknowns only for those members for which we have sufficient functional information, we subdivide superfamily members into subgroups using sequence information, and lastly into families, sets of enzymes known to catalyze the same reaction using the same mechanistic strategy. Browsing and searching options in the SFLD provide access to all of these levels. The SFLD offers manually curated as well as automatically classified superfamily sets, both accompanied by search and download options for all hierarchical levels. Additional information includes multiple sequence alignments, tab-separated files of functional and other attributes, and sequence similarity networks. The latter provide a new and intuitively powerful way to visualize functional trends mapped to the context of sequence similarity. PMID:24271399

  4. The efficiency of average linkage hierarchical clustering algorithm associated multi-scale bootstrap resampling in identifying homogeneous precipitation catchments

    Chuan, Zun Liang; Ismail, Noriszura; Shinyie, Wendy Ling; Lit Ken, Tan; Fam, Soo-Fen; Senawi, Azlyna; Yusoff, Wan Nur Syahidah Wan

    2018-04-01

    Due to the limited of historical precipitation records, agglomerative hierarchical clustering algorithms widely used to extrapolate information from gauged to ungauged precipitation catchments in yielding a more reliable projection of extreme hydro-meteorological events such as extreme precipitation events. However, identifying the optimum number of homogeneous precipitation catchments accurately based on the dendrogram resulted using agglomerative hierarchical algorithms are very subjective. The main objective of this study is to propose an efficient regionalized algorithm to identify the homogeneous precipitation catchments for non-stationary precipitation time series. The homogeneous precipitation catchments are identified using average linkage hierarchical clustering algorithm associated multi-scale bootstrap resampling, while uncentered correlation coefficient as the similarity measure. The regionalized homogeneous precipitation is consolidated using K-sample Anderson Darling non-parametric test. The analysis result shows the proposed regionalized algorithm performed more better compared to the proposed agglomerative hierarchical clustering algorithm in previous studies.

  5. Young people’s views about consenting to data linkage: findings from the PEARL qualitative study

    Suzanne Audrey

    2016-03-01

    Full Text Available Abstract Background Electronic administrative data exist in several domains which, if linked, are potentially useful for research. However, benefits from data linkage should be considered alongside risks such as the threat to privacy. Avon Longitudinal Study of Parents and Children (ALSPAC is a birth cohort study. The Project to Enhance ALSPAC through Record Linkage (PEARL was established to enrich the ALSPAC resource through linkage between ALSPAC participants and routine sources of health and social data. Qualitative research was incorporated in the PEARL study to examine participants’ views about data linkage and inform approaches to information sharing. This paper focusses on issues of consent. Methods Digitally recorded interviews were conducted with 55 participants aged 17–19 years. Terms and processes relating to consent, anonymization and data linkage were explained to interviewees. Scenarios were used to prompt consideration of linking different sources of data, and whether consent should be requested. Interview recordings were fully transcribed. Thematic analysis was undertaken using the Framework approach. Results Participant views on data linkage appeared to be most influenced by: considerations around the social sensitivity of the research question, and; the possibility of tangible health benefits in the public interest. Some participants appeared unsure about the effectiveness of anonymization, or did not always view effective anonymization as making consent unnecessary. This was related to notions of ownership of personal information and etiquette around asking permission for secondary use. Despite different consent procedures being explained, participants tended to equate consent with ‘opt-in’ consent through which participants are ‘asked’ if their data can be used for a specific study. Participants raising similar concerns came to differing conclusions about whether consent was needed. Views changed when presented

  6. Young people's views about consenting to data linkage: findings from the PEARL qualitative study.

    Audrey, Suzanne; Brown, Lindsey; Campbell, Rona; Boyd, Andy; Macleod, John

    2016-03-21

    Electronic administrative data exist in several domains which, if linked, are potentially useful for research. However, benefits from data linkage should be considered alongside risks such as the threat to privacy. Avon Longitudinal Study of Parents and Children (ALSPAC) is a birth cohort study. The Project to Enhance ALSPAC through Record Linkage (PEARL) was established to enrich the ALSPAC resource through linkage between ALSPAC participants and routine sources of health and social data. Qualitative research was incorporated in the PEARL study to examine participants' views about data linkage and inform approaches to information sharing. This paper focusses on issues of consent. Digitally recorded interviews were conducted with 55 participants aged 17-19 years. Terms and processes relating to consent, anonymization and data linkage were explained to interviewees. Scenarios were used to prompt consideration of linking different sources of data, and whether consent should be requested. Interview recordings were fully transcribed. Thematic analysis was undertaken using the Framework approach. Participant views on data linkage appeared to be most influenced by: considerations around the social sensitivity of the research question, and; the possibility of tangible health benefits in the public interest. Some participants appeared unsure about the effectiveness of anonymization, or did not always view effective anonymization as making consent unnecessary. This was related to notions of ownership of personal information and etiquette around asking permission for secondary use. Despite different consent procedures being explained, participants tended to equate consent with 'opt-in' consent through which participants are 'asked' if their data can be used for a specific study. Participants raising similar concerns came to differing conclusions about whether consent was needed. Views changed when presented with different scenarios, and were sometimes inconsistent. Findings

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

    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

  8. Linkages from DOE’s Vehicle Technologies R&D in Advanced Combustion to More Efficient, Cleaner-Burning Engines

    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).

  9. A consensus linkage map of the grass carp (Ctenopharyngodon idella based on microsatellites and SNPs

    Li Jiale

    2010-02-01

    Full Text Available Abstract Background Grass carp (Ctenopharyngodon idella belongs to the family Cyprinidae which includes more than 2000 fish species. It is one of the most important freshwater food fish species in world aquaculture. A linkage map is an essential framework for mapping traits of interest and is often the first step towards understanding genome evolution. The aim of this study is to construct a first generation genetic map of grass carp using microsatellites and SNPs to generate a new resource for mapping QTL for economically important traits and to conduct a comparative mapping analysis to shed new insights into the evolution of fish genomes. Results We constructed a first generation linkage map of grass carp with a mapping panel containing two F1 families including 192 progenies. Sixteen SNPs in genes and 263 microsatellite markers were mapped to twenty-four linkage groups (LGs. The number of LGs was corresponding to the haploid chromosome number of grass carp. The sex-specific map was 1149.4 and 888.8 cM long in females and males respectively whereas the sex-averaged map spanned 1176.1 cM. The average resolution of the map was 4.2 cM/locus. BLAST searches of sequences of mapped markers of grass carp against the whole genome sequence of zebrafish revealed substantial macrosynteny relationship and extensive colinearity of markers between grass carp and zebrafish. Conclusions The linkage map of grass carp presented here is the first linkage map of a food fish species based on co-dominant markers in the family Cyprinidae. This map provides a valuable resource for mapping phenotypic variations and serves as a reference to approach comparative genomics and understand the evolution of fish genomes and could be complementary to grass carp genome sequencing project.

  10. The power to detect linkage in complex disease by means of simple LOD-score analyses.

    Greenberg, D A; Abreu, P; Hodge, S E

    1998-09-01

    Maximum-likelihood analysis (via LOD score) provides the most powerful method for finding linkage when the mode of inheritance (MOI) is known. However, because one must assume an MOI, the application of LOD-score analysis to complex disease has been questioned. Although it is known that one can legitimately maximize the maximum LOD score with respect to genetic parameters, this approach raises three concerns: (1) multiple testing, (2) effect on power to detect linkage, and (3) adequacy of the approximate MOI for the true MOI. We evaluated the power of LOD scores to detect linkage when the true MOI was complex but a LOD score analysis assumed simple models. We simulated data from 14 different genetic models, including dominant and recessive at high (80%) and low (20%) penetrances, intermediate models, and several additive two-locus models. We calculated LOD scores by assuming two simple models, dominant and recessive, each with 50% penetrance, then took the higher of the two LOD scores as the raw test statistic and corrected for multiple tests. We call this test statistic "MMLS-C." We found that the ELODs for MMLS-C are >=80% of the ELOD under the true model when the ELOD for the true model is >=3. Similarly, the power to reach a given LOD score was usually >=80% that of the true model, when the power under the true model was >=60%. These results underscore that a critical factor in LOD-score analysis is the MOI at the linked locus, not that of the disease or trait per se. Thus, a limited set of simple genetic models in LOD-score analysis can work well in testing for linkage.

  11. Genome-wide linkage scan for maximum and length-dependent knee muscle strength in young men: significant evidence for linkage at chromosome 14q24.3.

    De Mars, G; Windelinckx, A; Huygens, W; Peeters, M W; Beunen, G P; Aerssens, J; Vlietinck, R; Thomis, M A I

    2008-05-01

    Maintenance of high muscular fitness is positively related to bone health, functionality in daily life and increasing insulin sensitivity, and negatively related to falls and fractures, morbidity and mortality. Heritability of muscle strength phenotypes ranges between 31% and 95%, but little is known about the identity of the genes underlying this complex trait. As a first attempt, this genome-wide linkage study aimed to identify chromosomal regions linked to muscle and bone cross-sectional area, isometric knee flexion and extension torque, and torque-length relationship for knee flexors and extensors. In total, 283 informative male siblings (17-36 years old), belonging to 105 families, were used to conduct a genome-wide SNP-based multipoint linkage analysis. The strongest evidence for linkage was found for the torque-length relationship of the knee flexors at 14q24.3 (LOD = 4.09; p<10(-5)). Suggestive evidence for linkage was found at 14q32.2 (LOD = 3.00; P = 0.005) for muscle and bone cross-sectional area, at 2p24.2 (LOD = 2.57; p = 0.01) for isometric knee torque at 30 degrees flexion, at 1q21.3, 2p23.3 and 18q11.2 (LOD = 2.33, 2.69 and 2.21; p<10(-4) for all) for the torque-length relationship of the knee extensors and at 18p11.31 (LOD = 2.39; p = 0.0004) for muscle-mass adjusted isometric knee extension torque. We conclude that many small contributing genes rather than a few important genes are involved in causing variation in different underlying phenotypes of muscle strength. Furthermore, some overlap in promising genomic regions were identified among different strength phenotypes.

  12. Spatial Linkage and Urban Expansion: AN Urban Agglomeration View

    Jiao, L. M.; Tang, X.; Liu, X. P.

    2017-09-01

    Urban expansion displays different characteristics in each period. From the perspective of the urban agglomeration, studying the spatial and temporal characteristics of urban expansion plays an important role in understanding the complex relationship between urban expansion and network structure of urban agglomeration. We analyze urban expansion in the Yangtze River Delta Urban Agglomeration (YRD) through accessibility to and spatial interaction intensity from core cities as well as accessibility of road network. Results show that: (1) Correlation between urban expansion intensity and spatial indicators such as location and space syntax variables is remarkable and positive, while it decreases after rapid expansion. (2) Urban expansion velocity displays a positive correlation with spatial indicators mentioned above in the first (1980-1990) and second (1990-2000) period. However, it exhibits a negative relationship in the third period (2000-2010), i.e., cities located in the periphery of urban agglomeration developing more quickly. Consequently, the hypothesis of convergence of urban expansion in rapid expansion stage is put forward. (3) Results of Zipf's law and Gibrat's law show urban expansion in YRD displays a convergent trend in rapid expansion stage, small and medium-sized cities growing faster. This study shows that spatial linkage plays an important but evolving role in urban expansion within the urban agglomeration. In addition, it serves as a reference to the planning of Yangtze River Delta Urban Agglomeration and regulation of urban expansion of other urban agglomerations.

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

    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....

  14. A gene-based SNP resource and linkage map for the copepod Tigriopus californicus

    Foley Brad R

    2011-11-01

    Full Text Available Abstract Background As yet, few genomic resources have been developed in crustaceans. This lack is particularly evident in Copepoda, given the extraordinary numerical abundance, and taxonomic and ecological diversity of this group. Tigriopus californicus is ideally suited to serve as a genetic model copepod and has been the subject of extensive work in environmental stress and reproductive isolation. Accordingly, we set out to develop a broadly-useful panel of genetic markers and to construct a linkage map dense enough for quantitative trait locus detection in an interval mapping framework for T. californicus--a first for copepods. Results One hundred and ninety Single Nucleotide Polymorphisms (SNPs were used to genotype our mapping population of 250 F2 larvae. We were able to construct a linkage map with an average intermarker distance of 1.8 cM, and a maximum intermarker distance of 10.3 cM. All markers were assembled into linkage groups, and the 12 linkage groups corresponded to the 12 known chromosomes of T. californicus. We estimate a total genome size of 401.0 cM, and a total coverage of 73.7%. Seventy five percent of the mapped markers were detected in 9 additional populations of T. californicus. Of available model arthropod genomes, we were able to show more colocalized pairs of homologues between T. californicus and the honeybee Apis mellifera, than expected by chance, suggesting preserved macrosynteny between Hymenoptera and Copepoda. Conclusions Our study provides an abundance of linked markers spanning all chromosomes. Many of these markers are also found in multiple populations of T. californicus, and in two other species in the genus. The genomic resource we have developed will enable mapping throughout the geographical range of this species and in closely related species. This linkage map will facilitate genome sequencing, mapping and assembly in an ecologically and taxonomically interesting group for which genomic resources are

  15. A gene-based SNP resource and linkage map for the copepod Tigriopus californicus

    2011-01-01

    Background As yet, few genomic resources have been developed in crustaceans. This lack is particularly evident in Copepoda, given the extraordinary numerical abundance, and taxonomic and ecological diversity of this group. Tigriopus californicus is ideally suited to serve as a genetic model copepod and has been the subject of extensive work in environmental stress and reproductive isolation. Accordingly, we set out to develop a broadly-useful panel of genetic markers and to construct a linkage map dense enough for quantitative trait locus detection in an interval mapping framework for T. californicus--a first for copepods. Results One hundred and ninety Single Nucleotide Polymorphisms (SNPs) were used to genotype our mapping population of 250 F2 larvae. We were able to construct a linkage map with an average intermarker distance of 1.8 cM, and a maximum intermarker distance of 10.3 cM. All markers were assembled into linkage groups, and the 12 linkage groups corresponded to the 12 known chromosomes of T. californicus. We estimate a total genome size of 401.0 cM, and a total coverage of 73.7%. Seventy five percent of the mapped markers were detected in 9 additional populations of T. californicus. Of available model arthropod genomes, we were able to show more colocalized pairs of homologues between T. californicus and the honeybee Apis mellifera, than expected by chance, suggesting preserved macrosynteny between Hymenoptera and Copepoda. Conclusions Our study provides an abundance of linked markers spanning all chromosomes. Many of these markers are also found in multiple populations of T. californicus, and in two other species in the genus. The genomic resource we have developed will enable mapping throughout the geographical range of this species and in closely related species. This linkage map will facilitate genome sequencing, mapping and assembly in an ecologically and taxonomically interesting group for which genomic resources are currently under development

  16. Reference Genome-Directed Resolution of Homologous and Homeologous Relationships within and between Different Oat Linkage Maps

    Juan J. Gutierrez-Gonzalez

    2011-11-01

    Full Text Available Genome research on oat ( L. has received less attention than wheat ( L. and barley ( L. because it is a less prominent component of the human food system. To assess the potential of the model grass (L P. Beauv. as a surrogate for oat genome research, the whole genome sequence (WGS of was employed for comparative analysis with oat genetic linkage maps. Sequences of mapped molecular markers from one diploid spp. and two hexaploid oat maps were aligned to the WGS to infer syntenic relationships. Diploid and exhibit a high degree of synteny with 18 syntenic blocks covering 87% of the oat genome, which permitted postulation of an ancestral spp. chromosome structure. Synteny between oat and was also prevalent, with 50 syntenic blocks covering 76.6% of the ‘Kanota’ × ‘Ogle’ linkage map. Coalignment of diploid and hexaploid maps to helped resolve homeologous relationships between different oat linkage groups but also revealed many major rearrangements in oat subgenomes. Extending the analysis to a second oat linkage map (Ogle × ‘TAM O-301’ allowed identification of several putative homologous linkage groups across the two oat populations. These results indicate that the genome sequence will be a useful resource to assist genetics and genomics research in oat. The analytical strategy employed here should be applicable for genome research in other temperate grass crops with modest amounts of genomic data.

  17. Review of the Linkages between Gender Equity and Climate ...

    Review of the Linkages between Gender Equity and Climate Change Issues in ... thereby exacerbating inequalities in health status and access to adequate food, clean ... Again, in traditional societies, women are even more vulnerable to the ...

  18. Solid-Phase Synthesis of RNA Analogs Containing Phosphorodithioate Linkages.

    Yang, Xianbin

    2017-09-18

    The oligoribonucleotide phosphorodithioate (PS2-RNA) modification uses two sulfur atoms to replace two non-bridging oxygen atoms at an internucleotide phosphorodiester backbone linkage. Like a natural phosphodiester RNA backbone linkage, a PS2-modified backbone linkage is achiral at phosphorus. PS2-RNAs are highly stable to nucleases and several in vitro assays have demonstrated their biological activity. For example, PS2-RNAs silenced mRNA in vitro and bound to protein targets in the form of PS2-aptamers (thioaptamers). Thus, the interest in and promise of PS2-RNAs has drawn attention to synthesizing, isolating, and characterizing these compounds. RNA-thiophosphoramidite monomers are commercially available from AM Biotechnologies and this unit describes an effective methodology for solid-phase synthesis, deprotection, and purification of RNAs having PS2 internucleotide linkages. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  19. Mapping organizational linkages in the agricultural innovation system of Azerbaijan

    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.

  20. Strengthening industry-research linkage for small scale industrial ...

    Strengthening industry-research linkage for small scale industrial development in Ghana - the relevance of scientific and technological information. ... Journal of Applied Science and Technology. Journal Home · ABOUT · Advanced Search ...

  1. Underreporting of maternal mortality in Taiwan: A data linkage study

    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.

  2. Estimating parameters for probabilistic linkage of privacy-preserved datasets.

    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

  3. Learning Expressive Linkage Rules for Entity Matching using Genetic Programming

    Isele, Robert

    2013-01-01

    A central problem in data integration and data cleansing is to identify pairs of entities in data sets that describe the same real-world object. Many existing methods for matching entities rely on explicit linkage rules, which specify how two entities are compared for equivalence. Unfortunately, writing accurate linkage rules by hand is a non-trivial problem that requires detailed knowledge of the involved data sets. Another important issue is the efficient execution of link...

  4. Clinical and linkage study of a large family with simple ectopia lentis linked to FBN1

    Edwards, M.J.; Roberts, J.; Partington, M.W. [Newcastle and Northern New South Wales Genetics Service (Australia); Colley, P.W. [John Hunter Hospital, Newcastle (Australia); Hollway, G.E.; Kozman, H.M.; Mulley, J.C. [Adelaide Children`s Hospital, North Adelaide (Australia)

    1994-10-15

    Simple ectopia lentis (EL) was studied in a large family, by clinical examination and analysis of linkage to markers in the region of FBN1, the gene for fibrillin which causes Marfan syndrome on chromosome 15. No patient had clinical or echocardiographic evidence of Marfan syndrome, although there was a trend towards relatively longer measurements of height; lower segment; arm span; middle finger, hand, and foot length in the affected members of the family, compared with unaffected sibs of the same sex. Analysis of linkage to intragenic FBN1 markers was inconclusive because they were relatively uninformative. Construction of a multipoint background map from the CEPH reference families identified microsatellite markers linked closely to FBN1 which could demonstrate linkage of EL in this family to the FBN1 region. LINKMAP analysis detected a multipoint lod score of 5.68 at D15S119, a marker approximately 6 cM distal to FBN1, and a multipoint lod score of 5.04 at FBN1. The EL gene in this family is likely to be allelic to Marfan syndrome, and molecular characterization of the FBN1 mutation should now be possible. 25 refs., 6 figs., 2 tabs.

  5. The prune belly anomaly: heterogeneity and superficial X-linkage mimicry.

    Riccardi, V M; Grum, C M

    1977-01-01

    The genetic, clinical, and necropsy findings of 2 brothers with the prune belly anomaly are presented and the literature reviewed. The combined data emphasise the clinical and genetic heterogeneity of the disorder and show that in at least some instances a heritable component may be the primary insult. The most likely heritable explanation involves a two-step autosomal dominant mutation with sex-limited expression that partially mimics X-linkage. PMID:144797

  6. Linkage Map of a Gene Controlling Zero Tannins (zt-1 in Faba Bean (Vicia faba L. with SSR and ISSR Markers

    Wanwei Hou

    2018-05-01

    Full Text Available Faba bean (Vicia faba L., a partially allogamous species, is rich in protein. Condensed tannins limit the use of faba beans as food and feed. Two recessive genes, zt-1 and zt-2, control the zero tannin content in faba bean and promote a white flower phenotype. To determine the inheritance and develop a linkage map for the zt-1 gene in the faba bean germplasm M3290, F2 and F3 progenies were derived from the purple flower and high tannin content genotypes Qinghai12 and zt-1 line M3290, respectively. Genetic analysis verified a single recessive gene for zero tannin content and flower colour. In total, 596 SSR markers and 100 ISSR markers were used to test the polymorphisms between the parents and bulks for the contrasting flower colour via Bulked Segregant Analysis (BSA. Subsequently, six SSR markers and seven ISSR markers were used to genotype the entire 413 F2 population. Linkage analysis showed that the zt-1 gene was closely linked to the SSR markers SSR84 and M78, with genetic distances of 2.9 and 5.8 cM, respectively. The two flanked SSR markers were used to test 34 faba bean genotypes with different flower colours. The closely linked SSR marker SSR84 predicted the zt-1 genotypes with absolute accuracy. The results from the marker-assisted selection (MAS from this study could provide a solid foundation for further faba bean breeding programmes.

  7. Linkage of microbial ecology to phenotype: correlation of rumen microbial ecology to cattle's feed efficiency.

    Guan, Le Luo; Nkrumah, Joshua D; Basarab, John A; Moore, Stephen S

    2008-11-01

    Linkage of rumen microbial structure to host phenotypical traits may enhance the understanding of host-microbial interactions in livestock species. This study used culture-independent PCR-denaturing gradient gel electrophoresis (PCR-DGGE) to investigate the microbial profiles in the rumen of cattle differing in feed efficiency. The analysis of detectable bacterial PCR-DGGE profiles showed that the profiles generated from efficient steers clustered together and were clearly separated from those obtained from inefficient steers, indicating that specific bacterial groups may only inhabit in efficient steers. In addition, the bacterial profiles were more likely clustered within a certain breed, suggesting that host genetics may play an important role in rumen microbial structure. The correlations between the concentrations of volatile fatty acids and feed efficiency traits were also observed. Significantly higher concentrations of butyrate (P < 0.001) and valerate (P = 0.006) were detected in the efficient steers. Our results revealed potential associations between the detectable rumen microbiota and its fermentation parameters with the feed efficiency of cattle.

  8. Detecting Recombination Hotspots from Patterns of Linkage Disequilibrium.

    Wall, Jeffrey D; Stevison, Laurie S

    2016-08-09

    With recent advances in DNA sequencing technologies, it has become increasingly easy to use whole-genome sequencing of unrelated individuals to assay patterns of linkage disequilibrium (LD) across the genome. One type of analysis that is commonly performed is to estimate local recombination rates and identify recombination hotspots from patterns of LD. One method for detecting recombination hotspots, LDhot, has been used in a handful of species to further our understanding of the basic biology of recombination. For the most part, the effectiveness of this method (e.g., power and false positive rate) is unknown. In this study, we run extensive simulations to compare the effectiveness of three different implementations of LDhot. We find large differences in the power and false positive rates of these different approaches, as well as a strong sensitivity to the window size used (with smaller window sizes leading to more accurate estimation of hotspot locations). We also compared our LDhot simulation results with comparable simulation results obtained from a Bayesian maximum-likelihood approach for identifying hotspots. Surprisingly, we found that the latter computationally intensive approach had substantially lower power over the parameter values considered in our simulations. Copyright © 2016 Wall and Stevison.

  9. Genome-wide linkage scan for primary open angle glaucoma: influences of ancestry and age at diagnosis.

    Kristy R Crooks

    Full Text Available Primary open-angle glaucoma (POAG is the most common form of glaucoma and one of the leading causes of vision loss worldwide. The genetic etiology of POAG is complex and poorly understood. The purpose of this work is to identify genomic regions of interest linked to POAG. This study is the largest genetic linkage study of POAG performed to date: genomic DNA samples from 786 subjects (538 Caucasian ancestry, 248 African ancestry were genotyped using either the Illumina GoldenGate Linkage 4 Panel or the Illumina Infinium Human Linkage-12 Panel. A total of 5233 SNPs was analyzed in 134 multiplex POAG families (89 Caucasian ancestry, 45 African ancestry. Parametric and non-parametric linkage analyses were performed on the overall dataset and within race-specific datasets (Caucasian ancestry and African ancestry. Ordered subset analysis was used to stratify the data on the basis of age of glaucoma diagnosis. Novel linkage regions were identified on chromosomes 1 and 20, and two previously described loci-GLC1D on chromosome 8 and GLC1I on chromosome 15--were replicated. These data will prove valuable in the context of interpreting results from genome-wide association studies for POAG.

  10. Construction of a genetic linkage map in Lilium using a RIL mapping population based on SRAP marker

    Chen Li-Jing

    2015-01-01

    Full Text Available A genetic linkage map of lily was constructed using RILs (recombinant inbred lines population of 180 individuals. This mapping population was developed by crossing Raizan No.1 (Formolongo and Gelria (Longiflomm cultivars through single-seed descent (SSD. SRAPs were generated by using restriction enzymes EcoRI in combination with either MseI. The resulting products were separated by electrophoresis on 6% denaturing polyacrylamide gel and visualized by silver staining. The segregation of each marker and linkage analysis was done using the program Mapmaker3.0. With 50 primer pairs, a total of 189 parental polymorphic bands were detected and 78 were used for mapping. The total map length was 2,135.5 cM consisted of 16 linkage groups. The number of markers in the linkage groups varied from 1 to 12. The length of linkage groups was range from 11.2 cM to 425.9 cM and mean marker interval distance range from 9.4 cM to 345.4 cM individually. The mean marker interval distance between markers was 27.4 cM. The map developed in the present study was the first sequence-related amplified polymorphism markers map of lily constructed with recombinant inbred lines, it could be used for genetic mapping and molecular marker assisted breeding and quantitative trait locus mapping of Lilium.

  11. Design, modeling and optimization of an underwater manipulator with four-bar mechanism and compliant linkage

    Jin, Sang Ok; Kim, Ji Hoon; Bae, Jang Ho; Kim, Jong Won [School of Mechanical and Aerospace Engineering, Seoul National University, Seoul (Korea, Republic of); Seo, Tae Won [School of Mechanical Engineering, Yeungnam University, Gyeongsan (Korea, Republic of)

    2016-09-15

    Underwater manipulators are very important for a robot to perform a specific operation in water. Conventional robot arm manipulators have been suggested for various operations but have not been suitable for repeated motion in gathering something. This paper presents a new underwater manipulator design for gathering things such as starfish on the sea floor. The manipulator is composed of a four-bar linkage to achieve repeated motion along a loop and compliant linkages to enhance the efficiency of the gathering work. Kinematic and quasi-static analyses were performed to calculate the loop path and the reaction force at the actuation point. Based on the analysis, optimal design was performed to maximize the working distance with the height difference and the reaction moments considered as constraints. A prototype was assembled to test the performance of the manipulator, and the empirical loop path was compared to simulation results.

  12. Design, modeling and optimization of an underwater manipulator with four-bar mechanism and compliant linkage

    Jin, Sang Ok; Kim, Ji Hoon; Bae, Jang Ho; Kim, Jong Won; Seo, Tae Won

    2016-01-01

    Underwater manipulators are very important for a robot to perform a specific operation in water. Conventional robot arm manipulators have been suggested for various operations but have not been suitable for repeated motion in gathering something. This paper presents a new underwater manipulator design for gathering things such as starfish on the sea floor. The manipulator is composed of a four-bar linkage to achieve repeated motion along a loop and compliant linkages to enhance the efficiency of the gathering work. Kinematic and quasi-static analyses were performed to calculate the loop path and the reaction force at the actuation point. Based on the analysis, optimal design was performed to maximize the working distance with the height difference and the reaction moments considered as constraints. A prototype was assembled to test the performance of the manipulator, and the empirical loop path was compared to simulation results

  13. Using Bureaucratic and Cultural Linkages to Improve Instruction: The Principal's Contribution.

    Firestone, William A.; Wilson, Bruce L.

    1985-01-01

    Principals can influence teachers and instructional behavior by working through linkage mechanisms within the organizational structure of the school. Two types of linkages are identified: bureaucratic and cultural. Principals have access to linkages of both kinds; using linkages effectively, they can generate a common purpose in their schools. (MD)

  14. THE NATIONAL SECURITY - MEDIA POWER LINKAGE. A THEORETICAL FRAMEWORK

    KARIN MEGHEŞAN

    2013-05-01

    Full Text Available The mechanism of national security policy is an issue of increasing interests in post cold war era. But what is the impact of the media upon national security policy decision making? New world wide events show us that more than ever national policy is often at the mercy of the media. The Wiki leaks, the Murdoch inquiry, the impact of new social media on Arab democratic movements are just some examples regarding the effect of nearly simultaneous presentation of information around the world.