WorldWideScience

Sample records for combined genome scans

  1. Combined genome scans for body stature in 6,602 European twins

    DEFF Research Database (Denmark)

    Perola, Markus; Sammalisto, Sampo; Hiekkalinna, Tero

    2007-01-01

    Twin cohorts provide a unique advantage for investigations of the role of genetics and environment in the etiology of variation in common complex traits by reducing the variance due to environment, age, and cohort differences. The GenomEUtwin (http://www.genomeutwin.org) consortium consists...... combined and related to the sequence positions using software developed by us, which is publicly available (https://apps.bioinfo.helsinki.fi/software/cartographer.aspx). Variance component linkage analysis was performed with age, sex, and country of origin as covariates. The covariate adjusted heritability...

  2. Combined genome scans for body stature in 6,602 European twins: evidence for common Caucasian loci.

    Directory of Open Access Journals (Sweden)

    Markus Perola

    2007-06-01

    Full Text Available Twin cohorts provide a unique advantage for investigations of the role of genetics and environment in the etiology of variation in common complex traits by reducing the variance due to environment, age, and cohort differences. The GenomEUtwin (http://www.genomeutwin.org consortium consists of eight twin cohorts (Australian, Danish, Dutch, Finnish, Italian, Norwegian, Swedish, and United Kingdom with the total resource of hundreds of thousands of twin pairs. We performed quantitative trait locus (QTL analysis of one of the most heritable human complex traits, adult stature (body height using genome-wide scans performed for 3,817 families (8,450 individuals derived from twin cohorts from Australia, Denmark, Finland, Netherlands, Sweden, and United Kingdom with an approximate ten-centimorgan microsatellite marker map. The marker maps for different studies differed and they were combined and related to the sequence positions using software developed by us, which is publicly available (https://apps.bioinfo.helsinki.fi/software/cartographer.aspx. Variance component linkage analysis was performed with age, sex, and country of origin as covariates. The covariate adjusted heritability was 81% for stature in the pooled dataset. We found evidence for a major QTL for human stature on 8q21.3 (multipoint logarithm of the odds 3.28, and suggestive evidence for loci on Chromosomes X, 7, and 20. Some evidence of sex heterogeneity was found, however, no obvious female-specific QTLs emerged. Several cohorts contributed to the identified loci, suggesting an evolutionarily old genetic variant having effects on stature in European-based populations. To facilitate the genetic studies of stature we have also set up a website that lists all stature genome scans published and their most significant loci (http://www.genomeutwin.org/stature_gene_map.htm.

  3. Horizon scanning for new genomic tests.

    Science.gov (United States)

    Gwinn, Marta; Grossniklaus, Daurice A; Yu, Wei; Melillo, Stephanie; Wulf, Anja; Flome, Jennifer; Dotson, W David; Khoury, Muin J

    2011-02-01

    The development of health-related genomic tests is decentralized and dynamic, involving government, academic, and commercial entities. Consequently, it is not easy to determine which tests are in development, currently available, or discontinued. We developed and assessed the usefulness of a systematic approach to identifying new genomic tests on the Internet. We devised targeted queries of Web pages, newspaper articles, and blogs (Google Alerts) to identify new genomic tests. We finalized search and review procedures during a pilot phase that ended in March 2010. Queries continue to run daily and are compiled weekly; selected data are indexed in an online database, the Genomic Applications in Practice and Prevention Finder. After the pilot phase, our scan detected approximately two to three new genomic tests per week. Nearly two thirds of all tests (122/188, 65%) were related to cancer; only 6% were related to hereditary disorders. Although 88 (47%) of the tests, including 2 marketed directly to consumers, were commercially available, only 12 (6%) claimed United States Food and Drug Administration licensure. Systematic surveillance of the Internet provides information about genomic tests that can be used in combination with other resources to evaluate genomic tests. The Genomic Applications in Practice and Prevention Finder makes this information accessible to a wide group of stakeholders.

  4. Clinical applications of Genome Polymorphism Scans

    Directory of Open Access Journals (Sweden)

    Weber James L

    2006-06-01

    Full Text Available Abstract Applications of Genome Polymorphism Scans range from the relatively simple such as gender determination and confirmation of biological relationships, to the relatively complex such as determination of autozygosity and propagation of genetic information throughout pedigrees. Unlike nearly all other clinical DNA tests, the Scan is a universal test – it covers all people and all genes. In balance, I argue that the Genome Polymorphism Scan is the most powerful, affordable clinical DNA test available today. Reviewers: This article was reviewed by Scott Weiss (nominated by Neil Smalheiser, Roberta Pagon (nominated by Jerzy Jurka and Val Sheffield (nominated by Neil Smalheiser.

  5. AluScan: a method for genome-wide scanning of sequence and structure variations in the human genome

    Directory of Open Access Journals (Sweden)

    Mei Lingling

    2011-11-01

    Full Text Available Abstract Background To complement next-generation sequencing technologies, there is a pressing need for efficient pre-sequencing capture methods with reduced costs and DNA requirement. The Alu family of short interspersed nucleotide elements is the most abundant type of transposable elements in the human genome and a recognized source of genome instability. With over one million Alu elements distributed throughout the genome, they are well positioned to facilitate genome-wide sequence amplification and capture of regions likely to harbor genetic variation hotspots of biological relevance. Results Here we report on the use of inter-Alu PCR with an enhanced range of amplicons in conjunction with next-generation sequencing to generate an Alu-anchored scan, or 'AluScan', of DNA sequences between Alu transposons, where Alu consensus sequence-based 'H-type' PCR primers that elongate outward from the head of an Alu element are combined with 'T-type' primers elongating from the poly-A containing tail to achieve huge amplicon range. To illustrate the method, glioma DNA was compared with white blood cell control DNA of the same patient by means of AluScan. The over 10 Mb sequences obtained, derived from more than 8,000 genes spread over all the chromosomes, revealed a highly reproducible capture of genomic sequences enriched in genic sequences and cancer candidate gene regions. Requiring only sub-micrograms of sample DNA, the power of AluScan as a discovery tool for genetic variations was demonstrated by the identification of 357 instances of loss of heterozygosity, 341 somatic indels, 274 somatic SNVs, and seven potential somatic SNV hotspots between control and glioma DNA. Conclusions AluScan, implemented with just a small number of H-type and T-type inter-Alu PCR primers, provides an effective capture of a diversity of genome-wide sequences for analysis. The method, by enabling an examination of gene-enriched regions containing exons, introns, and

  6. Scanning and Filling: Ultra-Dense SNP Genotyping Combining Genotyping-By-Sequencing, SNP Array and Whole-Genome Resequencing Data.

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    Davoud Torkamaneh

    Full Text Available Genotyping-by-sequencing (GBS represents a highly cost-effective high-throughput genotyping approach. By nature, however, GBS is subject to generating sizeable amounts of missing data and these will need to be imputed for many downstream analyses. The extent to which such missing data can be tolerated in calling SNPs has not been explored widely. In this work, we first explore the use of imputation to fill in missing genotypes in GBS datasets. Importantly, we use whole genome resequencing data to assess the accuracy of the imputed data. Using a panel of 301 soybean accessions, we show that over 62,000 SNPs could be called when tolerating up to 80% missing data, a five-fold increase over the number called when tolerating up to 20% missing data. At all levels of missing data examined (between 20% and 80%, the resulting SNP datasets were of uniformly high accuracy (96-98%. We then used imputation to combine complementary SNP datasets derived from GBS and a SNP array (SoySNP50K. We thus produced an enhanced dataset of >100,000 SNPs and the genotypes at the previously untyped loci were again imputed with a high level of accuracy (95%. Of the >4,000,000 SNPs identified through resequencing 23 accessions (among the 301 used in the GBS analysis, 1.4 million tag SNPs were used as a reference to impute this large set of SNPs on the entire panel of 301 accessions. These previously untyped loci could be imputed with around 90% accuracy. Finally, we used the 100K SNP dataset (GBS + SoySNP50K to perform a GWAS on seed oil content within this collection of soybean accessions. Both the number of significant marker-trait associations and the peak significance levels were improved considerably using this enhanced catalog of SNPs relative to a smaller catalog resulting from GBS alone at ≤20% missing data. Our results demonstrate that imputation can be used to fill in both missing genotypes and untyped loci with very high accuracy and that this leads to more

  7. A genome-wide scan for preeclampsia in the Netherlands

    NARCIS (Netherlands)

    Lachmeijer, AMA; Arngrimsson, R; Bastiaans, EJ; Frigge, ML; Pals, G; Sigurdardottir, S; Stefansson, H; Palsson, B; Nicolae, D; Kong, A; Aarnoudse, JG; Gulcher, [No Value; Dekker, GA; ten Kate, LP; Stefansson, K

    2001-01-01

    Preeclampsia, hallmarked by de novo hypertension and proteinuria in pregnancy, has a familial tendency. Recently, a large Icelandic genome-wide scan provided evidence for a maternal susceptibility locus for preeclampsia on chromosome 2p13 which was confirmed by a genome scan from Australia and New

  8. prokaryote genome annotation with GeneScan and GLIMMER

    Indian Academy of Sciences (India)

    Unknown

    The Fourier measure forms the basis for an efficient non-consensus method for gene prediction, and the algorithm GeneScan exploits ... these techniques for complete genome analysis. GeneScan and GLIMMER are of comparable .... of open reading frames (ORFs) which are ultimately noncoding. One of the objectives of ...

  9. Whole genome PCR scanning (WGPS) of Coxiella burnetii strains from ruminants.

    Science.gov (United States)

    Sidi-Boumedine, Karim; Adam, Gilbert; Angen, Øysten; Aspán, Anna; Bossers, Alex; Roest, Hendrik-Jan; Prigent, Myriam; Thiéry, Richard; Rousset, Elodie

    2015-01-01

    Coxiella burnetii is the causative agent of Q fever, a zoonosis that spreads from ruminants to humans via the inhalation of aerosols contaminated by livestock's birth products. This study aimed to compare the genomes of strains isolated from ruminants by "Whole Genome PCR Scanning (WGPS)" in order to identify genomic differences. C. burnetii isolated from different ruminant hosts were compared to the Nine Mile reference strain using WGPS. The identified genomic regions of differences (RDs) were confirmed by sequencing. A set of 219 primers for amplification of 10 kbp segments covering the entire genome was obtained. The analyses revealed the presence of: i) conserved genomic regions, ii) genomic polymorphism including insertions and deletions and iii) amplification failures in some cases as well. WGPS, a descriptive approach, allowed the identification and localization of divergent genetic loci from various strains of C. burnetii which consisted of deletions, insertions and maybe genomic rearrangements. It also substantiates the role played by the IS1111 element in the genomic plasticity of C. burnetii. We believe that this approach could be combined with new sequencing technologies, as a selective/directed sequencing approach, particularly when repeated sequences are present in the analysed genomes. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  10. Detecting positive selection from genome scans of linkage disequilibrium

    Directory of Open Access Journals (Sweden)

    Rogers Alan R

    2010-01-01

    Full Text Available Abstract Background Though a variety of linkage disequilibrium tests have recently been introduced to measure the signal of recent positive selection, the statistical properties of the various methods have not been directly compared. While most applications of these tests have suggested that positive selection has played an important role in recent human history, the results of these tests have varied dramatically. Results Here, we evaluate the performance of three statistics designed to detect incomplete selective sweeps, LRH and iHS, and ALnLH. To analyze the properties of these tests, we introduce a new computational method that can model complex population histories with migration and changing population sizes to simulate gene trees influenced by recent positive selection. We demonstrate that iHS performs substantially better than the other two statistics, with power of up to 0.74 at the 0.01 level for the variation best suited for full genome scans and a power of over 0.8 at the 0.01 level for the variation best suited for candidate gene tests. The performance of the iHS statistic was robust to complex demographic histories and variable recombination rates. Genome scans involving the other two statistics suffer from low power and high false positive rates, with false discovery rates of up to 0.96 for ALnLH. The difference in performance between iHS and ALnLH, did not result from the properties of the statistics, but instead from the different methods for mitigating the multiple comparison problem inherent in full genome scans. Conclusions We introduce a new method for simulating genealogies influenced by positive selection with complex demographic scenarios. In a power analysis based on this method, iHS outperformed LRH and ALnLH in detecting incomplete selective sweeps. We also show that the single-site iHS statistic is more powerful in a candidate gene test than the multi-site statistic, but that the multi-site statistic maintains a low

  11. Asthma and atopy - a total genome scan for susceptibility genes

    DEFF Research Database (Denmark)

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

    2002-01-01

    . Investigation of different populations will further clarify the topic. We therefore evaluated allergic asthma and increased total and specific IgE in 39, 45 and 57 sib-pairs from 100 Danish allergy families. METHODS: Affected sib-pairs meeting a narrow phenotype definition were selected for the three phenotypes...... atopy, allergic asthma and increased total IgE. We performed a total genome scan using 446 microsatellite markers and obtained nonparametric linkage results from the MAPMAKER/SIBS computer program. RESULTS: Our study revealed four candidate regions (MLS > 2) on chromosome 1p36, 3q21-q22, 5q31 and 6p24-p...

  12. A new approach for using genome scans to detect recent positive selection in the human genome.

    Directory of Open Access Journals (Sweden)

    Kun Tang

    2007-07-01

    Full Text Available Genome-wide scanning for signals of recent positive selection is essential for a comprehensive and systematic understanding of human adaptation. Here, we present a genomic survey of recent local selective sweeps, especially aimed at those nearly or recently completed. A novel approach was developed for such signals, based on contrasting the extended haplotype homozygosity (EHH profiles between populations. We applied this method to the genome single nucleotide polymorphism (SNP data of both the International HapMap Project and Perlegen Sciences, and detected widespread signals of recent local selection across the genome, consisting of both complete and partial sweeps. A challenging problem of genomic scans of recent positive selection is to clearly distinguish selection from neutral effects, given the high sensitivity of the test statistics to departures from neutral demographic assumptions and the lack of a single, accurate neutral model of human history. We therefore developed a new procedure that is robust across a wide range of demographic and ascertainment models, one that indicates that certain portions of the genome clearly depart from neutrality. Simulations of positive selection showed that our tests have high power towards strong selection sweeps that have undergone fixation. Gene ontology analysis of the candidate regions revealed several new functional groups that might help explain some important interpopulation differences in phenotypic traits.

  13. Genome-Wide Scan for Methylation Profiles in Keloids

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    Lamont R. Jones

    2015-01-01

    Full Text Available Keloids are benign fibroproliferative tumors of the skin which commonly occur after injury mainly in darker skinned patients. Medical treatment is fraught with high recurrence rates mainly because of an incomplete understanding of the biological mechanisms that lead to keloids. The purpose of this project was to examine keloid pathogenesis from the epigenome perspective of DNA methylation. Genome-wide profiling used the Infinium HumanMethylation450 BeadChip to interrogate DNA from 6 fresh keloid and 6 normal skin samples from 12 anonymous donors. A 3-tiered approach was used to call out genes most differentially methylated between keloid and normal. When compared to normal, of the 685 differentially methylated CpGs at Tier 3, 510 were hypomethylated and 175 were hypermethylated with 190 CpGs in promoter and 495 in nonpromoter regions. The 190 promoter region CpGs corresponded to 152 genes: 96 (63% were hypomethylated and 56 (37% hypermethylated. This exploratory genome-wide scan of the keloid methylome highlights a predominance of hypomethylated genomic landscapes, favoring nonpromoter regions. DNA methylation, as an additional mechanism for gene regulation in keloid pathogenesis, holds potential for novel treatments that reverse deleterious epigenetic changes. As an alternative mechanism for regulating genes, epigenetics may explain why gene mutations alone do not provide definitive mechanisms for keloid formation.

  14. Photon scanning tunneling microscope in combination with a force microscope

    NARCIS (Netherlands)

    Moers, M.H.P.; Moers, M.H.P.; Tack, R.G.; van Hulst, N.F.; Bölger, B.; Bölger, B.

    1994-01-01

    The simultaneous operation of a photon scanning tunneling microscope with an atomic force microscope is presented. The use of standard atomic force silicon nitride cantilevers as near-field optical probes offers the possibility to combine the two methods. Vertical forces and torsion are detected

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

    Energy Technology Data Exchange (ETDEWEB)

    Barr, C.L.; Livingston, J.; Williamson, R. [and others

    1994-09-01

    Gilles de la Tourette Syndrome (TS) is a familial, neuropsychiatric disorder characterized by chronic, intermittent motor and vocal tics. In addition to tics, affected individuals frequently display symptoms such as attention-deficit hyperactivity disorder and/or obsessive compulsive disorder. Genetic analyses of family data have suggested that susceptibility to the disorder is most likely due to a single genetic locus with a dominant mode of transmission and reduced penetrance. In the search for genetic linkage for TS, we have collected well-characterized pedigrees with multiple affected individuals on whom extensive diagnostic evaluations have been done. The first stage of our study is to scan the genome systematically using a panel of uniformly spaced (10 to 20 cM), highly polymorphic, microsatellite markers on 5 families segregating TS. To date, 290 markers have been typed and 3,660 non-overlapping cM of the genome have been excluded for possible linkage under the assumption of genetic homogeneity. Because of the possibility of locus heterogeneity overall summed exclusion is not considered tantamount to absolute exclusion of a disease locus in that region. The results from each family are carefully evaluated and a positive lod score in a single family is followed up by typing closely linked markers. Linkage to TS was examined by two-point analysis using the following genetic model: single autosomal dominant gene with gene frequency .003 and maximum penetrance of .99. An age-of-onset correction is included using a linear function increasing from age 2 years to 21 years. A small rate of phenocopies is also incorporated into the model. Only individuals with TS or CMT according to DSM III-R criteria were regarded as affected for the purposes of this summary. Additional markers are being tested to provide coverage at 5 cM intervals. Moreover, we are currently analyzing the data non-parametrically using the Affected-Pedigree-Member Method of linkage analysis.

  16. Genome-wide DNA methylation scan in major depressive disorder.

    Directory of Open Access Journals (Sweden)

    Sarven Sabunciyan

    Full Text Available While genome-wide association studies are ongoing to identify sequence variation influencing susceptibility to major depressive disorder (MDD, epigenetic marks, such as DNA methylation, which can be influenced by environment, might also play a role. Here we present the first genome-wide DNA methylation (DNAm scan in MDD. We compared 39 postmortem frontal cortex MDD samples to 26 controls. DNA was hybridized to our Comprehensive High-throughput Arrays for Relative Methylation (CHARM platform, covering 3.5 million CpGs. CHARM identified 224 candidate regions with DNAm differences >10%. These regions are highly enriched for neuronal growth and development genes. Ten of 17 regions for which validation was attempted showed true DNAm differences; the greatest were in PRIMA1, with 12-15% increased DNAm in MDD (p = 0.0002-0.0003, and a concomitant decrease in gene expression. These results must be considered pilot data, however, as we could only test replication in a small number of additional brain samples (n = 16, which showed no significant difference in PRIMA1. Because PRIMA1 anchors acetylcholinesterase in neuronal membranes, decreased expression could result in decreased enzyme function and increased cholinergic transmission, consistent with a role in MDD. We observed decreased immunoreactivity for acetylcholinesterase in MDD brain with increased PRIMA1 DNAm, non-significant at p = 0.08.While we cannot draw firm conclusions about PRIMA1 DNAm in MDD, the involvement of neuronal development genes across the set showing differential methylation suggests a role for epigenetics in the illness. Further studies using limbic system brain regions might shed additional light on this role.

  17. A genome scan for positive selection in thoroughbred horses.

    Directory of Open Access Journals (Sweden)

    Jingjing Gu

    2009-06-01

    Full Text Available Thoroughbred horses have been selected for exceptional racing performance resulting in system-wide structural and functional adaptations contributing to elite athletic phenotypes. Because selection has been recent and intense in a closed population that stems from a small number of founder animals Thoroughbreds represent a unique population within which to identify genomic contributions to exercise-related traits. Employing a population genetics-based hitchhiking mapping approach we performed a genome scan using 394 autosomal and X chromosome microsatellite loci and identified positively selected loci in the extreme tail-ends of the empirical distributions for (1 deviations from expected heterozygosity (Ewens-Watterson test in Thoroughbred (n = 112 and (2 global differentiation among four geographically diverse horse populations (F(ST. We found positively selected genomic regions in Thoroughbred enriched for phosphoinositide-mediated signalling (3.2-fold enrichment; P<0.01, insulin receptor signalling (5.0-fold enrichment; P<0.01 and lipid transport (2.2-fold enrichment; P<0.05 genes. We found a significant overrepresentation of sarcoglycan complex (11.1-fold enrichment; P<0.05 and focal adhesion pathway (1.9-fold enrichment; P<0.01 genes highlighting the role for muscle strength and integrity in the Thoroughbred athletic phenotype. We report for the first time candidate athletic-performance genes within regions targeted by selection in Thoroughbred horses that are principally responsible for fatty acid oxidation, increased insulin sensitivity and muscle strength: ACSS1 (acyl-CoA synthetase short-chain family member 1, ACTA1 (actin, alpha 1, skeletal muscle, ACTN2 (actinin, alpha 2, ADHFE1 (alcohol dehydrogenase, iron containing, 1, MTFR1 (mitochondrial fission regulator 1, PDK4 (pyruvate dehydrogenase kinase, isozyme 4 and TNC (tenascin C. Understanding the genetic basis for exercise adaptation will be crucial for the identification of genes

  18. Forest structure analysis combining laser scanning with digital airborne photogrammetry

    Science.gov (United States)

    Lissak, Candide; Onda, Yuichi; Kato, Hiroaki

    2017-04-01

    The interest of Light Detection and Ranging (LiDAR) for vegetation structure analysis has been demonstrated in several research context. Indeed, airborne or ground Lidar surveys can provide detailed three-dimensional data of the forest structure from understorey forest to the canopy. To characterize at different timescale the vegetation components in dense cedar forests we can combine several sources point clouds from Lidar survey and photogrammetry data. For our study, Terrestrial Laser Scanning (TLS-Leica ScanStation C10 processed with Cyclone software) have been lead in three forest areas (≈ 200m2 each zone) mainly composed of japanese cedar (Japonica cryptomeria), in the region of Fukushima (Japan). The study areas are characterized by various vegetation densities. For the 3 areas, Terrestrial laser scanning has been performed from several location points and several heights. Various floors shootings (ground, 4m, 6m and 18m high) were able with the use of a several meters high tower implanted to study the canopy evolution following the Fukushima Daiishi nuclear power plant accident. The combination of all scanners provides a very dense 3D point cloud of ground and canopy structure (average 300 000 000 points). For the Tochigi forest area, a first test of a low-cost Unmanned Aerial Vehicle (UAV) photogrammetry has been lead and calibrated by ground GPS measurements to determine the coordinates of points. TLS combined to UAV photogrammetry make it possible to obtain information on vertical and horizontal structure of the Tochigi forest. This combination of technologies will allow the forest structure mapping, morphometry analysis and the assessment of biomass volume evolution from multi-temporal point clouds. In our research, we used a low-cost UAV 3 Advanced (200 m2 cover, 1300 pictures...). Data processing were performed using PotoScan Pro software to obtain a very dense point clouds to combine to TLS data set. This low-cost UAV photogrammetry data has been

  19. Genome-wide association scan of trait depression

    Science.gov (United States)

    Terracciano, Antonio; Tanaka, Toshiko; Sutin, Angelina R.; Sanna, Serena; Deiana, Barbara; Lai, Sandra; Uda, Manuela; Schlessinger, David; Abecasis, Gonçalo R.; Ferrucci, Luigi; Costa, Paul T.

    2010-01-01

    Background Independent of temporal circumstances, some individuals have greater susceptibility to depressive affects, such as feelings of guilt, sadness, hopelessness, and loneliness. Identifying the genetic variants that contribute to these individual differences can point to biological pathways etiologically involved in psychiatric disorders. Methods Genome-wide association scans (GWA or GWAS) for the Depression scale of the Revised NEO Personality Inventory (NEO-PI-R) in community-based samples from a genetically homogeneous area of Sardinia, Italy (N = 3,972) and from the Baltimore Longitudinal Study of Aging in the US (N = 839). Results Meta-analytic results for genotyped or imputed single nucleotide polymorphisms (SNPs) indicate that the strongest association signals for trait depression were found in RORA (rs12912233; p= 6 × 10−7), a gene involved in circadian rhythm. A plausible biological association was also found with SNPs within GRM8 (rs17864092; p = 5 × 10−6), a metabotropic receptor for glutamate, a major excitatory neurotransmitter in the central nervous system. Conclusions These findings suggest shared genetic basis underlying the continuum from personality traits to psychopathology. PMID:20800221

  20. A bivariate whole-genome linkage scan suggests several shared genomic regions for obesity and osteoporosis.

    Science.gov (United States)

    Tang, Zi-Hui; Xiao, Peng; Lei, Shu-Feng; Deng, Fei-Yan; Zhao, Lan-Juan; Deng, Hong-Yi; Tan, Li-Jun; Shen, Hui; Xiong, Dong-Hai; Recker, Robert R; Deng, Hong-Wen

    2007-07-01

    A genome-wide bivariate analysis was conducted for body fat mass (BFM) and bone mineral density (BMD) in a large Caucasian sample. We found some quantitative trait loci shared by BFM and BMD in the total sample and the gender-specific subgroups, and quantitative trait loci with potential pleiotropy were disclosed. BFM and BMD, as the respective measure for obesity and osteoporosis, are phenotypically and genetically correlated. However, specific genomic regions accounting for their genetic correlation are unknown. To identify systemically the shared genomic regions for BFM and BMD, we performed a bivariate whole-genome linkage scan in 4498 Caucasian individuals from 451 families for BFM and BMD at the hip, spine, and wrist, respectively. Linkage analyses were performed in the total sample and the male and female subgroups, respectively. In the entire sample, suggestive linkages were detected at 7p22-p21 (LOD 2.69) for BFM and spine BMD, 6q27 (LOD 2.30) for BFM and hip BMD, and 11q13 (LOD 2.64) for BFM and wrist BMD. Male-specific suggestive linkages were found at 13q12 (LOD 3.23) for BFM and spine BMD and at 7q21 (LOD 2.59) for BFM and hip BMD. Female-specific suggestive LOD scores were 3.32 at 15q13 for BFM and spine BMD and 3.15 at 6p25-24 for BFM and wrist BMD. Several shared genomic regions for BFM and BMD were identified here. Our data may benefit further positional and functional studies, aimed at eventually uncovering the complex mechanism underlying the shared genetic determination of obesity and osteoporosis.

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

    Science.gov (United States)

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

    2010-01-01

    Genetic contribution to the development of attention deficit hyperactivity disorder (ADHD) is well established. Seven independent genome-wide linkage scans have been performed to map loci that increase the risk for ADHD. Although significant linkage signals were identified in some of the studies, there has been limited replications between the various independent datasets. The current study gathered the results from all seven of the ADHD linkage scans and performed a Genome Scan Meta Analysis (GSMA) to identify the genomic region with most consistent linkage evidence across the studies. Genome-wide significant linkage (PSR=0.00034, POR=0.04) was identified on chromosome 16 between 64 and 83 Mb. In addition there are nine other genomic regions from the GSMA showing nominal or suggestive evidence of linkage. All these linkage results may be informative and focus the search for novel ADHD susceptibility genes. PMID:18988193

  2. A Genome Scan for Quantitative Trait Loci Affecting Average Daily ...

    Indian Academy of Sciences (India)

    reviewer

    impairs neuronal development and causes autistic-like behaviour. Mol. Psychiatr. 20, 632-639. Bai Y., Sartor M. and Cavalcoli J. 2012. Current status and future perspectives for sequencing livestock genomes. J. anim. sci. biotechnol. 3, 1-6. Badenhorst M. A. 1990. The kleiber ratio as a possible selection for sire selection.

  3. Restriction landmark genomic scanning of mouse liver tumors for gene amplification: overexpression of cyclin A2.

    Science.gov (United States)

    Haddad, R; Morrow, A D; Plass, C; Held, W A

    2000-07-21

    SV40 T/t antigen-induced liver tumors from transgenic mice were analyzed by Restriction Landmark Genomic Scanning (RLGS). Using NotI as the restriction landmark, RLGS targets CpG islands found in gene-rich regions of the genome. Since many RLGS landmarks are mapped, the candidate gene approach can be used to help determine which genes are altered in tumors. RLGS analysis revealed one tumor-specific amplification mapping close to CcnA2 (cyclin A2) and Fgf2 (fibroblast growth factor 2). Southern analysis confirmed that both oncogenes are amplified in this tumor and in a second, independent liver tumor. Whereas Fgf2 RNA is undetectable in tumors, CcnA2 RNA and cyclin A2 protein was overexpressed in 25 and 50% of tumors, respectively. Combining RLGS with the candidate gene approach indicates that cyclin A2 amplification and overexpression is a likely selected event in transgenic mouse liver tumors. Our results also indicate that our mouse model for liver tumorigenesis in mice accurately recapitulates events observed in human hepatocellular carcinoma. Copyright 2000 Academic Press.

  4. Efficient strategies for genome scanning using maximum-likelihood affected-sib-pair analysis

    Energy Technology Data Exchange (ETDEWEB)

    Holmans, P.; Craddock, N. [Univ. of Wales College of Medicine, Cardiff (United Kingdom)

    1997-03-01

    Detection of linkage with a systematic genome scan in nuclear families including an affected sibling pair is an important initial step on the path to cloning susceptibility genes for complex genetic disorders, and it is desirable to optimize the efficiency of such studies. The aim is to maximize power while simultaneously minimizing the total number of genotypings and probability of type I error. One approach to increase efficiency, which has been investigated by other workers, is grid tightening: a sample is initially typed using a coarse grid of markers, and promising results are followed up by use of a finer grid. Another approach, not previously considered in detail in the context of an affected-sib-pair genome scan for linkage, is sample splitting: a portion of the sample is typed in the screening stage, and promising results are followed up in the whole sample. In the current study, we have used computer simulation to investigate the relative efficiency of two-stage strategies involving combinations of both grid tightening and sample splitting and found that the optimal strategy incorporates both approaches. In general, typing half the sample of affected pairs with a coarse grid of markers in the screening stage is an efficient strategy under a variety of conditions. If Hardy-Weinberg equilibrium holds, it is most efficient not to type parents in the screening stage. If Hardy-Weinberg equilibrium does not hold (e.g., because of stratification) failure to type parents in the first stage increases the amount of genotyping required, although the overall probability of type I error is not greatly increased, provided the parents are used in the final analysis. 23 refs., 4 figs., 5 tabs.

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

    Science.gov (United States)

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

    2010-04-01

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

  6. AFLP genome scanning reveals divergent selection in natural populations of Liriodendron chinense (Magnoliaceae along a latitudinal transect

    Directory of Open Access Journals (Sweden)

    Aihong eYang

    2016-05-01

    Full Text Available Understanding adaptive genetic variation and its relation to environmental factors are important for understanding how plants adapt to climate change and for managing genetic resources. Genome scans for the loci exhibiting either notably high or low levels of population differentiation (outlier loci provide one means of identifying genomic regions possibly associated with convergent or divergent selection. In this study, we combined AFLP genome scan and environmental association analysis to test for signals of natural selection in natural populations of Liriodendron chinense (Chinese Tulip Tree; Magnoliaceae along a latitudinal transect. We genotyped 276 individuals from 11 populations of L. chinense using 987 AFLP markers. Two complementary methods (Dfdist and BayeScan and association analysis between AFLP loci and climate factors were applied to detect outlier loci. Our analyses recovered both neutral and potentially adaptive genetic differentiation among populations of L. chinense. We found moderate genetic diversity within populations and high genetic differentiation among populations with reduced genetic diversity towards the periphery of the species ranges. Nine AFLP marker loci showed evidence of being outliers for population differentiation for both detection methods. Of these, six were strongly associated with at least one climate factor. Temperature, precipitation and radiation were found to be three important factors influencing local adaptation of L. chinense. The outlier AFLP loci are likely not the target of natural selection, but the neighboring genes of these loci might be involved in local adaptation. Hence, these candidates should be validated by further studies.

  7. Processing of Graphene combining Optical Detection and Scanning Probe Lithography

    Directory of Open Access Journals (Sweden)

    Zimmermann Sören

    2015-01-01

    Full Text Available This paper presents an experimental setup tailored for robotic processing of graphene with in-situ vision based control. A robust graphene detection approach is presented applying multiple image processing operations of the visual feedback provided by a high-resolution light microscope. Detected graphene flakes can be modified using a scanning probe based lithographical process that is directly linked to the in-situ optical images. The results of this process are discussed with respect to further application scenarios.

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  9. A Genome-wide Quantitative Linkage Scan of Niacin Skin Flush Response in Families With Schizophrenia

    Science.gov (United States)

    Lien, Yin-Ju; Huang, Sih-Syuan; Liu, Chih-Min; Hwu, Hai-Gwo; Faraone, Stephen V.; Tsuang, Ming T.; Chen, Wei J.

    2013-01-01

    Schizophrenia patients frequently display reduced niacin flush responses, and similar characteristics are also observed in their nonpsychotic relatives. This study aimed to identify loci influencing flush response to niacin in schizophrenia using genome-wide quantitative linkage scan. In a nationwide sample of families with at least 2 siblings affected with schizophrenia in each family, 115 families that had at least 2 affected siblings with information on the niacin skin test were subjected to quantitative trait loci linkage analysis, either involving affected individuals only or the whole family. Nonparametric linkage z (NPL-Z) scores were calculated for each of 386 microsatellite markers spaced at an average of 9-cM intervals. Niacin patches of 3 concentrations (0.001M, 0.01, and 0.1M) were applied to forearm skin, and the flush response was rated at 5, 10, and 15 minutes, respectively, with a 4-point scale. Determination of genome-wide empirical significance was implemented using 1000 simulated genome scans. One linkage peak attaining genome-wide significance was identified at chromosomal region 14q32.12 for 0.01M concentration at 5 minutes (NPL-Z scores = 3.39, genome-wide empirical P = .03) in affected individuals, and the corresponding linkage signal remained strong (NPL-Z scores = 2.87) for the analyses of the whole family. This locus is distinct from the chromosomal region identified in the previous genome-wide scan for the diagnosis of schizophrenia, and the signal was higher than the peak linkage signal in that study. These findings indicate that there might be modifier or susceptibility-modifier genes at 14q32.12 for schizophrenia-related attenuation of flush response to niacin. PMID:21653277

  10. Accuracy of genomic prediction when combining two related crossbred populations

    NARCIS (Netherlands)

    Vallee, A.A.A.; Arendonk, van J.A.M.; Bovenhuis, H.

    2014-01-01

    Charolais bulls are selected for their crossbreed performance when mated to Montbéliard or Holstein dams. To implement genomic prediction, one could build a reference population for each crossbred population independently. An alternative could be to combine both crossbred populations into a single

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    Quantitative phenotypes correlated with a complex disorder offer increased power to detect linkage in comparison to affected-unaffected classifications. Asthma is a complex disorder characterized by periods of bronchial obstruction and increased bronchial hyper reactivity. In childhood and early...... 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....

  12. High-throughput DNA Stretching in Continuous Elongational Flow for Genome Sequence Scanning

    Science.gov (United States)

    Meltzer, Robert; Griffis, Joshua; Safranovitch, Mikhail; Malkin, Gene; Cameron, Douglas

    2014-03-01

    Genome Sequence Scanning (GSS) identifies and compares bacterial genomes by stretching long (60 - 300 kb) genomic DNA restriction fragments and scanning for site-selective fluorescent probes. Practical application of GSS requires: 1) high throughput data acquisition, 2) efficient DNA stretching, 3) reproducible DNA elasticity in the presence of intercalating fluorescent dyes. GSS utilizes a pseudo-two-dimensional micron-scale funnel with convergent sheathing flows to stretch one molecule at a time in continuous elongational flow and center the DNA stream over diffraction-limited confocal laser excitation spots. Funnel geometry has been optimized to maximize throughput of DNA within the desired length range (>10 million nucleobases per second). A constant-strain detection channel maximizes stretching efficiency by applying a constant parabolic tension profile to each molecule, minimizing relaxation and flow-induced tumbling. The effect of intercalator on DNA elasticity is experimentally controlled by reacting one molecule of DNA at a time in convergent sheathing flows of the dye. Derivations of accelerating flow and non-linear tension distribution permit alignment of detected fluorescence traces to theoretical templates derived from whole-genome sequence data.

  13. Non-random mate choice in humans: insights from a genome scan.

    Science.gov (United States)

    Laurent, R; Toupance, B; Chaix, R

    2012-02-01

    Little is known about the genetic factors influencing mate choice in humans. Still, there is evidence for non-random mate choice with respect to physical traits. In addition, some studies suggest that the Major Histocompatibility Complex may affect pair formation. Nowadays, the availability of high density genomic data sets gives the opportunity to scan the genome for signatures of non-random mate choice without prior assumptions on which genes may be involved, while taking into account socio-demographic factors. Here, we performed a genome scan to detect extreme patterns of similarity or dissimilarity among spouses throughout the genome in three populations of African, European American, and Mexican origins from the HapMap 3 database. Our analyses identified genes and biological functions that may affect pair formation in humans, including genes involved in skin appearance, morphogenesis, immunity and behaviour. We found little overlap between the three populations, suggesting that the biological functions potentially influencing mate choice are population specific, in other words are culturally driven. Moreover, whenever the same functional category of genes showed a significant signal in two populations, different genes were actually involved, which suggests the possibility of evolutionary convergences. © 2011 Blackwell Publishing Ltd.

  14. Combining genomic and proteomic approaches for epigenetics research

    Science.gov (United States)

    Han, Yumiao; Garcia, Benjamin A

    2014-01-01

    Epigenetics is the study of changes in gene expression or cellular phenotype that do not change the DNA sequence. In this review, current methods, both genomic and proteomic, associated with epigenetics research are discussed. Among them, chromatin immunoprecipitation (ChIP) followed by sequencing and other ChIP-based techniques are powerful techniques for genome-wide profiling of DNA-binding proteins, histone post-translational modifications or nucleosome positions. However, mass spectrometry-based proteomics is increasingly being used in functional biological studies and has proved to be an indispensable tool to characterize histone modifications, as well as DNA–protein and protein–protein interactions. With the development of genomic and proteomic approaches, combination of ChIP and mass spectrometry has the potential to expand our knowledge of epigenetics research to a higher level. PMID:23895656

  15. Combined frequency modulated atomic force microscopy and scanning tunneling microscopy detection for multi-tip scanning probe microscopy applications

    Science.gov (United States)

    Morawski, Ireneusz; Spiegelberg, Richard; Korte, Stefan; Voigtländer, Bert

    2015-12-01

    A method which allows scanning tunneling microscopy (STM) tip biasing independent of the sample bias during frequency modulated atomic force microscopy (AFM) operation is presented. The AFM sensor is supplied by an electronic circuit combining both a frequency shift signal and a tunneling current signal by means of an inductive coupling. This solution enables a control of the tip potential independent of the sample potential. Individual tip biasing is specifically important in order to implement multi-tip STM/AFM applications. An extensional quartz sensor (needle sensor) with a conductive tip is applied to record simultaneously topography and conductivity of the sample. The high resonance frequency of the needle sensor (1 MHz) allows scanning of a large area of the surface being investigated in a reasonably short time. A recipe for the amplitude calibration which is based only on the frequency shift signal and does not require the tip being in contact is presented. Additionally, we show spectral measurements of the mechanical vibration noise of the scanning system used in the investigations.

  16. Genome-wide scan of healthy human connectome discovers SPON1 gene variant influencing dementia severity

    Science.gov (United States)

    Jahanshad, Neda; Rajagopalan, Priya; Hua, Xue; Hibar, Derrek P.; Nir, Talia M.; Toga, Arthur W.; Jack, Clifford R.; Saykin, Andrew J.; Green, Robert C.; Weiner, Michael W.; Medland, Sarah E.; Montgomery, Grant W.; Hansell, Narelle K.; McMahon, Katie L.; de Zubicaray, Greig I.; Martin, Nicholas G.; Wright, Margaret J.; Thompson, Paul M.; Weiner, Michael; Aisen, Paul; Weiner, Michael; Aisen, Paul; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowski, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Liu, Enchi; Green, Robert C.; Montine, Tom; Petersen, Ronald; Aisen, Paul; Gamst, Anthony; Thomas, Ronald G.; Donohue, Michael; Walter, Sarah; Gessert, Devon; Sather, Tamie; Beckett, Laurel; Harvey, Danielle; Gamst, Anthony; Donohue, Michael; Kornak, John; Jack, Clifford R.; Dale, Anders; Bernstein, Matthew; Felmlee, Joel; Fox, Nick; Thompson, Paul; Schuff, Norbert; Alexander, Gene; DeCarli, Charles; Jagust, William; Bandy, Dan; Koeppe, Robert A.; Foster, Norm; Reiman, Eric M.; Chen, Kewei; Mathis, Chet; Morris, John; Cairns, Nigel J.; Taylor-Reinwald, Lisa; Trojanowki, J.Q.; Shaw, Les; Lee, Virginia M.Y.; Korecka, Magdalena; Toga, Arthur W.; Crawford, Karen; Neu, Scott; Saykin, Andrew J.; Foroud, Tatiana M.; Potkin, Steven; Shen, Li; Khachaturian, Zaven; Frank, Richard; Snyder, Peter J.; Molchan, Susan; Kaye, Jeffrey; Quinn, Joseph; Lind, Betty; Dolen, Sara; Schneider, Lon S.; Pawluczyk, Sonia; Spann, Bryan M.; Brewer, James; Vanderswag, Helen; Heidebrink, Judith L.; Lord, Joanne L.; Petersen, Ronald; Johnson, Kris; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Morris, John C.; Ances, Beau; Carroll, Maria; Leon, Sue; Mintun, Mark A.; Schneider, Stacy; Marson, Daniel; Griffith, Randall; Clark, David; Grossman, Hillel; Mitsis, Effie; Romirowsky, Aliza; deToledo-Morrell, Leyla; Shah, Raj C.; Duara, Ranjan; Varon, Daniel; Roberts, Peggy; Albert, Marilyn; Onyike, Chiadi; Kielb, Stephanie; Rusinek, Henry; de Leon, Mony J.; Glodzik, Lidia; De Santi, Susan; Doraiswamy, P. Murali; Petrella, Jeffrey R.; Coleman, R. Edward; Arnold, Steven E.; Karlawish, Jason H.; Wolk, David; Smith, Charles D.; Jicha, Greg; Hardy, Peter; Lopez, Oscar L.; Oakley, MaryAnn; Simpson, Donna M.; Porsteinsson, Anton P.; Goldstein, Bonnie S.; Martin, Kim; Makino, Kelly M.; Ismail, M. Saleem; Brand, Connie; Mulnard, Ruth A.; Thai, Gaby; Mc-Adams-Ortiz, Catherine; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Diaz-Arrastia, Ramon; King, Richard; Weiner, Myron; Martin-Cook, Kristen; DeVous, Michael; Levey, Allan I.; Lah, James J.; Cellar, Janet S.; Burns, Jeffrey M.; Anderson, Heather S.; Swerdlow, Russell H.; Apostolova, Liana; Lu, Po H.; Bartzokis, George; Silverman, Daniel H.S.; Graff-Radford, Neill R.; Parfitt, Francine; Johnson, Heather; Farlow, Martin R.; Hake, Ann Marie; Matthews, Brandy R.; Herring, Scott; van Dyck, Christopher H.; Carson, Richard E.; MacAvoy, Martha G.; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Hsiung, Ging-Yuek Robin; Feldman, Howard; Mudge, Benita; Assaly, Michele; Kertesz, Andrew; Rogers, John; Trost, Dick; Bernick, Charles; Munic, Donna; Kerwin, Diana; Mesulam, Marek-Marsel; Lipowski, Kristina; Wu, Chuang-Kuo; Johnson, Nancy; Sadowsky, Carl; Martinez, Walter; Villena, Teresa; Turner, Raymond Scott; Johnson, Kathleen; Reynolds, Brigid; Sperling, Reisa A.; Johnson, Keith A.; Marshall, Gad; Frey, Meghan; Yesavage, Jerome; Taylor, Joy L.; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Sabbagh, Marwan; Belden, Christine; Jacobson, Sandra; Kowall, Neil; Killiany, Ronald; Budson, Andrew E.; Norbash, Alexander; Johnson, Patricia Lynn; Obisesan, Thomas O.; Wolday, Saba; Bwayo, Salome K.; Lerner, Alan; Hudson, Leon; Ogrocki, Paula; Fletcher, Evan; Carmichael, Owen; Olichney, John; DeCarli, Charles; Kittur, Smita; Borrie, Michael; Lee, T.-Y.; Bartha, Rob; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Potkin, Steven G.; Preda, Adrian; Nguyen, Dana; Tariot, Pierre; Fleisher, Adam; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Scharre, Douglas W.; Kataki, Maria; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Pearlson, Godfrey D.; Blank, Karen; Anderson, Karen; Saykin, Andrew J.; Santulli, Robert B.; Schwartz, Eben S.; Sink, Kaycee M.; Williamson, Jeff D.; Garg, Pradeep; Watkins, Franklin; Ott, Brian R.; Querfurth, Henry; Tremont, Geoffrey; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Rosen, Howard J.; Miller, Bruce L.; Mintzer, Jacobo; Longmire, Crystal Flynn; Spicer, Kenneth; Finger, Elizabeth; Rachinsky, Irina; Rogers, John; Kertesz, Andrew; Drost, Dick

    2013-01-01

    Aberrant connectivity is implicated in many neurological and psychiatric disorders, including Alzheimer’s disease and schizophrenia. However, other than a few disease-associated candidate genes, we know little about the degree to which genetics play a role in the brain networks; we know even less about specific genes that influence brain connections. Twin and family-based studies can generate estimates of overall genetic influences on a trait, but genome-wide association scans (GWASs) can screen the genome for specific variants influencing the brain or risk for disease. To identify the heritability of various brain connections, we scanned healthy young adult twins with high-field, high-angular resolution diffusion MRI. We adapted GWASs to screen the brain’s connectivity pattern, allowing us to discover genetic variants that affect the human brain’s wiring. The association of connectivity with the SPON1 variant at rs2618516 on chromosome 11 (11p15.2) reached connectome-wide, genome-wide significance after stringent statistical corrections were enforced, and it was replicated in an independent subsample. rs2618516 was shown to affect brain structure in an elderly population with varying degrees of dementia. Older people who carried the connectivity variant had significantly milder clinical dementia scores and lower risk of Alzheimer’s disease. As a posthoc analysis, we conducted GWASs on several organizational and topological network measures derived from the matrices to discover variants in and around genes associated with autism (MACROD2), development (NEDD4), and mental retardation (UBE2A) significantly associated with connectivity. Connectome-wide, genome-wide screening offers substantial promise to discover genes affecting brain connectivity and risk for brain diseases. PMID:23471985

  17. Revealing phenotype-associated functional differences by genome-wide scan of ancient haplotype blocks.

    Directory of Open Access Journals (Sweden)

    Ritsuko Onuki

    Full Text Available Genome-wide scans for positive selection have become important for genomic medicine, and many studies aim to find genomic regions affected by positive selection that are associated with risk allele variations among populations. Most such studies are designed to detect recent positive selection. However, we hypothesize that ancient positive selection is also important for adaptation to pathogens, and has affected current immune-mediated common diseases. Based on this hypothesis, we developed a novel linkage disequilibrium-based pipeline, which aims to detect regions associated with ancient positive selection across populations from single nucleotide polymorphism (SNP data. By applying this pipeline to the genotypes in the International HapMap project database, we show that genes in the detected regions are enriched in pathways related to the immune system and infectious diseases. The detected regions also contain SNPs reported to be associated with cancers and metabolic diseases, obesity-related traits, type 2 diabetes, and allergic sensitization. These SNPs were further mapped to biological pathways to determine the associations between phenotypes and molecular functions. Assessments of candidate regions to identify functions associated with variations in incidence rates of these diseases are needed in the future.

  18. Genome-wide scans of genetic variants for psychophysiological endophenotypes: A methodological overview

    Science.gov (United States)

    IACONO, WILLIAM. G.; MALONE, STEPHEN. M.; VAIDYANATHAN, UMA; VRIEZE, SCOTT I.

    2014-01-01

    This article provides an introductory overview of the investigative strategy employed to evaluate the genetic basis of 17 endophenotypes examined as part of a 20-year data collection effort from the Minnesota Center for Twin and Family Research. Included are characterization of the study samples, descriptive statistics for key properties of the psychophysiological measures, and rationale behind the steps taken in the molecular genetic study design. The statistical approach included (a) biometric analysis of twin and family data, (b) heritability analysis using 527,829 single nucleotide polymorphisms (SNPs), (c) genome-wide association analysis of these SNPs and 17,601 autosomal genes, (d) follow-up analyses of candidate SNPs and genes hypothesized to have an association with each endophenotype, (e) rare variant analysis of nonsynonymous SNPs in the exome, and (f) whole genome sequencing association analysis using 27 million genetic variants. These methods were used in the accompanying empirical articles comprising this special issue, Genome-Wide Scans of Genetic Variants for Psychophysiological Endophenotypes. PMID:25387703

  19. Genome-wide linkage scan for loci associated with epilepsy in Belgian shepherd dogs.

    Science.gov (United States)

    Oberbauer, Anita M; Belanger, Janelle M; Grossman, Deborah I; Regan, Kelly R; Famula, Thomas R

    2010-05-04

    Idiopathic epilepsy in the Belgian shepherd dog is known to have a substantial genetic component. The objective of this study was to identify genomic regions associated with the expression of generalized seizures in the Belgian Tervuren and Sheepdog. DNA from 366 dogs, of which 74 were classified as epileptic, representing two extended families were subjected to a genome-wide linkage scan using 410 microsatellite markers yielding informative coverage averaging 5.95 +/- 0.21 Mb. Though previous studies based on pedigree analyses proposed a major gene of influence, the present study demonstrated the trait to be highly polygenic. Studies of complex disorders in humans indicate that a liberal composite evaluation of genetic linkage is needed to identify underlying quantitative trait loci (QTLs). Four chromosomes yielded tentative linkage based upon LOD scores in excess of 1.0. Possible QTLs within these regions were supported also by analyses of multipoint linkage, allele frequency, TDT, and transmission of haplotype blocks. Taken together the data tentatively indicate six QTLs, three on CFA 2, and one on each of CFA 6, 12, and 37, that support fine mapping for mutations associated with epilepsy in the Belgian shepherd. The study also underscores the complexity of genomic linkage studies for polygenic disorders.

  20. Genome-wide linkage scan for loci associated with epilepsy in Belgian shepherd dogs

    Directory of Open Access Journals (Sweden)

    Regan Kelly R

    2010-05-01

    Full Text Available Abstract Background Idiopathic epilepsy in the Belgian shepherd dog is known to have a substantial genetic component. The objective of this study was to identify genomic regions associated with the expression of generalized seizures in the Belgian Tervuren and Sheepdog. Results DNA from 366 dogs, of which 74 were classified as epileptic, representing two extended families were subjected to a genome-wide linkage scan using 410 microsatellite markers yielding informative coverage averaging 5.95 ± 0.21 Mb. Though previous studies based on pedigree analyses proposed a major gene of influence, the present study demonstrated the trait to be highly polygenic. Studies of complex disorders in humans indicate that a liberal composite evaluation of genetic linkage is needed to identify underlying quantitative trait loci (QTLs. Four chromosomes yielded tentative linkage based upon LOD scores in excess of 1.0. Possible QTLs within these regions were supported also by analyses of multipoint linkage, allele frequency, TDT, and transmission of haplotype blocks. Conclusions Taken together the data tentatively indicate six QTLs, three on CFA 2, and one on each of CFA 6, 12, and 37, that support fine mapping for mutations associated with epilepsy in the Belgian shepherd. The study also underscores the complexity of genomic linkage studies for polygenic disorders.

  1. Opportunities and limitations for combined fly-scan ptychography and fluorescence microscopy

    Science.gov (United States)

    Deng, Junjing; Vine, David J.; Chen, Si; Nashed, Youssef S. G.; Peterka, Tom; Ross, Rob; Vogt, Stefan; Jacobsen, Chris J.

    2015-09-01

    X-ray fluorescence offers unparalleled sensitivity for imaging the nanoscale distribution of trace elements in micrometer thick samples, while x-ray ptychography offers an approach to image weakly fluorescing lighter elements at a resolution beyond that of the x-ray lens used. These methods can be used in combination, and in continuous scan mode for rapid data acquisition when using multiple probe mode reconstruction methods. We discuss here the opportunities and limitations of making use of additional information provided by ptychography to improve x-ray fluorescence images in two ways: by using position-error-correction algorithms to correct for scan distortions in fluorescence scans, and by considering the signal-to-noise limits on previously-demonstrated ptychographic probe deconvolution methods. This highlights the advantages of using a combined approach.

  2. Structural examination of lithium niobate ferroelectric crystals by combining scanning electron microscopy and atomic force microscopy

    Science.gov (United States)

    Efremova, P. V.; Ped'ko, B. B.; Kuznecova, Yu. V.

    2016-02-01

    The structure of lithium niobate single crystals is studied by a complex technique that combines scanning electron microscopy and atomic force microscopy. By implementing the piezoresponse force method on an atomic force microscope, the domain structure of lithium niobate crystals, which was not revealed without electron beam irradiation, is visualized

  3. Combining optical tweezers and scanning probe microscopy to study DNA-protein interactions

    NARCIS (Netherlands)

    Huisstede, Jurgen H G; Subramaniam, Vinod; Bennink, Martin L

    We present the first results obtained with a new instrument designed and built to study DNA-protein interactions at the single molecule level. This microscope combines optical tweezers with scanning probe microscopy and allows us to locate DNA-binding proteins on a single suspended DNA molecule. A

  4. Polarization contrast in photon scanning tunnelling microscopy combined with atomic force microscopy

    NARCIS (Netherlands)

    Propstra, K.; Propstra, K.; van Hulst, N.F.

    1995-01-01

    Photon scanning tunnelling microscopy combined with atomic force microscopy allows simultaneous acquisition and direct comparison of optical and topographical images, both with a lateral resolution of about 30 nm, far beyond the optical diffraction limit. The probe consists of a modified

  5. Ion Torrent sequencing for conducting genome-wide scans for mutation mapping analysis.

    Science.gov (United States)

    Damerla, Rama Rao; Chatterjee, Bishwanath; Li, You; Francis, Richard J B; Fatakia, Sarosh N; Lo, Cecilia W

    2014-04-01

    Mutation mapping in mice can be readily accomplished by genome wide segregation analysis of polymorphic DNA markers. In this study, we showed the efficacy of Ion Torrent next generation sequencing for conducting genome-wide scans to map and identify a mutation causing congenital heart disease in a mouse mutant, Bishu, recovered from a mouse mutagenesis screen. The Bishu mutant line generated in a C57BL/6J (B6) background was intercrossed with another inbred strain, C57BL/10J (B10), and the resulting B6/B10 hybrid offspring were intercrossed to generate mutants used for the mapping analysis. For each mutant sample, a panel of 123 B6/B10 polymorphic SNPs distributed throughout the mouse genome was PCR amplified, bar coded, and then pooled to generate a single library used for Ion Torrent sequencing. Sequencing carried out using the 314 chip yielded >600,000 usable reads. These were aligned and mapped using a custom bioinformatics pipeline. Each SNP was sequenced to a depth >500×, allowing accurate automated calling of the B6/B10 genotypes. This analysis mapped the mutation in Bishu to an interval on the proximal region of mouse chromosome 4. This was confirmed by parallel capillary sequencing of the 123 polymorphic SNPs. Further analysis of genes in the map interval identified a splicing mutation in Dnaic1(c.204+1G>A), an intermediate chain dynein, as the disease causing mutation in Bishu. Overall, our experience shows Ion Torrent amplicon sequencing is high throughput and cost effective for conducting genome-wide mapping analysis and is easily scalable for other high volume genotyping analyses.

  6. New technique combined with scanning and static method in true-color panel video display

    Science.gov (United States)

    Gu, Guohua; Chen, Qian; Bai, Lianfa; Zhang, Baomin

    1998-08-01

    A new technique, which combined with scanning and quasi- static method is presented. By the technique, when applied in true color panel video display, the matching of three primary colors can be more suitable, the brightness of the whole screen can be higher. At the same time, because of the using of scanning method, the cost of the system is not so high as that of ordinary system. Sampling of high distinguishability data, shaping and enhancing of image outline, nonlinear rectify of the primary colors are also discussed here.

  7. A Genome-wide Scan for Selective Sweeps in Racing Horses

    Science.gov (United States)

    Moon, Sunjin; Lee, Jin Woo; Shin, Donghyun; Shin, Kwang-Yun; Kim, Jun; Choi, Ik-Young; Kim, Jaemin; Kim, Heebal

    2015-01-01

    Using next-generation sequencing, we conducted a genome-wide scan of selective sweeps associated with selection toward genetic improvement in Thoroughbreds. We investigated potential phenotypic consequence of putative candidate loci by candidate gene association mapping for the finishing time in 240 Thoroughbred horses. We found a significant association with the trait for Ral GApase alpha 2 (RALGAP2) that regulates a variety of cellular processes of signal trafficking. Neighboring genes around RALGAP2 included insulinoma-associated 1 (INSM1), pallid (PLDN), and Ras and Rab interactor 2 (RIN2) genes have similar roles in signal trafficking, suggesting that a co-evolving gene cluster located on the chromosome 22 is under strong artificial selection in racehorses. PMID:26333666

  8. A Genome-wide Scan for Selective Sweeps in Racing Horses

    Directory of Open Access Journals (Sweden)

    Sunjin Moon

    2015-11-01

    Full Text Available Using next-generation sequencing, we conducted a genome-wide scan of selective sweeps associated with selection toward genetic improvement in Thoroughbreds. We investigated potential phenotypic consequence of putative candidate loci by candidate gene association mapping for the finishing time in 240 Thoroughbred horses. We found a significant association with the trait for Ral GApase alpha 2 (RALGAP2 that regulates a variety of cellular processes of signal trafficking. Neighboring genes around RALGAP2 included insulinoma-associated 1 (INSM1, pallid (PLDN, and Ras and Rab interactor 2 (RIN2 genes have similar roles in signal trafficking, suggesting that a co-evolving gene cluster located on the chromosome 22 is under strong artificial selection in racehorses.

  9. A genome scan conducted in a multigenerational pedigree with convergent strabismus supports a complex genetic determinism.

    Directory of Open Access Journals (Sweden)

    Anouk Georges

    Full Text Available A genome-wide linkage scan was conducted in a Northern-European multigenerational pedigree with nine of 40 related members affected with concomitant strabismus. Twenty-seven members of the pedigree including all affected individuals were genotyped using a SNP array interrogating > 300,000 common SNPs. We conducted parametric and non-parametric linkage analyses assuming segregation of an autosomal dominant mutation, yet allowing for incomplete penetrance and phenocopies. We detected two chromosome regions with near-suggestive evidence for linkage, respectively on chromosomes 8 and 18. The chromosome 8 linkage implied a penetrance of 0.80 and a rate of phenocopy of 0.11, while the chromosome 18 linkage implied a penetrance of 0.64 and a rate of phenocopy of 0. Our analysis excludes a simple genetic determinism of strabismus in this pedigree.

  10. A genome scan conducted in a multigenerational pedigree with convergent strabismus supports a complex genetic determinism.

    Science.gov (United States)

    Georges, Anouk; Cambisano, Nadine; Ahariz, Naïma; Karim, Latifa; Georges, Michel

    2013-01-01

    A genome-wide linkage scan was conducted in a Northern-European multigenerational pedigree with nine of 40 related members affected with concomitant strabismus. Twenty-seven members of the pedigree including all affected individuals were genotyped using a SNP array interrogating > 300,000 common SNPs. We conducted parametric and non-parametric linkage analyses assuming segregation of an autosomal dominant mutation, yet allowing for incomplete penetrance and phenocopies. We detected two chromosome regions with near-suggestive evidence for linkage, respectively on chromosomes 8 and 18. The chromosome 8 linkage implied a penetrance of 0.80 and a rate of phenocopy of 0.11, while the chromosome 18 linkage implied a penetrance of 0.64 and a rate of phenocopy of 0. Our analysis excludes a simple genetic determinism of strabismus in this pedigree.

  11. Fabrication and characterization of probes for combined scanning electrochemical/optical microscopy experiments.

    Science.gov (United States)

    Lee, Youngmi; Bard, Allen J

    2002-08-01

    A technique that combines scanning electrochemical microscopy (SECM) and optical microscopy (OM) was implemented with a new probe tip. The tip for scanning electrochemicaVoptical microscopy (SECM/OM) was constructed by insulating a typical gold-coated near-field scanning optical microscopy tip using electrophoretic anodic paint. Once fabricated, the tip was characterized by steady-state cyclic voltammetry, as well as optical and electrochemical approach experiments. This tip generated a stable steady-state current and well-defined SECM approach curves for both conductive and insulating substrates. Durable tips whose geometry was a ring with < 1 microm as outer ring radius could be consistently fabricated. Simultaneous electrochemical and optical images of an interdigitated array electrode were obtained with a resolution on the micrometer scale, demonstrating good performance of the tip as both an optical and an electrochemical probe for imaging microstructures. The SECM feedback current measurements were successfully employed to determine tip-substrate distances for imaging.

  12. An instrumental approach to combining confocal microspectroscopy and 3D scanning probe nanotomography.

    Science.gov (United States)

    Mochalov, Konstantin E; Chistyakov, Anton A; Solovyeva, Daria O; Mezin, Alexey V; Oleinikov, Vladimir A; Vaskan, Ivan S; Molinari, Michael; Agapov, Igor I; Nabiev, Igor; Efimov, Anton E

    2017-11-01

    In the past decade correlative microscopy, which combines the potentials of different types of high-resolution microscopies with a variety of optical microspectroscopy techniques, has been attracting increasing attention in material science and biological research. One of outstanding solutions in this area is the combination of scanning probe microscopy (SPM), which provides data on not only the topography, but also the spatial distribution of a wide range of physical properties (elasticity, conductivity, etc.), with ultramicrotomy, allowing 3D multiparametric examination of materials. The combination of SPM and ultramicrotomy (scanning probe nanotomography) is very appropriate for characterization of soft multicompound nanostructurized materials, such as polymer matrices and microstructures doped with different types of nanoparticles (magnetic nanoparticles, quantum dots, nanotubes, etc.), and biological materials. A serious problem of this technique is a lack of chemical and optical characterization tools, which may be solved by using optical microspectroscopy. Here, we report the development of an instrumental approach to combining confocal microspectroscopy and 3D scanning probe nanotomography in a single apparatus. This approach retains all the advantages of SPM and upright optical microspectroscopy and allows 3D multiparametric characterization using both techniques. As the first test of the system developed, we have performed correlative characterization of the morphology and the magnetic and fluorescent properties of fluorescent magnetic microspheres doped with a fluorescent dye and magnetic nanoparticles. The results of this study can be used to obtain 3D volume images of a specimen for most high-resolution near-field scanning probe microscopies: SNOM, TERS, AFM-IR, etc. This approach will result in development of unique techniques combining the advantages of SPM (nanoscale morphology and a wide range of physical parameters) and high-resolution optical

  13. Combining laser scan and photogrammetry for 3D object modeling using a single digital camera

    Science.gov (United States)

    Xiong, Hanwei; Zhang, Hong; Zhang, Xiangwei

    2009-07-01

    In the fields of industrial design, artistic design and heritage conservation, physical objects are usually digitalized by reverse engineering through some 3D scanning methods. Laser scan and photogrammetry are two main methods to be used. For laser scan, a video camera and a laser source are necessary, and for photogrammetry, a digital still camera with high resolution pixels is indispensable. In some 3D modeling tasks, two methods are often integrated to get satisfactory results. Although many research works have been done on how to combine the results of the two methods, no work has been reported to design an integrated device at low cost. In this paper, a new 3D scan system combining laser scan and photogrammetry using a single consumer digital camera is proposed. Nowadays there are many consumer digital cameras, such as Canon EOS 5D Mark II, they usually have features of more than 10M pixels still photo recording and full 1080p HD movie recording, so a integrated scan system can be designed using such a camera. A square plate glued with coded marks is used to place the 3d objects, and two straight wood rulers also glued with coded marks can be laid on the plate freely. In the photogrammetry module, the coded marks on the plate make up a world coordinate and can be used as control network to calibrate the camera, and the planes of two rulers can also be determined. The feature points of the object and the rough volume representation from the silhouettes can be obtained in this module. In the laser scan module, a hand-held line laser is used to scan the object, and the two straight rulers are used as reference planes to determine the position of the laser. The laser scan results in dense points cloud which can be aligned together automatically through calibrated camera parameters. The final complete digital model is obtained through a new a patchwise energy functional method by fusion of the feature points, rough volume and the dense points cloud. The design

  14. Genome-wide scan for autism susceptibility genes. Paris Autism Research International Sibpair Study.

    Science.gov (United States)

    Philippe, A; Martinez, M; Guilloud-Bataille, M; Gillberg, C; Råstam, M; Sponheim, E; Coleman, M; Zappella, M; Aschauer, H; Van Maldergem, L; Penet, C; Feingold, J; Brice, A; Leboyer, M; van Malldergerme, L

    1999-05-01

    Family and twin studies have suggested a genetic component in autism. We performed a genome-wide screen with 264 microsatellites markers in 51 multiplex families, using non-parametric linkage methods. Families were recruited by a collaborative group including clinicians from Sweden, France, Norway, the USA, Italy, Austria and Belgium. Using two-point and multipoint affected sib-pair analyses, 11 regions gave nominal P -values of 0.05 or lower. Four of these regions overlapped with regions on chromosomes 2q, 7q, 16p and 19p identified by the first genome-wide scan of autism performed by the International Molecular Genetic Study of Autism Consortium. Another of our potential susceptibility regions overlapped with the 15q11-q13 region identified in previous candidate gene studies. Our study revealed six additional regions on chromosomes 4q, 5p, 6q, 10q, 18q and Xp. We found that the most significant multipoint linkage was close to marker D6S283 (maximum lod score = 2.23, P = 0.0013).

  15. Comparative genome scan detects host-related divergent selection in the grasshopper Hesperotettix viridis.

    Science.gov (United States)

    Apple, Jennifer L; Grace, Tony; Joern, Anthony; St Amand, Paul; Wisely, Samantha M

    2010-09-01

    In this study, we used a comparative genome scan to examine patterns of population differentiation with respect to host plant use in Hesperotettix viridis, a Nearctic oligophagous grasshopper locally specialized on various Asteraceae including Solidago, Gutierrezia, and Ericameria. We identified amplified fragment length polymorphism (AFLP) loci with significantly elevated F(ST) (outlier loci) in multiple different-host and same-host comparisons of populations while controlling for geographic distance. By comparing the number and identities of outlier loci in different-host vs. same-host comparisons, we found evidence of host plant-related divergent selection for some population comparisons (Solidago- vs. Gutierrezia-feeders), while other comparisons (Ericameria- vs. Gutierrezia-feeders) failed to demonstrate a strong role for host association in population differentiation. In comparisons of Solidago- vs. Gutierrezia-feeding populations, a relatively high number of outlier loci observed repeatedly in different-host comparisons (35% of all outliers and 2.7% of all 625 AFLP loci) indicated a significant role for host-related selection in contributing to overall genomic differentiation in this grasshopper. Mitochondrial DNA sequence data revealed a star-shaped phylogeny with no host- or geography-related structure, low nucleotide diversity, and high haplotype diversity, suggesting a recent population expansion. mtDNA data do not suggest a long period of isolation in separate glacial refugia but are instead more compatible with a single glacial refugium and more recent divergence in host use. Our study adds to research documenting heterogeneity in differentiation across the genome as a consequence of divergent natural selection, a phenomenon that may occur as part of the process of ecological speciation. © 2010 Blackwell Publishing Ltd.

  16. Breaking RAD: an evaluation of the utility of restriction site-associated DNA sequencing for genome scans of adaptation.

    Science.gov (United States)

    Lowry, David B; Hoban, Sean; Kelley, Joanna L; Lotterhos, Katie E; Reed, Laura K; Antolin, Michael F; Storfer, Andrew

    2017-03-01

    Understanding how and why populations evolve is of fundamental importance to molecular ecology. Restriction site-associated DNA sequencing (RADseq), a popular reduced representation method, has ushered in a new era of genome-scale research for assessing population structure, hybridization, demographic history, phylogeography and migration. RADseq has also been widely used to conduct genome scans to detect loci involved in adaptive divergence among natural populations. Here, we examine the capacity of those RADseq-based genome scan studies to detect loci involved in local adaptation. To understand what proportion of the genome is missed by RADseq studies, we developed a simple model using different numbers of RAD-tags, genome sizes and extents of linkage disequilibrium (length of haplotype blocks). Under the best-case modelling scenario, we found that RADseq using six- or eight-base pair cutting restriction enzymes would fail to sample many regions of the genome, especially for species with short linkage disequilibrium. We then surveyed recent studies that have used RADseq for genome scans and found that the median density of markers across these studies was 4.08 RAD-tag markers per megabase (one marker per 245 kb). The length of linkage disequilibrium for many species is one to three orders of magnitude less than density of the typical recent RADseq study. Thus, we conclude that genome scans based on RADseq data alone, while useful for studies of neutral genetic variation and genetic population structure, will likely miss many loci under selection in studies of local adaptation. © 2016 John Wiley & Sons Ltd.

  17. Genomic scan of selective sweeps in thin and fat tail sheep breeds for identifying of candidate regions associated with fat deposition

    National Research Council Canada - National Science Library

    Moradi, Mohammad Hossein; Nejati-Javaremi, Ardeshir; Moradi-Shahrbabak, Mohammad; Dodds, Ken G; McEwan, John C

    2012-01-01

    .... In this study, a genome-wide scan using ~50,000 Single Nucleotide Polymorphisms (SNPs) was performed in an attempt to identify genomic regions associated with fat deposition in fat-tail breeds...

  18. Forest Resource Measurements by Combination of Terrestrial Laser Scanning and Drone Use

    Science.gov (United States)

    Cheung, K.; Katoh, M.; Horisawa, M.

    2017-10-01

    Using terrestrial laser scanning (TLS), forest attributes such as diameter at breast height (DBH) and tree location can be measured accurately. However, due to low penetration of laser pulses to tree tops, tree height measurements are typically underestimated. In this study, data acquired by TLS and drones were combined; DBH and tree locations were determined by TLS, and tree heights were measured by drone use. The average tree height error and root mean square error (RMSE) of tree height were 0.8 and 1.2 m, respectively, for the combined method, and -0.4 and 1.7 m using TLS alone. The tree height difference was compared using airborne laser scanning (ALS). Furthermore, a method to acquire 100 % tree detection rate based on TLS data is suggested in this study.

  19. FOREST RESOURCE MEASUREMENTS BY COMBINATION OF TERRESTRIAL LASER SCANNING AND DRONE USE

    Directory of Open Access Journals (Sweden)

    K. Cheung

    2017-10-01

    Full Text Available Using terrestrial laser scanning (TLS, forest attributes such as diameter at breast height (DBH and tree location can be measured accurately. However, due to low penetration of laser pulses to tree tops, tree height measurements are typically underestimated. In this study, data acquired by TLS and drones were combined; DBH and tree locations were determined by TLS, and tree heights were measured by drone use. The average tree height error and root mean square error (RMSE of tree height were 0.8 and 1.2 m, respectively, for the combined method, and –0.4 and 1.7 m using TLS alone. The tree height difference was compared using airborne laser scanning (ALS. Furthermore, a method to acquire 100 % tree detection rate based on TLS data is suggested in this study.

  20. Scanning the landscape of genome architecture of non-O1 and non-O139 Vibrio cholerae by whole genome mapping reveals extensive population genetic diversity.

    Science.gov (United States)

    Chapman, Carol; Henry, Matthew; Bishop-Lilly, Kimberly A; Awosika, Joy; Briska, Adam; Ptashkin, Ryan N; Wagner, Trevor; Rajanna, Chythanya; Tsang, Hsinyi; Johnson, Shannon L; Mokashi, Vishwesh P; Chain, Patrick S G; Sozhamannan, Shanmuga

    2015-01-01

    Historically, cholera outbreaks have been linked to V. cholerae O1 serogroup strains or its derivatives of the O37 and O139 serogroups. A genomic study on the 2010 Haiti cholera outbreak strains highlighted the putative role of non O1/non-O139 V. cholerae in causing cholera and the lack of genomic sequences of such strains from around the world. Here we address these gaps by scanning a global collection of V. cholerae strains as a first step towards understanding the population genetic diversity and epidemic potential of non O1/non-O139 strains. Whole Genome Mapping (Optical Mapping) based bar coding produces a high resolution, ordered restriction map, depicting a complete view of the unique chromosomal architecture of an organism. To assess the genomic diversity of non-O1/non-O139 V. cholerae, we applied a Whole Genome Mapping strategy on a well-defined and geographically and temporally diverse strain collection, the Sakazaki serogroup type strains. Whole Genome Map data on 91 of the 206 serogroup type strains support the hypothesis that V. cholerae has an unprecedented genetic and genomic structural diversity. Interestingly, we discovered chromosomal fusions in two unusual strains that possess a single chromosome instead of the two chromosomes usually found in V. cholerae. We also found pervasive chromosomal rearrangements such as duplications and indels in many strains. The majority of Vibrio genome sequences currently in public databases are unfinished draft sequences. The Whole Genome Mapping approach presented here enables rapid screening of large strain collections to capture genomic complexities that would not have been otherwise revealed by unfinished draft genome sequencing and thus aids in assembling and finishing draft sequences of complex genomes. Furthermore, Whole Genome Mapping allows for prediction of novel V. cholerae non-O1/non-O139 strains that may have the potential to cause future cholera outbreaks.

  1. Operation of a scanning near field optical microscope in reflection in combination with a scanning force microscope

    NARCIS (Netherlands)

    van Hulst, N.F.; Moers, M.H.P.; Moers, M.H.P.; Noordman, O.F.J.; Noordman, O.F.J.; Faulkner, T.; Segerink, Franciscus B.; van der Werf, Kees; de Grooth, B.G.; Bölger, B.; Bölger, B.

    1992-01-01

    Images obtained with a scanning near field optical microscope (SNOM) operating in reflection are presented. We have obtained the first results with a SiN tip as optical probe. The instrument is simultaneously operated as a scanning force microscope (SFM). Moreover, the instrument incorporates an

  2. Detection of combined genomic variants in a Jordanian family with ...

    Indian Academy of Sciences (India)

    TSHR) gene was performed by direct sequencing of genomic DNA extracted from peripheral blood leukocytes of all family members. The sequence analysis of all TSHR gene exons and intron borders revealed two genomic variants. The first ...

  3. Does parental expressed emotion moderate genetic effects in ADHD? : An exploration using a genome wide association scan

    NARCIS (Netherlands)

    Sonuga-Barke, E.; Lasky-Su, J.; Neale, B.M.; Oades, R.; Chen, W.; Franke, B.; Buitelaar, J.K.; Banaschewski, T.; Ebstein, R.; Gill, M.; Anney, R.; Miranda, A.; Mulas, F.; Roeyers, H.; Rothenberger, A.; Sergeant, J.A.; Steinhausen, H.C.; Thompson, M.; Asherson, P.; Faraone, S.V.

    2008-01-01

    Studies of gene x environment (G x E) interaction in ADHD have previously focused on known risk genes for ADHD and environmentally mediated biological risk. Here we use G x E analysis in the context of a genome-wide association scan to identify novel genes whose effects on ADHD symptoms and comorbid

  4. Identifying signatures of natural selection in Tibetan and Andean populations using dense genome scan data.

    Directory of Open Access Journals (Sweden)

    Abigail Bigham

    2010-09-01

    Full Text Available High-altitude hypoxia (reduced inspired oxygen tension due to decreased barometric pressure exerts severe physiological stress on the human body. Two high-altitude regions where humans have lived for millennia are the Andean Altiplano and the Tibetan Plateau. Populations living in these regions exhibit unique circulatory, respiratory, and hematological adaptations to life at high altitude. Although these responses have been well characterized physiologically, their underlying genetic basis remains unknown. We performed a genome scan to identify genes showing evidence of adaptation to hypoxia. We looked across each chromosome to identify genomic regions with previously unknown function with respect to altitude phenotypes. In addition, groups of genes functioning in oxygen metabolism and sensing were examined to test the hypothesis that particular pathways have been involved in genetic adaptation to altitude. Applying four population genetic statistics commonly used for detecting signatures of natural selection, we identified selection-nominated candidate genes and gene regions in these two populations (Andeans and Tibetans separately. The Tibetan and Andean patterns of genetic adaptation are largely distinct from one another, with both populations showing evidence of positive natural selection in different genes or gene regions. Interestingly, one gene previously known to be important in cellular oxygen sensing, EGLN1 (also known as PHD2, shows evidence of positive selection in both Tibetans and Andeans. However, the pattern of variation for this gene differs between the two populations. Our results indicate that several key HIF-regulatory and targeted genes are responsible for adaptation to high altitude in Andeans and Tibetans, and several different chromosomal regions are implicated in the putative response to selection. These data suggest a genetic role in high-altitude adaption and provide a basis for future genotype/phenotype association

  5. Identifying signatures of natural selection in Tibetan and Andean populations using dense genome scan data.

    Science.gov (United States)

    Bigham, Abigail; Bauchet, Marc; Pinto, Dalila; Mao, Xianyun; Akey, Joshua M; Mei, Rui; Scherer, Stephen W; Julian, Colleen G; Wilson, Megan J; López Herráez, David; Brutsaert, Tom; Parra, Esteban J; Moore, Lorna G; Shriver, Mark D

    2010-09-09

    High-altitude hypoxia (reduced inspired oxygen tension due to decreased barometric pressure) exerts severe physiological stress on the human body. Two high-altitude regions where humans have lived for millennia are the Andean Altiplano and the Tibetan Plateau. Populations living in these regions exhibit unique circulatory, respiratory, and hematological adaptations to life at high altitude. Although these responses have been well characterized physiologically, their underlying genetic basis remains unknown. We performed a genome scan to identify genes showing evidence of adaptation to hypoxia. We looked across each chromosome to identify genomic regions with previously unknown function with respect to altitude phenotypes. In addition, groups of genes functioning in oxygen metabolism and sensing were examined to test the hypothesis that particular pathways have been involved in genetic adaptation to altitude. Applying four population genetic statistics commonly used for detecting signatures of natural selection, we identified selection-nominated candidate genes and gene regions in these two populations (Andeans and Tibetans) separately. The Tibetan and Andean patterns of genetic adaptation are largely distinct from one another, with both populations showing evidence of positive natural selection in different genes or gene regions. Interestingly, one gene previously known to be important in cellular oxygen sensing, EGLN1 (also known as PHD2), shows evidence of positive selection in both Tibetans and Andeans. However, the pattern of variation for this gene differs between the two populations. Our results indicate that several key HIF-regulatory and targeted genes are responsible for adaptation to high altitude in Andeans and Tibetans, and several different chromosomal regions are implicated in the putative response to selection. These data suggest a genetic role in high-altitude adaption and provide a basis for future genotype/phenotype association studies necessary

  6. DETECTING SELECTION IN NATURAL POPULATIONS: MAKING SENSE OF GENOME SCANS AND TOWARDS ALTERNATIVE SOLUTIONS

    Science.gov (United States)

    Haasl, Ryan J.; Payseur, Bret A.

    2016-01-01

    Genomewide scans for natural selection (GWSS) have become increasingly common over the last 15 years due to increased availability of genome-scale genetic data. Here, we report a representative survey of GWSS from 1999 to present and find that (i) between 1999 and 2009, 35 of 49 (71%) GWSS focused on human, while from 2010 to present, only 38 of 83 (46%) of GWSS focused on human, indicating increased focus on nonmodel organisms; (ii) the large majority of GWSS incorporate interpopulation or interspecific comparisons using, for example FST, cross-population extended haplotype homozygosity or the ratio of nonsynonymous to synonymous substitutions; (iii) most GWSS focus on detection of directional selection rather than other modes such as balancing selection; and (iv) in human GWSS, there is a clear shift after 2004 from microsatellite markers to dense SNP data. A survey of GWSS meant to identify loci positively selected in response to severe hypoxic conditions support an approach to GWSS in which a list of a priori candidate genes based on potential selective pressures are used to filter the list of significant hits a posteriori. We also discuss four frequently ignored determinants of genomic heterogeneity that complicate GWSS: mutation, recombination, selection and the genetic architecture of adaptive traits. We recommend that GWSS methodology should better incorporate aspects of genomewide heterogeneity using empirical estimates of relevant parameters and/or realistic, whole-chromosome simulations to improve interpretation of GWSS results. Finally, we argue that knowledge of potential selective agents improves interpretation of GWSS results and that new methods focused on correlations between environmental variables and genetic variation can help automate this approach. PMID:26224644

  7. Genome scan identifies a locus affecting gamma-globin expression in human beta-cluster YAC transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Lin, S.D.; Cooper, P.; Fung, J.; Weier, H.U.G.; Rubin, E.M.

    2000-03-01

    Genetic factors affecting post-natal g-globin expression - a major modifier of the severity of both b-thalassemia and sickle cell anemia, have been difficult to study. This is especially so in mice, an organism lacking a globin gene with an expression pattern equivalent to that of human g-globin. To model the human b-cluster in mice, with the goal of screening for loci affecting human g-globin expression in vivo, we introduced a human b-globin cluster YAC transgene into the genome of FVB mice . The b-cluster contained a Greek hereditary persistence of fetal hemoglobin (HPFH) g allele resulting in postnatal expression of human g-globin in transgenic mice. The level of human g-globin for various F1 hybrids derived from crosses between the FVB transgenics and other inbred mouse strains was assessed. The g-globin level of the C3HeB/FVB transgenic mice was noted to be significantly elevated. To map genes affecting postnatal g-globin expression, a 20 centiMorgan (cM) genome scan of a C3HeB/F VB transgenics [prime] FVB backcross was performed, followed by high-resolution marker analysis of promising loci. From this analysis we mapped a locus within a 2.2 cM interval of mouse chromosome 1 at a LOD score of 4.2 that contributes 10.4% of variation in g-globin expression level. Combining transgenic modeling of the human b-globin gene cluster with quantitative trait analysis, we have identified and mapped a murine locus that impacts on human g-globin expression in vivo.

  8. A genome-wide scan of Ashkenazi Jewish Crohn's disease suggests novel susceptibility loci.

    Directory of Open Access Journals (Sweden)

    Eimear E Kenny

    Full Text Available Crohn's disease (CD is a complex disorder resulting from the interaction of intestinal microbiota with the host immune system in genetically susceptible individuals. The largest meta-analysis of genome-wide association to date identified 71 CD-susceptibility loci in individuals of European ancestry. An important epidemiological feature of CD is that it is 2-4 times more prevalent among individuals of Ashkenazi Jewish (AJ descent compared to non-Jewish Europeans (NJ. To explore genetic variation associated with CD in AJs, we conducted a genome-wide association study (GWAS by combining raw genotype data across 10 AJ cohorts consisting of 907 cases and 2,345 controls in the discovery stage, followed up by a replication study in 971 cases and 2,124 controls. We confirmed genome-wide significant associations of 9 known CD loci in AJs and replicated 3 additional loci with strong signal (p<5×10⁻⁶. Novel signals detected among AJs were mapped to chromosomes 5q21.1 (rs7705924, combined p = 2×10⁻⁸; combined odds ratio OR = 1.48, 2p15 (rs6545946, p = 7×10⁻⁹; OR = 1.16, 8q21.11 (rs12677663, p = 2×10⁻⁸; OR = 1.15, 10q26.3 (rs10734105, p = 3×10⁻⁸; OR = 1.27, and 11q12.1 (rs11229030, p = 8×10⁻⁹; OR = 1.15, implicating biologically plausible candidate genes, including RPL7, CPAMD8, PRG2, and PRG3. In all, the 16 replicated and newly discovered loci, in addition to the three coding NOD2 variants, accounted for 11.2% of the total genetic variance for CD risk in the AJ population. This study demonstrates the complementary value of genetic studies in the Ashkenazim.

  9. Population genomic scan for candidate signatures of balancing selection to guide antigen characterization in malaria parasites.

    Directory of Open Access Journals (Sweden)

    Alfred Amambua-Ngwa

    Full Text Available Acquired immunity in vertebrates maintains polymorphisms in endemic pathogens, leading to identifiable signatures of balancing selection. To comprehensively survey for genes under such selection in the human malaria parasite Plasmodium falciparum, we generated paired-end short-read sequences of parasites in clinical isolates from an endemic Gambian population, which were mapped to the 3D7 strain reference genome to yield high-quality genome-wide coding sequence data for 65 isolates. A minority of genes did not map reliably, including the hypervariable var, rifin, and stevor families, but 5,056 genes (90.9% of all in the genome had >70% sequence coverage with minimum read depth of 5 for at least 50 isolates, of which 2,853 genes contained 3 or more single nucleotide polymorphisms (SNPs for analysis of polymorphic site frequency spectra. Against an overall background of negatively skewed frequencies, as expected from historical population expansion combined with purifying selection, the outlying minority of genes with signatures indicating exceptionally intermediate frequencies were identified. Comparing genes with different stage-specificity, such signatures were most common in those with peak expression at the merozoite stage that invades erythrocytes. Members of clag, PfMC-2TM, surfin, and msp3-like gene families were highly represented, the strongest signature being in the msp3-like gene PF10_0355. Analysis of msp3-like transcripts in 45 clinical and 11 laboratory adapted isolates grown to merozoite-containing schizont stages revealed surprisingly low expression of PF10_0355. In diverse clonal parasite lines the protein product was expressed in a minority of mature schizonts (<1% in most lines and ∼10% in clone HB3, and eight sub-clones of HB3 cultured separately had an intermediate spectrum of positive frequencies (0.9 to 7.5%, indicating phase variable expression of this polymorphic antigen. This and other identified targets of balancing

  10. A Genome-Wide Scan of DNA Methylation Markers for Distinguishing Monozygotic Twins.

    Science.gov (United States)

    Du, Qingqing; Zhu, Guijun; Fu, Guangping; Zhang, Xiaojing; Fu, Lihong; Li, Shujin; Cong, Bin

    2015-12-01

    Identification of individuals within pairs of monozygotic (MZ) twins remains unresolved using common forensic DNA typing technology. For some criminal cases involving MZ twins as suspects, the twins had to be released due to inability to identify which of the pair was the perpetrator. In this study, we performed a genome-wide scan on whole blood-derived DNA from four pairs of healthy phenotypically concordant MZ twins using the methylated DNA immunoprecipitation sequencing technology to identify candidate DNA methylation markers with capacity to distinguish MZ twins within a pair. We identified 38 differential methylation regions showing within-pair methylation differences in all four MZ pairs. These are all located in CpG islands, 17 of which are promoter-associated, 17 are intergenic islands, and four are intragenic islands. Genes associated with these markers are related with cell proliferation, differentiation, and growth and development, including zinc finger proteins, PRRX2, RBBP9, or are involved in G-protein signaling, such as the regulator of G-protein signaling 16. Further validation studies on additional MZ twins are now required to evaluate the broader utility of these 38 markers for forensic use.

  11. Hyb-Seq: combining target enrichment and genome skimming for plant phylogenomics

    Science.gov (United States)

    Kevin Weitemier; Shannon C.K. Straub; Richard C. Cronn; Mark Fishbein; Roswitha Schmickl; Angela McDonnell; Aaron. Liston

    2014-01-01

    • Premise of the study: Hyb-Seq, the combination of target enrichment and genome skimming, allows simultaneous data collection for low-copy nuclear genes and high-copy genomic targets for plant systematics and evolution studies. • Methods and Results: Genome and transcriptome assemblies for milkweed ( Asclepias syriaca ) were used to design enrichment probes for 3385...

  12. A genome-wide scan for common alleles affecting risk for autism.

    LENUS (Irish Health Repository)

    Anney, Richard

    2010-10-15

    Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner\\'s curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.

  13. A genome-wide scan for common alleles affecting risk for autism

    Science.gov (United States)

    Anney, Richard; Klei, Lambertus; Pinto, Dalila; Regan, Regina; Conroy, Judith; Magalhaes, Tiago R.; Correia, Catarina; Abrahams, Brett S.; Sykes, Nuala; Pagnamenta, Alistair T.; Almeida, Joana; Bacchelli, Elena; Bailey, Anthony J.; Baird, Gillian; Battaglia, Agatino; Berney, Tom; Bolshakova, Nadia; Bölte, Sven; Bolton, Patrick F.; Bourgeron, Thomas; Brennan, Sean; Brian, Jessica; Carson, Andrew R.; Casallo, Guillermo; Casey, Jillian; Chu, Su H.; Cochrane, Lynne; Corsello, Christina; Crawford, Emily L.; Crossett, Andrew; Dawson, Geraldine; de Jonge, Maretha; Delorme, Richard; Drmic, Irene; Duketis, Eftichia; Duque, Frederico; Estes, Annette; Farrar, Penny; Fernandez, Bridget A.; Folstein, Susan E.; Fombonne, Eric; Freitag, Christine M.; Gilbert, John; Gillberg, Christopher; Glessner, Joseph T.; Goldberg, Jeremy; Green, Jonathan; Guter, Stephen J.; Hakonarson, Hakon; Heron, Elizabeth A.; Hill, Matthew; Holt, Richard; Howe, Jennifer L.; Hughes, Gillian; Hus, Vanessa; Igliozzi, Roberta; Kim, Cecilia; Klauck, Sabine M.; Kolevzon, Alexander; Korvatska, Olena; Kustanovich, Vlad; Lajonchere, Clara M.; Lamb, Janine A.; Laskawiec, Magdalena; Leboyer, Marion; Le Couteur, Ann; Leventhal, Bennett L.; Lionel, Anath C.; Liu, Xiao-Qing; Lord, Catherine; Lotspeich, Linda; Lund, Sabata C.; Maestrini, Elena; Mahoney, William; Mantoulan, Carine; Marshall, Christian R.; McConachie, Helen; McDougle, Christopher J.; McGrath, Jane; McMahon, William M.; Melhem, Nadine M.; Merikangas, Alison; Migita, Ohsuke; Minshew, Nancy J.; Mirza, Ghazala K.; Munson, Jeff; Nelson, Stanley F.; Noakes, Carolyn; Noor, Abdul; Nygren, Gudrun; Oliveira, Guiomar; Papanikolaou, Katerina; Parr, Jeremy R.; Parrini, Barbara; Paton, Tara; Pickles, Andrew; Piven, Joseph; Posey, David J; Poustka, Annemarie; Poustka, Fritz; Prasad, Aparna; Ragoussis, Jiannis; Renshaw, Katy; Rickaby, Jessica; Roberts, Wendy; Roeder, Kathryn; Roge, Bernadette; Rutter, Michael L.; Bierut, Laura J.; Rice, John P.; Salt, Jeff; Sansom, Katherine; Sato, Daisuke; Segurado, Ricardo; Senman, Lili; Shah, Naisha; Sheffield, Val C.; Soorya, Latha; Sousa, Inês; Stoppioni, Vera; Strawbridge, Christina; Tancredi, Raffaella; Tansey, Katherine; Thiruvahindrapduram, Bhooma; Thompson, Ann P.; Thomson, Susanne; Tryfon, Ana; Tsiantis, John; Van Engeland, Herman; Vincent, John B.; Volkmar, Fred; Wallace, Simon; Wang, Kai; Wang, Zhouzhi; Wassink, Thomas H.; Wing, Kirsty; Wittemeyer, Kerstin; Wood, Shawn; Yaspan, Brian L.; Zurawiecki, Danielle; Zwaigenbaum, Lonnie; Betancur, Catalina; Buxbaum, Joseph D.; Cantor, Rita M.; Cook, Edwin H.; Coon, Hilary; Cuccaro, Michael L.; Gallagher, Louise; Geschwind, Daniel H.; Gill, Michael; Haines, Jonathan L.; Miller, Judith; Monaco, Anthony P.; Nurnberger, John I.; Paterson, Andrew D.; Pericak-Vance, Margaret A.; Schellenberg, Gerard D.; Scherer, Stephen W.; Sutcliffe, James S.; Szatmari, Peter; Vicente, Astrid M.; Vieland, Veronica J.; Wijsman, Ellen M.; Devlin, Bernie; Ennis, Sean; Hallmayer, Joachim

    2010-01-01

    Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C. PMID:20663923

  14. Univariate/multivariate genome-wide association scans using data from families and unrelated samples.

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    2009-08-01

    Full Text Available As genome-wide association studies (GWAS are becoming more popular, two approaches, among others, could be considered in order to improve statistical power for identifying genes contributing subtle to moderate effects to human diseases. The first approach is to increase sample size, which could be achieved by combining both unrelated and familial subjects together. The second approach is to jointly analyze multiple correlated traits. In this study, by extending generalized estimating equations (GEEs, we propose a simple approach for performing univariate or multivariate association tests for the combined data of unrelated subjects and nuclear families. In particular, we correct for population stratification by integrating principal component analysis and transmission disequilibrium test strategies. The proposed method allows for multiple siblings as well as missing parental information. Simulation studies show that the proposed test has improved power compared to two popular methods, EIGENSTRAT and FBAT, by analyzing the combined data, while correcting for population stratification. In addition, joint analysis of bivariate traits has improved power over univariate analysis when pleiotropic effects are present. Application to the Genetic Analysis Workshop 16 (GAW16 data sets attests to the feasibility and applicability of the proposed method.

  15. Combined nanoprobes for scanning probe microscopy: laser technology for processing and testing

    Science.gov (United States)

    Veiko, V. P.; Golubok, A. O.; Zuong, Z.; Varkentina, N. V.; Yakovlev, E. B.

    2008-02-01

    Scanning probe microscopy (SPM) is a high spatial resolution method of surface topography visualization and measurement of its local properties. The detecting of interaction arising between the sharp solid-state probe and the sample surface is the foundation of SPM. In dependence from nature of this interaction the scanning tunnel microscopy (STM), scanning force microscopy (SFM), scanning near field optical microscopy (SNOM), etc. are distinguished. The spatial resolution of all types of probe microscopy determins both sharpness of increasing of interaction between a probe and a sample at their approach, and shape and size of a top of a solid-state probe. So, the progress in SPM information capabilities is highly depends from probe properties and first of all from properly fabricated aperture size. Fabrication procedures are rather complicated because of nanometric scale size of aperture and hard requirements to reproducibility and need to be improved. The way how to do it is involving of feed-back in a processing procedure-results in two types of feedback for the process of drawing-out has been suggested, tested and installed into the technological set-up. Different probes have been fabricated by laser-assisted drawing-out during this work: SNOM types from optical fibers, micropipettes from quartz glass capillaries, micropipettes with microwires inside and with metallic covers outside. Some examples of application of above mentioned combined probes for cell membrane technology are described. Most important from them are topographical studying of cells and bacteria in living condition (in liquid) and studying of the mechanical properties of cell (rigidity of cell membrane) using the nanopipette as a tip of a force sensor. Also measurement of ion current that runs through cell membrane during its metabolic process using the nanopipette as well as in the well-known patch-clamp method have been done.

  16. Combining SNPs in latent variables to improve genomic prediction

    DEFF Research Database (Denmark)

    Heuven, Henri C M; Rosa, G J M; Janss, Luc

    The objective of this study was to develop and test hierarchical genomic models with latent variables that represent parts of the genomic values. An interaction model and a chromosome model were compared with a model based on variable selection in a simulated and real dataset. The program Bayz......: Hierarchical genetic model; Predictive value; Gibbs sampling; Variable selection....

  17. Genomic scan reveals loci under altitude adaptation in Tibetan and Dahe pigs.

    Directory of Open Access Journals (Sweden)

    Kunzhe Dong

    Full Text Available High altitude environments are of particular interest in the studies of local adaptation as well as their implications in physiology and clinical medicine in human. Some Chinese pig breeds, such as Tibetan pig (TBP that is well adapted to the high altitude and Dahe pig (DHP that dwells at the moderate altitude, provide ideal materials to study local adaptation to altitudes. Yet, it is still short of in-depth analysis and understanding of the genetic adaptation to high altitude in the two pig populations. In this study we conducted a genomic scan for selective sweeps using FST to identify genes showing evidence of local adaptations in TBP and DHP, with Wuzhishan pig (WZSP as the low-altitude reference. Totally, we identified 12 specific selective genes (CCBE1, F2RL1, AGGF1, ZFPM2, IL2, FGF5, PLA2G4A, ADAMTS9, NRBF2, JMJD1C, VEGFC and ADAM19 for TBP and six (OGG1, FOXM, FLT3, RTEL1, CRELD1 and RHOG for DHP. In addition, six selective genes (VPS13A, GNA14, GDAP1, PARP8, FGF10 and ADAMTS16 were shared by the two pig breeds. Among these selective genes, three (VEGFC, FGF10 and ADAMTS9 were previously reported to be linked to the local adaptation to high altitudes in pigs, while many others were newly identified by this study. Further bioinformatics analysis demonstrated that majority of these selective signatures have some biological functions relevant to the altitude adaptation, for examples, response to hypoxia, development of blood vessels, DNA repair and several hematological involvements. These results suggest that the local adaptation to high altitude environments is sophisticated, involving numerous genes and multiple biological processes, and the shared selective signatures by the two pig breeds may provide an effective avenue to identify the common adaptive mechanisms to different altitudes.

  18. COL4A1 Is Associated With Arterial Stiffness By Genome Wide Association Scan

    Science.gov (United States)

    Tarasov, Kirill V; Sanna, Serena; Scuteri, Angelo; Strait, James B; Orrù, Marco; Parsa, Afshin; Lin, Ping-I; Maschio, Andrea; Lai, Sandra; Piras, Maria Grazia; Masala, Marco; Tanaka, Toshiko; Post, Wendy; O’Connell, Jeffrey R.; Schlessinger, David; Cao, Antonio; Nagaraja, Ramaiah; Mitchell, Braxton D.; Abecasis, Gonçalo R.; Shuldiner, Alan R.; Uda, Manuela; Lakatta, Edward G.; Najjar, Samer S.

    2009-01-01

    Background Pulse wave velocity (PWV), a non-invasive index of central arterial stiffness, is a potent predictor of cardiovascular mortality and morbidity. Heritability and linkage studies have pointed toward a genetic component affecting PWV. We conducted a genome-wide association study to identify single nucleotide polymorphisms (SNPs) associated with PWV. Methods and Results The study cohort included participants from the SardiNIA study for whom PWV measures were available. Genotyping was performed in 4,221 individuals, using either the Affymetrix 500K or the Affymetrix 10K mapping array sets (with imputation of the missing genotypes). Associations with PWV were evaluated using an additive genetic model that included age, age2 and sex as covariates. The findings were tested for replication in an independent internal Sardinian cohort of 1,828 individuals, using a custom-chip designed to include the top 43 non-redundant SNPs associated with PWV. Of the loci that were tested for association with PWV, the nonsynonymous SNP rs3742207 in the COL4A1 gene on chromosome 13 and SNP rs1495448 in the MAGI1 gene on chromosome 3 were successfully replicated (p=7.08×10−7 and p=1.06×10−5 respectively for the combined analyses). The association between rs3742207 and PWV was also successfully replicated (p=0.02) in an independent population, the Old Order Amish, leading to an overall p=5.16×10−8. Conclusions A genome-wide association study identified a SNP in the COL4A1 gene that was significantly associated with PWV in two populations. Collagen type 4 is the major structural component of basement membranes, suggesting that previously unrecognized cell-matrix interactions may exert an important role in regulating arterial stiffness. PMID:20031579

  19. Beyond an AFLP genome scan towards the identification of immune genes involved in plague resistance in Rattus rattus from Madagascar.

    Science.gov (United States)

    Tollenaere, C; Jacquet, S; Ivanova, S; Loiseau, A; Duplantier, J-M; Streiff, R; Brouat, C

    2013-01-01

    Genome scans using amplified fragment length polymorphism (AFLP) markers became popular in nonmodel species within the last 10 years, but few studies have tried to characterize the anonymous outliers identified. This study follows on from an AFLP genome scan in the black rat (Rattus rattus), the reservoir of plague (Yersinia pestis infection) in Madagascar. We successfully sequenced 17 of the 22 markers previously shown to be potentially affected by plague-mediated selection and associated with a plague resistance phenotype. Searching these sequences in the genome of the closely related species Rattus norvegicus assigned them to 14 genomic regions, revealing a random distribution of outliers in the genome (no clustering). We compared these results with those of an in silico AFLP study of the R. norvegicus genome, which showed that outlier sequences could not have been inferred by this method in R. rattus (only four of the 15 sequences were predicted). However, in silico analysis allowed the prediction of AFLP markers distribution and the estimation of homoplasy rates, confirming its potential utility for designing AFLP studies in nonmodel species. The 14 genomic regions surrounding AFLP outliers (less than 300 kb from the marker) contained 75 genes encoding proteins of known function, including nine involved in immune function and pathogen defence. We identified the two interleukin 1 genes (Il1a and Il1b) that share homology with an antigen of Y. pestis, as the best candidates for genes subject to plague-mediated natural selection. At least six other genes known to be involved in proinflammatory pathways may also be affected by plague-mediated selection. © 2012 Blackwell Publishing Ltd.

  20. A scan statistic to extract causal gene clusters from case-control genome-wide rare CNV data

    Directory of Open Access Journals (Sweden)

    Scherer Stephen W

    2011-05-01

    Full Text Available Abstract Background Several statistical tests have been developed for analyzing genome-wide association data by incorporating gene pathway information in terms of gene sets. Using these methods, hundreds of gene sets are typically tested, and the tested gene sets often overlap. This overlapping greatly increases the probability of generating false positives, and the results obtained are difficult to interpret, particularly when many gene sets show statistical significance. Results We propose a flexible statistical framework to circumvent these problems. Inspired by spatial scan statistics for detecting clustering of disease occurrence in the field of epidemiology, we developed a scan statistic to extract disease-associated gene clusters from a whole gene pathway. Extracting one or a few significant gene clusters from a global pathway limits the overall false positive probability, which results in increased statistical power, and facilitates the interpretation of test results. In the present study, we applied our method to genome-wide association data for rare copy-number variations, which have been strongly implicated in common diseases. Application of our method to a simulated dataset demonstrated the high accuracy of this method in detecting disease-associated gene clusters in a whole gene pathway. Conclusions The scan statistic approach proposed here shows a high level of accuracy in detecting gene clusters in a whole gene pathway. This study has provided a sound statistical framework for analyzing genome-wide rare CNV data by incorporating topological information on the gene pathway.

  1. A genome-wide association scan in admixed Latin Americans identifies loci influencing facial and scalp hair features

    Science.gov (United States)

    Adhikari, Kaustubh; Fontanil, Tania; Cal, Santiago; Mendoza-Revilla, Javier; Fuentes-Guajardo, Macarena; Chacón-Duque, Juan-Camilo; Al-Saadi, Farah; Johansson, Jeanette A.; Quinto-Sanchez, Mirsha; Acuña-Alonzo, Victor; Jaramillo, Claudia; Arias, William; Barquera Lozano, Rodrigo; Macín Pérez, Gastón; Gómez-Valdés, Jorge; Villamil-Ramírez, Hugo; Hunemeier, Tábita; Ramallo, Virginia; Silva de Cerqueira, Caio C.; Hurtado, Malena; Villegas, Valeria; Granja, Vanessa; Gallo, Carla; Poletti, Giovanni; Schuler-Faccini, Lavinia; Salzano, Francisco M.; Bortolini, Maria-Cátira; Canizales-Quinteros, Samuel; Rothhammer, Francisco; Bedoya, Gabriel; Gonzalez-José, Rolando; Headon, Denis; López-Otín, Carlos; Tobin, Desmond J.; Balding, David; Ruiz-Linares, Andrés

    2016-01-01

    We report a genome-wide association scan in over 6,000 Latin Americans for features of scalp hair (shape, colour, greying, balding) and facial hair (beard thickness, monobrow, eyebrow thickness). We found 18 signals of association reaching genome-wide significance (P values 5 × 10−8 to 3 × 10−119), including 10 novel associations. These include novel loci for scalp hair shape and balding, and the first reported loci for hair greying, monobrow, eyebrow and beard thickness. A newly identified locus influencing hair shape includes a Q30R substitution in the Protease Serine S1 family member 53 (PRSS53). We demonstrate that this enzyme is highly expressed in the hair follicle, especially the inner root sheath, and that the Q30R substitution affects enzyme processing and secretion. The genome regions associated with hair features are enriched for signals of selection, consistent with proposals regarding the evolution of human hair. PMID:26926045

  2. Combining Frequency Doubling Technology Perimetry and Scanning Laser Polarimetry for Glaucoma Detection.

    Science.gov (United States)

    Mwanza, Jean-Claude; Warren, Joshua L; Hochberg, Jessica T; Budenz, Donald L; Chang, Robert T; Ramulu, Pradeep Y

    2015-01-01

    To determine the ability of frequency doubling technology (FDT) and scanning laser polarimetry with variable corneal compensation (GDx-VCC) to detect glaucoma when used individually and in combination. One hundred ten normal and 114 glaucomatous subjects were tested with FDT C-20-5 screening protocol and the GDx-VCC. The discriminating ability was tested for each device individually and for both devices combined using GDx-NFI, GDx-TSNIT, number of missed points of FDT, and normal or abnormal FDT. Measures of discrimination included sensitivity, specificity, area under the curve (AUC), Akaike's information criterion (AIC), and prediction confidence interval lengths. For detecting glaucoma regardless of severity, the multivariable model resulting from the combination of GDx-TSNIT, number of abnormal points on FDT (NAP-FDT), and the interaction GDx-TSNIT×NAP-FDT (AIC: 88.28, AUC: 0.959, sensitivity: 94.6%, specificity: 89.5%) outperformed the best single-variable model provided by GDx-NFI (AIC: 120.88, AUC: 0.914, sensitivity: 87.8%, specificity: 84.2%). The multivariable model combining GDx-TSNIT, NAP-FDT, and interaction GDx-TSNIT×NAP-FDT consistently provided better discriminating abilities for detecting early, moderate, and severe glaucoma than the best single-variable models. The multivariable model including GDx-TSNIT, NAP-FDT, and the interaction GDx-TSNIT×NAP-FDT provides the best glaucoma prediction compared with all other multivariable and univariable models. Combining the FDT C-20-5 screening protocol and GDx-VCC improves glaucoma detection compared with using GDx or FDT alone.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  4. Family-Based Genome-Wide Association Scan of Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Mick, Eric; Todorov, Alexandre; Smalley, Susan; Hu, Xiaolan; Loo, Sandra; Todd, Richard D.; Biederman, Joseph; Byrne, Deirdre; Dechairo, Bryan; Guiney, Allan; McCracken, James; McGough, James; Nelson, Stanley F.; Reiersen, Angela M.; Wilens, Timothy E.; Wozniak, Janet; Neale, Benjamin M.; Faraone, Stephen V.

    2010-01-01

    Objective: Genes likely play a substantial role in the etiology of attention-deficit/hyperactivity disorder (ADHD). However, the genetic architecture of the disorder is unknown, and prior genome-wide association studies (GWAS) have not identified a genome-wide significant association. We have conducted a third, independent, multisite GWAS of…

  5. High-throughput scanning of the rat genome using interspersed repetitive sequence-PCR markers.

    Science.gov (United States)

    Gösele, C; Hong, L; Kreitler, T; Rossmann, M; Hieke, B; Gross, U; Kramer, M; Himmelbauer, H; Bihoreau, M T; Kwitek-Black, A E; Twigger, S; Tonellato, P J; Jacob, H J; Schalkwyk, L C; Lindpaintner, K; Ganten, D; Lehrach, H; Knoblauch, M

    2000-11-01

    We report the establishment of a hybridization-based marker system for the rat genome based on the PCR amplification of interspersed repetitive sequences (IRS). Overall, 351 IRS markers were mapped within the rat genome. The IRS marker panel consists of 210 nonpolymorphic and 141 polymorphic markers that were screened for presence/absence polymorphism patterns in 38 different rat strains and substrains that are commonly used in biomedical research. The IRS marker panel was demonstrated to be useful for rapid genome screening in experimental rat crosses and high-throughput characterization of large-insert genomic library clones. Information on corresponding YAC clones is made available for this IRS marker set distributed over the whole rat genome. The two existing rat radiation hybrid maps were integrated by placing the IRS markers in both maps. The genetic and physical mapping data presented provide substantial information for ongoing positional cloning projects in the rat. Copyright 2000 Academic Press.

  6. Classification of Defoliated Trees Using Tree-Level Airborne Laser Scanning Data Combined with Aerial Images

    Directory of Open Access Journals (Sweden)

    Juha Hyyppa

    2010-11-01

    Full Text Available Climate change and rising temperatures have been observed to be related to the increase of forest insect damage in the boreal zone. The common pine sawfly (Diprion pini L. (Hymenoptera, Diprionidae is regarded as a significant threat to boreal pine forests. Defoliation by D. pini can cause severe growth loss and tree mortality in Scots pine (Pinus sylvestris L. (Pinaceae. In this study, logistic LASSO regression, Random Forest (RF and Most Similar Neighbor method (MSN were investigated for predicting the defoliation level of individual Scots pines using the features derived from airborne laser scanning (ALS data and aerial images. Classification accuracies from 83.7% (kappa 0.67 to 88.1% (kappa 0.76 were obtained depending on the method. The most accurate result was produced using RF with a combination of data from the two sensors, while the accuracies when using ALS and image features separately were 80.7% and 87.4%, respectively. Evidently, the combination of ALS and aerial images in detecting needle losses is capable of providing satisfactory estimates for individual trees.

  7. A bi-dimensional genome scan for prolificacy traits in pigs shows the existence of multiple epistatic QTL

    Directory of Open Access Journals (Sweden)

    Bidanel Jean P

    2009-12-01

    Full Text Available Abstract Background Prolificacy is the most important trait influencing the reproductive efficiency of pig production systems. The low heritability and sex-limited expression of prolificacy have hindered to some extent the improvement of this trait through artificial selection. Moreover, the relative contributions of additive, dominant and epistatic QTL to the genetic variance of pig prolificacy remain to be defined. In this work, we have undertaken this issue by performing one-dimensional and bi-dimensional genome scans for number of piglets born alive (NBA and total number of piglets born (TNB in a three generation Iberian by Meishan F2 intercross. Results The one-dimensional genome scan for NBA and TNB revealed the existence of two genome-wide highly significant QTL located on SSC13 (P SSC17 (P P P P P Conclusions The complex inheritance of prolificacy traits in pigs has been evidenced by identifying multiple additive (SSC13 and SSC17, dominant and epistatic QTL in an Iberian × Meishan F2 intercross. Our results demonstrate that a significant fraction of the phenotypic variance of swine prolificacy traits can be attributed to first-order gene-by-gene interactions emphasizing that the phenotypic effects of alleles might be strongly modulated by the genetic background where they segregate.

  8. Whole genome PCR scanning reveals the syntenic genome structure of toxigenic Vibrio cholerae strains in the O1/O139 population.

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    Bo Pang

    Full Text Available Vibrio cholerae is commonly found in estuarine water systems. Toxigenic O1 and O139 V. cholerae strains have caused cholera epidemics and pandemics, whereas the nontoxigenic strains within these serogroups only occasionally lead to disease. To understand the differences in the genome and clonality between the toxigenic and nontoxigenic strains of V. cholerae serogroups O1 and O139, we employed a whole genome PCR scanning (WGPScanning method, an rrn operon-mediated fragment rearrangement analysis and comparative genomic hybridization (CGH to analyze the genome structure of different strains. WGPScanning in conjunction with CGH revealed that the genomic contents of the toxigenic strains were conservative, except for a few indels located mainly in mobile elements. Minor nucleotide variation in orthologous genes appeared to be the major difference between the toxigenic strains. rrn operon-mediated rearrangements were infrequent in El Tor toxigenic strains tested using I-CeuI digested pulsed-field gel electrophoresis (PFGE analysis and PCR analysis based on flanking sequence of rrn operons. Using these methods, we found that the genomic structures of toxigenic El Tor and O139 strains were syntenic. The nontoxigenic strains exhibited more extensive sequence variations, but toxin coregulated pilus positive (TCP+ strains had a similar structure. TCP+ nontoxigenic strains could be subdivided into multiple lineages according to the TCP type, suggesting the existence of complex intermediates in the evolution of toxigenic strains. The data indicate that toxigenic O1 El Tor and O139 strains were derived from a single lineage of intermediates from complex clones in the environment. The nontoxigenic strains with non-El Tor type TCP may yet evolve into new epidemic clones after attaining toxigenic attributes.

  9. Genome-wide scans reveal variants at EDAR predominantly affecting hair straightness in Han Chinese and Uyghur populations.

    Science.gov (United States)

    Wu, Sijie; Tan, Jingze; Yang, Yajun; Peng, Qianqian; Zhang, Manfei; Li, Jinxi; Lu, Dongsheng; Liu, Yu; Lou, Haiyi; Feng, Qidi; Lu, Yan; Guan, Yaqun; Zhang, Zhaoxia; Jiao, Yi; Sabeti, Pardis; Krutmann, Jean; Tang, Kun; Jin, Li; Xu, Shuhua; Wang, Sijia

    2016-11-01

    Hair straightness/curliness is one of the most conspicuous features of human variation and is particularly diverse among populations. A recent genome-wide scan found common variants in the Trichohyalin (TCHH) gene that are associated with hair straightness in Europeans, but different genes might affect this phenotype in other populations. By sampling 2899 Han Chinese, we performed the first genome-wide scan of hair straightness in East Asians, and found EDAR (rs3827760) as the predominant gene (P = 4.67 × 10-16), accounting for 3.66 % of the total variance. The candidate gene approach did not find further significant associations, suggesting that hair straightness may be affected by a large number of genes with subtle effects. Notably, genetic variants associated with hair straightness in Europeans are generally low in frequency in Han Chinese, and vice versa. To evaluate the relative contribution of these variants, we performed a second genome-wide scan in 709 samples from the Uyghur, an admixed population with both eastern and western Eurasian ancestries. In Uyghurs, both EDAR (rs3827760: P = 1.92 × 10-12) and TCHH (rs11803731: P = 1.46 × 10-3) are associated with hair straightness, but EDAR (OR 0.415) has a greater effect than TCHH (OR 0.575). We found no significant interaction between EDAR and TCHH (P = 0.645), suggesting that these two genes affect hair straightness through different mechanisms. Furthermore, haplotype analysis indicates that TCHH is not subject to selection. While EDAR is under strong selection in East Asia, it does not appear to be subject to selection after the admixture in Uyghurs. These suggest that hair straightness is unlikely a trait under selection.

  10. Combined Use of Terrestrial Laser Scanning and IR Thermography Applied to a Historical Building

    Directory of Open Access Journals (Sweden)

    Antonio Costanzo

    2014-12-01

    Full Text Available The conservation of architectural heritage usually requires a multidisciplinary approach involving a variety of specialist expertise and techniques. Nevertheless, destructive techniques should be avoided, wherever possible, in order to preserve the integrity of the historical buildings, therefore the development of non-destructive and non-contact techniques is extremely important. In this framework, a methodology for combining the terrestrial laser scanning and the infrared thermal images is proposed, in order to obtain a reconnaissance of the conservation state of a historical building. The proposed case study is represented by St. Augustine Monumental Compound, located in the historical centre of the town of Cosenza (Calabria, South Italy. Adopting the proposed methodology, the paper illustrates the main results obtained for the building test overlaying and comparing the collected data with both techniques, in order to outline the capabilities both to detect the anomalies and to improve the knowledge on health state of the masonry building. The 3D model, also, allows to provide a reference model, laying the groundwork for implementation of a monitoring multisensor system based on the use of non-destructive techniques.

  11. Combining confocal laser scanning microscopy with serial section reconstruction in the study of adult neurogenesis.

    Directory of Open Access Journals (Sweden)

    Federico eLuzzati

    2011-05-01

    Full Text Available Current advances in imaging techniques have extended the possibility of visualizing small structures within large volumes of both fixed and live specimens without sectioning. These techniques have contributed valuable information to study neuronal plasticity in the adult brain. However, technical limits still hamper the use of these approaches to investigate neurogenic regions located far from the ventricular surface such as parenchymal neurogenic niches, or the scattered neuroblasts induced by brain lesions. Here, we present a method to combine confocal laser scanning microscopy (CLSM and serial section reconstruction in order to reconstruct large volumes of brain tissue at cellular resolution. In this method a series of thick sections are imaged with CLSM and the resulting stacks of images are registered and 3D reconstructed. This approach is based on existing freeware software and can be performed on ordinary laboratory personal computers (PC. By using this technique we have investigated the morphology and spatial organization of a group of doublecortin (DCX+ neuroblasts located in the lateral striatum of the late post-natal guinea pig. The 3D study unravelled a complex network of long and poorly ramified cell processes, often fascicled and mostly oriented along the internal capsule fibre bundles. These data support CLSM serial section reconstruction as a reliable alternative to the whole mount approaches to analyze cyto-architectural features of adult germinative niches.

  12. The Application of Restriction Landmark Genome Scanning Method for Surveillance of Non-Mendelian Inheritance in F1 Hybrids

    Directory of Open Access Journals (Sweden)

    Tomoko Takamiya

    2009-01-01

    Full Text Available We analyzed inheritance of DNA methylation in reciprocal F1 hybrids (subsp. japonica cv. Nipponbare × subsp. indica cv. Kasalath of rice (Oryza sativa L. using restriction landmark genome scanning (RLGS, and detected differing RLGS spots between the parents and reciprocal F1 hybrids. MspI/HpaII restriction sites in the DNA from these different spots were suspected to be heterozygously methylated in the Nipponbare parent. These spots segregated in F1 plants, but did not segregate in selfed progeny of Nipponbare, showing non-Mendelian inheritance of the methylation status. As a result of RT-PCR and sequencing, a specific allele of the gene nearest to the methylated sites was expressed in reciprocal F1 plants, showing evidence of biased allelic expression. These results show the applicability of RLGS for scanning of non-Mendelian inheritance of DNA methylation and biased allelic expression.

  13. A sea urchin genome project: Sequence scan, virtual map, and additional resources

    Science.gov (United States)

    Cameron, R. Andrew; Mahairas, Gregory; Rast, Jonathan P.; Martinez, Pedro; Biondi, Ted R.; Swartzell, Steven; Wallace, James C.; Poustka, Albert J.; Livingston, Brian T.; Wray, Gregory A.; Ettensohn, Charles A.; Lehrach, Hans; Britten, Roy J.; Davidson, Eric H.; Hood, Leroy

    2000-01-01

    Results of a first-stage Sea Urchin Genome Project are summarized here. The species chosen was Strongylocentrotus purpuratus, a research model of major importance in developmental and molecular biology. A virtual map of the genome was constructed by sequencing the ends of 76,020 bacterial artificial chromosome (BAC) recombinants (average length, 125 kb). The BAC-end sequence tag connectors (STCs) occur an average of 10 kb apart, and, together with restriction digest patterns recorded for the same BAC clones, they provide immediate access to contigs of several hundred kilobases surrounding any gene of interest. The STCs survey >5% of the genome and provide the estimate that this genome contains ≈27,350 protein-coding genes. The frequency distribution and canonical sequences of all middle and highly repetitive sequence families in the genome were obtained from the STCs as well. The 500-kb Hox gene complex of this species is being sequenced in its entirety. In addition, arrayed cDNA libraries of >105 clones each were constructed from every major stage of embryogenesis, several individual cell types, and adult tissues and are available to the community. The accumulated STC data and an expanding expressed sequence tag database (at present including >12,000 sequences) have been reported to GenBank and are accessible on public web sites. PMID:10920195

  14. Identification of Tumor Suppressor Genes by Genetic and Epigenetic Genome-Scanning

    Science.gov (United States)

    2008-04-01

    band intensity was measured for the SMRT -PCR bands. Together with genomic DNA as a control, the results of a normal breast, a normal prostate, primary...functional significance remains to be elucidated. The first difference we observed between the SMRT -PCR and DNA microarray hybridization experiments was

  15. Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution

    NARCIS (Netherlands)

    C.M. Lindgren (Cecilia); I.M. Heid (Iris); J.C. Randall (Joshua); C. Lamina (Claudia); V. Steinthorsdottir (Valgerdur); L. Qi (Lu); E.K. Speliotes (Elizabeth); G. Thorleifsson (Gudmar); C.J. Willer (Cristen); B.M. Herrera (Blanca); A.U. Jackson (Anne); N. Lim (Noha); P. Scheet (Paul); N. Soranzo (Nicole); N. Amin (Najaf); Y.S. Aulchenko (Yurii); J.C. Chambers (John); A. Drong (Alexander); J. Luan; H.N. Lyon (Helen); F. Rivadeneira Ramirez (Fernando); S. Sanna (Serena); N.J. Timpson (Nicholas); M.C. Zillikens (Carola); H.Z. Jing; P. Almgren (Peter); S. Bandinelli (Stefania); A.J. Bennett (Amanda); R.N. Bergman (Richard); L.L. Bonnycastle (Lori); S. Bumpstead (Suzannah); S.J. Chanock (Stephen); L. Cherkas (Lynn); P.S. Chines (Peter); L. Coin (Lachlan); C. Cooper (Charles); G. Crawford (Gabe); A. Doering (Angela); A. Dominiczak (Anna); A.S.F. Doney (Alex); S. Ebrahim (Shanil); P. Elliott (Paul); M.R. Erdos (Michael); K. Estrada Gil (Karol); L. Ferrucci (Luigi); G. Fischer (Guido); N.G. Forouhi (Nita); C. Gieger (Christian); H. Grallert (Harald); C.J. Groves (Christopher); S.M. Grundy (Scott); C. Guiducci (Candace); D. Hadley (David); A. Hamsten (Anders); A.S. Havulinna (Aki); A. Hofman (Albert); R. Holle (Rolf); J.W. Holloway (John); T. Illig (Thomas); B. Isomaa (Bo); L.C. Jacobs (Leonie); K. Jameson (Karen); P. Jousilahti (Pekka); F. Karpe (Fredrik); J. Kuusisto (Johanna); J. Laitinen (Jaana); G.M. Lathrop (Mark); D.A. Lawlor (Debbie); M. Mangino (Massimo); W.L. McArdle (Wendy); T. Meitinger (Thomas); M.A. Morken (Mario); A.P. Morris (Andrew); P. Munroe (Patricia); N. Narisu (Narisu); A. Nordström (Anna); B.A. Oostra (Ben); C.N.A. Palmer (Colin); F. Payne (Felicity); J. Peden (John); I. Prokopenko (Inga); F. Renström (Frida); A. Ruokonen (Aimo); V. Salomaa (Veikko); M.S. Sandhu (Manjinder); L.J. Scott (Laura); A. Scuteri (Angelo); K. Silander (Kaisa); K. Song (Kijoung); X. Yuan (Xin); H.M. Stringham (Heather); A.J. Swift (Amy); T. Tuomi (Tiinamaija); M. Uda (Manuela); P. Vollenweider (Peter); G. Waeber (Gérard); C. Wallace (Chris); G.B. Walters (Bragi); M.N. Weedon (Michael); J.C.M. Witteman (Jacqueline); C. Zhang (Cuilin); M. Caulfield (Mark); F.S. Collins (Francis); G.D. Smith; I.N.M. Day (Ian); P.W. Franks (Paul); A.T. Hattersley (Andrew); F.B. Hu (Frank); M.-R. Jarvelin (Marjo-Riitta); A. Kong (Augustine); J.S. Kooner (Jaspal); M. Laakso (Markku); E. Lakatta (Edward); V. Mooser (Vincent); L. Peltonen (Leena Johanna); N.J. Samani (Nilesh); T.D. Spector (Timothy); D.P. Strachan (David); T. Tanaka (Toshiko); J. Tuomilehto (Jaakko); A.G. Uitterlinden (André); P. Tikka-Kleemola (Päivi); N.J. Wareham (Nick); H. Watkins (Hugh); D. Waterworth (Dawn); M. Boehnke (Michael); P. Deloukas (Panagiotis); L. Groop (Leif); D.J. Hunter (David); U. Thorsteinsdottir (Unnur); D. Schlessinger (David); H.E. Wichmann (Erich); T.M. Frayling (Timothy); G.R. Abecasis (Gonçalo); J.N. Hirschhorn (Joel); R.J.F. Loos (Ruth); J-A. Zwart (John-Anker); K.L. Mohlke (Karen); I. Barroso (Inês); M.I. McCarthy (Mark)

    2009-01-01

    textabstractTo identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the

  16. SARS CTL vaccine candidates; HLA supertype-, genome-wide scanning and biochemical validation

    DEFF Research Database (Denmark)

    Sylvester-Hvid, C; Nielsen, M; Lamberth, K

    2004-01-01

    % of all individuals of all major human populations (Sette & Sidney, Immunogenetics 1999: 50: 201-12). For each HLA supertype, we have selected the 15 top candidates for test in biochemical binding assays. At this time (approximately 6 months after the genome was established), we have tested the majority...

  17. SARS CTL vaccine candidates; HLA supertype-, genome-wide scanning and biochemical validation

    DEFF Research Database (Denmark)

    Sylvester-Hvid, C.; Nielsen, Morten; Lamberth, K.

    2004-01-01

    % of all individuals of all major human populations (Sette & Sidney, Immunogenetics 1999: 50: 201-12). For each HLA supertype, we have selected the 15 top candidates for test in biochemical binding assays. At this time (approximately 2 6 months after the genome was established), we have tested the majority...

  18. A Genome-Wide Scan for Breast Cancer Risk Haplotypes among African American Women

    Science.gov (United States)

    Song, Chi; Chen, Gary K.; Millikan, Robert C.; Ambrosone, Christine B.; John, Esther M.; Bernstein, Leslie; Zheng, Wei; Hu, Jennifer J.; Ziegler, Regina G.; Nyante, Sarah; Bandera, Elisa V.; Ingles, Sue A.; Press, Michael F.; Deming, Sandra L.; Rodriguez-Gil, Jorge L.; Chanock, Stephen J.; Wan, Peggy; Sheng, Xin; Pooler, Loreall C.; Van Den Berg, David J.; Le Marchand, Loic; Kolonel, Laurence N.; Henderson, Brian E.; Haiman, Chris A.; Stram, Daniel O.

    2013-01-01

    Genome-wide association studies (GWAS) simultaneously investigating hundreds of thousands of single nucleotide polymorphisms (SNP) have become a powerful tool in the investigation of new disease susceptibility loci. Haplotypes are sometimes thought to be superior to SNPs and are promising in genetic association analyses. The application of genome-wide haplotype analysis, however, is hindered by the complexity of haplotypes themselves and sophistication in computation. We systematically analyzed the haplotype effects for breast cancer risk among 5,761 African American women (3,016 cases and 2,745 controls) using a sliding window approach on the genome-wide scale. Three regions on chromosomes 1, 4 and 18 exhibited moderate haplotype effects. Furthermore, among 21 breast cancer susceptibility loci previously established in European populations, 10p15 and 14q24 are likely to harbor novel haplotype effects. We also proposed a heuristic of determining the significance level and the effective number of independent tests by the permutation analysis on chromosome 22 data. It suggests that the effective number was approximately half of the total (7,794 out of 15,645), thus the half number could serve as a quick reference to evaluating genome-wide significance if a similar sliding window approach of haplotype analysis is adopted in similar populations using similar genotype density. PMID:23468962

  19. A genome-wide scan for breast cancer risk haplotypes among African American women.

    Directory of Open Access Journals (Sweden)

    Chi Song

    Full Text Available Genome-wide association studies (GWAS simultaneously investigating hundreds of thousands of single nucleotide polymorphisms (SNP have become a powerful tool in the investigation of new disease susceptibility loci. Haplotypes are sometimes thought to be superior to SNPs and are promising in genetic association analyses. The application of genome-wide haplotype analysis, however, is hindered by the complexity of haplotypes themselves and sophistication in computation. We systematically analyzed the haplotype effects for breast cancer risk among 5,761 African American women (3,016 cases and 2,745 controls using a sliding window approach on the genome-wide scale. Three regions on chromosomes 1, 4 and 18 exhibited moderate haplotype effects. Furthermore, among 21 breast cancer susceptibility loci previously established in European populations, 10p15 and 14q24 are likely to harbor novel haplotype effects. We also proposed a heuristic of determining the significance level and the effective number of independent tests by the permutation analysis on chromosome 22 data. It suggests that the effective number was approximately half of the total (7,794 out of 15,645, thus the half number could serve as a quick reference to evaluating genome-wide significance if a similar sliding window approach of haplotype analysis is adopted in similar populations using similar genotype density.

  20. Whole-Genome Scans Provide Evidence of Adaptive Evolution in Malawian Plasmodium falciparum Isolates

    DEFF Research Database (Denmark)

    Ocholla, Harold; Preston, Mark D; Mipando, Mwapatsa

    2014-01-01

    BACKGROUND:  Selection by host immunity and antimalarial drugs has driven extensive adaptive evolution in Plasmodium falciparum and continues to produce ever-changing landscapes of genetic variation. METHODS:  We performed whole-genome sequencing of 69 P. falciparum isolates from Malawi and used...

  1. AFLP genome scan to detect genetic structure and candidate loci under selection for local adaptation of the invasive weed Mikania micrantha.

    Directory of Open Access Journals (Sweden)

    Ting Wang

    Full Text Available Why some species become successful invaders is an important issue in invasive biology. However, limited genomic resources make it very difficult for identifying candidate genes involved in invasiveness. Mikania micrantha H.B.K. (Asteraceae, one of the world's most invasive weeds, has adapted rapidly in response to novel environments since its introduction to southern China. In its genome, we expect to find outlier loci under selection for local adaptation, critical to dissecting the molecular mechanisms of invasiveness. An explorative amplified fragment length polymorphism (AFLP genome scan was used to detect candidate loci under selection in 28 M. micrantha populations across its entire introduced range in southern China. We also estimated population genetic parameters, bottleneck signatures, and linkage disequilibrium. In binary characters, such as presence or absence of AFLP bands, if all four character combinations are present, it is referred to as a character incompatibility. Since character incompatibility is deemed to be rare in populations with extensive asexual reproduction, a character incompatibility analysis was also performed in order to infer the predominant mating system in the introduced M. micrantha populations. Out of 483 AFLP loci examined using stringent significance criteria, 14 highly credible outlier loci were identified by Dfdist and Bayescan. Moreover, remarkable genetic variation, multiple introductions, substantial bottlenecks and character compatibility were found to occur in M. micrantha. Thus local adaptation at the genome level indeed exists in M. micrantha, and may represent a major evolutionary mechanism of successful invasion. Interactions between genetic diversity, multiple introductions, and reproductive modes contribute to increase the capacity of adaptive evolution.

  2. A genome-wide scan for selection signatures in Nellore cattle.

    Science.gov (United States)

    Somavilla, A L; Sonstegard, T S; Higa, R H; Rosa, A N; Siqueira, F; Silva, L O C; Torres Júnior, R A A; Coutinho, L L; Mudadu, M A; Alencar, M M; Regitano, L C A

    2014-12-01

    Brazilian Nellore cattle (Bos indicus) have been selected for growth traits for over more than four decades. In recent years, reproductive and meat quality traits have become more important because of increasing consumption, exports and consumer demand. The identification of genome regions altered by artificial selection can potentially permit a better understanding of the biology of specific phenotypes that are useful for the development of tools designed to increase selection efficiency. Therefore, the aims of this study were to detect evidence of recent selection signatures in Nellore cattle using extended haplotype homozygosity methodology and BovineHD marker genotypes (>777,000 single nucleotide polymorphisms) as well as to identify corresponding genes underlying these signals. Thirty-one significant regions (P selection signatures were detected, and 19 of these overlapped quantitative trait loci related to reproductive traits, growth, feed efficiency, meat quality, fatty acid profiles and immunity. In addition, 545 genes were identified in regions harboring selection signatures. Within this group, 58 genes were associated with growth, muscle and adipose tissue metabolism, reproductive traits or the immune system. Using relative extended haplotype homozygosity to analyze high-density single nucleotide polymorphism marker data allowed for the identification of regions potentially under artificial selection pressure in the Nellore genome, which might be used to better understand autozygosity and the effects of selection on the Nellore genome. © 2014 Stichting International Foundation for Animal Genetics.

  3. Genome-Wide Scans for Candidate Genes Involved in the Aquatic Adaptation of Dolphins

    Science.gov (United States)

    Liu, He-Qun; Irwin, David M.; Shen, Yong-Yi; Zhang, Ya-Ping

    2013-01-01

    Since their divergence from the terrestrial artiodactyls, cetaceans have fully adapted to an aquatic lifestyle, which represents one of the most dramatic transformations in mammalian evolutionary history. Numerous morphological and physiological characters of cetaceans have been acquired in response to this drastic habitat transition, such as thickened blubber, echolocation, and ability to hold their breath for a long period of time. However, knowledge about the molecular basis underlying these adaptations is still limited. The sequence of the genome of Tursiops truncates provides an opportunity for a comparative genomic analyses to examine the molecular adaptation of this species. Here, we constructed 11,838 high-quality orthologous gene alignments culled from the dolphin and four other terrestrial mammalian genomes and screened for positive selection occurring in the dolphin lineage. In total, 368 (3.1%) of the genes were identified as having undergone positive selection by the branch-site model. Functional characterization of these genes showed that they are significantly enriched in the categories of lipid transport and localization, ATPase activity, sense perception of sound, and muscle contraction, areas that are potentially related to cetacean adaptations. In contrast, we did not find a similar pattern in the cow, a closely related species. We resequenced some of the positively selected sites (PSSs), within the positively selected genes, and showed that most of our identified PSSs (50/52) could be replicated. The results from this study should have important implications for our understanding of cetacean evolution and their adaptations to the aquatic environment. PMID:23246795

  4. Combination of scanning probe microscopy techniques for evaluating the electrical parameters of individual multiwalled carbon nanotubes

    Science.gov (United States)

    Sokolov, D. V.; Davletkildeev, N. A.; Bolotov, V. V.; Lobov, I. A.

    2017-10-01

    Using two techniques of scanning probe microscopy, the electrical properties (work function, Fermi level position, free carriers’ concentration, electrical resistance, conductivity, and carriers’ mobility) of individual multiwalled carbon nanotubes were evaluated.

  5. 3D chemical mapping: application of scanning transmission (soft) X-ray microscopy (STXM) in combination with angle-scan tomography in bio-, geo-, and environmental sciences.

    Science.gov (United States)

    Obst, Martin; Schmid, Gregor

    2014-01-01

    The identification of environmental processes and mechanisms often requires information on the organochemical and inorganic composition of specimens at high spatial resolution. X-ray spectroscopy (XAS) performed in the soft X-ray range (100-2,200 eV) provides chemical speciation information for elements that are of high biogeochemical relevance such as carbon, nitrogen, and oxygen but also includes transition metals such as iron, manganese, or nickel. Synchrotron-based scanning transmission X-ray microscopy (STXM) combines XAS with high resolution mapping on the 20-nm scale. This provides two-dimensional (2D) quantitative information about the distribution of chemical species such as organic macromolecules, metals, or mineral phases within environmental samples. Furthermore, the combination of STXM with angle-scan tomography allows for three-dimensional (3D) spectromicroscopic analysis of bio-, geo-, or environmental samples. For the acquisition of STXM tomography data, the sample is rotated around an axis perpendicular to the X-ray beam. Various sample preparation approaches such as stripes cut from TEM grids or the preparation of wet cells allow for preparing environmentally relevant specimens in a dry or in a fully hydrated state for 2D and 3D STXM measurements. In this chapter we give a short overview about the principles of STXM, its application to environmental sciences, different preparation techniques, and the analysis and 3D reconstruction of STXM tomography data.

  6. Combining terrestrial laser scanning and UAV photogrammetry for fast and lightweight surveying

    Science.gov (United States)

    Conforti, Dario

    2015-04-01

    To create detailed and accurate 3D maps of small- to medium-sized areas surveyors often turn to a terrestrial laser scanner (TLS). A TLS can make thousands of lidar measurements per second with centimeter-level accuracy even at long ranges, using scanning mirrors to aim the laser up/down and left/right for full coverage of the target area. One limitation of using a TLS is that complex objects may require many more TLS survey positions than simpler ones. Since protrusions may block line of sight to certain areas that can only be seen from particular angles, surveyors must survey from several additional locations to make sure the entire area is covered. This is particularly true for setups where the scanner cannot be elevated to gain line of sight to all the areas that are required to be surveyed. To resolve this issue, surveyors often turn to aerial survey vehicles. An aerial vehicle's bird's-eye perspective resolves features easily and its mobility lets the surveyor quickly capture the whole survey region from multiple angles. To survey more efficiently, surveyors can combine the strengths of TLS and airborne systems, resulting in a cost-effective method of mapping small- to medium-sized sites with 3D data and imagery. This process uses a standard TLS to survey from a few points around the area of interest, particularly vertical faces that would be difficult to survey from the air. Simultaneously, the surveyor uses a lightweight UAV equipped with a camera, gimbal, and basic GPS receiver to collect photogrammetric imagery over the site. During post-processing, the aerial imagery is processed to create 3D data of its own using automated triangulation software. This aerial 3D data is then merged with the 3D data created by the TLS. The aerial 3D data is discarded where it conflicts with the more precise TLS data, but is used to fill in the gaps in the areas where the TLS could not collect any data at all. Finally, the resultant 3D data is merged with the original

  7. A genome-wide scan for signatures of differential artificial selection in ten cattle breeds.

    Science.gov (United States)

    Rothammer, Sophie; Seichter, Doris; Förster, Martin; Medugorac, Ivica

    2013-12-21

    Since the times of domestication, cattle have been continually shaped by the influence of humans. Relatively recent history, including breed formation and the still enduring enormous improvement of economically important traits, is expected to have left distinctive footprints of selection within the genome. The purpose of this study was to map genome-wide selection signatures in ten cattle breeds and thus improve the understanding of the genome response to strong artificial selection and support the identification of the underlying genetic variants of favoured phenotypes. We analysed 47,651 single nucleotide polymorphisms (SNP) using Cross Population Extended Haplotype Homozygosity (XP-EHH). We set the significance thresholds using the maximum XP-EHH values of two essentially artificially unselected breeds and found up to 229 selection signatures per breed. Through a confirmation process we verified selection for three distinct phenotypes typical for one breed (polledness in Galloway, double muscling in Blanc-Bleu Belge and red coat colour in Red Holstein cattle). Moreover, we detected six genes strongly associated with known QTL for beef or dairy traits (TG, ABCG2, DGAT1, GH1, GHR and the Casein Cluster) within selection signatures of at least one breed. A literature search for genes lying in outstanding signatures revealed further promising candidate genes. However, in concordance with previous genome-wide studies, we also detected a substantial number of signatures without any yet known gene content. These results show the power of XP-EHH analyses in cattle to discover promising candidate genes and raise the hope of identifying phenotypically important variants in the near future. The finding of plausible functional candidates in some short signatures supports this hope. For instance, MAP2K6 is the only annotated gene of two signatures detected in Galloway and Gelbvieh cattle and is already known to be associated with carcass weight, back fat thickness and

  8. A genome-wide scan for signatures of directional selection in domesticated pigs.

    Science.gov (United States)

    Moon, Sunjin; Kim, Tae-Hun; Lee, Kyung-Tai; Kwak, Woori; Lee, Taeheon; Lee, Si-Woo; Kim, Myung-Jick; Cho, Kyuho; Kim, Namshin; Chung, Won-Hyong; Sung, Samsun; Park, Taesung; Cho, Seoae; Groenen, Martien Am; Nielsen, Rasmus; Kim, Yuseob; Kim, Heebal

    2015-02-25

    Animal domestication involved drastic phenotypic changes driven by strong artificial selection and also resulted in new populations of breeds, established by humans. This study aims to identify genes that show evidence of recent artificial selection during pig domestication. Whole-genome resequencing of 30 individual pigs from domesticated breeds, Landrace and Yorkshire, and 10 Asian wild boars at ~16-fold coverage was performed resulting in over 4.3 million SNPs for 19,990 genes. We constructed a comprehensive genome map of directional selection by detecting selective sweeps using an F ST-based approach that detects directional selection in lineages leading to the domesticated breeds and using a haplotype-based test that detects ongoing selective sweeps within the breeds. We show that candidate genes under selection are significantly enriched for loci implicated in quantitative traits important to pig reproduction and production. The candidate gene with the strongest signals of directional selection belongs to group III of the metabolomics glutamate receptors, known to affect brain functions associated with eating behavior, suggesting that loci under strong selection include loci involved in behaviorial traits in domesticated pigs including tameness. We show that a significant proportion of selection signatures coincide with loci that were previously inferred to affect phenotypic variation in pigs. We further identify functional enrichment related to behavior, such as signal transduction and neuronal activities, for those targets of selection during domestication in pigs.

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    Quantitative phenotypes correlated with a complex disorder offer increased power to detect linkage in comparison to affected-unaffected classifications. Asthma is a complex disorder characterized by periods of bronchial obstruction and increased bronchial hyper reactivity. In childhood and early...... adulthood, asthma is frequently associated also with quantitative measures of atopy. Genome wide quantitative multipoint linkage analysis was conducted for serum IgE levels and percentage of positive skin prick test (SPT(per)) using three large groups of families originally ascertained for asthma....... In this report, 438 and 429 asthma families were informative for linkage using IgE and SPT(per) which represents 690 independent families. Suggestive linkage (LOD >/= 2) was found on chromosomes 1, 3, and 8q with maximum LODs of 2.34 (IgE), 2.03 (SPT(per)), and 2.25 (IgE) near markers D1S1653, D3S2322-D3S1764...

  10. A genome-wide association scan in pig identifies novel regions associated with feed efficiency trait

    DEFF Research Database (Denmark)

    Sahana, Goutam; Kadlecová, Veronika; Hornshøj, Henrik

    2013-01-01

    and to study the genetic architecture of the trait. After quality control, a total of 30,847 SNPs that could be mapped to the 18 porcine autosomes (SSC) following the pig genome assembly 10.2, were used in the analyses. Deregressed estimated breeding value was used as the response variable. A total of 3......Feed conversion ratio (FCR) is an economically important trait in pigs and feed accounts for a significant proportion of the costs involved in pig production. In this study we used a high density SNP chip panel, Porcine SNP60 BeadChip, to identify association between FCR and SNP markers......,071 Duroc pigs had both FCR data and genotype data. The linkage disequilibrium (r2) between adjacent markers was 0.56. Two association mapping approaches were used: linear mixed model (LMM) based on single locus regression analysis and a Bayesian variable selection approach (BVS). A total of 79 significant...

  11. High Resolution Genomic Scans Reveal Genetic Architecture Controlling Alcohol Preference in Bidirectionally Selected Rat Model.

    Directory of Open Access Journals (Sweden)

    Chiao-Ling Lo

    2016-08-01

    Full Text Available Investigations on the influence of nature vs. nurture on Alcoholism (Alcohol Use Disorder in human have yet to provide a clear view on potential genomic etiologies. To address this issue, we sequenced a replicated animal model system bidirectionally-selected for alcohol preference (AP. This model is uniquely suited to map genetic effects with high reproducibility, and resolution. The origin of the rat lines (an 8-way cross resulted in small haplotype blocks (HB with a corresponding high level of resolution. We sequenced DNAs from 40 samples (10 per line of each replicate to determine allele frequencies and HB. We achieved ~46X coverage per line and replicate. Excessive differentiation in the genomic architecture between lines, across replicates, termed signatures of selection (SS, were classified according to gene and region. We identified SS in 930 genes associated with AP. The majority (50% of the SS were confined to single gene regions, the greatest numbers of which were in promoters (284 and intronic regions (169 with the least in exon's (4, suggesting that differences in AP were primarily due to alterations in regulatory regions. We confirmed previously identified genes and found many new genes associated with AP. Of those newly identified genes, several demonstrated neuronal function involved in synaptic memory and reward behavior, e.g. ion channels (Kcnf1, Kcnn3, Scn5a, excitatory receptors (Grin2a, Gria3, Grip1, neurotransmitters (Pomc, and synapses (Snap29. This study not only reveals the polygenic architecture of AP, but also emphasizes the importance of regulatory elements, consistent with other complex traits.

  12. High Resolution Genomic Scans Reveal Genetic Architecture Controlling Alcohol Preference in Bidirectionally Selected Rat Model.

    Science.gov (United States)

    Lo, Chiao-Ling; Lossie, Amy C; Liang, Tiebing; Liu, Yunlong; Xuei, Xiaoling; Lumeng, Lawrence; Zhou, Feng C; Muir, William M

    2016-08-01

    Investigations on the influence of nature vs. nurture on Alcoholism (Alcohol Use Disorder) in human have yet to provide a clear view on potential genomic etiologies. To address this issue, we sequenced a replicated animal model system bidirectionally-selected for alcohol preference (AP). This model is uniquely suited to map genetic effects with high reproducibility, and resolution. The origin of the rat lines (an 8-way cross) resulted in small haplotype blocks (HB) with a corresponding high level of resolution. We sequenced DNAs from 40 samples (10 per line of each replicate) to determine allele frequencies and HB. We achieved ~46X coverage per line and replicate. Excessive differentiation in the genomic architecture between lines, across replicates, termed signatures of selection (SS), were classified according to gene and region. We identified SS in 930 genes associated with AP. The majority (50%) of the SS were confined to single gene regions, the greatest numbers of which were in promoters (284) and intronic regions (169) with the least in exon's (4), suggesting that differences in AP were primarily due to alterations in regulatory regions. We confirmed previously identified genes and found many new genes associated with AP. Of those newly identified genes, several demonstrated neuronal function involved in synaptic memory and reward behavior, e.g. ion channels (Kcnf1, Kcnn3, Scn5a), excitatory receptors (Grin2a, Gria3, Grip1), neurotransmitters (Pomc), and synapses (Snap29). This study not only reveals the polygenic architecture of AP, but also emphasizes the importance of regulatory elements, consistent with other complex traits.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Hyb-Seq: Combining Target Enrichment and Genome Skimming for Plant Phylogenomics

    Directory of Open Access Journals (Sweden)

    Kevin Weitemier

    2014-08-01

    Full Text Available Premise of the study: Hyb-Seq, the combination of target enrichment and genome skimming, allows simultaneous data collection for low-copy nuclear genes and high-copy genomic targets for plant systematics and evolution studies. Methods and Results: Genome and transcriptome assemblies for milkweed (Asclepias syriaca were used to design enrichment probes for 3385 exons from 768 genes (>1.6 Mbp followed by Illumina sequencing of enriched libraries. Hyb-Seq of 12 individuals (10 Asclepias species and two related genera resulted in at least partial assembly of 92.6% of exons and 99.7% of genes and an average assembly length >2 Mbp. Importantly, complete plastomes and nuclear ribosomal DNA cistrons were assembled using off-target reads. Phylogenomic analyses demonstrated signal conflict between genomes. Conclusions: The Hyb-Seq approach enables targeted sequencing of thousands of low-copy nuclear exons and flanking regions, as well as genome skimming of high-copy repeats and organellar genomes, to efficiently produce genome-scale data sets for phylogenomics.

  15. Genome-wide Scan of 29,141 African Americans Finds No Evidence of Directional Selection since Admixture

    Science.gov (United States)

    Bhatia, Gaurav; Tandon, Arti; Patterson, Nick; Aldrich, Melinda C.; Ambrosone, Christine B.; Amos, Christopher; Bandera, Elisa V.; Berndt, Sonja I.; Bernstein, Leslie; Blot, William J.; Bock, Cathryn H.; Caporaso, Neil; Casey, Graham; Deming, Sandra L.; Diver, W. Ryan; Gapstur, Susan M.; Gillanders, Elizabeth M.; Harris, Curtis C.; Henderson, Brian E.; Ingles, Sue A.; Isaacs, William; De Jager, Phillip L.; John, Esther M.; Kittles, Rick A.; Larkin, Emma; McNeill, Lorna H.; Millikan, Robert C.; Murphy, Adam; Neslund-Dudas, Christine; Nyante, Sarah; Press, Michael F.; Rodriguez-Gil, Jorge L.; Rybicki, Benjamin A.; Schwartz, Ann G.; Signorello, Lisa B.; Spitz, Margaret; Strom, Sara S.; Tucker, Margaret A.; Wiencke, John K.; Witte, John S.; Wu, Xifeng; Yamamura, Yuko; Zanetti, Krista A.; Zheng, Wei; Ziegler, Regina G.; Chanock, Stephen J.; Haiman, Christopher A.; Reich, David; Price, Alkes L.

    2014-01-01

    The extent of recent selection in admixed populations is currently an unresolved question. We scanned the genomes of 29,141 African Americans and failed to find any genome-wide-significant deviations in local ancestry, indicating no evidence of selection influencing ancestry after admixture. A recent analysis of data from 1,890 African Americans reported that there was evidence of selection in African Americans after their ancestors left Africa, both before and after admixture. Selection after admixture was reported on the basis of deviations in local ancestry, and selection before admixture was reported on the basis of allele-frequency differences between African Americans and African populations. The local-ancestry deviations reported by the previous study did not replicate in our very large sample, and we show that such deviations were expected purely by chance, given the number of hypotheses tested. We further show that the previous study’s conclusion of selection in African Americans before admixture is also subject to doubt. This is because the FST statistics they used were inflated and because true signals of unusual allele-frequency differences between African Americans and African populations would be best explained by selection that occurred in Africa prior to migration to the Americas. PMID:25242497

  16. Genome-wide scan of 29,141 African Americans finds no evidence of directional selection since admixture.

    Science.gov (United States)

    Bhatia, Gaurav; Tandon, Arti; Patterson, Nick; Aldrich, Melinda C; Ambrosone, Christine B; Amos, Christopher; Bandera, Elisa V; Berndt, Sonja I; Bernstein, Leslie; Blot, William J; Bock, Cathryn H; Caporaso, Neil; Casey, Graham; Deming, Sandra L; Diver, W Ryan; Gapstur, Susan M; Gillanders, Elizabeth M; Harris, Curtis C; Henderson, Brian E; Ingles, Sue A; Isaacs, William; De Jager, Phillip L; John, Esther M; Kittles, Rick A; Larkin, Emma; McNeill, Lorna H; Millikan, Robert C; Murphy, Adam; Neslund-Dudas, Christine; Nyante, Sarah; Press, Michael F; Rodriguez-Gil, Jorge L; Rybicki, Benjamin A; Schwartz, Ann G; Signorello, Lisa B; Spitz, Margaret; Strom, Sara S; Tucker, Margaret A; Wiencke, John K; Witte, John S; Wu, Xifeng; Yamamura, Yuko; Zanetti, Krista A; Zheng, Wei; Ziegler, Regina G; Chanock, Stephen J; Haiman, Christopher A; Reich, David; Price, Alkes L

    2014-10-02

    The extent of recent selection in admixed populations is currently an unresolved question. We scanned the genomes of 29,141 African Americans and failed to find any genome-wide-significant deviations in local ancestry, indicating no evidence of selection influencing ancestry after admixture. A recent analysis of data from 1,890 African Americans reported that there was evidence of selection in African Americans after their ancestors left Africa, both before and after admixture. Selection after admixture was reported on the basis of deviations in local ancestry, and selection before admixture was reported on the basis of allele-frequency differences between African Americans and African populations. The local-ancestry deviations reported by the previous study did not replicate in our very large sample, and we show that such deviations were expected purely by chance, given the number of hypotheses tested. We further show that the previous study's conclusion of selection in African Americans before admixture is also subject to doubt. This is because the FST statistics they used were inflated and because true signals of unusual allele-frequency differences between African Americans and African populations would be best explained by selection that occurred in Africa prior to migration to the Americas. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  17. Genome-wide linkage scan of antisocial behavior, depression, and impulsive substance use in the UCSF family alcoholism study.

    Science.gov (United States)

    Gizer, Ian R; Ehlers, Cindy L; Vieten, Cassandra; Feiler, Heidi S; Gilder, David A; Wilhelmsen, Kirk C

    2012-10-01

    Epidemiological and clinical studies suggest that the rates of antisocial behavior, depression, and impulsive substance use are increased among individuals diagnosed with alcohol dependence relative to those who are not. Thus, the present study conducted genome-wide linkage scans of antisocial behavior, depression, and impulsive substance use in the University of California at San Francisco Family Alcoholism Study. Antisocial behavior, depressive symptoms, and impulsive substance use were assessed using three scales from the Minnesota Multiphasic Personality Inventory - 2nd ed.: the Antisocial Practices content scale, the Depression content scale, and the revised MacAndrew Alcoholism scale. Linkage analyses were carried out using a variance components approach. Suggestive evidence of linkage to three genomic regions independent of alcohol and cannabis dependence diagnostic status was observed: the Antisocial Practices content scale showed evidence of linkage to chromosome 13 at 11 cM, the MacAndrew Alcoholism scale showed evidence of linkage to chromosome 15 at 47 cM, and all three scales showed evidence of linkage to chromosome 17 at 57-58 cM. Each of these regions has shown previous evidence of linkage and association to substance dependence as well as other psychiatric disorders such as mood and anxiety disorders, attention-deficit hyperactivity disorder, and schizophrenia, thus suggesting potentially broad relations between these regions and psychopathology.

  18. OS046. Genome-wide association scans identify novel maternalsusceptibility loci for preeclampsia.

    Science.gov (United States)

    Johnson, M; Brennecke, S; Iversen, A-C; East, C; Olsen, G; Kent, J; Dyer, T; Said, J; Roten, L; Abraham, L; Zwart, J-A; Winsvold, B; Håberg, A; Huentelman, M; Krokan, H; Gabrielsen, M; Austgulen, R; Blangero, J; Moses, E

    2012-07-01

    We have successfully utilized a family-based study design to localize several positional candidate preeclampsia susceptibility genes to chromosomes 2q22(ACVR2A,LCT,LRP1B,RND3,GCA),5q (ERAP2) and 13q(TNFSF13B). We now report on our continued positional cloning efforts using an alternative genome-wide association (GWA) mapping strategy in large Caucasian case-control cohorts from Australia and Norway. To identify maternal genetic risk loci for preeclampsia. The unrelated Australian samples (545 cases,547 controls) were genotyped using Illumina BeadChip technology (700K loci) and have been analyzed using PLINK. All unrelated Norwegian samples were genotyped across several Illumina BeadChip substrates and consist of 847 cases (700K loci) and 638 controls. The Norwegian control samples originate from other HUNT studies pertaining to migraine (n=95,700K loci), lung cancer (n=89,370K loci) and normal brain pathology (n=454,2.5M loci). To analyze a concordant set of 2.5-3 million genotypes across all Norwegian samples we are currently using MaCH to impute those loci not directly genotyped. The Norwegian GWA data will be analyzed in SOLAR utilizing empirical kinship estimates to account for any distant relatedness. 1078 Australian samples (538 cases,540 controls) and 648, 175 SNPs passed our quality control metrics. Two SNP associations (rs7579169,p=3.6×10(-7); rs12711941,p=4.3×10(-7)) satisfied our genome-wide significant threshold (p1.56) and are in strong linkage disequilibrium with each other (r(2)>0.9) but not with any other genotyped SNP ±200kb. The analysis of the Norwegian GWAS is underway. The Australian GWAS has identified a novel preeclampsia risk locus on chromosome 2q. The INHBB gene closest to our SNP associations is a plausible positional candidate susceptibility gene. There is a substantive body of evidence implicating inhibins, activins and other members of the TGF-βsuperfamily to have a role in the development of preeclampsia. The biological connection

  19. Genome scan for locus involved in mandibular prognathism in pedigrees from China.

    Directory of Open Access Journals (Sweden)

    Qin Li

    Full Text Available BACKGROUND: It is well known that genetic components play an important role in the etiology of mandibular prognathism, but few susceptibility loci have been mapped. METHODOLOGY: In order to identify linkage regions for mandibular prognathism, we analyzed two Chinese pedigrees with 6,090 genome-wide single-nucleotide polymorphism (SNP markers from Illumina Linkage-12 DNA Analysis Kit (average spacing 0.58 cM. Multipoint parametric and non-parametric (model-free linkage analyses were used for the pedigrees. PRINCIPAL FINDING: The most statistically significant linkage results were with markers on chromosome 4 (LOD=3.166 and NPL=3.65 with rs 875864, 4p16.1, 8.38 cM. Candidate genes within the 4p16.1 include EVC, EVC2. CONCLUSION: We detected a novel suggestive linkage locus for mandibular prognathism in two Chinese pedigrees, and this linkage region provides target for susceptibility gene identification, a process that will provide important insights into the molecular and cellular basis of mandibular prognathism.

  20. Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.

    Directory of Open Access Journals (Sweden)

    Cecilia M Lindgren

    2009-06-01

    Full Text Available To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580 informative for adult waist circumference (WC and waist-hip ratio (WHR. We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11 and MSRA (WC, P = 8.9x10(-9. A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8. The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.

  1. Copy Number Variation of UGT 2B Genes in Indian Families Using Whole Genome Scans

    Directory of Open Access Journals (Sweden)

    Avinash M. Veerappa

    2016-01-01

    Full Text Available Background and Objectives. Uridine diphospho-glucuronosyltransferase 2B (UGT2B is a family of genes involved in metabolizing steroid hormones and several other xenobiotics. These UGT2B genes are highly polymorphic in nature and have distinct polymorphisms associated with specific regions around the globe. Copy number variations (CNVs status of UGT2B17 in Indian population is not known and their disease associations have been inconclusive. It was therefore of interest to investigate the CNV profile of UGT2B genes. Methods. We investigated the presence of CNVs in UGT2B genes in 31 members from eight Indian families using Affymetrix Genome-Wide Human SNP Array 6.0 chip. Results. Our data revealed >50% of the study members carried CNVs in UGT2B genes, of which 76% showed deletion polymorphism. CNVs were observed more in UGT2B17 (76.4% than in UGT2B15 (17.6%. Molecular network and pathway analysis found enrichment related to steroid metabolic process, carboxylesterase activity, and sequence specific DNA binding. Interpretation and Conclusion. We report the presence of UGT2B gene deletion and duplication polymorphisms in Indian families. Network analysis indicates the substitutive role of other possible genes in the UGT activity. The CNVs of UGT2B genes are very common in individuals indicating that the effect is neutral in causing any suspected diseases.

  2. A genome scan for quantitative trait loci affecting the Salmonella carrier-state in the chicken

    Directory of Open Access Journals (Sweden)

    Bumstead Nat

    2005-09-01

    Full Text Available Abstract Selection for increased resistance to Salmonella colonisation and excretion could reduce the risk of foodborne Salmonella infection. In order to identify potential loci affecting resistance, differences in resistance were identified between the N and 61 inbred lines and two QTL research performed. In an F2 cross, the animals were inoculated at one week of age with Salmonella enteritidis and cloacal swabs were carried out 4 and 5 wk post inoculation (thereafter called CSW4F2 and CSW4F2 and caecal contamination (CAECF2 was assessed 1 week later. The animals from the (N × 61 × N backcross were inoculated at six weeks of age with Salmonella typhimurium and cloacal swabs were studied from wk 1 to 4 (thereafter called CSW1BC to CSW4BC. A total of 33 F2 and 46 backcross progeny were selectively genotyped for 103 and 135 microsatellite markers respectively. The analysis used least-squares-based and non-parametric interval mapping. Two genome-wise significant QTL were observed on Chromosome 1 for CSW2BC and on Chromosome 2 for CSW4F2, and four suggestive QTL for CSW5F2 on Chromosome 2, for CSW5F2 and CSW2BC on chromosome 5 and for CAECF2 on chromosome 16. These results suggest new regions of interest and the putative role of SAL1.

  3. Reliabilities of genomic prediction using combined reference data of the Nordic Red dairy cattle production

    DEFF Research Database (Denmark)

    Brøndum, Rasmus Froberg; Rius-Vilarrasa, E; Strandén, I

    2011-01-01

    This study investigated the possibility of increasing the reliability of direct genomic values (DGV) by combining reference opulations. The data were from 3,735 bulls from Danish, Swedish, and Finnish Red dairy cattle populations. Single nucleotide polymorphism markers were fitted as random...

  4. Methods to improve genomic prediction and GWAS using combined Holstein populations

    DEFF Research Database (Denmark)

    Li, Xiujin

    The thesis focuses on methods to improve GWAS and genomic prediction using combined Holstein populations and investigations G by E interaction. The conclusions are: 1) Prediction reliabilities for Brazilian Holsteins can be increased by adding Nordic and Frensh genotyped bulls and a large G by E ...

  5. Meta-analysis of genome-wide scans for human adult stature identifies novel Loci and associations with measures of skeletal frame size.

    Directory of Open Access Journals (Sweden)

    Nicole Soranzo

    2009-04-01

    Full Text Available Recent genome-wide (GW scans have identified several independent loci affecting human stature, but their contribution through the different skeletal components of height is still poorly understood. We carried out a genome-wide scan in 12,611 participants, followed by replication in an additional 7,187 individuals, and identified 17 genomic regions with GW-significant association with height. Of these, two are entirely novel (rs11809207 in CATSPER4, combined P-value = 6.1x10(-8 and rs910316 in TMED10, P-value = 1.4x10(-7 and two had previously been described with weak statistical support (rs10472828 in NPR3, P-value = 3x10(-7 and rs849141 in JAZF1, P-value = 3.2x10(-11. One locus (rs1182188 at GNA12 identifies the first height eQTL. We also assessed the contribution of height loci to the upper- (trunk and lower-body (hip axis and femur skeletal components of height. We find evidence for several loci associated with trunk length (including rs6570507 in GPR126, P-value = 4x10(-5 and rs6817306 in LCORL, P-value = 4x10(-4, hip axis length (including rs6830062 at LCORL, P-value = 4.8x10(-4 and rs4911494 at UQCC, P-value = 1.9x10(-4, and femur length (including rs710841 at PRKG2, P-value = 2.4x10(-5 and rs10946808 at HIST1H1D, P-value = 6.4x10(-6. Finally, we used conditional analyses to explore a possible differential contribution of the height loci to these different skeletal size measurements. In addition to validating four novel loci controlling adult stature, our study represents the first effort to assess the contribution of genetic loci to three skeletal components of height. Further statistical tests in larger numbers of individuals will be required to verify if the height loci affect height preferentially through these subcomponents of height.

  6. Comparative genomic analysis of novel Acinetobacter symbionts: A combined systems biology and genomics approach.

    Science.gov (United States)

    Gupta, Vipin; Haider, Shazia; Sood, Utkarsh; Gilbert, Jack A; Ramjee, Meenakshi; Forbes, Ken; Singh, Yogendra; Lopes, Bruno S; Lal, Rup

    2016-07-05

    The increasing trend of antibiotic resistance in Acinetobacter drastically limits the range of therapeutic agents required to treat multidrug resistant (MDR) infections. This study focused on analysis of novel Acinetobacter strains using a genomics and systems biology approach. Here we used a network theory method for pathogenic and non-pathogenic Acinetobacter spp. to identify the key regulatory proteins (hubs) in each strain. We identified nine key regulatory proteins, guaA, guaB, rpsB, rpsI, rpsL, rpsE, rpsC, rplM and trmD, which have functional roles as hubs in a hierarchical scale-free fractal protein-protein interaction network. Two key hubs (guaA and guaB) were important for insect-associated strains, and comparative analysis identified guaA as more important than guaB due to its role in effective module regulation. rpsI played a significant role in all the novel strains, while rplM was unique to sheep-associated strains. rpsM, rpsB and rpsI were involved in the regulation of overall network topology across all Acinetobacter strains analyzed in this study. Future analysis will investigate whether these hubs are useful as drug targets for treating Acinetobacter infections.

  7. MiRFinder: an improved approach and software implementation for genome-wide fast microRNA precursor scans

    Directory of Open Access Journals (Sweden)

    Li Kui

    2007-09-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are recognized as one of the most important families of non-coding RNAs that serve as important sequence-specific post-transcriptional regulators of gene expression. Identification of miRNAs is an important requirement for understanding the mechanisms of post-transcriptional regulation. Hundreds of miRNAs have been identified by direct cloning and computational approaches in several species. However, there are still many miRNAs that remain to be identified due to lack of either sequence features or robust algorithms to efficiently identify them. Results We have evaluated features valuable for pre-miRNA prediction, such as the local secondary structure differences of the stem region of miRNA and non-miRNA hairpins. We have also established correlations between different types of mutations and the secondary structures of pre-miRNAs. Utilizing these features and combining some improvements of the current pre-miRNA prediction methods, we implemented a computational learning method SVM (support vector machine to build a high throughput and good performance computational pre-miRNA prediction tool called MiRFinder. The tool was designed for genome-wise, pair-wise sequences from two related species. The method built into the tool consisted of two major steps: 1 genome wide search for hairpin candidates and 2 exclusion of the non-robust structures based on analysis of 18 parameters by the SVM method. Results from applying the tool for chicken/human and D. melanogaster/D. pseudoobscura pair-wise genome alignments showed that the tool can be used for genome wide pre-miRNA predictions. Conclusion The MiRFinder can be a good alternative to current miRNA discovery software. This tool is available at http://www.bioinformatics.org/mirfinder/.

  8. Impact of MR-safe headphones on PET attenuation in combined PET/MRI scans.

    Science.gov (United States)

    Büther, Florian; Vrachimis, Alexis; Becker, Anne; Stegger, Lars

    2016-12-01

    MR headphones are attenuation sources affecting PET quantification in hybrid PET/MRI. Despite potentially better patient communication, usage in PET/MRI scans is not approved by the vendor. This study aims to determine the impact of headphones on PET by means of phantom and patient scans. Additionally, the perceived benefit of using headphones was evaluated. A cylinder phantom was scanned without and with dedicated MR headphones in a PET/CT scanner. Headphone attenuation was additionally assessed in a clinical setup in 10 patients on a PET/MR scanner using F-18-fluoro-deoxy-glucose. The difference in tracer uptake with and without headset was determined for the various brain regions. Additionally, the patients were asked for differences in noise levels, patient comfort, communication quality, and preference. CT data revealed headphone attenuation values of 350-500 HU. Neglecting headphone attenuation leads to a decrease in PET values between the earcups of about 11 % when compared to the correctly reconstructed data. Regions further away from the headphones were less affected. Patient images demonstrated a decrease of 11 % on average in the cerebellum and temporal lobes, while other regions were less affected. No visual artefacts in the images were noticed. On average, no advantage in terms of noise and patient comfort and only slightly better quality of communication were imparted by the patients. Using headphones during PET/MR acquisition leads to a negative bias in brain uptake values without introducing obvious image artefacts. Since they lack benefits for the patients, they should be avoided if PET quantification of the brain is needed.

  9. A genome scan for quantitative trait loci and imprinted regions affecting reproduction in pigs.

    Science.gov (United States)

    Holl, J W; Cassady, J P; Pomp, D; Johnson, R K

    2004-12-01

    Quantitative trait loci for reproductive traits in a three-generation resource population of a cross between low-indexing pigs from a control line and high-indexing pigs from a line selected 10 generations for increased index of ovulation rate and embryonic survival are reported. Phenotypic data were collected in F2 females for birth weight (BWT, n = 428), weaning weight (WWT, n = 405), age at puberty (AP, n = 295), ovulation rate (OR, n = 423), number of fully formed pigs (FF, n = 370), number of pigs born alive (NBA, n = 370), number of mummified pigs (MUM, n = 370), and number of stillborn pigs (NSB, n = 370). Grandparent, F1, and F2 animals were genotyped for 151 microsatellite markers. Sixteen putative QTL (P reproductive traits were identified in previous analyses of these data with single QTL line-cross models. Data were reanalyzed with multiple QTL models, including imprinting effects. Data also were analyzed with half-sib models. Permutation was used to establish genome-wide significance levels ( = 0.01, 0.05, and 0.10). Thirty-one putative QTL for reproductive traits and two QTL for birth weight were identified (P < 0.10). One Mendelian QTL for FF (P < 0.05), one for NBA (P < 0.05), three for NSB (P < 0.05), three for NN (P < 0.05), seven for AP (P < 0.10), five for MUM (P < 0.10), and one for BWT (P < 0.10) were found. Partial imprinting of QTL affecting OR (P < 0.01), BWT (P < 0.05), and MUM (P < 0.05) was detected. There were four paternally expressed QTL for NN (P < 0.10) and one each for AP (P < 0.05) and MUM (P < 0.10). Maternally expressed QTL affecting NSB (P < 0.10), NN (P < 0.10), and MUM (P < 0.10) were detected. No QTL were detected with half-sib analyses. Multiple QTL models with imprinting effects are more appropriate for analyzing F2 data than single Mendelian QTL line-cross models.

  10. Fast Measurement and Reconstruction of Large Workpieces with Freeform Surfaces by Combining Local Scanning and Global Position Data

    Directory of Open Access Journals (Sweden)

    Zhe Chen

    2015-06-01

    Full Text Available In this paper, we propose a new approach for the measurement and reconstruction of large workpieces with freeform surfaces. The system consists of a handheld laser scanning sensor and a position sensor. The laser scanning sensor is used to acquire the surface and geometry information, and the position sensor is utilized to unify the scanning sensors into a global coordinate system. The measurement process includes data collection, multi-sensor data fusion and surface reconstruction. With the multi-sensor data fusion, errors accumulated during the image alignment and registration process are minimized, and the measuring precision is significantly improved. After the dense accurate acquisition of the three-dimensional (3-D coordinates, the surface is reconstructed using a commercial software piece, based on the Non-Uniform Rational B-Splines (NURBS surface. The system has been evaluated, both qualitatively and quantitatively, using reference measurements provided by a commercial laser scanning sensor. The method has been applied for the reconstruction of a large gear rim and the accuracy is up to 0.0963 mm. The results prove that this new combined method is promising for measuring and reconstructing the large-scale objects with complex surface geometry. Compared with reported methods of large-scale shape measurement, it owns high freedom in motion, high precision and high measurement speed in a wide measurement range.

  11. Plasma-deposited fluorocarbon films: insulation material for microelectrodes and combined atomic force microscopy-scanning electrochemical microscopy probes.

    Science.gov (United States)

    Wiedemair, Justyna; Balu, Balamurali; Moon, Jong-Seok; Hess, Dennis W; Mizaikoff, Boris; Kranz, Christine

    2008-07-01

    Pinhole-free insulation of micro- and nanoelectrodes is the key to successful microelectrochemical experiments performed in vivo or in combination with scanning probe experiments. A novel insulation technique based on fluorocarbon insulation layers deposited from pentafluoroethane (PFE, CF3CHF2) plasmas is presented as a promising electrical insulation approach for microelectrodes and combined atomic force microscopy-scanning electrochemical microscopy (AFM-SECM) probes. The deposition allows reproducible and uniform coating, which is essential for many analytical applications of micro- and nanoelectrodes such as, e.g., in vivo experiments and SECM experiments. Disk-shaped microelectrodes and frame-shaped AFM tip-integrated electrodes have been fabricated by postinsulation focused ion beam (FIB) milling. The thin insulation layer for combined AFM-SECM probes renders this fabrication technique particularly useful for submicro insulation providing radius ratios of the outer insulation versus the disk electrode (RG values) suitable for SECM experiments. Characterization of PFE-insulated AFM-SECM probes will be presented along with combined AFM-SECM approach curves and imaging.

  12. Genome-wide scan for visceral leishmaniasis in mixed-breed dogs identifies candidate genes involved in T helper cells and macrophage signaling

    Science.gov (United States)

    We conducted a genome-wide scan for visceral leishmaniasis in mixed-breed dogs from a highly endemic area in Brazil using 149,648 single nucleotide polymorphism (SNP) markers genotyped in 20 cases and 28 controls. Using a mixed model approach, we found two candidate loci on canine autosomes 1 and 2....

  13. A whole-genome scan in 164 Dutch sib pairs with attention-deficit/hyperactivity disorder : Suggestive evidence for linkage on chromosomes 7p and 15q

    NARCIS (Netherlands)

    Bakker, SC; van der Meulen, EM; Buitelaar, JK; Sandkuijl, LA; Pauls, DL; Monsuur, AJ; van't Slot, R; Minderaa, RB; Gunning, WB; Pearson, PL; Sinke, RJ

    A genome scan was performed on 164 Dutch affected sib pairs (ASPs) with attention-deficit/hyperactivity disorder (ADHD). All subjects were white and of Dutch descent and were phenotyped according to criteria set out in the Diagnostic and Statistical Manual Of Mental Disorders, 4th edition.

  14. A whole-genome scan in 164 Dutch sib pairs with attention-deficit/hyperactivity disorder: suggestive evidence for linkage on chromosomes 7p and 15q.

    NARCIS (Netherlands)

    Bakker, S.C.; Meulen, E.M. van der; Sandkuijl, L.A.; Pauls, D.L.; Monsuur, A.J.; Slot, R. van 't; Minderaa, R.B.; Gunning, W.B.; Pearson, P.L.; Sinke, R.J.

    2003-01-01

    A genome scan was performed on 164 Dutch affected sib pairs (ASPs) with attention-deficit/hyperactivity disorder (ADHD). All subjects were white and of Dutch descent and were phenotyped according to criteria set out in the Diagnostic and Statistical Manual Of Mental Disorders, 4th edition.

  15. A fast spatial scanning combination emissive and Mach probe for edge plasma diagnosis

    Science.gov (United States)

    Lehmer, R. D.; Labombard, B.; Conn, R. W.

    1989-04-01

    A fast spatially scanning emissive and Mach probe has been developed for the measurement of plasma profiles in the PISCES facility at UCLA. A pneumatic cylinder is used to drive a multiple tip probe along a 15 cm stroke in less than 400 msec, giving single shot profiles while limiting power deposition to the probe. A differentially pumped sliding O-ring seal allows the probe to be moved between shots to infer two and three dimensional profiles. The probe system has been used to investigate the plasma potential, density, and parallel Mach number profiles of the presheath induced by a wall surface and scrape-off-layer profile modifications in biased limiter simulation experiments. Details of the hardware, data acquisition electronics, and tests of probe reliability are discussed.

  16. Genome-wide scan identifies TNIP1, PSORS1C1, and RHOB as novel risk loci for systemic sclerosis.

    Directory of Open Access Journals (Sweden)

    Yannick Allanore

    2011-07-01

    Full Text Available Systemic sclerosis (SSc is an orphan, complex, inflammatory disease affecting the immune system and connective tissue. SSc stands out as a severely incapacitating and life-threatening inflammatory rheumatic disease, with a largely unknown pathogenesis. We have designed a two-stage genome-wide association study of SSc using case-control samples from France, Italy, Germany, and Northern Europe. The initial genome-wide scan was conducted in a French post quality-control sample of 564 cases and 1,776 controls, using almost 500 K SNPs. Two SNPs from the MHC region, together with the 6 loci outside MHC having at least one SNP with a P<10(-5 were selected for follow-up analysis. These markers were genotyped in a post-QC replication sample of 1,682 SSc cases and 3,926 controls. The three top SNPs are in strong linkage disequilibrium and located on 6p21, in the HLA-DQB1 gene: rs9275224, P = 9.18×10(-8, OR = 0.69, 95% CI [0.60-0.79]; rs6457617, P = 1.14×10(-7 and rs9275245, P = 1.39×10(-7. Within the MHC region, the next most associated SNP (rs3130573, P = 1.86×10(-5, OR = 1.36 [1.18-1.56] is located in the PSORS1C1 gene. Outside the MHC region, our GWAS analysis revealed 7 top SNPs (P<10(-5 that spanned 6 independent genomic regions. Follow-up of the 17 top SNPs in an independent sample of 1,682 SSc and 3,926 controls showed associations at PSORS1C1 (overall P = 5.70×10(-10, OR:1.25, TNIP1 (P = 4.68×10(-9, OR:1.31, and RHOB loci (P = 3.17×10(-6, OR:1.21. Because of its biological relevance, and previous reports of genetic association at this locus with connective tissue disorders, we investigated TNIP1 expression. A markedly reduced expression of the TNIP1 gene and also its protein product were observed both in lesional skin tissue and in cultured dermal fibroblasts from SSc patients. Furthermore, TNIP1 showed in vitro inhibitory effects on inflammatory cytokine-induced collagen production. The genetic signal of

  17. Visual and quantitative evaluation of selected image combination schemes in ultrasound spatial compound scanning

    DEFF Research Database (Denmark)

    Wilhjelm, Jens E.; Jensen, M.S.; Jespersen, S.K.

    2004-01-01

    Multi-angle spatial compound images are normally generated by averaging the recorded single-angle images (SAIs). To exploit possible advantages associated with alternative combination schemes, this paper investigates both the effect of number of angles (Ntheta) as well as operator (mean, median, ...

  18. Genome-wide linkage scan for loci of musical aptitude in Finnish families: evidence for a major locus at 4q22

    Science.gov (United States)

    Pulli, K; Karma, K; Norio, R; Sistonen, P; Göring, H H H; Järvelä, I

    2008-01-01

    Background: Music perception and performance are comprehensive human cognitive functions and thus provide an excellent model system for studying human behaviour and brain function. However, the molecules involved in mediating music perception and performance are so far uncharacterised. Objective: To unravel the biological background of music perception, using molecular and statistical genetic approaches. Methods: 15 Finnish multigenerational families (with a total of 234 family members) were recruited via a nationwide search. The phenotype of all family members was determined using three tests used in defining musical aptitude: a test for auditory structuring ability (Karma Music test; KMT) commonly used in Finland, and the Seashore pitch and time discrimination subtests (SP and ST respectively) used internationally. We calculated heritabilities and performed a genome-wide variance components-based linkage scan using genotype data for 1113 microsatellite markers. Results: The heritability estimates were 42% for KMT, 57% for SP, 21% for ST and 48% for the combined music test scores. Significant evidence of linkage was obtained on chromosome 4q22 (LOD 3.33) and suggestive evidence of linkage at 8q13-21 (LOD 2.29) with the combined music test scores, using variance component linkage analyses. The major contribution of the 4q22 locus was obtained for the KMT (LOD 2.91). Interestingly, a positive LOD score of 1.69 was shown at 18q, a region previously linked to dyslexia (DYX6) using combined music test scores. Conclusion: Our results show that there is a genetic contribution to musical aptitude that is likely to be regulated by several predisposing genes or variants. PMID:18424507

  19. Genome-wide linkage scan for loci of musical aptitude in Finnish families: evidence for a major locus at 4q22.

    Science.gov (United States)

    Pulli, K; Karma, K; Norio, R; Sistonen, P; Göring, H H H; Järvelä, I

    2008-07-01

    Music perception and performance are comprehensive human cognitive functions and thus provide an excellent model system for studying human behaviour and brain function. However, the molecules involved in mediating music perception and performance are so far uncharacterised. To unravel the biological background of music perception, using molecular and statistical genetic approaches. 15 Finnish multigenerational families (with a total of 234 family members) were recruited via a nationwide search. The phenotype of all family members was determined using three tests used in defining musical aptitude: a test for auditory structuring ability (Karma Music test; KMT) commonly used in Finland, and the Seashore pitch and time discrimination subtests (SP and ST respectively) used internationally. We calculated heritabilities and performed a genome-wide variance components-based linkage scan using genotype data for 1113 microsatellite markers. The heritability estimates were 42% for KMT, 57% for SP, 21% for ST and 48% for the combined music test scores. Significant evidence of linkage was obtained on chromosome 4q22 (LOD 3.33) and suggestive evidence of linkage at 8q13-21 (LOD 2.29) with the combined music test scores, using variance component linkage analyses. The major contribution of the 4q22 locus was obtained for the KMT (LOD 2.91). Interestingly, a positive LOD score of 1.69 was shown at 18q, a region previously linked to dyslexia (DYX6) using combined music test scores. Our results show that there is a genetic contribution to musical aptitude that is likely to be regulated by several predisposing genes or variants.

  20. Plasma Levels of Soluble Interleukin-2 Receptor α: Associations With Clinical Cardiovascular Events and Genome-Wide Association Scan.

    Science.gov (United States)

    Durda, Peter; Sabourin, Jeremy; Lange, Ethan M; Nalls, Mike A; Mychaleckyj, Josyf C; Jenny, Nancy Swords; Li, Jin; Walston, Jeremy; Harris, Tamara B; Psaty, Bruce M; Valdar, William; Liu, Yongmei; Cushman, Mary; Reiner, Alex P; Tracy, Russell P; Lange, Leslie A

    2015-10-01

    Interleukin (IL) -2 receptor subunit α regulates lymphocyte activation, which plays an important role in atherosclerosis. Associations between soluble IL-2Rα (sIL-2Rα) and cardiovascular disease (CVD) have not been widely studied and little is known about the genetic determinants of sIL-2Rα levels. We measured baseline levels of sIL-2Rα in 4408 European American (EA) and 766 African American (AA) adults from the Cardiovascular Health Study (CHS) and examined associations with baseline CVD risk factors, subclinical CVD, and incident CVD events. We also performed a genome-wide association study for sIL-2Rα in CHS (2964 EAs and 683 AAs) and further combined CHS EA results with those from two other EA cohorts in a meta-analysis (n=4464 EAs). In age, sex- and race- adjusted models, sIL-2Rα was positively associated with current smoking, type 2 diabetes mellitus, hypertension, insulin, waist circumference, C-reactive protein, IL-6, fibrinogen, internal carotid wall thickness, all-cause mortality, CVD mortality, and incident CVD, stroke, and heart failure. When adjusted for baseline CVD risk factors and subclinical CVD, associations with all-cause mortality, CVD mortality, and heart failure remained significant in both EAs and AAs. In the EA genome-wide association study analysis, we observed 52 single-nucleotide polymorphisms in the chromosome 10p15-14 region, which contains IL2RA, IL15RA, and RMB17, that reached genome-wide significance (Passociated single-nucleotide polymorphisms at chromosome 10p15-14. © 2015 American Heart Association, Inc.

  1. STRUCTURED LIGHT BASED 3D SCANNING FOR SPECULAR SURFACE BY THE COMBINATION OF GRAY CODE AND PHASE SHIFTING

    Directory of Open Access Journals (Sweden)

    Y. Zhang

    2016-06-01

    Full Text Available Surface reconstruction using coded structured light is considered one of the most reliable techniques for high-quality 3D scanning. With a calibrated projector-camera stereo system, a light pattern is projected onto the scene and imaged by the camera. Correspondences between projected and recovered patterns are computed in the decoding process, which is used to generate 3D point cloud of the surface. However, the indirect illumination effects on the surface, such as subsurface scattering and interreflections, will raise the difficulties in reconstruction. In this paper, we apply maximum min-SW gray code to reduce the indirect illumination effects of the specular surface. We also analysis the errors when comparing the maximum min-SW gray code and the conventional gray code, which justifies that the maximum min-SW gray code has significant superiority to reduce the indirect illumination effects. To achieve sub-pixel accuracy, we project high frequency sinusoidal patterns onto the scene simultaneously. But for specular surface, the high frequency patterns are susceptible to decoding errors. Incorrect decoding of high frequency patterns will result in a loss of depth resolution. Our method to resolve this problem is combining the low frequency maximum min-SW gray code and the high frequency phase shifting code, which achieves dense 3D reconstruction for specular surface. Our contributions include: (i A complete setup of the structured light based 3D scanning system; (ii A novel combination technique of the maximum min-SW gray code and phase shifting code. First, phase shifting decoding with sub-pixel accuracy. Then, the maximum min-SW gray code is used to resolve the ambiguity resolution. According to the experimental results and data analysis, our structured light based 3D scanning system enables high quality dense reconstruction of scenes with a small number of images. Qualitative and quantitative comparisons are performed to extract the

  2. Automated lesion detection on MRI scans using combined unsupervised and supervised methods.

    Science.gov (United States)

    Guo, Dazhou; Fridriksson, Julius; Fillmore, Paul; Rorden, Christopher; Yu, Hongkai; Zheng, Kang; Wang, Song

    2015-10-30

    Accurate and precise detection of brain lesions on MR images (MRI) is paramount for accurately relating lesion location to impaired behavior. In this paper, we present a novel method to automatically detect brain lesions from a T1-weighted 3D MRI. The proposed method combines the advantages of both unsupervised and supervised methods. First, unsupervised methods perform a unified segmentation normalization to warp images from the native space into a standard space and to generate probability maps for different tissue types, e.g., gray matter, white matter and fluid. This allows us to construct an initial lesion probability map by comparing the normalized MRI to healthy control subjects. Then, we perform non-rigid and reversible atlas-based registration to refine the probability maps of gray matter, white matter, external CSF, ventricle, and lesions. These probability maps are combined with the normalized MRI to construct three types of features, with which we use supervised methods to train three support vector machine (SVM) classifiers for a combined classifier. Finally, the combined classifier is used to accomplish lesion detection. We tested this method using T1-weighted MRIs from 60 in-house stroke patients. Using leave-one-out cross validation, the proposed method can achieve an average Dice coefficient of 73.1% when compared to lesion maps hand-delineated by trained neurologists. Furthermore, we tested the proposed method on the T1-weighted MRIs in the MICCAI BRATS 2012 dataset. The proposed method can achieve an average Dice coefficient of 66.5% in comparison to the expert annotated tumor maps provided in MICCAI BRATS 2012 dataset. In addition, on these two test datasets, the proposed method shows competitive performance to three state-of-the-art methods, including Stamatakis et al., Seghier et al., and Sanjuan et al. In this paper, we introduced a novel automated procedure for lesion detection from T1-weighted MRIs by combining both an unsupervised and a

  3. Teflon laryngeal granuloma presenting as laryngeal cancer on combined positron emission tomography and computed tomography scanning.

    Science.gov (United States)

    Ondik, M P; Kang, J; Bayerl, M G; Bruno, M; Goldenberg, D

    2009-05-01

    Positron emission tomography with 18F-fluorodeoxyglucose (18FDG) has been increasingly used in the diagnostic investigation of patients with neoplasms of the head and neck. Positron emission tomography and computed tomography have also proven useful for surveillance of thyroid cancers that no longer concentrate radioiodine. However, certain benign or inflammatory lesions can also accumulate 18F-fluorodeoxyglucose and lead to misdiagnosis. We review and discuss the pitfalls of using positron emission tomography and computed tomography for surveillance of thyroid cancer. We present the case of a 48-year-old woman who was diagnosed with a laryngeal neoplasm on integrated positron emission tomography and computed tomography scanning, after a routine ultrasound demonstrated an enlarged thyroid nodule. On physical examination, she had a laryngeal mass overlying an immobile vocal fold. The mass was biopsied and found to harbour a Teflon granuloma. Positron emission tomography positive Teflon granulomas have previously been reported in the nasopharynx and vocal folds, and should be considered in the differential diagnosis of patients who have undergone prior surgery involving Teflon injection. It is important for otolaryngologists and radiologists to recognise potential causes of false positive positron emission tomography and computed tomography findings, including Teflon granulomas.

  4. Combined Differential scanning calorimetry, Raman and Brillouin spectroscopies: A multiscale approach for materials investigation.

    Science.gov (United States)

    Veber, A; Cicconi, M R; Reinfelder, H; de Ligny, D

    2018-01-15

    A new experimental setup combining DSC, Raman and Brillouin spectroscopies was developed. In order to estimate its accuracy and stability a study of silicon and the alpha-beta quartz phase transition were performed. The data obtained demonstrated good agreement with previous studies using these three different techniques. For quartz, the temperature behavior of its 147 cm-1 Raman mode was studied in detail. Using a two-phonon coupling treatment of the Raman band, we show for the first time that its behavior can be well described by Landau theory of first-order phase transitions. The combined DSC-Raman-Brillouin technique is a powerful tool for material science capable of studying thermal, structural and elastic properties simultaneously. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Annotation of plant gene function via combined genomics, metabolomics and informatics

    OpenAIRE

    Tohge, T.; Fernie, A.

    2012-01-01

    Given the ever expanding number of model plant species for which complete genome sequences are available and the abundance of bio-resources such as knockout mutants, wild accessions and advanced breeding populations, there is a rising burden for gene functional annotation. In this protocol, annotation of plant gene function using combined co-expression gene analysis, metabolomics and informatics is provided (Figure 1). This approach is based on the theory of using target genes of known functi...

  6. Scanning electron microscopy combined with image processing technique: Microstructure and texture analysis of legumes and vegetables for instant meal.

    Science.gov (United States)

    Pieniazek, Facundo; Messina, Valeria

    2016-04-01

    Development and innovation of new technologies are necessary especially in food quality; due that most instrumental technique for measuring quality properties involves a considerable amount of manual work. Image analysis is a technique that allows to provide objective evaluations from digitalized images that can estimate quality parameters for consumer's acceptance. The aim of the present research was to study the effect of freeze drying on the microstructure and texture of legume and vegetables using scanning electron microscopy at different magnifications' combined with image analysis. Cooked and cooked freeze dried rehydrated legumes and vegetables were analyzed individually by scanning electron microscopy at different magnifications' (250, 500, and 1000×).Texture properties were analyzed by texture analyzer and image analysis. Significant differences (P image and instrumental texture parameters. A linear trend with a linear correlation was applied for instrumental and image features. Results showed that image features calculated from Grey level co-occurrence matrix at 1,000× had high correlations with instrumental features. In rice, homogeneity and contrast can be applied to evaluate texture parameters gumminess and adhesiviness; Lentils: contrast, correlation, energy, homogeneity, and entropy for hardness, adhesiviness, gumminess, and chewiness; Potato and carrots: contrast, energy, homogeneity and entropy for adhesiviness, chewiness, hardness, cohesiviness, and resilence. Results revealed that combing scanning electron microscopy with image analysis can be a useful tool to analyze quality parameters in legumes and vegetables. © 2016 Wiley Periodicals, Inc.

  7. Lumbar spine CT scan

    Science.gov (United States)

    CAT scan - lumbar spine; Computed axial tomography scan - lumbar spine; Computed tomography scan - lumbar spine; CT - lower ... The lumbar CT scan is good for evaluating large herniated disks, ... smaller ones. This test can be combined with a myelogram to get ...

  8. A Combined Intensity and Gradient-Based Similarity Criterion for Interindividual SPECT Brain Scan Registration

    Directory of Open Access Journals (Sweden)

    Bengtsson Ewert

    2003-01-01

    Full Text Available An evaluation of a new similarity criterion for interindividual image registration is presented. The proposed criterion combines intensity and gradient information from the images to achieve a more robust and accurate registration. It builds on a combination of the normalised mutual information (NMI cost function and a gradient-weighting function, calculated from gradient magnitude and relative gradient angle values from the images. An investigation was made to determine the best settings for the number of bins in the NMI joint histograms, subsampling, and smoothing of the images prior to the registration. The new method was compared with the NMI and correlation-coefficient (CC criterions for interindividual SPECT image registration. Two different validation tests were performed, based on the displacement of voxels inside the brain relative to their estimated true positions after registration. The results show that the registration quality was improved when compared with the NMI and CC measures. The actual improvements, in one of the tests, were in the order of 30-40% for the mean voxel displacement error measured within 20 different SPECT images. A conclusion from the studies is that the new similarity measure significantly improves the registration quality, compared with the NMI and CC similarity measures.

  9. Functional imaging in differentiating bronchial masses: an initial experience with a combination of (18)F-FDG PET-CT scan and (68)Ga DOTA-TOC PET-CT scan.

    Science.gov (United States)

    Kumar, Arvind; Jindal, Tarun; Dutta, Roman; Kumar, Rakesh

    2009-10-01

    To evaluate the role of combination of (18)F-FDG PET-CT scan and (68)Ga DOTA-TOC PET-CT scan in differentiating bronchial tumors observed in contrast enhanced computed tomography scan of chest. Prospective observational study. Place of study: All India Institute of Medical Sciences, New Delhi, India. 7 patients with bronchial mass detected in computed tomography scan of the chest were included in this study. All patients underwent (18)F-FDG PET-CT scan, (68)Ga DOTA-TOC PET-CT scan and fiberoptic bronchoscope guided biopsy followed by definitive surgical excision. The results of functional imaging studies were analyzed and the results are correlated with the final histopathology of the tumor. Histopathological examination of 7 bronchial masses revealed carcinoid tumors (2 typical, 1 atypical), inflammatory myofibroblastic tumor (1), mucoepidermoid carcinoma (1), hamartoma (1), and synovial cell sarcoma (1). The typical carcinoids had mild (18)F-FDG uptake and high (68)Ga DOTA-TOC uptake. Atypical carcinoid had moderate uptake of (18)F-FDG and high (68)Ga DOTA-TOC uptake. Inflammatory myofibroblastic tumor showed high uptake of (18)F-FDG and no uptake of (68)Ga DOTA-TOC. Mucoepidermoid carcinoma showed mild (18)F-FDG uptake and no (68)Ga DOTA-TOC uptake. Hamartoma showed no uptake on either scans. Synovial cell sarcoma showed moderate (18)F-FDG uptake and mild focal (68)Ga DOTA-TOC uptake. This initial experience with the combined use of (18)F-FDG and (68)Ga DOTA-TOC PET-CT scan reveals different uptake patterns in various bronchial tumors. Bronchoscopic biopsy will continue to be the gold standard; however, the interesting observations made in this study merits further evaluation of the utility of the combination of (18)F-FDG PET-CT scan and (68)Ga DOTA-TOC PET-CT scan in larger number of patients with bronchial masses.

  10. Studies on effect of psychological intervention combination with music therapy on nursing for abdominal MRI scans

    Directory of Open Access Journals (Sweden)

    Yun-xia SUN

    2014-06-01

    Full Text Available Objective: To investigate the effectiveness and significance of the Psychological intervention combined with music therapy in abdominal MRI examination. Methods: 230 cases who underwent abdominal MRI examination between 2010 January and 2012 December were collected. They were divided into three groups randomly: routine nursing group, Psychological intervention group and music therapy group. Differences in age, gender, educational level, blood pressure and heart rate were compared between the three groups; To analyze the changes of vital signs after MRI examination, MRI examination results , psychological reaction before and after MRI examination of the three groups. Results: (1There was no significant difference in the general information (P>0.05; (2The heart rate, respiration and blood pressure after MRI examination of patients with routine nursing increased significantly than the other two groups. And psychological nursing group was higher than the music therapy group to some extent;The MRI detection time of routine nursing group was significantly longer than the other two groups (P <0.05; (3The one-time completion rate of the last two groups was significantly higher than the routine nursing  group (P <0.05, and music therapy group was significantly higher than that of the psychological intervention group.The adverse psychological reaction in Psychological intervention group was significantly decreased compared with routine nursing group; and music therapy group decreased significantly compared with the psychological  intervention  group (P <0.05; (4Although the anxiety / depression score of psychological  intervention  group increased slightly ,but it significantly lower than the usual care group (P <0.05; The anxiety / depression scores of music therapy group were significantly decreased, significantly lower than the other two groups (P <0.05. Conclusion: Psychological nursing combined with music therapy is a good way to eliminate the

  11. Increasing Genome Sampling and Improving SNP Genotyping for Genotyping-by-Sequencing with New Combinations of Restriction Enzymes.

    Science.gov (United States)

    Fu, Yong-Bi; Peterson, Gregory W; Dong, Yibo

    2016-04-07

    Genotyping-by-sequencing (GBS) has emerged as a useful genomic approach for exploring genome-wide genetic variation. However, GBS commonly samples a genome unevenly and can generate a substantial amount of missing data. These technical features would limit the power of various GBS-based genetic and genomic analyses. Here we present software called IgCoverage for in silico evaluation of genomic coverage through GBS with an individual or pair of restriction enzymes on one sequenced genome, and report a new set of 21 restriction enzyme combinations that can be applied to enhance GBS applications. These enzyme combinations were developed through an application of IgCoverage on 22 plant, animal, and fungus species with sequenced genomes, and some of them were empirically evaluated with different runs of Illumina MiSeq sequencing in 12 plant species. The in silico analysis of 22 organisms revealed up to eight times more genome coverage for the new combinations consisted of pairing four- or five-cutter restriction enzymes than the commonly used enzyme combination PstI + MspI. The empirical evaluation of the new enzyme combination (HinfI + HpyCH4IV) in 12 plant species showed 1.7-6 times more genome coverage than PstI + MspI, and 2.3 times more genome coverage in dicots than monocots. Also, the SNP genotyping in 12 Arabidopsis and 12 rice plants revealed that HinfI + HpyCH4IV generated 7 and 1.3 times more SNPs (with 0-16.7% missing observations) than PstI + MspI, respectively. These findings demonstrate that these novel enzyme combinations can be utilized to increase genome sampling and improve SNP genotyping in various GBS applications. Copyright © 2016 Fu et al.

  12. Increasing Genome Sampling and Improving SNP Genotyping for Genotyping-by-Sequencing with New Combinations of Restriction Enzymes

    Directory of Open Access Journals (Sweden)

    Yong-Bi Fu

    2016-04-01

    Full Text Available Genotyping-by-sequencing (GBS has emerged as a useful genomic approach for exploring genome-wide genetic variation. However, GBS commonly samples a genome unevenly and can generate a substantial amount of missing data. These technical features would limit the power of various GBS-based genetic and genomic analyses. Here we present software called IgCoverage for in silico evaluation of genomic coverage through GBS with an individual or pair of restriction enzymes on one sequenced genome, and report a new set of 21 restriction enzyme combinations that can be applied to enhance GBS applications. These enzyme combinations were developed through an application of IgCoverage on 22 plant, animal, and fungus species with sequenced genomes, and some of them were empirically evaluated with different runs of Illumina MiSeq sequencing in 12 plant species. The in silico analysis of 22 organisms revealed up to eight times more genome coverage for the new combinations consisted of pairing four- or five-cutter restriction enzymes than the commonly used enzyme combination PstI + MspI. The empirical evaluation of the new enzyme combination (HinfI + HpyCH4IV in 12 plant species showed 1.7–6 times more genome coverage than PstI + MspI, and 2.3 times more genome coverage in dicots than monocots. Also, the SNP genotyping in 12 Arabidopsis and 12 rice plants revealed that HinfI + HpyCH4IV generated 7 and 1.3 times more SNPs (with 0–16.7% missing observations than PstI + MspI, respectively. These findings demonstrate that these novel enzyme combinations can be utilized to increase genome sampling and improve SNP genotyping in various GBS applications.

  13. Genome-Wide Association Scan Shows Genetic Variants in the FTO Gene Are Associated with Obesity-Related Traits

    Science.gov (United States)

    Chen, Wei-Min; Uda, Manuela; Albai, Giuseppe; Strait, James; Najjar, Samer; Nagaraja, Ramaiah; Orrú, Marco; Usala, Gianluca; Dei, Mariano; Lai, Sandra; Maschio, Andrea; Busonero, Fabio; Mulas, Antonella; Ehret, Georg B; Fink, Ashley A; Weder, Alan B; Cooper, Richard S; Galan, Pilar; Chakravarti, Aravinda; Schlessinger, David; Cao, Antonio; Lakatta, Edward; Abecasis, Gonçalo R

    2007-01-01

    The obesity epidemic is responsible for a substantial economic burden in developed countries and is a major risk factor for type 2 diabetes and cardiovascular disease. The disease is the result not only of several environmental risk factors, but also of genetic predisposition. To take advantage of recent advances in gene-mapping technology, we executed a genome-wide association scan to identify genetic variants associated with obesity-related quantitative traits in the genetically isolated population of Sardinia. Initial analysis suggested that several SNPs in the FTO and PFKP genes were associated with increased BMI, hip circumference, and weight. Within the FTO gene, rs9930506 showed the strongest association with BMI (p = 8.6 ×10− 7), hip circumference (p = 3.4 × 10− 8), and weight (p = 9.1 × 10− 7). In Sardinia, homozygotes for the rare “G” allele of this SNP (minor allele frequency = 0.46) were 1.3 BMI units heavier than homozygotes for the common “A” allele. Within the PFKP gene, rs6602024 showed very strong association with BMI (p = 4.9 × 10− 6). Homozygotes for the rare “A” allele of this SNP (minor allele frequency = 0.12) were 1.8 BMI units heavier than homozygotes for the common “G” allele. To replicate our findings, we genotyped these two SNPs in the GenNet study. In European Americans (N = 1,496) and in Hispanic Americans (N = 839), we replicated significant association between rs9930506 in the FTO gene and BMI (p-value for meta-analysis of European American and Hispanic American follow-up samples, p = 0.001), weight (p = 0.001), and hip circumference (p = 0.0005). We did not replicate association between rs6602024 and obesity-related traits in the GenNet sample, although we found that in European Americans, Hispanic Americans, and African Americans, homozygotes for the rare “A” allele were, on average, 1.0–3.0 BMI units heavier than homozygotes for the more common “G” allele. In summary, we have completed a whole

  14. AFLP genome scan in the black rat (Rattus rattus) from Madagascar: detecting genetic markers undergoing plague-mediated selection.

    Science.gov (United States)

    Tollenaere, C; Duplantier, J-M; Rahalison, L; Ranjalahy, M; Brouat, C

    2011-03-01

    The black rat (Rattus rattus) is the main reservoir of plague (Yersinia pestis infection) in Madagascar's rural zones. Black rats are highly resistant to plague within the plague focus (central highland), whereas they are susceptible where the disease is absent (low altitude zone). To better understand plague wildlife circulation and host evolution in response to a highly virulent pathogen, we attempted to determine genetic markers associated with plague resistance in this species. To this purpose, we combined a population genomics approach and an association study, both performed on 249 AFLP markers, in Malagasy R. rattus. Simulated distributions of genetic differentiation were compared to observed data in four independent pairs, each consisting of one population from the plague focus and one from the plague-free zone. We found 22 loci (9% of 249) with higher differentiation in at least two independent population pairs or with combining P-values over the four pairs significant. Among the 22 outlier loci, 16 presented significant association with plague zone (plague focus vs. plague-free zone). Population genetic structure inferred from outlier loci was structured by plague zone, whereas the neutral loci dataset revealed structure by geography (eastern vs. western populations). A phenotype association study revealed that two of the 22 loci were significantly associated with differentiation between dying and surviving rats following experimental plague challenge. The 22 outlier loci identified in this study may undergo plague selective pressure either directly or more probably indirectly due to hitchhiking with selected loci. © 2010 Blackwell Publishing Ltd.

  15. glbase: a framework for combining, analyzing and displaying heterogeneous genomic and high-throughput sequencing data

    Directory of Open Access Journals (Sweden)

    Andrew Paul Hutchins

    2014-01-01

    Full Text Available Genomic datasets and the tools to analyze them have proliferated at an astonishing rate. However, such tools are often poorly integrated with each other: each program typically produces its own custom output in a variety of non-standard file formats. Here we present glbase, a framework that uses a flexible set of descriptors that can quickly parse non-binary data files. glbase includes many functions to intersect two lists of data, including operations on genomic interval data and support for the efficient random access to huge genomic data files. Many glbase functions can produce graphical outputs, including scatter plots, heatmaps, boxplots and other common analytical displays of high-throughput data such as RNA-seq, ChIP-seq and microarray expression data. glbase is designed to rapidly bring biological data into a Python-based analytical environment to facilitate analysis and data processing. In summary, glbase is a flexible and multifunctional toolkit that allows the combination and analysis of high-throughput data (especially next-generation sequencing and genome-wide data, and which has been instrumental in the analysis of complex data sets. glbase is freely available at http://bitbucket.org/oaxiom/glbase/.

  16. Combining operando synchrotron X-ray tomographic microscopy and scanning X-ray diffraction to study lithium ion batteries

    Science.gov (United States)

    Pietsch, Patrick; Hess, Michael; Ludwig, Wolfgang; Eller, Jens; Wood, Vanessa

    2016-06-01

    We present an operando study of a lithium ion battery combining scanning X-ray diffraction (SXRD) and synchrotron radiation X-ray tomographic microscopy (SRXTM) simultaneously for the first time. This combination of techniques facilitates the investigation of dynamic processes in lithium ion batteries containing amorphous and/or weakly attenuating active materials. While amorphous materials pose a challenge for diffraction techniques, weakly attenuating material systems pose a challenge for attenuation-contrast tomography. Furthermore, combining SXRD and SRXTM can be used to correlate processes occurring at the atomic level in the crystal lattices of the active materials with those at the scale of electrode microstructure. To demonstrate the benefits of this approach, we investigate a silicon powder electrode in lithium metal half-cell configuration. Combining SXRD and SRXTM, we are able to (i) quantify the dissolution of the metallic lithium electrode and the expansion of the silicon electrode, (ii) better understand the formation of the Li15Si4 phase, and (iii) non-invasively probe kinetic limitations within the silicon electrode. A simple model based on the 1D diffusion equation allows us to qualitatively understand the observed kinetics and demonstrates why high-capacity electrodes are more prone to inhomogeneous lithiation reactions.

  17. Evaluation of the genetic overlap between osteoarthritis with body mass index and height using genome-wide association scan data

    Science.gov (United States)

    Elliott, Katherine S; Chapman, Kay; Day-Williams, Aaron; Panoutsopoulou, Kalliope; Southam, Lorraine; Lindgren, Cecilia M; Arden, Nigel; Aslam, Nadim; Birrell, Fraser; Carluke, Ian; Carr, Andrew; Deloukas, Panos; Doherty, Michael; Loughlin, John; McCaskie, Andrew; Ollier, William E R; Rai, Ashok; Ralston, Stuart; Reed, Mike R; Spector, Timothy D; Valdes, Ana M; Wallis, Gillian A; Wilkinson, Mark; Zeggini, Eleftheria

    2013-01-01

    Objectives Obesity as measured by body mass index (BMI) is one of the major risk factors for osteoarthritis. In addition, genetic overlap has been reported between osteoarthritis and normal adult height variation. We investigated whether this relationship is due to a shared genetic aetiology on a genome-wide scale. Methods We compared genetic association summary statistics (effect size, p value) for BMI and height from the GIANT consortium genome-wide association study (GWAS) with genetic association summary statistics from the arcOGEN consortium osteoarthritis GWAS. Significance was evaluated by permutation. Replication of osteoarthritis association of the highlighted signals was investigated in an independent dataset. Phenotypic information of height and BMI was accounted for in a separate analysis using osteoarthritis-free controls. Results We found significant overlap between osteoarthritis and height (p=3.3×10−5 for signals with p≤0.05) when the GIANT and arcOGEN GWAS were compared. For signals with p≤0.001 we found 17 shared signals between osteoarthritis and height and four between osteoarthritis and BMI. However, only one of the height or BMI signals that had shown evidence of association with osteoarthritis in the arcOGEN GWAS was also associated with osteoarthritis in the independent dataset: rs12149832, within the FTO gene (combined p=2.3×10−5). As expected, this signal was attenuated when we adjusted for BMI. Conclusions We found a significant excess of shared signals between both osteoarthritis and height and osteoarthritis and BMI, suggestive of a common genetic aetiology. However, only one signal showed association with osteoarthritis when followed up in a new dataset. PMID:22956599

  18. Genome-wide association of lipid-lowering response to statins in combined study populations.

    Directory of Open Access Journals (Sweden)

    Mathew J Barber

    2010-03-01

    Full Text Available Statins effectively lower total and plasma LDL-cholesterol, but the magnitude of decrease varies among individuals. To identify single nucleotide polymorphisms (SNPs contributing to this variation, we performed a combined analysis of genome-wide association (GWA results from three trials of statin efficacy.Bayesian and standard frequentist association analyses were performed on untreated and statin-mediated changes in LDL-cholesterol, total cholesterol, HDL-cholesterol, and triglyceride on a total of 3932 subjects using data from three studies: Cholesterol and Pharmacogenetics (40 mg/day simvastatin, 6 weeks, Pravastatin/Inflammation CRP Evaluation (40 mg/day pravastatin, 24 weeks, and Treating to New Targets (10 mg/day atorvastatin, 8 weeks. Genotype imputation was used to maximize genomic coverage and to combine information across studies. Phenotypes were normalized within each study to account for systematic differences among studies, and fixed-effects combined analysis of the combined sample were performed to detect consistent effects across studies. Two SNP associations were assessed as having posterior probability greater than 50%, indicating that they were more likely than not to be genuinely associated with statin-mediated lipid response. SNP rs8014194, located within the CLMN gene on chromosome 14, was strongly associated with statin-mediated change in total cholesterol with an 84% probability by Bayesian analysis, and a p-value exceeding conventional levels of genome-wide significance by frequentist analysis (P = 1.8 x 10(-8. This SNP was less significantly associated with change in LDL-cholesterol (posterior probability = 0.16, P = 4.0 x 10(-6. Bayesian analysis also assigned a 51% probability that rs4420638, located in APOC1 and near APOE, was associated with change in LDL-cholesterol.Using combined GWA analysis from three clinical trials involving nearly 4,000 individuals treated with simvastatin, pravastatin, or atorvastatin, we

  19. Reproductive technologies combine well with genomic selection in dairy breeding programs.

    Science.gov (United States)

    Thomasen, J R; Willam, A; Egger-Danner, C; Sørensen, A C

    2016-02-01

    The objective of the present study was to examine whether genomic selection of females interacts with the use of reproductive technologies (RT) to increase annual monetary genetic gain (AMGG). This was tested using a factorial design with 3 factors: genomic selection of females (0 or 2,000 genotyped heifers per year), RT (0 or 50 donors selected at 14 mo of age for producing 10 offspring), and 2 reliabilities of genomic prediction. In addition, different strategies for use of RT and how strategies interact with the reliability of genomic prediction were investigated using stochastic simulation by varying (1) number of donors (25, 50, 100, 200), (2) number of calves born per donor (10 or 20), (3) age of donor (2 or 14 mo), and (4) number of sires (25, 50, 100, 200). In total, 72 different breeding schemes were investigated. The profitability of the different breeding strategies was evaluated by deterministic simulation by varying the costs of a born calf with reproductive technologies at levels of €500, €1,000, and €1,500. The results confirm our hypothesis that combining genomic selection of females with use of RT increases AMGG more than in a reference scheme without genomic selection in females. When the reliability of genomic prediction is high, the effect on rate of inbreeding (ΔF) is small. The study also demonstrates favorable interaction effects between the components of the breeder's equation (selection intensity, selection accuracy, generation interval) for the bull dam donor path, leading to higher AMGG. Increasing the donor program and number of born calves to achieve higher AMGG is associated with the undesirable effect of increased ΔF. This can be alleviated, however, by increasing the numbers of sires without compromising AMGG remarkably. For the major part of the investigated donor schemes, the investment in RT is profitable in dairy cattle populations, even at high levels of costs for RT. Copyright © 2016 American Dairy Science Association

  20. A new approach for heparin standardization: combination of scanning UV spectroscopy, nuclear magnetic resonance and principal component analysis.

    Directory of Open Access Journals (Sweden)

    Marcelo A Lima

    Full Text Available The year 2007 was marked by widespread adverse clinical responses to heparin use, leading to a global recall of potentially affected heparin batches in 2008. Several analytical methods have since been developed to detect impurities in heparin preparations; however, many are costly and dependent on instrumentation with only limited accessibility. A method based on a simple UV-scanning assay, combined with principal component analysis (PCA, was developed to detect impurities, such as glycosaminoglycans, other complex polysaccharides and aromatic compounds, in heparin preparations. Results were confirmed by NMR spectroscopy. This approach provides an additional, sensitive tool to determine heparin purity and safety, even when NMR spectroscopy failed, requiring only standard laboratory equipment and computing facilities.

  1. Combined neural network/Phillips-Tikhonov approach to aerosol retrievals over land from the NASA Research Scanning Polarimeter

    Science.gov (United States)

    Di Noia, Antonio; Hasekamp, Otto P.; Wu, Lianghai; van Diedenhoven, Bastiaan; Cairns, Brian; Yorks, John E.

    2017-11-01

    In this paper, an algorithm for the retrieval of aerosol and land surface properties from airborne spectropolarimetric measurements - combining neural networks and an iterative scheme based on Phillips-Tikhonov regularization - is described. The algorithm - which is an extension of a scheme previously designed for ground-based retrievals - is applied to measurements from the Research Scanning Polarimeter (RSP) on board the NASA ER-2 aircraft. A neural network, trained on a large data set of synthetic measurements, is applied to perform aerosol retrievals from real RSP data, and the neural network retrievals are subsequently used as a first guess for the Phillips-Tikhonov retrieval. The resulting algorithm appears capable of accurately retrieving aerosol optical thickness, fine-mode effective radius and aerosol layer height from RSP data. Among the advantages of using a neural network as initial guess for an iterative algorithm are a decrease in processing time and an increase in the number of converging retrievals.

  2. Effect of the combination of sodium hypochlorite and chlorhexidine on dentinal permeability and scanning electron microscopy precipitate observation.

    Science.gov (United States)

    Akisue, Eduardo; Tomita, Viviane S; Gavini, Giulio; Poli de Figueiredo, Jose Antonio

    2010-05-01

    This study compared the combined use of sodium hypochlorite (NaOCl) and chlorhexidine (CXH) with citric acid and CXH on dentinal permeability and precipitate formation. Thirty-four upper anterior teeth were prepared by rotary instrumentation and NaOCl. The root canal surfaces were conditioned for smear layer removal using 15% citric acid solution under ultrasonic activation and a final wash with distilled water. All teeth were dried, and 30 specimens were randomly divided into three equal groups as follows: positive control group (PC), no irrigation; 15% citric acid + 2% CHX group (CA + CHX); and 1% NaOCl + 2% CHX group (NaOCl + CHX). All roots were immersed in a 0.2% Rhodamine B solution for 24 hours. One-millimeter-thick slices from the cementum-enamel junction were scanned at 400 dpi and analyzed using the software ImageLab (LIDO-USP, Sao Paulo, Brazil) for the assessment of leakage in percentage. For scanning electron microscopy analysis, four teeth, irrigated for NaOCl + CHX samples, were split in half, and each third was evaluated at 1,000x and 5,000x (at the precipitate). Using the analysis of variance test followed by the Bonferroni comparison method, no statistical differences between groups were found when analyzed at the cervical and medium thirds. At the apical third, differences between the PC and NaOCl + CHX (p < 0.05) and CA + CHX and NaOCl + CHX could be seen (p < 0.05). The combination of 1% NaOCl and 2% CHX solutions results in the formation of a flocculate precipitate that acts as a chemical smear layer reducing the dentinal permeability in the apical third. Copyright (c) 2010 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  3. Homogeneity study of proton and carbon ion scanning beams using combinations of different spot sizes and grid sizes.

    Science.gov (United States)

    Xing, Ying; Wu, Xianwei; Li, Yongqiang; Zhao, Jun

    2017-09-08

    Different scanning ion beam delivery systems have different delivery accuracies, and the resulting delivery errors will affect field homogeneity. This study was performed to determine an appropriate combination of spot size (FWHM) and spot grid size (GS), which can provide homogenous dose distributions for both proton and carbon ion scanning beam radiotherapy. The combination of the two parameters is represented by a combination factor named n, which is the quotient of FWHM divided by GS. Delivery uncertainties of our beam delivery system were analyzed using log files from the treatment of 28 patients. Square fields for different n values were simulated with and without considering the delivery uncertainties, and the homogeneity of these square fields was analyzed. All spots were located on a rectilinear grid with equal spacing in the x and y directions. In addition to the simulations, we performed experimental measurements using both protons and carbon ions. We selected six energy levels for both proton and carbon ions. For each energy level, we created six square field plans with different n values (1, 1.5, 2, 2.5, 3, 3.5). These plans were delivered and the field homogeneity was determined using a film measurement. The simulations demonstrated that under ideal condition (i.e., the delivery system has no delivery errors), the homogeneity is within 3% when n ≥ 1.1. When delivery uncertainties were included in the simulation, the homogeneity is within 3% when n ≥ 2.3. For film measurements, homogeneity under 3% was achieved when n ≥ 2.5. A practical method to determine the appropriate combination of spot size and grid size is here presented. Considering the uncertainties of the beam delivery system, an n value of 2.5 is good enough to meet the lateral homogeneity requests in our center. The methods used here can be easily repeated in other particle therapy centers. © 2017 American Association of Physicists in Medicine.

  4. Combining Chromosomal Arm Status and Significantly Aberrant Genomic Locations Reveals New Cancer Subtypes

    Directory of Open Access Journals (Sweden)

    Tal Shay

    2009-01-01

    Full Text Available Many types of tumors exhibit characteristic chromosomal losses or gains, as well as local amplifications and deletions. Within any given tumor type, sample specific amplifications and deletions are also observed. Typically, a region that is aberrant in more tumors, or whose copy number change is stronger, would be considered as a more promising candidate to be biologically relevant to cancer. We sought for an intuitive method to define such aberrations and prioritize them. We define V, the “volume” associated with an aberration, as the product of three factors: (a fraction of patients with the aberration, (b the aberration’s length and (c its amplitude. Our algorithm compares the values of V derived from the real data to a null distribution obtained by permutations, and yields the statistical significance (p-value of the measured value of V. We detected genetic locations that were significantly aberrant, and combine them with chromosomal arm status (gain/loss to create a succinct fingerprint of the tumor genome. This genomic fingerprint is used to visualize the tumors, highlighting events that are co-occurring or mutually exclusive. We apply the method on three different public array CGH datasets of Medulloblastoma and Neuroblastoma, and demonstrate its ability to detect chromosomal regions that were known to be altered in the tested cancer types, as well as to suggest new genomic locations to be tested. We identified a potential new subtype of Medulloblastoma, which is analogous to Neuroblastoma type 1.

  5. Combining airborne laser scanning and Landsat data for statistical modeling of soil carbon and tree biomass in Tanzanian Miombo woodlands.

    Science.gov (United States)

    Egberth, Mikael; Nyberg, Gert; Næsset, Erik; Gobakken, Terje; Mauya, Ernest; Malimbwi, Rogers; Katani, Josiah; Chamuya, Nurudin; Bulenga, George; Olsson, Håkan

    2017-12-01

    Soil carbon and biomass depletion can be used to identify and quantify degraded soils, and by using remote sensing, there is potential to map soil conditions over large areas. Landsat 8 Operational Land Imager satellite data and airborne laser scanning data were evaluated separately and in combination for modeling soil organic carbon, above ground tree biomass and below ground tree biomass. The test site is situated in the Liwale district in southeastern Tanzania and is dominated by Miombo woodlands. Tree data from 15 m radius field-surveyed plots and samples of soil carbon down to a depth of 30 cm were used as reference data for tree biomass and soil carbon estimations. Cross-validated plot level error (RMSE) for predicting soil organic carbon was 28% using only Landsat 8, 26% using laser only, and 23% for the combination of the two. The plot level error for above ground tree biomass was 66% when using only Landsat 8, 50% for laser and 49% for the combination of Landsat 8 and laser data. Results for below ground tree biomass were similar to above ground biomass. Additionally it was found that an early dry season satellite image was preferable for modelling biomass while images from later in the dry season were better for modelling soil carbon. The results show that laser data is superior to Landsat 8 when predicting both soil carbon and biomass above and below ground in landscapes dominated by Miombo woodlands. Furthermore, the combination of laser data and Landsat data were marginally better than using laser data only.

  6. Genomic comparison of Yersinia pestis and Yersinia pseudotuberculosis by combination of suppression subtractive hybridization and DNA microarray

    DEFF Research Database (Denmark)

    Wang, Xiaoyi; Zhou, Dongsheng; Qin, Long

    2006-01-01

    a combination of suppression subtractive hybridization (SSH) and comparative genomic hybridization with DNAs from a diverse panel of Y. pestis and Y. pseudotuberculosis strains. SSH followed by BLAST analysis revealed 112 SSH fragments specific to strain ATCC29833, compared to the genomic sequence data of Y....... pestis strains CO92, KIM and 91001. We identified 17 SSH fragments that appeared to be newly determined genetic contents of Y. pseudotuberculosis. The combination of SSH and microarray analysis showed that the parallel loss of genes contributed greatly not only to the significant genomic divergence...

  7. A genome-wide association scan on the levels of markers of inflammation in Sardinians reveals associations that underpin its complex regulation.

    Directory of Open Access Journals (Sweden)

    Silvia Naitza

    2012-01-01

    Full Text Available Identifying the genes that influence levels of pro-inflammatory molecules can help to elucidate the mechanisms underlying this process. We first conducted a two-stage genome-wide association scan (GWAS for the key inflammatory biomarkers Interleukin-6 (IL-6, the general measure of inflammation erythrocyte sedimentation rate (ESR, monocyte chemotactic protein-1 (MCP-1, and high-sensitivity C-reactive protein (hsCRP in a large cohort of individuals from the founder population of Sardinia. By analysing 731,213 autosomal or X chromosome SNPs and an additional ∼1.9 million imputed variants in 4,694 individuals, we identified several SNPs associated with the selected quantitative trait loci (QTLs and replicated all the top signals in an independent sample of 1,392 individuals from the same population. Next, to increase power to detect and resolve associations, we further genotyped the whole cohort (6,145 individuals for 293,875 variants included on the ImmunoChip and MetaboChip custom arrays. Overall, our combined approach led to the identification of 9 genome-wide significant novel independent signals-5 of which were identified only with the custom arrays-and provided confirmatory evidence for an additional 7. Novel signals include: for IL-6, in the ABO gene (rs657152, p = 2.13×10(-29; for ESR, at the HBB (rs4910472, p = 2.31×10(-11 and UCN119B/SPPL3 (rs11829037, p = 8.91×10(-10 loci; for MCP-1, near its receptor CCR2 (rs17141006, p = 7.53×10(-13 and in CADM3 (rs3026968, p = 7.63×10(-13; for hsCRP, within the CRP gene (rs3093077, p = 5.73×10(-21, near DARC (rs3845624, p = 1.43×10(-10, UNC119B/SPPL3 (rs11829037, p = 1.50×10(-14, and ICOSLG/AIRE (rs113459440, p = 1.54×10(-08 loci. Confirmatory evidence was found for IL-6 in the IL-6R gene (rs4129267; for ESR at CR1 (rs12567990 and TMEM57 (rs10903129; for MCP-1 at DARC (rs12075; and for hsCRP at CRP (rs1205, HNF1A (rs225918, and APOC-I (rs4420638. Our

  8. Genome-wide linkage scan and association study of PARL to the expression of LHON families in Thailand.

    Science.gov (United States)

    Phasukkijwatana, Nopasak; Kunhapan, Bussaraporn; Stankovich, Jim; Chuenkongkaew, Wanicha L; Thomson, Russell; Thornton, Timothy; Bahlo, Melanie; Mushiroda, Taisei; Nakamura, Yusuke; Mahasirimongkol, Surakameth; Tun, Aung Win; Srisawat, Chatchawan; Limwongse, Chanin; Peerapittayamongkol, Chayanon; Sura, Thanyachai; Suthammarak, Wichit; Lertrit, Patcharee

    2010-07-01

    Leber hereditary optic neuropathy (LHON) is the most common mitochondrially inherited disease causing blindness, preferentially in young adult males. Most of the patients carry the G11778A mitochondrial DNA (mtDNA) mutation. However, the marked incomplete penetrance and the gender bias indicate some additional genetic and/or environmental factors to disease expression. Herein, we first conducted a genome-wide linkage scan with 400 microsatellite markers in 9 large Thai LHON G11778A pedigrees. Using an affecteds-only nonparametric linkage analysis, 4 regions on chromosomes 3, 12, 13 and 18 showed Zlr scores greater than 2 (P 2 in 10 of 16 allele sharing models tested) was then expanded to include the region 3q26.2-3q28 covering SLC7A14 (3q26.2), MFN1 (3q26.32), MRPL47 (3q26.33), MCCC1 (3q27.1), PARL (3q27.1) and OPA1 (3q28-q29). All of these candidate genes were selected from the Maestro database and had known to be localized in mitochondria. Sixty tag SNPs were genotyped in 86 cases, 211 of their relatives and 32 unrelated Thai controls, by multiplex-PCR-based Invader assay. Analyses using a powerful association testing tool that adjusts for relatedness (the M(QLS) statistic) showed the most evidence of association between two SNPs, rs3749446 and rs1402000 (located in PARL presenilins-associated rhomboid-like) and LHON expression (both P = 8.8 x 10(-5)). The mitochondrial PARL protease has been recently known to play a role with a dynamin-related OPA1 protein in preventing apoptotic events by slowing down the release of cytochrome c out of mitochondrial cristae junctions. Moreover, PARL is required to activate the intramembranous proteolyses resulting in the degradation of an accumulated pro-apoptotic protein in the outer mitochondrial membrane. Under these circumstances, variants of PARL are suggested to influence cell death by apoptosis which has long been believed to intrigue the neurodegeneration of LHON.

  9. Insight into the Recent Genome Duplication of the Halophilic Yeast Hortaea werneckii: Combining an Improved Genome with Gene Expression and Chromatin Structure

    Directory of Open Access Journals (Sweden)

    Sunita Sinha

    2017-07-01

    Full Text Available Extremophilic organisms demonstrate the flexibility and adaptability of basic biological processes by highlighting how cell physiology adapts to environmental extremes. Few eukaryotic extremophiles have been well studied and only a small number are amenable to laboratory cultivation and manipulation. A detailed characterization of the genome architecture of such organisms is important to illuminate how they adapt to environmental stresses. One excellent example of a fungal extremophile is the halophile Hortaea werneckii (Pezizomycotina, Dothideomycetes, Capnodiales, a yeast-like fungus able to thrive at near-saturating concentrations of sodium chloride and which is also tolerant to both UV irradiation and desiccation. Given its unique lifestyle and its remarkably recent whole genome duplication, H. werneckii provides opportunities for testing the role of genome duplications and adaptability to extreme environments. We previously assembled the genome of H. werneckii using short-read sequencing technology and found a remarkable degree of gene duplication. Technology limitations, however, precluded high-confidence annotation of the entire genome. We therefore revisited the H. wernickii genome using long-read, single-molecule sequencing and provide an improved genome assembly which, combined with transcriptome and nucleosome analysis, provides a useful resource for fungal halophile genomics. Remarkably, the ∼50 Mb H. wernickii genome contains 15,974 genes of which 95% (7608 are duplicates formed by a recent whole genome duplication (WGD, with an average of 5% protein sequence divergence between them. We found that the WGD is extraordinarily recent, and compared to Saccharomyces cerevisiae, the majority of the genome’s ohnologs have not diverged at the level of gene expression of chromatin structure.

  10. Segmenting the thoracic, abdominal and pelvic musculature on CT scans combining atlas-based model and active contour model

    Science.gov (United States)

    Zhang, Weidong; Liu, Jiamin; Yao, Jianhua; Summers, Ronald M.

    2013-03-01

    Segmentation of the musculature is very important for accurate organ segmentation, analysis of body composition, and localization of tumors in the muscle. In research fields of computer assisted surgery and computer-aided diagnosis (CAD), muscle segmentation in CT images is a necessary pre-processing step. This task is particularly challenging due to the large variability in muscle structure and the overlap in intensity between muscle and internal organs. This problem has not been solved completely, especially for all of thoracic, abdominal and pelvic regions. We propose an automated system to segment the musculature on CT scans. The method combines an atlas-based model, an active contour model and prior segmentation of fat and bones. First, body contour, fat and bones are segmented using existing methods. Second, atlas-based models are pre-defined using anatomic knowledge at multiple key positions in the body to handle the large variability in muscle shape. Third, the atlas model is refined using active contour models (ACM) that are constrained using the pre-segmented bone and fat. Before refining using ACM, the initialized atlas model of next slice is updated using previous atlas. The muscle is segmented using threshold and smoothed in 3D volume space. Thoracic, abdominal and pelvic CT scans were used to evaluate our method, and five key position slices for each case were selected and manually labeled as the reference. Compared with the reference ground truth, the overlap ratio of true positives is 91.1%+/-3.5%, and that of false positives is 5.5%+/-4.2%.

  11. Family-based genome scan for age at onset of late-onset Alzheimer's disease in whole exome sequencing data.

    Science.gov (United States)

    Saad, M; Brkanac, Z; Wijsman, E M

    2015-11-01

    Alzheimer's disease (AD) is a common and complex neurodegenerative disease. Age at onset (AAO) of AD is an important component phenotype with a genetic basis, and identification of genes in which variation affects AAO would contribute to identification of factors that affect timing of onset. Increase in AAO through prevention or therapeutic measures would have enormous benefits by delaying AD and its associated morbidities. In this paper, we performed a family-based genome-wide association study for AAO of late-onset AD in whole exome sequence data generated in multigenerational families with multiple AD cases. We conducted single marker and gene-based burden tests for common and rare variants, respectively. We combined association analyses with variance component linkage analysis, and with reference to prior studies, in order to enhance evidence of the identified genes. For variants and genes implicated by the association study, we performed a gene-set enrichment analysis to identify potential novel pathways associated with AAO of AD. We found statistically significant association with AAO for three genes (WRN, NTN4 and LAMC3) with common associated variants, and for four genes (SLC8A3, SLC19A3, MADD and LRRK2) with multiple rare-associated variants that have a plausible biological function related to AD. The genes we have identified are in pathways that are strong candidates for involvement in the development of AD pathology and may lead to a better understanding of AD pathogenesis. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  12. Enhanced phase contrast transfer using ptychography combined with a pre-specimen phase plate in a scanning transmission electron microscope

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Hao; Ercius, Peter [Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Nellist, Peter D. [Department of Materials, University of Oxford, Parks Road, Oxford OX1 3PH (United Kingdom); Ophus, Colin, E-mail: clophus@lbl.gov [Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States)

    2016-12-15

    The ability to image light elements in both crystalline and noncrystalline materials at near atomic resolution with an enhanced contrast is highly advantageous to understand the structure and properties of a wide range of beam sensitive materials including biological specimens and molecular hetero-structures. This requires the imaging system to have an efficient phase contrast transfer at both low and high spatial frequencies. In this work we introduce a new phase contrast imaging method in a scanning transmission electron microscope (STEM) using a pre-specimen phase plate in the probe forming aperture, combined with a fast pixelated detector to record diffraction patterns at every probe position, and phase reconstruction using ptychography. The phase plate significantly enhances the contrast transfer of low spatial frequency information, and ptychography maximizes the extraction of the phase information at all spatial frequencies. In addition, the STEM probe with the presence of the phase plate retains its atomic resolution, allowing simultaneous incoherent Z-contrast imaging to be obtained along with the ptychographic phase image. An experimental image of Au nanoparticles on a carbon support shows high contrast for both materials. Multislice image simulations of a DNA molecule shows the capability of imaging soft matter at low dose conditions, which implies potential applications of low dose imaging of a wide range of beam sensitive materials. - Highlights: • This work demonstrates a phase contrast imaging method by combining a pre-specimen phase plate with ptychogrpahy. • This method is shown to have a high phase contrast transfer efficiency at both low and high spatial frequencies. • Unlike CTEM which uses a heavy defocus to gain contrast, the phase plate gives a linear phase contrast at zero defocus aberrations. • Image simulations of DNA suggest this method is highly attractive for imaging beam sensitive materials at a low dose.

  13. A Bayesian geostatistical estimation of biomass in semi-arid rangelands by combining airborne and terrestrial laser scanning data

    Science.gov (United States)

    Li, A.; Glenn, N. F.

    2012-12-01

    Biomass of vegetation is critical for carbon cycle research. Estimating biomass from field survey data is laborious and/or destructive and thus retrieving biomass from remote sensing data may be advantageous. Most remote sensing biomass studies have focused on forest ecosystems, while few have focused on low stature vegetation, such as grasses in semi-arid environments. Biomass estimates for grass are significant for studying wildlife habitat, assessing fuel loads, and studying climate change response in semi-arid regions. Recent research has demonstrated the ability of small footprint airborne laser scanning (ALS) data to extract sagebrush height characteristics and the ability of terrestrial laser scanning (TLS) data to estimate vegetation volume over semi-arid rangelands. ALS has somewhat lower resolution than TLS, but has improved spatial coverage over TLS. Combining ALS and TLS is a powerful tool to estimate biomass on regional scales. Bayesian geostatistics, also known as Bayesian Maximum Entropy (BME), can fuse multiple data sources across scales and provide estimation uncertainties for the integration of ALS and TLS data for grass biomass. Regression models are used to approximately delineate the relationship between field biomass measurements and TLS derived height and shape metrics. We then consider TLS plot-level data at the point scale with ALS data at the area scale. The regularization method is utilized to establish the scaling relations between TLS-derived and ALS-derived metrics. The metric maps from the ALS level are reconstructed using a BME method based on regularized variograms. We gain biomass and estimation uncertainty on the regional scale by introducing updated metrics into the model. In order to evaluate the effectiveness of the BME method, we develop simple independent regression models by assuming the TLS-derived metrics as ground reference data. Therefore, the regression model is used to correct the ALS-estimated values and we retrieve

  14. Brain PET scan

    Science.gov (United States)

    ... have false results on a PET scan. Blood sugar or insulin levels may affect the test results in people with diabetes . PET scans may be done along with a CT scan. This combination scan is called a PET/CT. Alternative Names Brain positron emission tomography; PET scan - brain References Chernecky ...

  15. Genome-wide scan of gastrointestinal nematode resistance in closed Angus population selected for minimized influence of MHC.

    Directory of Open Access Journals (Sweden)

    Eui-Soo Kim

    Full Text Available Genetic markers associated with parasite indicator traits are ideal targets for study of marker assisted selection aimed at controlling infections that reduce herd use of anthelminthics. For this study, we collected gastrointestinal (GI nematode fecal egg count (FEC data from post-weaning animals of an Angus resource population challenged to a 26 week natural exposure on pasture. In all, data from 487 animals was collected over a 16 year period between 1992 and 2007, most of which were selected for a specific DRB1 allele to reduce the influence of potential allelic variant effects of the MHC locus. A genome-wide association study (GWAS based on BovineSNP50 genotypes revealed six genomic regions located on bovine Chromosomes 3, 5, 8, 15 and 27; which were significantly associated (-log10 p=4.3 with Box-Cox transformed mean FEC (BC-MFEC. DAVID analysis of the genes within the significant genomic regions suggested a correlation between our results and annotation for genes involved in inflammatory response to infection. Furthermore, ROH and selection signature analyses provided strong evidence that the genomic regions associated BC-MFEC have not been affected by local autozygosity or recent experimental selection. These findings provide useful information for parasite resistance prediction for young grazing cattle and suggest new candidate gene targets for development of disease-modifying therapies or future studies of host response to GI parasite infection.

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2011-11-15

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

  18. Genome-wide scans of genetic variants for psychophysiological endophenotypes: introduction to this special issue of Psychophysiology.

    Science.gov (United States)

    Iacono, William G

    2014-12-01

    This special issue addresses the heritability and molecular genetic basis of 17 putative endophenotypes involving resting EEG power, P300 event-related potential amplitude, electrodermal orienting and habituation, antisaccade eye tracking, and affective modulation of the startle eye blink. These measures were collected from approximately 4,900 twins and parents who provided DNA samples through their participation in the Minnesota Twin Family Study. Included are papers that detail the methodology followed, genome-wide association analyses of single nucleotide polymorphisms and genes, analysis of rare variants in the human exome, and a whole genome sequencing study. Also included are 11 articles by leading experts in psychophysiology and genetics that provide perspective and commentary. A final integrative report summarizes findings and addresses issues raised. This introduction provides an overview of the aims and rationale behind these studies. Copyright © 2014 Society for Psychophysiological Research.

  19. Improved accuracy of genomic prediction for dry matter intake of dairy cattle from combined European and Australian data sets

    NARCIS (Netherlands)

    Haas, de Y.; Calus, M.P.L.; Veerkamp, R.F.; Wall, E.; Coffey, M.P.; Daetwyler, H.D.; Hayes, B.J.; Pryce, J.

    2012-01-01

    With the aim of increasing the accuracy of genomic estimated breeding values for dry matter intake (DMI) in dairy cattle, data from Australia (AU), the United Kingdom (UK), and the Netherlands (NL) were combined using both single-trait and multi-trait models. In total, DMI records were available on

  20. Genome-wide association scan identifies candidate polymorphisms associated with differential response to anti-TNF treatment in rheumatoid arthritis.

    OpenAIRE

    C Liu; Batliwalla, F.; W. Li; Van Der Lee, A.; Roubenoff, R.; Beckman, E.; Khalili, H; Damle, A.; Kern, M; Furie, R.; Dupuis, J.; Plenge, R..M.; Coenen, M.J.H.; Behrens, T W; Carulli, J.P.

    2008-01-01

    The prediction of response (or non-response) to anti-TNF treatment for rheumatoid arthritis (RA) is a pressing clinical problem. We conducted a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning anti-TNF therapy as part of Autoimmune Biomarkers Collaborative Network (ABCoN [Autoimmune Bio-markers Collaborative Network]) patient cohort. Response to therapy was determined by the change in Disease Activity Score (DAS28) ob...

  1. A combined analysis of genome-wide expression profiling of bipolar disorder in human prefrontal cortex.

    Science.gov (United States)

    Wang, Jinglu; Qu, Susu; Wang, Weixiao; Guo, Liyuan; Zhang, Kunlin; Chang, Suhua; Wang, Jing

    2016-11-01

    Numbers of gene expression profiling studies of bipolar disorder have been published. Besides different array chips and tissues, variety of the data processes in different cohorts aggravated the inconsistency of results of these genome-wide gene expression profiling studies. By searching the gene expression databases, we obtained six data sets for prefrontal cortex (PFC) of bipolar disorder with raw data and combinable platforms. We used standardized pre-processing and quality control procedures to analyze each data set separately and then combined them into a large gene expression matrix with 101 bipolar disorder subjects and 106 controls. A standard linear mixed-effects model was used to calculate the differentially expressed genes (DEGs). Multiple levels of sensitivity analyses and cross validation with genetic data were conducted. Functional and network analyses were carried out on basis of the DEGs. In the result, we identified 198 unique differentially expressed genes in the PFC of bipolar disorder and control. Among them, 115 DEGs were robust to at least three leave-one-out tests or different pre-processing methods; 51 DEGs were validated with genetic association signals. Pathway enrichment analysis showed these DEGs were related with regulation of neurological system, cell death and apoptosis, and several basic binding processes. Protein-protein interaction network further identified one key hub gene. We have contributed the most comprehensive integrated analysis of bipolar disorder expression profiling studies in PFC to date. The DEGs, especially those with multiple validations, may denote a common signature of bipolar disorder and contribute to the pathogenesis of disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Annotation of plant gene function via combined genomics, metabolomics and informatics.

    Science.gov (United States)

    Tohge, Takayuki; Fernie, Alisdair R

    2012-06-17

    Given the ever expanding number of model plant species for which complete genome sequences are available and the abundance of bio-resources such as knockout mutants, wild accessions and advanced breeding populations, there is a rising burden for gene functional annotation. In this protocol, annotation of plant gene function using combined co-expression gene analysis, metabolomics and informatics is provided (Figure 1). This approach is based on the theory of using target genes of known function to allow the identification of non-annotated genes likely to be involved in a certain metabolic process, with the identification of target compounds via metabolomics. Strategies are put forward for applying this information on populations generated by both forward and reverse genetics approaches in spite of none of these are effortless. By corollary this approach can also be used as an approach to characterise unknown peaks representing new or specific secondary metabolites in the limited tissues, plant species or stress treatment, which is currently the important trial to understanding plant metabolism.

  3. Combined endeavor of Neutrosophic Set and Chan-Vese model to extract accurate liver image from CT scan.

    Science.gov (United States)

    Siri, Sangeeta K; Latte, Mrityunjaya V

    2017-11-01

    Many different diseases can occur in the liver, including infections such as hepatitis, cirrhosis, cancer and over effect of medication or toxins. The foremost stage for computer-aided diagnosis of liver is the identification of liver region. Liver segmentation algorithms extract liver image from scan images which helps in virtual surgery simulation, speedup the diagnosis, accurate investigation and surgery planning. The existing liver segmentation algorithms try to extort exact liver image from abdominal Computed Tomography (CT) scan images. It is an open problem because of ambiguous boundaries, large variation in intensity distribution, variability of liver geometry from patient to patient and presence of noise. A novel approach is proposed to meet challenges in extracting the exact liver image from abdominal CT scan images. The proposed approach consists of three phases: (1) Pre-processing (2) CT scan image transformation to Neutrosophic Set (NS) and (3) Post-processing. In pre-processing, the noise is removed by median filter. The "new structure" is designed to transform a CT scan image into neutrosophic domain which is expressed using three membership subset: True subset (T), False subset (F) and Indeterminacy subset (I). This transform approximately extracts the liver image structure. In post processing phase, morphological operation is performed on indeterminacy subset (I) and apply Chan-Vese (C-V) model with detection of initial contour within liver without user intervention. This resulted in liver boundary identification with high accuracy. Experiments show that, the proposed method is effective, robust and comparable with existing algorithm for liver segmentation of CT scan images. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Atomic structure of screw dislocations intersecting the Au(111) surface: A combined scanning tunneling microscopy and molecular dynamics study

    DEFF Research Database (Denmark)

    Engbæk, Jakob; Schiøtz, Jakob; Dahl-Madsen, Bjarke

    2006-01-01

    The atomic-scale structure of naturally occurring screw dislocations intersecting a Au(111) surface has been investigated both experimentally by scanning tunneling microscopy (STM) and theoretically using molecular dynamics (MD) simulations. The step profiles of 166 dislocations were measured using...

  5. Combined use of fine-needle aspiration biopsy, MIBI scans and frozen section biopsy offers the best diagnostic accuracy in the assessment of the hypofunctioning solitary thyroid nodule

    Energy Technology Data Exchange (ETDEWEB)

    Hurtado-Lopez, Luis Mauricio; Arellano-Montano, Sara; Torres-Acosta, Evelyn Migdalia; Zaldivar-Ramirez, Felipe Rafael; Duarte-Torres, Reyna Margarita; Alonso-de-Ruiz, Patricia; Martinez-Duncker, Ivan [Thyroid Clinic, General Hospital of Mexico, Mexico City (Mexico); Martinez-Duncker, Carlos [Thyroid Clinic, General Hospital of Mexico, Mexico City (Mexico); Molecular Nuclear Medicine, Hospital Infantil de Mexico, Mexico (Mexico)

    2004-09-01

    The probability of malignancy is increased in hypofunctioning solitary thyroid nodules (HFNs). Fine-needle aspiration biopsy (FNA), {sup 99m}Tc-methoxyisobutylisonitrile (MIBI) and frozen section biopsy (FS) have limited independent diagnostic accuracy for the differential diagnosis of HFNs. The goal of this study was to assess the accuracy of the three independent diagnostic methods in distinguishing between benign and malignant disease. A total of 130 patients with an HFN on the {sup 99m}Tc-pertechnetate scan were included in this study. FNA, MIBI scans, FS, thyroidectomy and histological analysis of surgical specimens for final diagnosis were performed in all patients. Of the 130 patients, 80 (61.54%) had benign lesions and 50 (38.46%), malignant lesions. FNA was diagnostic in 78/130 (60%) patients and non-diagnostic in 52/130 (40%) patients. None of the patients with a negative MIBI scan had a final histological diagnosis of malignancy, and MIBI scans were negative in 38.46% of patients with non-diagnostic FNA results. FS was diagnostic in 104/130 (80%) patients and non-diagnostic in 26/130 (20%) patients. Sensitivity, specificity, positive and negative predictive values and positive and negative likelihood ratios were 81.3%, 97.8%, 96%, 88%, 36.95 and 0.19 respectively for FNA; 100%, 61.3%, 61.7%, 100%, 2.58 and 0 respectively for MIBI; and 80.5%, 100%, 100%, 89%, 0 and 0.2 respectively for FS. Use of both MIBI scans and FS in patients with non-diagnostic FNA rendered a specificity and sensitivity of 100%. MIBI scans exclude malignancy in a significant proportion of patients with non-diagnostic FNAs (38% in this study). Cystic nodules with a positive MIBI scan should be further investigated even when the FNA result indicates a benign lesion. Combined use of FNA, MIBI and FS offers the best diagnostic accuracy. (orig.)

  6. Genome-wide scan for signatures of human population differentiation and their relationship with natural selection, functional pathways and diseases.

    Directory of Open Access Journals (Sweden)

    Roberto Amato

    Full Text Available Genetic differences both between individuals and populations are studied for their evolutionary relevance and for their potential medical applications. Most of the genetic differentiation among populations are caused by random drift that should affect all loci across the genome in a similar manner. When a locus shows extraordinary high or low levels of population differentiation, this may be interpreted as evidence for natural selection. The most used measure of population differentiation was devised by Wright and is known as fixation index, or F(ST. We performed a genome-wide estimation of F(ST on about 4 millions of SNPs from HapMap project data. We demonstrated a heterogeneous distribution of F(ST values between autosomes and heterochromosomes. When we compared the F(ST values obtained in this study with another evolutionary measure obtained by comparative interspecific approach, we found that genes under positive selection appeared to show low levels of population differentiation. We applied a gene set approach, widely used for microarray data analysis, to detect functional pathways under selection. We found that one pathway related to antigen processing and presentation showed low levels of F(ST, while several pathways related to cell signalling, growth and morphogenesis showed high F(ST values. Finally, we detected a signature of selection within genes associated with human complex diseases. These results can help to identify which process occurred during human evolution and adaptation to different environments. They also support the hypothesis that common diseases could have a genetic background shaped by human evolution.

  7. A genome-wide "pleiotropy scan" does not identify new susceptibility loci for estrogen receptor negative breast cancer.

    Directory of Open Access Journals (Sweden)

    Daniele Campa

    Full Text Available Approximately 15-30% of all breast cancer tumors are estrogen receptor negative (ER-. Compared with ER-positive (ER+ disease they have an earlier age at onset and worse prognosis. Despite the vast number of risk variants identified for numerous cancer types, only seven loci have been unambiguously identified for ER-negative breast cancer. With the aim of identifying new susceptibility SNPs for this disease we performed a pleiotropic genome-wide association study (GWAS. We selected 3079 SNPs associated with a human complex trait or disease at genome-wide significance level (P<5 × 10(-8 to perform a secondary analysis of an ER-negative GWAS from the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3, including 1998 cases and 2305 controls from prospective studies. We then tested the top ten associations (i.e. with the lowest P-values using three additional populations with a total sample size of 3509 ER+ cases, 2543 ER- cases and 7031 healthy controls. None of the 3079 selected variants in the BPC3 ER-GWAS were significant at the adjusted threshold. 186 variants were associated with ER- breast cancer risk at a conventional threshold of P<0.05, with P-values ranging from 0.049 to 2.3 × 10(-4. None of the variants reached statistical significance in the replication phase. In conclusion, this study did not identify any novel susceptibility loci for ER-breast cancer using a "pleiotropic approach".

  8. Revealing the selection history of adaptive loci using genome-wide scans for selection: an example from domestic sheep.

    Science.gov (United States)

    Rochus, Christina Marie; Tortereau, Flavie; Plisson-Petit, Florence; Restoux, Gwendal; Moreno-Romieux, Carole; Tosser-Klopp, Gwenola; Servin, Bertrand

    2018-01-23

    One of the approaches to detect genetics variants affecting fitness traits is to identify their surrounding genomic signatures of past selection. With established methods for detecting selection signatures and the current and future availability of large datasets, such studies should have the power to not only detect these signatures but also to infer their selective histories. Domesticated animals offer a powerful model for these approaches as they adapted rapidly to environmental and human-mediated constraints in a relatively short time. We investigated this question by studying a large dataset of 542 individuals from 27 domestic sheep populations raised in France, genotyped for more than 500,000 SNPs. Population structure analysis revealed that this set of populations harbour a large part of European sheep diversity in a small geographical area, offering a powerful model for the study of adaptation. Identification of extreme SNP and haplotype frequency differences between populations listed 126 genomic regions likely affected by selection. These signatures revealed selection at loci commonly identified as selection targets in many species ("selection hotspots") including ABCG2, LCORL/NCAPG, MSTN, and coat colour genes such as ASIP, MC1R, MITF, and TYRP1. For one of these regions (ABCG2, LCORL/NCAPG), we could propose a historical scenario leading to the introgression of an adaptive allele into a new genetic background. Among selection signatures, we found clear evidence for parallel selection events in different genetic backgrounds, most likely for different mutations. We confirmed this allelic heterogeneity in one case by resequencing the MC1R gene in three black-faced breeds. Our study illustrates how dense genetic data in multiple populations allows the deciphering of evolutionary history of populations and of their adaptive mutations.

  9. Directed evolution combined with synthetic biology strategies expedite semi-rational engineering of genes and genomes.

    Science.gov (United States)

    Kang, Zhen; Zhang, Junli; Jin, Peng; Yang, Sen

    2015-01-01

    Owing to our limited understanding of the relationship between sequence and function and the interaction between intracellular pathways and regulatory systems, the rational design of enzyme-coding genes and de novo assembly of a brand-new artificial genome for a desired functionality or phenotype are difficult to achieve. As an alternative approach, directed evolution has been widely used to engineer genomes and enzyme-coding genes. In particular, significant developments toward DNA synthesis, DNA assembly (in vitro or in vivo), recombination-mediated genetic engineering, and high-throughput screening techniques in the field of synthetic biology have been matured and widely adopted, enabling rapid semi-rational genome engineering to generate variants with desired properties. In this commentary, these novel tools and their corresponding applications in the directed evolution of genomes and enzymes are discussed. Moreover, the strategies for genome engineering and rapid in vitro enzyme evolution are also proposed.

  10. A genome-wide scan for evidence of selection in a maize population under long-term artificial selection for ear number.

    Science.gov (United States)

    Beissinger, Timothy M; Hirsch, Candice N; Vaillancourt, Brieanne; Deshpande, Shweta; Barry, Kerrie; Buell, C Robin; Kaeppler, Shawn M; Gianola, Daniel; de Leon, Natalia

    2014-03-01

    A genome-wide scan to detect evidence of selection was conducted in the Golden Glow maize long-term selection population. The population had been subjected to selection for increased number of ears per plant for 30 generations, with an empirically estimated effective population size ranging from 384 to 667 individuals and an increase of more than threefold in the number of ears per plant. Allele frequencies at >1.2 million single-nucleotide polymorphism loci were estimated from pooled whole-genome resequencing data, and FST values across sliding windows were employed to assess divergence between the population preselection and the population postselection. Twenty-eight highly divergent regions were identified, with half of these regions providing gene-level resolution on potentially selected variants. Approximately 93% of the divergent regions do not demonstrate a significant decrease in heterozygosity, which suggests that they are not approaching fixation. Also, most regions display a pattern consistent with a soft-sweep model as opposed to a hard-sweep model, suggesting that selection mostly operated on standing genetic variation. For at least 25% of the regions, results suggest that selection operated on variants located outside of currently annotated coding regions. These results provide insights into the underlying genetic effects of long-term artificial selection and identification of putative genetic elements underlying number of ears per plant in maize.

  11. A genome-wide scan study identifies a single nucleotide substitution in ASIP associated with white versus non-white coat-colour variation in sheep (Ovis aries).

    Science.gov (United States)

    Li, M-H; Tiirikka, T; Kantanen, J

    2014-02-01

    In sheep, coat colour (and pattern) is one of the important traits of great biological, economic and social importance. However, the genetics of sheep coat colour has not yet been fully clarified. We conducted a genome-wide association study of sheep coat colours by genotyping 47 303 single-nucleotide polymorphisms (SNPs) in the Finnsheep population in Finland. We identified 35 SNPs associated with all the coat colours studied, which cover genomic regions encompassing three known pigmentation genes (TYRP1, ASIP and MITF) in sheep. Eighteen of these associations were confirmed in further tests between white versus non-white individuals, but none of the 35 associations were significant in the analysis of only non-white colours. Across the tests, the s66432.1 in ASIP showed significant association (P=4.2 × 10(-11) for all the colours; P=2.3 × 10(-11) for white versus non-white colours) with the variation in coat colours and strong linkage disequilibrium with other significant variants surrounding the ASIP gene. The signals detected around the ASIP gene were explained by differences in white versus non-white alleles. Further, a genome scan for selection for white coat pigmentation identified a strong and striking selection signal spanning ASIP. Our study identified the main candidate gene for the coat colour variation between white and non-white as ASIP, an autosomal gene that has been directly implicated in the pathway regulating melanogenesis. Together with ASIP, the two other newly identified genes (TYRP1 and MITF) in the Finnsheep, bordering associated SNPs, represent a new resource for enriching sheep coat-colour genetics and breeding.

  12. 3D wake measurements from a scanning wind lidar in combination with a fast wind field reconstruction model

    DEFF Research Database (Denmark)

    Mikkelsen, Torben Krogh; Herges, T. G.; Astrup, Poul

    2017-01-01

    -Stokes CFD code “Lincom Cyclop-buster model,”3 the corresponding 3D wind vector field (u, v, w) can be reconstructed under constraints for conservation of mass and momentum. The resulting model calculated line-of-sight projections of the 3D wind velocity vectors will become consistent with the line......High-resolution lidar wake measurements are part of an ongoing field campaign being conducted at the Scaled Wind Farm Technology (SWiFT) facility1 by Sandia National Laboratories and the National Renewable Energy Laboratory using a customized scanning “DTU SpinnerLidar”2 from the Technical...... University of Denmark. The purpose of the SpinnerLidar measurements at SWIFT is to measure the response of a V27 turbine wake to varying inflow conditions and turbine operating states. Although our fast scanning SpinnerLidar is able to measure the line-of-sight projected wind speed at up to 400 points per...

  13. Nanocrystals of [Cu3(btc)2] (HKUST-1): a combined time-resolved light scattering and scanning electron microscopy study.

    Science.gov (United States)

    Zacher, Denise; Liu, Jianing; Huber, Klaus; Fischer, Roland A

    2009-03-07

    The formation of [Cu(3)(btc)(2)] (HKUST-1; btc = 1,3,5-benzenetricarboxylate) nanocrystals from a super-saturated mother solution at room temperature was monitored by time-resolved light scattering (TLS); the system is characterized by a rapid growth up to a size limit of 200 nm within a few minutes, and the size and shape of the crystallites were also determined by scanning electron microscopy (SEM).

  14. Differential Scanning Calorimetry and Infrared Spectroscopy Combined with Chemometric Analysis to the Determination of Coffee Adulteration by Corn

    OpenAIRE

    Brondi, Ariadne M.; Torres, Claudia; Garcia, Jerusa S.; Trevisan, Marcello G.

    2017-01-01

    Roasted and ground coffee is targeted by fraudulent addiction of products. In this way the determination of contaminants in coffee has economic and nutritional importance. In this study, the coffee adulteration by corn were detected using DSC (differential scanning calorimetry) and FTIR (Fourier transform infrared spectroscopy) coupled to PCA (principal component analysis), and PLS (partial least squares) models. Three different levels of roasted and ground Coffea arabica L. were used to prep...

  15. Construction of a four tip scanning tunneling microscope/scanning electron microscope combination and conductivity measurements of silicide nanowires; Aufbau einer Vierspitzen-Rastertunnelmikroskop/Rasterelektronenmikroskop-Kombination und Leitfaehigkeitsmessungen an Silizid Nanodraehten

    Energy Technology Data Exchange (ETDEWEB)

    Zubkov, Evgeniy

    2013-09-01

    In this work the combination of a four-tip scanning tunneling microscope with a scanning electron microscope is presented. By means of this apparatus it is possible to perform the conductivity measurements on the in-situ prepared nanostructures in ultra-high vacuum. With the aid of a scanning electron microscope (SEM), it becomes possible to position the tunneling tips of the four-tip scanning tunneling microscope (STM), so that an arrangement for a four-point probe measurement on nanostructures can be obtained. The STM head was built according to the novel coaxial Beetle concept. This concept allows on the one hand, a very compact arrangement of the components of the STM and on the other hand, the new-built STM head has a good mechanical stability, in order to achieve atomic resolution with all four STM units. The atomic resolution of the STM units was confirmed by scanning a Si(111)-7 x 7 surface. The thermal drift during the STM operation, as well as the resonant frequencies of the mechanical structure of the STM head, were determined. The scanning electron microscope allows the precise and safe navigation of the tunneling tips on the sample surface. Multi tip spectroscopy with up to four STM units can be performed synchronously. To demonstrate the capabilities of the new-built apparatus the conductivity measurements were carried out on metallic yttrium silicide nanowires. The nanowires were prepared by the in-situ deposition of yttrium on a heated Si(110) sample surface. Current-voltage curves were recorded on the nanowires and on the wetting layer in-between. The curves indicate an existence of the Schottky barrier between the yttrium silicide nanowires and the silicon bulk. By means of the two-tip measurements with a gate, the insulating property of the Schottky barrier has been confirmed. Using this Schottky barrier, it is possible to limit the current to the nanowire and to prevent it from flowing through the silicon bulk. A four-tip resistance measurement

  16. Genome-wide scan for bats and dolphin to detect their genetic basis for new locomotive styles.

    Directory of Open Access Journals (Sweden)

    Yong-Yi Shen

    Full Text Available For most mammals, running is their major locomotive style, however, cetaceans and bats are two mammalian groups that have independently developed new locomotive styles (swimming and flying from their terrestrial ancestors. In this study, we used a genome-wide comparative analysis in an attempt to identify the selective imprint of the development of new locomotive styles by cetaceans and bats to adapt to their new ecological niches. We found that an elevated proportion of mitochondrion-associated genes show evidence of adaptive evolution in cetaceans and on the common ancestral lineage leading to bats, compared to other terrestrial mammals. This result is consistent with the fact that during the independent developments of swimming and flying in these two groups, the changes of energy metabolism ratios would be among the most important factors to overcome elevated energy demands. Furthermore, genes that show evidence of sequence convergence or parallel evolution in these two lineages were overrepresented in the categories of energy metabolism, muscle contraction, heart, and glucose metabolism, genes that perform functions which are essential for locomotion. In conclusion, our analyses showed that on the dolphin and bat lineages, genes associated with locomotion not only both show a greater propensity to adaptively evolve, but also show evidence of sequence convergence, which likely reflects a response to a common requirement during their development of these two drastic locomotive styles.

  17. Genome-wide scan for bats and dolphin to detect their genetic basis for new locomotive styles.

    Science.gov (United States)

    Shen, Yong-Yi; Zhou, Wei-Ping; Zhou, Tai-Cheng; Zeng, Yan-Ni; Li, Gui-Mei; Irwin, David M; Zhang, Ya-Ping

    2012-01-01

    For most mammals, running is their major locomotive style, however, cetaceans and bats are two mammalian groups that have independently developed new locomotive styles (swimming and flying) from their terrestrial ancestors. In this study, we used a genome-wide comparative analysis in an attempt to identify the selective imprint of the development of new locomotive styles by cetaceans and bats to adapt to their new ecological niches. We found that an elevated proportion of mitochondrion-associated genes show evidence of adaptive evolution in cetaceans and on the common ancestral lineage leading to bats, compared to other terrestrial mammals. This result is consistent with the fact that during the independent developments of swimming and flying in these two groups, the changes of energy metabolism ratios would be among the most important factors to overcome elevated energy demands. Furthermore, genes that show evidence of sequence convergence or parallel evolution in these two lineages were overrepresented in the categories of energy metabolism, muscle contraction, heart, and glucose metabolism, genes that perform functions which are essential for locomotion. In conclusion, our analyses showed that on the dolphin and bat lineages, genes associated with locomotion not only both show a greater propensity to adaptively evolve, but also show evidence of sequence convergence, which likely reflects a response to a common requirement during their development of these two drastic locomotive styles.

  18. LeasyScan: a novel concept combining 3D imaging and lysimetry for high-throughput phenotyping of traits controlling plant water budget.

    Science.gov (United States)

    Vadez, Vincent; Kholová, Jana; Hummel, Grégoire; Zhokhavets, Uladzimir; Gupta, S K; Hash, C Tom

    2015-09-01

    In this paper, we describe the thought process and initial data behind the development of an imaging platform (LeasyScan) combined with lysimetric capacity, to assess canopy traits affecting water use (leaf area, leaf area index, transpiration). LeasyScan is based on a novel 3D scanning technique to capture leaf area development continuously, a scanner-to-plant concept to increase imaging throughput and analytical scales to combine gravimetric transpiration measurements. The paper presents how the technology functions, how data are visualised via a web-based interface and how data extraction and analysis is interfaced through 'R' libraries. Close agreement between scanned and observed leaf area data of individual plants in different crops was found (R(2) between 0.86 and 0.94). Similar agreement was found when comparing scanned and observed area of plants cultivated at densities reflecting field conditions (R(2) between 0.80 and 0.96). An example in monitoring plant transpiration by the analytical scales is presented. The last section illustrates some of the early ongoing applications of the platform to target key phenotypes: (i) the comparison of the leaf area development pattern of fine mapping recombinants of pearl millet; (ii) the leaf area development pattern of pearl millet breeding material targeted to different agro-ecological zones; (iii) the assessment of the transpiration response to high VPD in sorghum and pearl millet. This new platform has the potential to phenotype for traits controlling plant water use at a high rate and precision, of critical importance for drought adaptation, and creates an opportunity to harness their genetics for the breeding of improved varieties. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  19. Asymmetric introgression in the horticultural living fossil cycas sect. Asiorientales using a genome-wide scanning approach.

    Science.gov (United States)

    Chiang, Yu-Chung; Huang, Bing-Hong; Chang, Chun-Wen; Wan, Yu-Ting; Lai, Shih-Jie; Huang, Shong; Liao, Pei-Chun

    2013-04-15

    The Asian cycads are mostly allopatric, distributed in small population sizes. Hybridization between allopatric species provides clues in determining the mechanism of species divergence. Horticultural introduction provides the chance of interspecific gene flow between allopatric species. Two allopatrically eastern Asian Cycas sect. Asiorientales species, C. revoluta and C. taitungensis, which are widely distributed in Ryukyus and Fujian Province and endemic to Taiwan, respectively, were planted in eastern Taiwan for horticultural reason. Higher degrees of genetic admixture in cultivated samples than wild populations in both cycad species were detected based on multilocus scans by neutral AFLP markers. Furthermore, bidirectional but asymmetric introgression by horticultural introduction of C. revoluta is evidenced by the reanalyses of species associated loci, which are assumed to be diverged after species divergence. Partial loci introgressed from native cycad to the invaders were also detected at the loci of strong species association. Consistent results tested by all neutral loci, and the species-associated loci, specify the recent introgression from the paradox of sharing of ancestral polymorphisms. Phenomenon of introgression of cultivated cycads implies niche conservation among two geographic-isolated cycads, even though the habitats of the extant wild populations of two species are distinct.

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

    DEFF Research Database (Denmark)

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

    2001-01-01

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

  1. Binning_refiner: improving genome bins through the combination of different binning programs.

    Science.gov (United States)

    Song, Wei-Zhi; Thomas, Torsten

    2017-06-15

    Microbial genomes have recently been reconstructed from metagenomic datasets using binning approaches. Inconsistent binning results are however often observed between different binning programs, likely due to the different algorithms or statistical models used. We present Binning_refiner, a pipeline that merges the results of different binning programs. Our results demonstrated that Binning_refiner can significantly reduce the contamination level of genome bins and increase the total size of contamination-free and 'good-quality' genome bins. Binning_refiner is thus an useful tool to improve the quality of genome bins derived from metagenomic data. Binning_refiner is implemented in Python3 and is freely available at: https://github.com/songweizhi/Binning_refiner . songwz03@gmail.com or t.thomas@unsw.edu.au. Supplementary data are available at Bioinformatics online.

  2. Imputation and quality control steps for combining multiple genome-wide datasets

    Directory of Open Access Journals (Sweden)

    Shefali S Verma

    2014-12-01

    Full Text Available The electronic MEdical Records and GEnomics (eMERGE network brings together DNA biobanks linked to electronic health records (EHRs from multiple institutions. Approximately 52,000 DNA samples from distinct individuals have been genotyped using genome-wide SNP arrays across the nine sites of the network. The eMERGE Coordinating Center and the Genomics Workgroup developed a pipeline to impute and merge genomic data across the different SNP arrays to maximize sample size and power to detect associations with a variety of clinical endpoints. The 1000 Genomes cosmopolitan reference panel was used for imputation. Imputation results were evaluated using the following metrics: accuracy of imputation, allelic R2 (estimated correlation between the imputed and true genotypes, and the relationship between allelic R2 and minor allele frequency. Computation time and memory resources required by two different software packages (BEAGLE and IMPUTE2 were also evaluated. A number of challenges were encountered due to the complexity of using two different imputation software packages, multiple ancestral populations, and many different genotyping platforms. We present lessons learned and describe the pipeline implemented here to impute and merge genomic data sets. The eMERGE imputed dataset will serve as a valuable resource for discovery, leveraging the clinical data that can be mined from the EHR.

  3. Scanning electron microscopy combined with image processing technique: Analysis of microstructure, texture and tenderness in Semitendinous and Gluteus Medius bovine muscles.

    Science.gov (United States)

    Pieniazek, Facundo; Messina, Valeria

    2016-11-01

    In this study the effect of freeze drying on the microstructure, texture, and tenderness of Semitendinous and Gluteus Medius bovine muscles were analyzed applying Scanning Electron Microscopy combined with image analysis. Samples were analyzed by Scanning Electron Microscopy at different magnifications (250, 500, and 1,000×). Texture parameters were analyzed by Texture analyzer and by image analysis. Tenderness by Warner-Bratzler shear force. Significant differences (p image and instrumental texture features. A linear trend with a linear correlation was applied for instrumental and image features. Image texture features calculated from Gray Level Co-occurrence Matrix (homogeneity, contrast, entropy, correlation and energy) at 1,000× in both muscles had high correlations with instrumental features (chewiness, hardness, cohesiveness, and springiness). Tenderness showed a positive correlation in both muscles with image features (energy and homogeneity). Combing Scanning Electron Microscopy with image analysis can be a useful tool to analyze quality parameters in meat.Summary SCANNING 38:727-734, 2016. © 2016 Wiley Periodicals, Inc. © Wiley Periodicals, Inc.

  4. Combined genomic and structural analyses of a cultured magnetotactic bacterium reveals its niche adaptation to a dynamic environment

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    Ana Carolina Vieira Araujo

    2016-10-01

    Full Text Available Abstract Background Magnetotactic bacteria (MTB are a unique group of prokaryotes that have a potentially high impact on global geochemical cycling of significant primary elements because of their metabolic plasticity and the ability to biomineralize iron-rich magnetic particles called magnetosomes. Understanding the genetic composition of the few cultivated MTB along with the unique morphological features of this group of bacteria may provide an important framework for discerning their potential biogeochemical roles in natural environments. Results Genomic and ultrastructural analyses were combined to characterize the cultivated magnetotactic coccus Magnetofaba australis strain IT-1. Cells of this species synthesize a single chain of elongated, cuboctahedral magnetite (Fe3O4 magnetosomes that cause them to align along magnetic field lines while they swim being propelled by two bundles of flagella at velocities up to 300 μm s−1. High-speed microscopy imaging showed the cells move in a straight line rather than in the helical trajectory described for other magnetotactic cocci. Specific genes within the genome of Mf. australis strain IT-1 suggest the strain is capable of nitrogen fixation, sulfur reduction and oxidation, synthesis of intracellular polyphosphate granules and transporting iron with low and high affinity. Mf. australis strain IT-1 and Magnetococcus marinus strain MC-1 are closely related phylogenetically although similarity values between their homologous proteins are not very high. Conclusion Mf. australis strain IT-1 inhabits a constantly changing environment and its complete genome sequence reveals a great metabolic plasticity to deal with these changes. Aside from its chemoautotrophic and chemoheterotrophic metabolism, genomic data indicate the cells are capable of nitrogen fixation, possess high and low affinity iron transporters, and might be capable of reducing and oxidizing a number of sulfur compounds. The relatively

  5. The Combination of Laser Scanning and Structure from Motion Technology for Creation of Accurate Exterior and Interior Orthophotos of ST. Nicholas Baroque Church

    Science.gov (United States)

    Koska, B.; Křemen, T.

    2013-02-01

    Terrestrial laser scanning technology is used for creation of building documentation and 3D building model from its emerging at the turn of the millennium. Photogrammetry has even longer tradition in this field. Both technologies have some technical limitations if they are used for creation of a façade or even an interior orthophoto, but combination of both technologies seems profitable. Laser scanning can be used for creation of an accurate 3D model and photogrammetry for consequent application of high quality colour information. Both technologies were used in synergy to create the building plans, 2D drawing documentation of facades and interior views and the orthophotos of St. Nicholas Baroque church in Prague. The case study is described in details in the paper.

  6. Combined 18F-Fluoride and 18F-FDG PET/CT Scanning for Evaluation of Malignancy: Results of an International Multicenter Trial

    DEFF Research Database (Denmark)

    Iagaru, Andrei; Mittra, Erik; Mosci, Camila

    2012-01-01

    PET/CT examination for evaluation of cancer patients and compared it with separate 18F2 PET/CT and 18F-FDG PET/CT scans. Methods: One hundred fifteen participants with cancer were prospectively enrolled in an international multicenter trial evaluating 18F2 PET/CT, 18F-FDG PET/CT, and combined 18F2/18F......-FDG PET/CT. The 3 PET/CT scans were performed sequentially within 4 wk of one another for each patient. Results: 18F2/18FFDG PET/CT allowed for accurate interpretation of radiotracer uptake outside the skeleton, with findings similar to those of 18F-FDG PET/CT. In 19 participants, skeletal disease...

  7. High-Resolution Imaging of Polyethylene Glycol Coated Dendrimers via Combined Atomic Force and Scanning Tunneling Microscopy

    Directory of Open Access Journals (Sweden)

    Shawn Riechers

    2015-01-01

    Full Text Available Dendrimers have shown great promise as drug delivery vehicles in recent years because they can be synthesized with designed size and functionalities for optimal transportation, targeting, and biocompatibility. One of the most well-known termini used for biocompatibility is polyethylene glycol (PEG, whose performance is affected by its actual conformation. However, the conformation of individual PEG bound to soft materials such as dendrimers has not been directly observed. Using atomic force microscopy (AFM and scanning tunneling microscopy (STM, this work characterizes the structure adopted by PEGylated dendrimers with the highest resolution reported to date. AFM imaging enables visualization of the individual dendrimers, as well as the differentiation and characterization of the dendrimer core and PEG shell. STM provides direct imaging of the PEG extensions with high-resolution. Collectively, this investigation provides important insight into the structure of coated dendrimers, which is crucial for the design and development of better drug delivery vehicles.

  8. Genome scan of age-at-onset in the NIMH Alzheimer disease sample uncovers multiple loci, along with evidence of both genetic and sample heterogeneity.

    Science.gov (United States)

    Choi, Yoonha; Marchani, Elizabeth E; Bird, Thomas D; Steinbart, Ellen J; Blacker, Deborah; Wijsman, Ellen M

    2011-12-01

    Alzheimer's disease (AD) is a common neurodegenerative disorder of late life with a complex genetic basis. Although several genes are known to play a role in rare early onset AD, only the APOE gene is known to have a high contribution to risk of the common late-onset form of the disease (LOAD, onset >60 years). APOE genotypes vary in their AD risk as well as age-at-onset distributions, and it is likely that other loci will similarly affect AD age-at-onset. Here we present the first analysis of age-at-onset in the NIMH LOAD sample that allows for both a multilocus trait model and genetic heterogeneity among the contributing sites, while at the same time accommodating age censoring, effects of known genetic covariates, and full pedigree and marker information. The results provide evidence for genomic regions not previously implicated in this data set, including regions on chromosomes 7q, 15, and 19p. They also affirm evidence for loci on chromosomes 1q, 6p, 9q, 11, and, of course, the APOE locus on 19q, all of which have been reported previously in the same sample. The analyses failed to find evidence for linkage to chromosome 10 with inclusion of unaffected subjects and extended pedigrees. Several regions implicated in these analyses in the NIMH sample have been previously reported in genome scans of other AD samples. These results, therefore, provide independent confirmation of AD loci in family-based samples on chromosomes 1q, 7q, 19p, and suggest that further efforts towards identifying the underlying causal loci are warranted. Copyright © 2011 Wiley-Liss, Inc.

  9. A novel scoring strategy combining statistics and functional genomics supports a possible role for common polygenic variation in autism

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    Jérôme eCarayol

    2014-02-01

    Full Text Available Autism spectrum disorders (ASD are highly heritable complex neurodevelopmental disorders with a 4:1 male: female ratio. Common genetic variation could explain 40-60% of the variance in liability to autism. Because of their small effect, genome-wide association studies (GWASs have only identified a small number of individual single-nucleotide polymorphisms (SNPs. To increase the power of GWASs in complex disorders, methods like convergent functional genomics (CFG have emerged to extract true association signals from noise and to identify and prioritize genes from SNPs using a scoring strategy combining statistics and functional genomics. We adapted and applied this approach to analyze data from a GWAS performed on families with multiple children affected with autism from Autism Speaks Autism Genetic Resource Exchange (AGRE. We identified a set of 133 candidate markers that were localized in or close to genes with functional relevance in ASD from a discovery population (545 multiplex families; a gender specific genetic score based on these common variants explained 1% (P = 0.01 in males and 5% (P = 8.7x10-7 in females of genetic variance in an independent sample of multiplex families. Overall, our work demonstrates that prioritization of GWAS data based on functional genomics identified common variants associated with autism and provided additional support for a common polygenic background in autism.

  10. Efficient Construction of Large Genomic Deletion in Agrobacterium tumefaciens by Combination of Cre/loxP System and Triple Recombineering.

    Science.gov (United States)

    Liu, Zhengqiang; Xie, Yali; Zhang, Xu; Hu, Xiaofeng; Li, Yusheng; Ding, Xuezhi; Xia, Liqiu; Hu, Shengbiao

    2016-04-01

    In order to develop an efficient system for deleting genomic segment in Agrobacterium tumefaciens to analyze gene functions and construct marker gene-free recombinant strains, a Cre recombinase expression plasmid was constructed by placing its encoding gene under the control of Ptet promoter and cloning into the plasmid replicable in both A. tumefaciens and E. coli. Triple recombineering was applied to efficiently construct integrative vectors which were used to introduce loxP sites and selection markers into the chromosome of A. tumefaciens. Cre recombinase could be properly induced by anhydrotetracycline in A. tumefaciens, which was revealed by the fact that kanamycin resistance gene flanked by two parallel loxP sites was excised from the genome of A. tumefaciens with virtually 100% efficiency. And what is more, an A. tumefaciens mutant carrying large-deletion (~85 kb) in genome was successfully constructed by Cre/loxP system. Here, we described the application of combination of Cre/loxP system and triple recombineering to efficiently excise genomic segment in A. tumefaciens, which also would facilitate efficient construction of multiple gene disruptions in A. tumefaciens.

  11. A fungal phylogeny based on 42 complete genomes derived from supertree and combined gene analysis

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    Stajich Jason E

    2006-11-01

    Full Text Available Abstract Background To date, most fungal phylogenies have been derived from single gene comparisons, or from concatenated alignments of a small number of genes. The increase in fungal genome sequencing presents an opportunity to reconstruct evolutionary events using entire genomes. As a tool for future comparative, phylogenomic and phylogenetic studies, we used both supertrees and concatenated alignments to infer relationships between 42 species of fungi for which complete genome sequences are available. Results A dataset of 345,829 genes was extracted from 42 publicly available fungal genomes. Supertree methods were employed to derive phylogenies from 4,805 single gene families. We found that the average consensus supertree method may suffer from long-branch attraction artifacts, while matrix representation with parsimony (MRP appears to be immune from these. A genome phylogeny was also reconstructed from a concatenated alignment of 153 universally distributed orthologs. Our MRP supertree and concatenated phylogeny are highly congruent. Within the Ascomycota, the sub-phyla Pezizomycotina and Saccharomycotina were resolved. Both phylogenies infer that the Leotiomycetes are the closest sister group to the Sordariomycetes. There is some ambiguity regarding the placement of Stagonospora nodurum, the sole member of the class Dothideomycetes present in the dataset. Within the Saccharomycotina, a monophyletic clade containing organisms that translate CTG as serine instead of leucine is evident. There is also strong support for two groups within the CTG clade, one containing the fully sexual species Candida lusitaniae, Candida guilliermondii and Debaryomyces hansenii, and the second group containing Candida albicans, Candida dubliniensis, Candida tropicalis, Candida parapsilosis and Lodderomyces elongisporus. The second major clade within the Saccharomycotina contains species whose genomes have undergone a whole genome duplication (WGD, and their close

  12. Combination of native and denaturing PAGE for the detection of protein binding regions in long fragments of genomic DNA

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    Metsis Madis

    2008-06-01

    Full Text Available Abstract Background In a traditional electrophoresis mobility shift assay (EMSA a 32P-labeled double-stranded DNA oligonucleotide or a restriction fragment bound to a protein is separated from the unbound DNA by polyacrylamide gel electrophoresis (PAGE in nondenaturing conditions. An extension of this method uses the large population of fragments derived from long genomic regions (approximately 600 kb for the identification of fragments containing protein binding regions. With this method, genomic DNA is fragmented by restriction enzymes, fragments are amplified by PCR, radiolabeled, incubated with nuclear proteins and the resulting DNA-protein complexes are separated by two-dimensional PAGE. Shifted DNA fragments containing protein binding sites are identified by using additional procedures, i. e. gel elution, PCR amplification, cloning and sequencing. Although the method allows simultaneous analysis of a large population of fragments, it is relatively laborious and can be used to detect only high affinity protein binding sites. Here we propose an alternative and straightforward strategy which is based on a combination of native and denaturing PAGE. This strategy allows the identification of DNA fragments containing low as well as high affinity protein binding regions, derived from genomic DNA ( Results We have combined an EMSA-based selection step with subsequent denaturing PAGE for the localization of protein binding regions in long (up to10 kb fragments of genomic DNA. Our strategy consists of the following steps: digestion of genomic DNA with a 4-cutter restriction enzyme (AluI, BsuRI, TruI, etc, separation of low and high molecular weight fractions of resultant DNA fragments, 32P-labeling with Klenow polymerase, traditional EMSA, gel elution and identification of the shifted bands (or smear by denaturing PAGE. The identification of DNA fragments containing protein binding sites is carried out by running the gel-eluted fragments alongside

  13. Detection of heavy metals released at the sediment/water interface by combining Anodic Stripping Voltammetry (ASV) and Scanning Electrochemical Microscopy (SECM) measurements

    Science.gov (United States)

    Daniele, S.; Ciani, I.; Bragato, C.; Baldo, M. A.

    2003-05-01

    Hemisphere mercury microelectrodes are investigated in combine anodic stripping voltammetry (ASV) and scanning electrochemical microscopy (SECM) experiments for the detection of heavy metal ions at the solid/solution interface of a sediment sample. Relatively large anodic stripping peaks due to lead are monitored at μm distances from the solid particles, while, under the same experimental conditions, no or lower ASV peaks are found in the bulk solution. This suggests that diffusion gradients at sediment/water interface is monitored. This method, therefore, offers a new possibility for investigating on spatial differences of immobilization and remobilization processes of heavy metals at sediment/water interfaces.

  14. A rapid method for combined laser scanning confocal microscopic and electron microscopic visualization of biocytin or neurobiotin-labeled neurons.

    Science.gov (United States)

    Sun, X J; Tolbert, L P; Hildebrand, J G; Meinertzhagen, I A

    1998-02-01

    Intracellular recording and dye filling are widely used to correlate the morphology of a neuron with its physiology. With laser scanning confocal microscopy, the complex shapes of labeled neurons in three dimensions can be reconstructed rapidly, but this requires fluorescent dyes. These dyes are neither permanent nor electron dense and therefore do not allow investigation by electron microscopy. Here we report a technique that quickly and easily converts a fluorescent label into a more stable and electron-dense stain. With this technique, a neuron is filled with Neurobiotin or biocytin, reacted with fluorophore-conjugated avidin, and imaged by confocal microscopy. To permit long-term storage or EM study, the fluorescent label is then converted to a stable electron-dense material by a single-step conversion using a commercially available ABC kit. We find that the method, which apparently relies on recognition of avidin's excess biotin binding sites by the biotin-peroxidase conjugate, is both faster and less labor intensive than photo-oxidation procedures in common use. The technique is readily adaptable to immunocytochemistry with biotinylated probes, as we demonstrate using anti-serotonin as an example.

  15. Combining high-throughput phenotyping and genome-wide association studies to reveal natural genetic variation in rice.

    Science.gov (United States)

    Yang, Wanneng; Guo, Zilong; Huang, Chenglong; Duan, Lingfeng; Chen, Guoxing; Jiang, Ni; Fang, Wei; Feng, Hui; Xie, Weibo; Lian, Xingming; Wang, Gongwei; Luo, Qingming; Zhang, Qifa; Liu, Qian; Xiong, Lizhong

    2014-10-08

    Even as the study of plant genomics rapidly develops through the use of high-throughput sequencing techniques, traditional plant phenotyping lags far behind. Here we develop a high-throughput rice phenotyping facility (HRPF) to monitor 13 traditional agronomic traits and 2 newly defined traits during the rice growth period. Using genome-wide association studies (GWAS) of the 15 traits, we identify 141 associated loci, 25 of which contain known genes such as the Green Revolution semi-dwarf gene, SD1. Based on a performance evaluation of the HRPF and GWAS results, we demonstrate that high-throughput phenotyping has the potential to replace traditional phenotyping techniques and can provide valuable gene identification information. The combination of the multifunctional phenotyping tools HRPF and GWAS provides deep insights into the genetic architecture of important traits.

  16. Genome-wide scan for serum ghrelin detects linkage on chromosome 1p36 in Hispanic children: results from the Viva La Familia study.

    Science.gov (United States)

    Voruganti, V Saroja; Göring, Harald H H; Diego, Vincent P; Cai, Guowen; Mehta, Nitesh R; Haack, Karin; Cole, Shelley A; Butte, Nancy F; Comuzzie, Anthony G

    2007-10-01

    This study was conducted to investigate genetic influence on serum ghrelin and its relationship with adiposity-related phenotypes in Hispanic children (n=1030) from the Viva La Familia study (VFS). Anthropometric measurements and levels of serum ghrelin were estimated and genetic analyses conducted according to standard procedures. Mean age, body mass index (BMI), and serum ghrelin were 11+/-0.13 y, 25+/-0.24 kg/m2 and 38+/-0.5 ng/mL, respectively. Significant heritabilities (p<0.001) were obtained for BMI, weight, fat mass, percent fat, waist circumference, waist-to-height ratio, and ghrelin. Bivariate analyses of ghrelin with adiposity traits showed significant negative genetic correlations (p<0.0001) with weight, BMI, fat mass, percent fat, waist circumference, and waist-to-height ratio. A genome-wide scan for ghrelin detected significant linkage on chromosome 1p36.2 between STR markers D1S2697 and D1S199 (LOD=3.2). The same region on chromosome 1 was the site of linkage for insulin (LOD=3.3), insulinlike growth factor binding protein 1 (IGFBP1) (LOD=3.4), homeostatic model assessment method (HOMA) (LOD=2.9), and C-peptide (LOD=2.0). Several family-based studies have reported linkages for obesity-related phenotypes in the region of 1p36. These results indicate the importance of this region in relation to adiposity in children from the VFS.

  17. A Genome-wide Linkage Scan in German Shepherd Dogs Localizes Canine Platelet Procoagulant Deficiency (Scott Syndrome) to Canine Chromosome 27

    Science.gov (United States)

    Brooks, Marjory; Etter, Krystal; Catalfamo, James; Brisbin, Abra; Bustamante, Carlos; Mezey, Jason

    2011-01-01

    Scott syndrome is a rare hereditary bleeding disorder associated with an inability of stimulated platelets to externalize the negatively charged phospholipid, phosphatidylserine (PS). Canine Scott syndrome (CSS) is the only naturally-occurring animal model of this defect and therefore represents a unique tool to discover a disease gene capable of producing this platelet phenotype. We undertook platelet function studies and linkage analyses in a pedigree of CSS-affected German shepherd dogs. Based on residual serum prothrombin and flow cytometric assays, CSS segregates as an autosomal recessive trait. An initial genome scan, performed by genotyping 48 dogs for 280 microsatellite markers, suggested linkage with markers on chromosome 27. Genotypes ultimately obtained for a total of 56 dogs at 11 markers on chromosome 27 revealed significant LOD scores for 2 markers near the centromere, with multipoint linkage indicating a CSS trait locus spanning approximately 14 cM. These results provide the basis for fine mapping studies to narrow the disease interval and target the evaluation of putative disease genes. PMID:19854246

  18. Specific patterns of gene space organisation revealed in wheat by using the combination of barley and wheat genomic resources

    Directory of Open Access Journals (Sweden)

    Waugh Robbie

    2010-12-01

    Full Text Available Abstract Background Because of its size, allohexaploid nature and high repeat content, the wheat genome has always been perceived as too complex for efficient molecular studies. We recently constructed the first physical map of a wheat chromosome (3B. However gene mapping is still laborious in wheat because of high redundancy between the three homoeologous genomes. In contrast, in the closely related diploid species, barley, numerous gene-based markers have been developed. This study aims at combining the unique genomic resources developed in wheat and barley to decipher the organisation of gene space on wheat chromosome 3B. Results Three dimensional pools of the minimal tiling path of wheat chromosome 3B physical map were hybridised to a barley Agilent 15K expression microarray. This led to the fine mapping of 738 barley orthologous genes on wheat chromosome 3B. In addition, comparative analyses revealed that 68% of the genes identified were syntenic between the wheat chromosome 3B and barley chromosome 3 H and 59% between wheat chromosome 3B and rice chromosome 1, together with some wheat-specific rearrangements. Finally, it indicated an increasing gradient of gene density from the centromere to the telomeres positively correlated with the number of genes clustered in islands on wheat chromosome 3B. Conclusion Our study shows that novel structural genomics resources now available in wheat and barley can be combined efficiently to overcome specific problems of genetic anchoring of physical contigs in wheat and to perform high-resolution comparative analyses with rice for deciphering the organisation of the wheat gene space.

  19. Radiation injury vs. recurrent brain metastasis: combining textural feature radiomics analysis and standard parameters may increase {sup 18}F-FET PET accuracy without dynamic scans

    Energy Technology Data Exchange (ETDEWEB)

    Lohmann, Philipp; Stoffels, Gabriele; Stegmayr, Carina; Neumaier, Bernd [Forschungszentrum Juelich, Institute of Neuroscience and Medicine, Juelich (Germany); Ceccon, Garry [University of Cologne, Department of Neurology, Cologne (Germany); Rapp, Marion; Sabel, Michael; Kamp, Marcel A. [Heinrich Heine University Duesseldorf, Department of Neurosurgery, Duesseldorf (Germany); Filss, Christian P. [Forschungszentrum Juelich, Institute of Neuroscience and Medicine, Juelich (Germany); RWTH Aachen University Hospital, Department of Nuclear Medicine, Aachen (Germany); Shah, Nadim J. [Forschungszentrum Juelich, Institute of Neuroscience and Medicine, Juelich (Germany); RWTH Aachen University Hospital, Department of Neurology, Aachen (Germany); Juelich-Aachen Research Alliance (JARA) - Section JARA-Brain, Department of Neurology, Juelich (Germany); Langen, Karl-Josef [Forschungszentrum Juelich, Institute of Neuroscience and Medicine, Juelich (Germany); RWTH Aachen University Hospital, Department of Nuclear Medicine, Aachen (Germany); Juelich-Aachen Research Alliance (JARA) - Section JARA-Brain, Department of Neurology, Juelich (Germany); Galldiks, Norbert [Forschungszentrum Juelich, Institute of Neuroscience and Medicine, Juelich (Germany); University of Cologne, Department of Neurology, Cologne (Germany); University of Cologne, Center of Integrated Oncology (CIO), Cologne (Germany)

    2017-07-15

    We investigated the potential of textural feature analysis of O-(2-[{sup 18}F]fluoroethyl)-L-tyrosine ({sup 18}F-FET) PET to differentiate radiation injury from brain metastasis recurrence. Forty-seven patients with contrast-enhancing brain lesions (n = 54) on MRI after radiotherapy of brain metastases underwent dynamic {sup 18}F-FET PET. Tumour-to-brain ratios (TBRs) of {sup 18}F-FET uptake and 62 textural parameters were determined on summed images 20-40 min post-injection. Tracer uptake kinetics, i.e., time-to-peak (TTP) and patterns of time-activity curves (TAC) were evaluated on dynamic PET data from 0-50 min post-injection. Diagnostic accuracy of investigated parameters and combinations thereof to discriminate between brain metastasis recurrence and radiation injury was compared. Diagnostic accuracy increased from 81 % for TBR{sub mean} alone to 85 % when combined with the textural parameter Coarseness or Short-zone emphasis. The accuracy of TBR{sub max} alone was 83 % and increased to 85 % after combination with the textural parameters Coarseness, Short-zone emphasis, or Correlation. Analysis of TACs resulted in an accuracy of 70 % for kinetic pattern alone and increased to 83 % when combined with TBR{sub max}. Textural feature analysis in combination with TBRs may have the potential to increase diagnostic accuracy for discrimination between brain metastasis recurrence and radiation injury, without the need for dynamic {sup 18}F-FET PET scans. (orig.)

  20. Augmenting transcriptome assembly by combining de novo and genome-guided tools

    Directory of Open Access Journals (Sweden)

    Prachi Jain

    2013-08-01

    Full Text Available Researchers interested in studying and constructing transcriptomes, especially for non-model species, face the conundrum of choosing from a number of available de novo and genome-guided assemblers. None of the popular assembly tools in use today achieve requisite sensitivity, specificity or recovery of full-length transcripts on their own. Here, we present a comprehensive comparative study of the performance of various assemblers. Additionally, we present an approach to combinatorially augment transciptome assembly by using both de novo and genome-guided tools. In our study, we obtained the best recovery and most full-length transcripts with Trinity and TopHat1-Cufflinks, respectively. The sensitivity of the assembly and isoform recovery was superior, without compromising much on the specificity, when transcripts from Trinity were augmented with those from TopHat1-Cufflinks.

  1. Combining genomic sequencing methods to explore viral diversity and reveal potential virus-host interactions

    Directory of Open Access Journals (Sweden)

    Cheryl-Emiliane Tien Chow

    2015-04-01

    Full Text Available Viral diversity and virus-host interactions in oxygen-starved regions of the ocean, also known as oxygen minimum zones (OMZs, remain relatively unexplored. Microbial community metabolism in OMZs alters nutrient and energy flow through marine food webs, resulting in biological nitrogen loss and greenhouse gas production. Thus, viruses infecting OMZ microbes have the potential to modulate community metabolism with resulting feedback on ecosystem function. Here, we describe viral communities inhabiting oxic surface (10m and oxygen-starved basin (200m waters of Saanich Inlet, a seasonally anoxic fjord on the coast of Vancouver Island, British Columbia using viral metagenomics and complete viral fosmid sequencing on samples collected between April 2007 and April 2010. Of 6459 open reading frames (ORFs predicted across all 34 viral fosmids, 77.6% (n=5010 had no homology to reference viral genomes. These fosmids recruited a higher proportion of viral metagenomic sequences from Saanich Inlet than from nearby northeastern subarctic Pacific Ocean (Line P waters, indicating differences in the viral communities between coastal and open ocean locations. While functional annotations of fosmid ORFs were limited, recruitment to NCBI’s non-redundant ‘nr’ database and publicly available single-cell genomes identified putative viruses infecting marine thaumarchaeal and SUP05 proteobacteria to provide potential host linkages with relevance to coupled biogeochemical cycling processes in OMZ waters. Taken together, these results highlight the power of coupled analyses of multiple sequence data types, such as viral metagenomic and fosmid sequence data with prokaryotic single cell genomes, to chart viral diversity, elucidate genomic and ecological contexts for previously unclassifiable viral sequences, and identify novel host interactions in natural and engineered ecosystems.

  2. Evaluation of Breast Cancer Polyclonality by Combined Chromosome Banding and Comparative Genomic Hybridization Analysis

    Directory of Open Access Journals (Sweden)

    Manuel R. Teixeira

    2001-01-01

    Full Text Available Cytogenetically unrelated clones have been detected by chromosome banding analysis in many breast carcinomas. Because these karyotypic studies were performed on short-term cultured samples, it may be argued that in vitro selection occurred or that small clones may have arisen during culturing. To address this issue, we analyzed 37 breast carcinomas by Gbanding and comparative genomic hybridization (CGH, a fluorescent in situ hybridization-based screening technique that does not require culturing or tumor metaphases. All but two of the 37 karyotypically abnormal cases presented copy number changes by CGH. The picture of genomic alterations revealed by the two techniques overlapped only partly. Sometimes the CGH analysis revealed genomic imbalances that belonged to cell populations not picked up by the cytogenetic analysis and in other cases, especially when the karyotypes had many markers and chromosomes with additional material of unknown origin, CGH gave a more reliable overall picture of the copy number gains and losses. However, besides sometimes revealing cell populations with balanced chromosome aberrations or unbalanced changes that nevertheless remained undetected by CGH, G-banding analysis was essential to understand how the genomic imbalances arose in the many cases in which both techniques detected the same clonal abnormalities. Furthermore, because CGH pictures only imbalances present in a significant proportion of the test sample, the very detection by this technique of imbalances belonging to apparently small, cytogenetically unrelated clones of cells proves that these clones must have been present in vivo. This constitutes compelling evidence that the cytogenetic polyclonality observed after short-term culturing of breast carcinomas is not an artifact.

  3. Focused ion beam (FIB) combined with high resolution scanning electron microscopy: a promising tool for 3D analysis of chromosome architecture.

    Science.gov (United States)

    Schroeder-Reiter, Elizabeth; Pérez-Willard, Fabián; Zeile, Ulrike; Wanner, Gerhard

    2009-02-01

    Focused ion beam (FIB) milling in combination with field emission scanning electron microscopy (FESEM) was applied to investigations of metaphase barley chromosomes, providing new insight into the chromatin packaging in the chromosome interior and 3D distribution of histone variants in the centromeric region. Whole mount chromosomes were sectioned with FIB with thicknesses in the range of 7-20nm, resulting in up to 2000 sections, which allow high resolution three-dimensional reconstruction. For the first time, it could be shown that the chromosome interior is characterized by a network of interconnected cavities, with openings to the chromosome surface. In combination with immunogold labeling, the centromere-correlated distribution of histone variants (phosphorylated histone H3, CENH3) could be investigated with FIB in three dimensions. Limitations of classical SEM analysis of whole mount chromosomes with back-scattered electrons requiring higher accelerating voltages, e.g. faint and blurred interior signals, could be overcome with FIB milling: from within the chromosome even very small labels in the range of 10nm could be precisely visualized. This allowed direct quantification of marker molecules in a three-dimensional context. Distribution of DNA in the chromosome interior could be directly analyzed after staining with a DNA-specific platinorganic compound Platinum Blue. Higher resolution visualization of DNA distribution could be performed by preparation of FIB lamellae with the in situ lift-out technique followed by investigation in dark field with a scanning transmission electron detector (STEM) at 30kV.

  4. Profiling and classification of French propolis by combined multivariate data analysis of planar chromatograms and scanning direct analysis in real time mass spectra.

    Science.gov (United States)

    Chasset, Thibaut; Häbe, Tim T; Ristivojevic, Petar; Morlock, Gertrud E

    2016-09-23

    Quality control of propolis is challenging, as it is a complex natural mixture of compounds, and thus, very difficult to analyze and standardize. Shown on the example of 30 French propolis samples, a strategy for an improved quality control was demonstrated in which high-performance thin-layer chromatography (HPTLC) fingerprints were evaluated in combination with selected mass signals obtained by desorption-based scanning mass spectrometry (MS). The French propolis sample extracts were separated by a newly developed reversed phase (RP)-HPTLC method. The fingerprints obtained by two different detection modes, i.e. after (1) derivatization and fluorescence detection (FLD) at UV 366nm and (2) scanning direct analysis in real time (DART)-MS, were analyzed by multivariate data analysis. Thus, RP-HPTLC-FLD and RP-HPTLC-DART-MS fingerprints were explored and the best classification was obtained using both methods in combination with pattern recognition techniques, such as principal component analysis. All investigated French propolis samples were divided in two types and characteristic patterns were observed. Phenolic compounds such as caffeic acid, p-coumaric acid, chrysin, pinobanksin, pinobanksin-3-acetate, galangin, kaempferol, tectochrysin and pinocembrin were identified as characteristic marker compounds of French propolis samples. This study expanded the research on the European poplar type of propolis and confirmed the presence of two botanically different types of propolis, known as the blue and orange types. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Gold-FISH: a new approach for the in situ detection of single microbial cells combining fluorescence and scanning electron microscopy.

    Science.gov (United States)

    Schmidt, Hannes; Eickhorst, Thilo; Mussmann, Marc

    2012-12-01

    A novel fluorescence in situ hybridisation (FISH) method is presented that allows the combination of epifluorescence and scanning electron microscopy (SEM) to identify single microbial cells. First, the rRNA of whole cells is hybridised with horseradish peroxidase-labelled oligonucleotide probes and this is followed by catalysed reporter deposition (CARD) of biotinylated tyramides. This facilitates an amplification of binding sites for streptavidin conjugates covalently labelled with both fluorophores and nanogold particles. The deposition of Alexa Fluor 488 fluoro-nanogold-streptavidin conjugates was confirmed via epifluorescence microscopy and cells could be quantified in a similar way to standard CARD-FISH approaches. To detect cells by SEM, an autometallographic enhancement of the nanogold particles was essential, and allowed the in situ localisation of the target organisms at resolutions beyond light microscopy. Energy dispersive X-ray spectroscopy (EDS) was used to verify the effects of CARD and autometallography on gold deposition in target cells. The gold-FISH protocol was developed and optimised using pure cultures and environmental samples, such as rice roots and marine sediments. The combination of epifluorescence and scanning electron microscopy provides a promising tool for investigating microorganisms at levels of high resolution. Correlative characterisation of physicochemical properties by EDS will allow for the analysis of microbe-surface interactions. Copyright © 2012 Elsevier GmbH. All rights reserved.

  6. Combined de novo and genome guided assembly and annotation of the Pinus patula juvenile shoot transcriptome.

    Science.gov (United States)

    Visser, Erik A; Wegrzyn, Jill L; Steenkmap, Emma T; Myburg, Alexander A; Naidoo, Sanushka

    2015-12-12

    Pines are the most important tree species to the international forestry industry, covering 42 % of the global industrial forest plantation area. One of the most pressing threats to cultivation of some pine species is the pitch canker fungus, Fusarium circinatum, which can have devastating effects in both the field and nursery. Investigation of the Pinus-F. circinatum host-pathogen interaction is crucial for development of effective disease management strategies. As with many non-model organisms, investigation of host-pathogen interactions in pine species is hampered by limited genomic resources. This was partially alleviated through release of the 22 Gbp Pinus taeda v1.01 genome sequence ( http://pinegenome.org/pinerefseq/ ) in 2014. Despite the fact that the fragmented state of the genome may hamper comprehensive transcriptome analysis, it is possible to leverage the inherent redundancy resulting from deep RNA sequencing with Illumina short reads to assemble transcripts in the absence of a completed reference sequence. These data can then be integrated with available genomic data to produce a comprehensive transcriptome resource. The aim of this study was to provide a foundation for gene expression analysis of disease response mechanisms in Pinus patula through transcriptome assembly. Eighteen de novo and two reference based assemblies were produced for P. patula shoot tissue. For this purpose three transcriptome assemblers, Trinity, Velvet/OASES and SOAPdenovo-Trans, were used to maximise diversity and completeness of assembled transcripts. Redundancy in the assembly was reduced using the EvidentialGene pipeline. The resulting 52 Mb P. patula v1.0 shoot transcriptome consists of 52 112 unigenes, 60 % of which could be functionally annotated. The assembled transcriptome will serve as a major genomic resource for future investigation of P. patula and represents the largest gene catalogue produced to date for this species. Furthermore, this assembly can help detect

  7. Combined analysis of the chloroplast genome and transcriptome of the Antarctic vascular plant Deschampsia antarctica Desv.

    Directory of Open Access Journals (Sweden)

    Jungeun Lee

    Full Text Available BACKGROUND: Antarctic hairgrass (Deschampsia antarctica Desv. is the only natural grass species in the maritime Antarctic. It has been researched as an important ecological marker and as an extremophile plant for studies on stress tolerance. Despite its importance, little genomic information is available for D. antarctica. Here, we report the complete chloroplast genome, transcriptome profiles of the coding/noncoding genes, and the posttranscriptional processing by RNA editing in the chloroplast system. RESULTS: The complete chloroplast genome of D. antarctica is 135,362 bp in length with a typical quadripartite structure, including the large (LSC: 79,881 bp and small (SSC: 12,519 bp single-copy regions, separated by a pair of identical inverted repeats (IR: 21,481 bp. It contains 114 unique genes, including 81 unique protein-coding genes, 29 tRNA genes, and 4 rRNA genes. Sequence divergence analysis with other plastomes from the BEP clade of the grass family suggests a sister relationship between D. antarctica, Festuca arundinacea and Lolium perenne of the Poeae tribe, based on the whole plastome. In addition, we conducted high-resolution mapping of the chloroplast-derived transcripts. Thus, we created an expression profile for 81 protein-coding genes and identified ndhC, psbJ, rps19, psaJ, and psbA as the most highly expressed chloroplast genes. Small RNA-seq analysis identified 27 small noncoding RNAs of chloroplast origin that were preferentially located near the 5'- or 3'-ends of genes. We also found >30 RNA-editing sites in the D. antarctica chloroplast genome, with a dominance of C-to-U conversions. CONCLUSIONS: We assembled and characterized the complete chloroplast genome sequence of D. antarctica and investigated the features of the plastid transcriptome. These data may contribute to a better understanding of the evolution of D. antarctica within the Poaceae family for use in molecular phylogenetic studies and may also help researchers

  8. Full Genomic Characterization of a Novel Genotype Combination, G4P[14], of a Human Rotavirus Strain from Barbados

    OpenAIRE

    Tam, Ka Ian; Roy, Sunando; Esona, Mathew D.; Jones, Starlene; Sobers, Stephanie; Morris-Glasgow, Victoria; Rey-Benito, Gloria; Gentsch, Jon R.; Bowen, Michael D.

    2014-01-01

    Since 2004, the Pan American Health Organization (PAHO) has carried out rotavirus surveillance in Latin America and the Caribbean. Here we report the characterization of human rotavirus with the novel G-P combination of G4P[14], detected through PAHO surveillance in Barbados. Full genome sequencing of strain RVA/Human-wt/BRB/CDC1133/2012/G4P[14] revealed that its genotype is G4-P[14]-I1-R1-C1-M1-A8-N1-T1-E1-H1. The possession of a Genogroup 1 (Wa-like) backbone distinguishes this strain from ...

  9. An Islet-Targeted Genome-Wide Association Scan Identifies Novel Genes Implicated in Cytokine-Mediated Islet Stress in Type 2 Diabetes.

    Science.gov (United States)

    Sharma, Poonam R; Mackey, Aaron J; Dejene, Eden A; Ramadan, James W; Langefeld, Carl D; Palmer, Nicholette D; Taylor, Kent D; Wagenknecht, Lynne E; Watanabe, Richard M; Rich, Stephen S; Nunemaker, Craig S

    2015-09-01

    Genome-wide association studies in human type 2 diabetes (T2D) have renewed interest in the pancreatic islet as a contributor to T2D risk. Chronic low-grade inflammation resulting from obesity is a risk factor for T2D and a possible trigger of β-cell failure. In this study, microarray data were collected from mouse islets after overnight treatment with cytokines at concentrations consistent with the chronic low-grade inflammation in T2D. Genes with a cytokine-induced change of >2-fold were then examined for associations between single nucleotide polymorphisms and the acute insulin response to glucose (AIRg) using data from the Genetics Underlying Diabetes in Hispanics (GUARDIAN) Consortium. Significant evidence of association was found between AIRg and single nucleotide polymorphisms in Arap3 (5q31.3), F13a1 (6p25.3), Klhl6 (3q27.1), Nid1 (1q42.3), Pamr1 (11p13), Ripk2 (8q21.3), and Steap4 (7q21.12). To assess the potential relevance to islet function, mouse islets were exposed to conditions modeling low-grade inflammation, mitochondrial stress, endoplasmic reticulum (ER) stress, glucotoxicity, and lipotoxicity. RT-PCR revealed that one or more forms of stress significantly altered expression levels of all genes except Arap3. Thapsigargin-induced ER stress up-regulated both Pamr1 and Klhl6. Three genes confirmed microarray predictions of significant cytokine sensitivity: F13a1 was down-regulated 3.3-fold by cytokines, Ripk2 was up-regulated 1.5- to 3-fold by all stressors, and Steap4 was profoundly cytokine sensitive (167-fold up-regulation). Three genes were thus closely associated with low-grade inflammation in murine islets and also with a marker for islet function (AIRg) in a diabetes-prone human population. This islet-targeted genome-wide association scan identified several previously unrecognized candidate genes related to islet dysfunction during the development of T2D.

  10. Investigation of Yersinia pestis Laboratory Adaptation through a Combined Genomics and Proteomics Approach.

    Directory of Open Access Journals (Sweden)

    Owen P Leiser

    Full Text Available The bacterial pathogen Yersinia pestis, the cause of plague in humans and animals, normally has a sylvatic lifestyle, cycling between fleas and mammals. In contrast, laboratory-grown Y. pestis experiences a more constant environment and conditions that it would not normally encounter. The transition from the natural environment to the laboratory results in a vastly different set of selective pressures, and represents what could be considered domestication. Understanding the kinds of adaptations Y. pestis undergoes as it becomes domesticated will contribute to understanding the basic biology of this important pathogen. In this study, we performed a parallel serial passage experiment (PSPE to explore the mechanisms by which Y. pestis adapts to laboratory conditions, hypothesizing that cells would undergo significant changes in virulence and nutrient acquisition systems. Two wild strains were serially passaged in 12 independent populations each for ~750 generations, after which each population was analyzed using whole-genome sequencing, LC-MS/MS proteomic analysis, and GC/MS metabolomics. We observed considerable parallel evolution in the endpoint populations, detecting multiple independent mutations in ail, pepA, and zwf, suggesting that specific selective pressures are shaping evolutionary responses. Complementary LC-MS/MS proteomic data provide physiological context to the observed mutations, and reveal regulatory changes not necessarily associated with specific mutations, including changes in amino acid metabolism and cell envelope biogenesis. Proteomic data support hypotheses generated by genomic data in addition to suggesting future mechanistic studies, indicating that future whole-genome sequencing studies be designed to leverage proteomics as a critical complement.

  11. Genome characterisation of the newly discovered avian influenza A H5N7 virus subtype combination

    DEFF Research Database (Denmark)

    Bragstad, K.; Jørgensen, Poul Henrik; Handberg, K.J.

    2007-01-01

    In Denmark, in 2003, a previously unknown subtype combination of avian influenza A virus, H5N7 (A/Mallard/Denmark/64650/03), was isolated from a flock of 12,000 mallards. The H5N7 subtype combination might be a reassortant between recent European avian influenza A H5, H7, and a third subtype, pos...

  12. Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo.

    Science.gov (United States)

    Yin, Hao; Song, Chun-Qing; Dorkin, Joseph R; Zhu, Lihua J; Li, Yingxiang; Wu, Qiongqiong; Park, Angela; Yang, Junghoon; Suresh, Sneha; Bizhanova, Aizhan; Gupta, Ankit; Bolukbasi, Mehmet F; Walsh, Stephen; Bogorad, Roman L; Gao, Guangping; Weng, Zhiping; Dong, Yizhou; Koteliansky, Victor; Wolfe, Scot A; Langer, Robert; Xue, Wen; Anderson, Daniel G

    2016-03-01

    The combination of Cas9, guide RNA and repair template DNA can induce precise gene editing and the correction of genetic diseases in adult mammals. However, clinical implementation of this technology requires safe and effective delivery of all of these components into the nuclei of the target tissue. Here, we combine lipid nanoparticle-mediated delivery of Cas9 mRNA with adeno-associated viruses encoding a sgRNA and a repair template to induce repair of a disease gene in adult animals. We applied our delivery strategy to a mouse model of human hereditary tyrosinemia and show that the treatment generated fumarylacetoacetate hydrolase (Fah)-positive hepatocytes by correcting the causative Fah-splicing mutation. Treatment rescued disease symptoms such as weight loss and liver damage. The efficiency of correction was >6% of hepatocytes after a single application, suggesting potential utility of Cas9-based therapeutic genome editing for a range of diseases.

  13. Combining genome shuffling and interspecific hybridization among Streptomyces improved ε-poly-L-lysine production.

    Science.gov (United States)

    Li, Shu; Chen, Xusheng; Dong, Chuanliang; Zhao, Fulin; Tang, Lei; Mao, Zhonggui

    2013-01-01

    Here we first improved the ε-PL productivity in five species of wild-type strains in Streptomyces (Streptomyces padanus, Streptomyces griseofuscus, Streptomyces graminearus, Streptomyces hygroscopicus, and Streptomyces albulus) by genome shuffling. Then all the shuffled strains were suffered from an interspecific hybridization through stochastic protoplast fusion. One hybrid designated FEEL-1 was selected by morphology and spore color with ε-PL production of 1.12 g/L in shake flask, about 2.75-fold higher than that in wild types. The ε-PL production of FEEL-1 was then obtained as 24.5 g/L in fed-batch fermentation, which was 63-81 % higher than those in shuffled strains. Random amplified polymorphic DNA revealed that FEEL-1 was probably hybridized from S. padanus, S. griseofuscus, and S. albulus. Activities of several enzymes in FEEL-1 (hexokinase, phosphoenolpyruvate carboxylase, aspartokinase, and citrate synthase) were more active than those in shuffled strains, which was a possible reason for the enhancement of ε-PL production. This research highlights the importance of genome shuffling along with interspecific hybridization as a new breeding strategy for improving phenotype of industrial strains.

  14. Combining applications and remote databases view in a common SQL distributed genomic database

    Directory of Open Access Journals (Sweden)

    Pierre-Emmanuel Gros

    2006-01-01

    Full Text Available Huge volumes of bioinformatics data are emerging from sequencing efforts, gene expression assays, X-ray crystallography of proteins, and many other activities. High-throughput experimental methods produce masses of data, so that the whole of biology has changed from a data-light science into a data-driven science. Currently there are a lot of databases and software tools dealing with these genomic data. In general, each tool and database uses a different type of data in exchange protocols, and usually they offer specific services. These Databases are design with different languages and run on different operating systems. Therefore biologists are in a difficult situation where they have to use, process and store heterogeneous data when using heterogeneous software tools and databases. Our framework, GenoMEDIA provides two main middleware to help for this integration, Lydia and Antje. On the one hand, the Lydia middleware offers us facilities for working simultaneously with a variety of Services and Databases. On the other hand, the Antje one ,with the concept of remote view, is designed to allow users to manage multiple heterogeneous remote databases in a uniform vision. The aim of this paper is to present GenoMEDIA and how heterogeneous databases and remote services are integrated, in particular how Antje was designed, implemented and tested with various genomic

  15. Genomic scans detect signatures of selection along a salinity gradient in populations of the intertidal seaweed Fucus serratus on a 12 km scale.

    Science.gov (United States)

    Coyer, J A; Hoarau, G; Pearson, G; Mota, C; Jüterbock, A; Alpermann, T; John, U; Olsen, J L

    2011-03-01

    Detecting natural selection in wild populations is a central challenge in evolutionary biology and genomic scans are an important means of detecting allele frequencies that deviate from neutral expectations among marker loci. We used nine anonymous and 15 EST-linked microsatellites, 362 AFLP loci, and several neutrality tests, to identify outlier loci when comparing four populations of the seaweed Fucus serratus spaced along a 12km intertidal shore with a steep salinity gradient. Under criteria of at least two significant tests in at least two population pairs, three EST-derived and three anonymous loci revealed putative signatures of selection. Anonymous locus FsB113 was a consistent outlier when comparing least saline to fully marine sites. Locus F37 was an outlier when comparing the least saline to more saline areas, and was annotated as a polyol transporter/putative mannitol transporter - an important sugar-alcohol associated with osmoregulation by brown algae. The remaining loci could not be annotated using six different data bases. Exclusion of microsatellite outlier loci did not change either the degree or direction of differentiation among populations. In one outlier test, the number of AFLP outlier loci increased as the salinity differences between population pairs increased (up to 14); only four outliers were detected with the second test and only one was consistent with both tests. Consistency may be improved with a much more rigorous approach to replication and/or may be dependent upon the class of marker used. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. Analysis of subglacial hydrodynamics and ice dynamics through combined terrestrial laser scanning and ground penetrating radar survey

    Science.gov (United States)

    Gabbud, Chrystelle; Rüttimann, Sébastien; Micheletti, Natan; Irving, James; Lane, Stuart

    2015-04-01

    This study shows how high resolution surveys of subglacial channel morphology combined with high resolution terrestrial laser scanner survey of an Alpine glacier help to understand subglacial hydrological forcing of ice dynamics. The study area is the Haut Glacier d'Arolla in Switzerland, an Alpine valley glacier for which subglacial drainage system has been well studied. A new generation of terrestrial laser scanners was used to investigate glacier surface ablation and other elements of glacial hydrodynamics at exceptionally high spatial and temporal resolution. The LiDAR RIEGL VZ-6000 scanner, with a laser 3B specifically designed for measurements of snow and ice cover surfaces, was tested at seasonal and daily scales. The data revealed spatial variations in the patterns of surface melt, controlled by both aspect and differential debris cover at the seasonal scale, and controlled by ogive-related differences in ice surface debris content at the daily scale. More tentatively, intra-daily scale measurements pointed to possible hydraulic jacking of the glacier associated with short-term water pressure rises at the downstream part of the glacier. A ground-penetrating radar (GPR) field campaign was conducted a year later in the location where possible hydraulic jacking had been detected previously. The aims of this campaign were (i) to assess GPR usage for subglacial channel detection; (ii) identify more precisely the channel morphology; and (iii) investigate further the hydraulic jacking hypothesis. 100 MHz antennas were used to map a 240 x 34 m area near the glacier snout where the ice thickness did not exceed 50 m. The corresponding data, after processing, allowed reconstruction of the bed topography and the morphology of subglacial channels in 3D, showing two of the latter in this area. One channel was followed for approximately 20 m upglacier and corresponding morphology estimates were performed. These data allowed for 3D reconstructions of both the bed

  17. Increasing Genome Sampling and Improving SNP Genotyping for Genotyping-by-Sequencing with New Combinations of Restriction Enzymes

    OpenAIRE

    Yong-Bi Fu; Gregory W. Peterson; Yibo Dong

    2016-01-01

    Genotyping-by-sequencing (GBS) has emerged as a useful genomic approach for exploring genome-wide genetic variation. However, GBS commonly samples a genome unevenly and can generate a substantial amount of missing data. These technical features would limit the power of various GBS-based genetic and genomic analyses. Here we present software called IgCoverage for in silico evaluation of genomic coverage through GBS with an individual or pair of restriction enzymes on one sequenced genome, and ...

  18. Nuclear Scans

    Science.gov (United States)

    Nuclear scans use radioactive substances to see structures and functions inside your body. They use a special ... images. Most scans take 20 to 45 minutes. Nuclear scans can help doctors diagnose many conditions, including ...

  19. Radiation injury vs. recurrent brain metastasis: combining textural feature radiomics analysis and standard parameters may increase18F-FET PET accuracy without dynamic scans.

    Science.gov (United States)

    Lohmann, Philipp; Stoffels, Gabriele; Ceccon, Garry; Rapp, Marion; Sabel, Michael; Filss, Christian P; Kamp, Marcel A; Stegmayr, Carina; Neumaier, Bernd; Shah, Nadim J; Langen, Karl-Josef; Galldiks, Norbert

    2017-07-01

    We investigated the potential of textural feature analysis of O-(2-[ 18 F]fluoroethyl)-L-tyrosine ( 18 F-FET) PET to differentiate radiation injury from brain metastasis recurrence. Forty-seven patients with contrast-enhancing brain lesions (n = 54) on MRI after radiotherapy of brain metastases underwent dynamic 18 F-FET PET. Tumour-to-brain ratios (TBRs) of 18 F-FET uptake and 62 textural parameters were determined on summed images 20-40 min post-injection. Tracer uptake kinetics, i.e., time-to-peak (TTP) and patterns of time-activity curves (TAC) were evaluated on dynamic PET data from 0-50 min post-injection. Diagnostic accuracy of investigated parameters and combinations thereof to discriminate between brain metastasis recurrence and radiation injury was compared. Diagnostic accuracy increased from 81 % for TBR mean alone to 85 % when combined with the textural parameter Coarseness or Short-zone emphasis. The accuracy of TBR max alone was 83 % and increased to 85 % after combination with the textural parameters Coarseness, Short-zone emphasis, or Correlation. Analysis of TACs resulted in an accuracy of 70 % for kinetic pattern alone and increased to 83 % when combined with TBR max . Textural feature analysis in combination with TBRs may have the potential to increase diagnostic accuracy for discrimination between brain metastasis recurrence and radiation injury, without the need for dynamic 18 F-FET PET scans. • Textural feature analysis provides quantitative information about tumour heterogeneity • Textural features help improve discrimination between brain metastasis recurrence and radiation injury • Textural features might be helpful to further understand tumour heterogeneity • Analysis does not require a more time consuming dynamic PET acquisition.

  20. Combining functional and structural genomics to sample the essential Burkholderia structome.

    Directory of Open Access Journals (Sweden)

    Loren Baugh

    Full Text Available The genus Burkholderia includes pathogenic gram-negative bacteria that cause melioidosis, glanders, and pulmonary infections of patients with cancer and cystic fibrosis. Drug resistance has made development of new antimicrobials critical. Many approaches to discovering new antimicrobials, such as structure-based drug design and whole cell phenotypic screens followed by lead refinement, require high-resolution structures of proteins essential to the parasite.We experimentally identified 406 putative essential genes in B. thailandensis, a low-virulence species phylogenetically similar to B. pseudomallei, the causative agent of melioidosis, using saturation-level transposon mutagenesis and next-generation sequencing (Tn-seq. We selected 315 protein products of these genes based on structure-determination criteria, such as excluding very large and/or integral membrane proteins, and entered them into the Seattle Structural Genomics Center for Infection Disease (SSGCID structure determination pipeline. To maximize structural coverage of these targets, we applied an "ortholog rescue" strategy for those producing insoluble or difficult to crystallize proteins, resulting in the addition of 387 orthologs (or paralogs from seven other Burkholderia species into the SSGCID pipeline. This structural genomics approach yielded structures from 31 putative essential targets from B. thailandensis, and 25 orthologs from other Burkholderia species, yielding an overall structural coverage for 49 of the 406 essential gene families, with a total of 88 depositions into the Protein Data Bank. Of these, 25 proteins have properties of a potential antimicrobial drug target i.e., no close human homolog, part of an essential metabolic pathway, and a deep binding pocket. We describe the structures of several potential drug targets in detail.This collection of structures, solubility and experimental essentiality data provides a resource for development of drugs against

  1. Combining functional and structural genomics to sample the essential Burkholderia structome.

    Science.gov (United States)

    Baugh, Loren; Gallagher, Larry A; Patrapuvich, Rapatbhorn; Clifton, Matthew C; Gardberg, Anna S; Edwards, Thomas E; Armour, Brianna; Begley, Darren W; Dieterich, Shellie H; Dranow, David M; Abendroth, Jan; Fairman, James W; Fox, David; Staker, Bart L; Phan, Isabelle; Gillespie, Angela; Choi, Ryan; Nakazawa-Hewitt, Steve; Nguyen, Mary Trang; Napuli, Alberto; Barrett, Lynn; Buchko, Garry W; Stacy, Robin; Myler, Peter J; Stewart, Lance J; Manoil, Colin; Van Voorhis, Wesley C

    2013-01-01

    The genus Burkholderia includes pathogenic gram-negative bacteria that cause melioidosis, glanders, and pulmonary infections of patients with cancer and cystic fibrosis. Drug resistance has made development of new antimicrobials critical. Many approaches to discovering new antimicrobials, such as structure-based drug design and whole cell phenotypic screens followed by lead refinement, require high-resolution structures of proteins essential to the parasite. We experimentally identified 406 putative essential genes in B. thailandensis, a low-virulence species phylogenetically similar to B. pseudomallei, the causative agent of melioidosis, using saturation-level transposon mutagenesis and next-generation sequencing (Tn-seq). We selected 315 protein products of these genes based on structure-determination criteria, such as excluding very large and/or integral membrane proteins, and entered them into the Seattle Structural Genomics Center for Infection Disease (SSGCID) structure determination pipeline. To maximize structural coverage of these targets, we applied an "ortholog rescue" strategy for those producing insoluble or difficult to crystallize proteins, resulting in the addition of 387 orthologs (or paralogs) from seven other Burkholderia species into the SSGCID pipeline. This structural genomics approach yielded structures from 31 putative essential targets from B. thailandensis, and 25 orthologs from other Burkholderia species, yielding an overall structural coverage for 49 of the 406 essential gene families, with a total of 88 depositions into the Protein Data Bank. Of these, 25 proteins have properties of a potential antimicrobial drug target i.e., no close human homolog, part of an essential metabolic pathway, and a deep binding pocket. We describe the structures of several potential drug targets in detail. This collection of structures, solubility and experimental essentiality data provides a resource for development of drugs against infections and diseases

  2. Investigation of atomic species in Pt-induced nanowires on Ge(001) surface by combined atomic force and scanning tunneling microscopy

    Science.gov (United States)

    Inami, Eiichi; Sugimoto, Yoshiaki; Shinozaki, Takuya; Gurlu, Oguzhan; Yurtsever, Ayhan

    2017-10-01

    We have studied identification of atomic species in Pt-induced nanowires self-assembled on the Ge(001) surface by combining scanning tunneling microscopy (STM) and atomic force microscopy (AFM). A small number of Sn atoms substituted in the top atomic chains were utilized as references to identify the target atomic species. Force spectroscopy data taken above single atoms on the Sn-substituted nanowires showed that the ratio between the maximum attractive forces above the Sn and the pristine chain atoms exhibited a constant value of 0.86. The obtained ratio was identical to that between Sn and Ge atoms, strongly suggestive that the top ridge of the Pt-induced nanowire was composed of Ge dimers. Our findings also demonstrate that AFM chemical identification method can be used to identify the unknown atomic species on surfaces, regardless of the homogeneity in the atomic composition, which has not been addressed so far.

  3. A high-resolution combined scanning laser and widefield polarizing microscope for imaging at temperatures from 4 K to 300 K.

    Science.gov (United States)

    Lange, M; Guénon, S; Lever, F; Kleiner, R; Koelle, D

    2017-12-01

    Polarized light microscopy, as a contrast-enhancing technique for optically anisotropic materials, is a method well suited for the investigation of a wide variety of effects in solid-state physics, as, for example, birefringence in crystals or the magneto-optical Kerr effect (MOKE). We present a microscopy setup that combines a widefield microscope and a confocal scanning laser microscope with polarization-sensitive detectors. By using a high numerical aperture objective, a spatial resolution of about 240 nm at a wavelength of 405 nm is achieved. The sample is mounted on a 4He continuous flow cryostat providing a temperature range between 4 K and 300 K, and electromagnets are used to apply magnetic fields of up to 800 mT with variable in-plane orientation and 20 mT with out-of-plane orientation. Typical applications of the polarizing microscope are the imaging of the in-plane and out-of-plane magnetization via the longitudinal and polar MOKE, imaging of magnetic flux structures in superconductors covered with a magneto-optical indicator film via the Faraday effect, or imaging of structural features, such as twin-walls in tetragonal SrTiO3. The scanning laser microscope furthermore offers the possibility to gain local information on electric transport properties of a sample by detecting the beam-induced voltage change across a current-biased sample. This combination of magnetic, structural, and electric imaging capabilities makes the microscope a viable tool for research in the fields of oxide electronics, spintronics, magnetism, and superconductivity.

  4. A high-resolution combined scanning laser and widefield polarizing microscope for imaging at temperatures from 4 K to 300 K

    Science.gov (United States)

    Lange, M.; Guénon, S.; Lever, F.; Kleiner, R.; Koelle, D.

    2017-12-01

    Polarized light microscopy, as a contrast-enhancing technique for optically anisotropic materials, is a method well suited for the investigation of a wide variety of effects in solid-state physics, as, for example, birefringence in crystals or the magneto-optical Kerr effect (MOKE). We present a microscopy setup that combines a widefield microscope and a confocal scanning laser microscope with polarization-sensitive detectors. By using a high numerical aperture objective, a spatial resolution of about 240 nm at a wavelength of 405 nm is achieved. The sample is mounted on a 4He continuous flow cryostat providing a temperature range between 4 K and 300 K, and electromagnets are used to apply magnetic fields of up to 800 mT with variable in-plane orientation and 20 mT with out-of-plane orientation. Typical applications of the polarizing microscope are the imaging of the in-plane and out-of-plane magnetization via the longitudinal and polar MOKE, imaging of magnetic flux structures in superconductors covered with a magneto-optical indicator film via the Faraday effect, or imaging of structural features, such as twin-walls in tetragonal SrTiO3. The scanning laser microscope furthermore offers the possibility to gain local information on electric transport properties of a sample by detecting the beam-induced voltage change across a current-biased sample. This combination of magnetic, structural, and electric imaging capabilities makes the microscope a viable tool for research in the fields of oxide electronics, spintronics, magnetism, and superconductivity.

  5. Genome-wide scan identifies variant in TNFSF13 associated with serum IgM in a healthy Chinese male population.

    Directory of Open Access Journals (Sweden)

    Ming Yang

    Full Text Available IgM provides a first line of defense during microbial infections. Serum IgM levels are detected routinely in clinical practice. And IgM is a genetically complex trait. We conducted a two-stage genome-wide association study (GWAS to identify genetic variants affecting serum IgM levels in a Chinese population of 3495, including 1999 unrelated subjects in the first stage and 1496 independent individuals in the second stage. Our data show that a common single nucleotide polymorphism (SNP, rs11552708 located in the TNFSF13 gene was significantly associated with IgM levels (p = 5.00×10(-7 in first stage, p = 1.34×10(-3 in second stage, and p = 4.22×10(-9 when combined. Besides, smoking was identified to be associated with IgM levels in both stages (P0.05. It is suggested that TNFSF13 may be a susceptibility gene affecting serum IgM levels in Chinese male population.

  6. Using regulatory and epistatic networks to extend the findings of a genome scan: identifying the gene drivers of pigmentation in merino sheep.

    Directory of Open Access Journals (Sweden)

    Elsa García-Gámez

    Full Text Available Extending genome wide association analysis by the inclusion of gene expression data may assist in the dissection of complex traits. We examined piebald, a pigmentation phenotype in both human and Merino sheep, by analysing multiple data types using a systems approach. First, a case control analysis of 49,034 ovine SNP was performed which confirmed a multigenic basis for the condition. We combined these results with gene expression data from five tissue types analysed with a skin-specific microarray. Promoter sequence analysis of differentially expressed genes allowed us to reverse-engineer a regulatory network. Likewise, by testing two-loci models derived from all pair-wise comparisons across piebald-associated SNP, we generated an epistatic network. At the intersection of both networks, we identified thirteen genes with insulin-like growth factor binding protein 7 (IGFBP7, platelet-derived growth factor alpha (PDGFRA and the tetraspanin platelet activator CD9 at the kernel of the intersection. Further, we report a number of differentially expressed genes in regions containing highly associated SNP including ATRN, DOCK7, FGFR1OP, GLI3, SILV and TBX15. The application of network theory facilitated co-analysis of genetic variation with gene expression, recapitulated aspects of the known molecular biology of skin pigmentation and provided insights into the transcription regulation and epistatic interactions involved in piebald Merino sheep.

  7. Combining Multiple Hypothesis Testing with Machine Learning Increases the Statistical Power of Genome-wide Association Studies

    Science.gov (United States)

    Mieth, Bettina; Kloft, Marius; Rodríguez, Juan Antonio; Sonnenburg, Sören; Vobruba, Robin; Morcillo-Suárez, Carlos; Farré, Xavier; Marigorta, Urko M.; Fehr, Ernst; Dickhaus, Thorsten; Blanchard, Gilles; Schunk, Daniel; Navarro, Arcadi; Müller, Klaus-Robert

    2016-01-01

    The standard approach to the analysis of genome-wide association studies (GWAS) is based on testing each position in the genome individually for statistical significance of its association with the phenotype under investigation. To improve the analysis of GWAS, we propose a combination of machine learning and statistical testing that takes correlation structures within the set of SNPs under investigation in a mathematically well-controlled manner into account. The novel two-step algorithm, COMBI, first trains a support vector machine to determine a subset of candidate SNPs and then performs hypothesis tests for these SNPs together with an adequate threshold correction. Applying COMBI to data from a WTCCC study (2007) and measuring performance as replication by independent GWAS published within the 2008–2015 period, we show that our method outperforms ordinary raw p-value thresholding as well as other state-of-the-art methods. COMBI presents higher power and precision than the examined alternatives while yielding fewer false (i.e. non-replicated) and more true (i.e. replicated) discoveries when its results are validated on later GWAS studies. More than 80% of the discoveries made by COMBI upon WTCCC data have been validated by independent studies. Implementations of the COMBI method are available as a part of the GWASpi toolbox 2.0. PMID:27892471

  8. Combining Multiple Hypothesis Testing with Machine Learning Increases the Statistical Power of Genome-wide Association Studies

    Science.gov (United States)

    Mieth, Bettina; Kloft, Marius; Rodríguez, Juan Antonio; Sonnenburg, Sören; Vobruba, Robin; Morcillo-Suárez, Carlos; Farré, Xavier; Marigorta, Urko M.; Fehr, Ernst; Dickhaus, Thorsten; Blanchard, Gilles; Schunk, Daniel; Navarro, Arcadi; Müller, Klaus-Robert

    2016-11-01

    The standard approach to the analysis of genome-wide association studies (GWAS) is based on testing each position in the genome individually for statistical significance of its association with the phenotype under investigation. To improve the analysis of GWAS, we propose a combination of machine learning and statistical testing that takes correlation structures within the set of SNPs under investigation in a mathematically well-controlled manner into account. The novel two-step algorithm, COMBI, first trains a support vector machine to determine a subset of candidate SNPs and then performs hypothesis tests for these SNPs together with an adequate threshold correction. Applying COMBI to data from a WTCCC study (2007) and measuring performance as replication by independent GWAS published within the 2008-2015 period, we show that our method outperforms ordinary raw p-value thresholding as well as other state-of-the-art methods. COMBI presents higher power and precision than the examined alternatives while yielding fewer false (i.e. non-replicated) and more true (i.e. replicated) discoveries when its results are validated on later GWAS studies. More than 80% of the discoveries made by COMBI upon WTCCC data have been validated by independent studies. Implementations of the COMBI method are available as a part of the GWASpi toolbox 2.0.

  9. A novel method, digital genome scanning detects KRAS gene amplification in gastric cancers: involvement of overexpressed wild-type KRAS in downstream signaling and cancer cell growth

    Directory of Open Access Journals (Sweden)

    Yanagihara Kazuyoshi

    2009-06-01

    Full Text Available Abstract Background Gastric cancer is the third most common malignancy affecting the general population worldwide. Aberrant activation of KRAS is a key factor in the development of many types of tumor, however, oncogenic mutations of KRAS are infrequent in gastric cancer. We have developed a novel quantitative method of analysis of DNA copy number, termed digital genome scanning (DGS, which is based on the enumeration of short restriction fragments, and does not involve PCR or hybridization. In the current study, we used DGS to survey copy-number alterations in gastric cancer cells. Methods DGS of gastric cancer cell lines was performed using the sequences of 5000 to 15000 restriction fragments. We screened 20 gastric cancer cell lines and 86 primary gastric tumors for KRAS amplification by quantitative PCR, and investigated KRAS amplification at the DNA, mRNA and protein levels by mutational analysis, real-time PCR, immunoblot analysis, GTP-RAS pull-down assay and immunohistochemical analysis. The effect of KRAS knock-down on the activation of p44/42 MAP kinase and AKT and on cell growth were examined by immunoblot and colorimetric assay, respectively. Results DGS analysis of the HSC45 gastric cancer cell line revealed the amplification of a 500-kb region on chromosome 12p12.1, which contains the KRAS gene locus. Amplification of the KRAS locus was detected in 15% (3/20 of gastric cancer cell lines (8–18-fold amplification and 4.7% (4/86 of primary gastric tumors (8–50-fold amplification. KRAS mutations were identified in two of the three cell lines in which KRAS was amplified, but were not detected in any of the primary tumors. Overexpression of KRAS protein correlated directly with increased KRAS copy number. The level of GTP-bound KRAS was elevated following serum stimulation in cells with amplified wild-type KRAS, but not in cells with amplified mutant KRAS. Knock-down of KRAS in gastric cancer cells that carried amplified wild

  10. Smear layer removal efficacy of combination of herbal extracts in two different ratios either alone or supplemented with sonic agitation: An in vitro scanning electron microscope study.

    Science.gov (United States)

    Chhabra, Naveen; Gyanani, Hitesh; Kamatagi, Laxmikant

    2015-01-01

    The study aimed to evaluate the effectiveness of the combination of two natural extracts in varying ratios for removal of smear layer either alone or supplemented with sonic agitation. Fifty extracted single-rooted teeth were collected, disinfected and decoronated below the cementoenamel junction to obtain standardized root length of 10 mm. Root canals were instrumented using rotary files at working length 1 mm short of the apex. Specimens were divided into six groups according to the irrigation protocol as follows: Group A - Distilled water, Group B - 17% ethylenediaminetetraacetic acid, Group C - Herbal extracts in 1:1 ratio, Group D - Herbal extracts in 1:1 ratio supplemented with sonic agitation, Group E - Herbal extracts in 2:1 ratio, Group F - Herbal extracts in 2:1 ratio supplemented with sonic agitation. Specimens were longitudinally sectioned and evaluated under scanning electron microscope for smear layer removal efficacy. Obtained scores were statistically analyzed using one-way analysis of variance and post-hoc test. Among all, Group B showed the best results followed by Group F. Remaining other groups showed inferior outcome (P < 0.05). The combination of two extracts in 2:1 ratio was slightly better than 1:1 ratio and the smear layer removal efficacy was further improved when accompanied with sonic agitation.

  11. Smear layer removal efficacy of combination of herbal extracts in two different ratios either alone or supplemented with sonic agitation: An in vitro scanning electron microscope study

    Science.gov (United States)

    Chhabra, Naveen; Gyanani, Hitesh; Kamatagi, Laxmikant

    2015-01-01

    Objectives: The study aimed to evaluate the effectiveness of the combination of two natural extracts in varying ratios for removal of smear layer either alone or supplemented with sonic agitation. Materials and Methods: Fifty extracted single-rooted teeth were collected, disinfected and decoronated below the cementoenamel junction to obtain standardized root length of 10 mm. Root canals were instrumented using rotary files at working length 1 mm short of the apex. Specimens were divided into six groups according to the irrigation protocol as follows: Group A – Distilled water, Group B – 17% ethylenediaminetetraacetic acid, Group C – Herbal extracts in 1:1 ratio, Group D – Herbal extracts in 1:1 ratio supplemented with sonic agitation, Group E – Herbal extracts in 2:1 ratio, Group F – Herbal extracts in 2:1 ratio supplemented with sonic agitation. Specimens were longitudinally sectioned and evaluated under scanning electron microscope for smear layer removal efficacy. Obtained scores were statistically analyzed using one-way analysis of variance and post-hoc test. Results: Among all, Group B showed the best results followed by Group F. Remaining other groups showed inferior outcome (P < 0.05). Conclusion: The combination of two extracts in 2:1 ratio was slightly better than 1:1 ratio and the smear layer removal efficacy was further improved when accompanied with sonic agitation. PMID:26430300

  12. New insights into the painting stratigraphy of L'Homme blesse by Gustave Courbet combining scanning macro-XRF and confocal micro-XRF

    Energy Technology Data Exchange (ETDEWEB)

    Reiche, Ina [Staatliche Museen zu Berlin-Preussischer Kulturbesitz, Rathgen-Forschungslabor, Berlin (Germany); Laboratoire d' Archeologie Moleculaire et Structurale, Sorbonne Universites, Univ. Paris 06, CNRS, UMR 8220, Paris (France); Eveno, Myriam; Pichon, Laurent; Laval, Eric; Mottin, Bruno [Centre de Recherche et de Restauration des Musees de France (C2RMF), Paris (France); Mueller, Katharina [Laboratoire d' Archeologie Moleculaire et Structurale, Sorbonne Universites, Univ. Paris 06, CNRS, UMR 8220, Paris (France); Calligaro, Thomas [Centre de Recherche et de Restauration des Musees de France (C2RMF), Paris (France); PSL Research University, Chimie ParisTech-CNRS, Institut de Recherche Chimie Paris, Paris (France); Mysak, Erin [Centre de Recherche et de Restauration des Musees de France (C2RMF), Paris (France); Yale University, Institute for the Preservation of Cultural Heritage, New Haven, CT (United States)

    2016-11-15

    The painting L'Homme blesse by Gustave Courbet kept at the Musee d'Orsay in Paris has been recently studied by X-ray radiography, SEM-EDX observation of paint cross sections and confocal micro-X-ray fluorescence analyses (CXRF) at locations where the cross section samples were taken. This study allowed the establishment of the paint palette used by Courbet for the three paint compositions. Eight or more paint layers could be evidenced. In the view of the complexity of this painting, further analyses using two-dimensional scanning macro-X-ray fluorescence imaging (MA-XRF) providing chemical images corresponding to the superimposition of all detectable paint layers were employed. This method is combined with CXRF for depth-resolved paint layer analysis. Large elemental maps of Hg, Cu, As, Fe, Zn, Cr, Ba, Pb and Ca were obtained by MA-XRF on the painting and are discussed in combination with depth profiles obtained by CXRF on strategic points where three painting compositions overlap. The order of three successive compositions of this painting were determined in this study. This work also highlights the benefits of using complementary imaging methods to obtain a complete three-dimensional vision of the chemistry and stratigraphy of paintings. (orig.)

  13. Detection of clonal evolution in hematopoietic malignancies by combining comparative genomic hybridization and single nucleotide polymorphism arrays.

    Science.gov (United States)

    Hartmann, Luise; Stephenson, Christine F; Verkamp, Stephanie R; Johnson, Krystal R; Burnworth, Bettina; Hammock, Kelle; Brodersen, Lisa Eidenschink; de Baca, Monica E; Wells, Denise A; Loken, Michael R; Zehentner, Barbara K

    2014-12-01

    Array comparative genomic hybridization (aCGH) has become a powerful tool for analyzing hematopoietic neoplasms and identifying genome-wide copy number changes in a single assay. aCGH also has superior resolution compared with fluorescence in situ hybridization (FISH) or conventional cytogenetics. Integration of single nucleotide polymorphism (SNP) probes with microarray analysis allows additional identification of acquired uniparental disomy, a copy neutral aberration with known potential to contribute to tumor pathogenesis. However, a limitation of microarray analysis has been the inability to detect clonal heterogeneity in a sample. This study comprised 16 samples (acute myeloid leukemia, myelodysplastic syndrome, chronic lymphocytic leukemia, plasma cell neoplasm) with complex cytogenetic features and evidence of clonal evolution. We used an integrated manual peak reassignment approach combining analysis of aCGH and SNP microarray data for characterization of subclonal abnormalities. We compared array findings with results obtained from conventional cytogenetic and FISH studies. Clonal heterogeneity was detected in 13 of 16 samples by microarray on the basis of log2 values. Use of the manual peak reassignment analysis approach improved resolution of the sample's clonal composition and genetic heterogeneity in 10 of 13 (77%) patients. Moreover, in 3 patients, clonal disease progression was revealed by array analysis that was not evident by cytogenetic or FISH studies. Genetic abnormalities originating from separate clonal subpopulations can be identified and further characterized by combining aCGH and SNP hybridization results from 1 integrated microarray chip by use of the manual peak reassignment technique. Its clinical utility in comparison to conventional cytogenetic or FISH studies is demonstrated. © 2014 American Association for Clinical Chemistry.

  14. Combining Genome-Wide Information with a Functional Structural Plant Model to Simulate 1-Year-Old Apple Tree Architecture

    Science.gov (United States)

    Migault, Vincent; Pallas, Benoît; Costes, Evelyne

    2017-01-01

    In crops, optimizing target traits in breeding programs can be fostered by selecting appropriate combinations of architectural traits which determine light interception and carbon acquisition. In apple tree, architectural traits were observed to be under genetic control. However, architectural traits also result from many organogenetic and morphological processes interacting with the environment. The present study aimed at combining a FSPM built for apple tree, MAppleT, with genetic determinisms of architectural traits, previously described in a bi-parental population. We focused on parameters related to organogenesis (phyllochron and immediate branching) and morphogenesis processes (internode length and leaf area) during the first year of tree growth. Two independent datasets collected in 2004 and 2007 on 116 genotypes, issued from a ‘Starkrimson’ × ‘Granny Smith’ cross, were used. The phyllochron was estimated as a function of thermal time and sylleptic branching was modeled subsequently depending on phyllochron. From a genetic map built with SNPs, marker effects were estimated on four MAppleT parameters with rrBLUP, using 2007 data. These effects were then considered in MAppleT to simulate tree development in the two climatic conditions. The genome wide prediction model gave consistent estimations of parameter values with correlation coefficients between observed values and estimated values from SNP markers ranging from 0.79 to 0.96. However, the accuracy of the prediction model following cross validation schemas was lower. Three integrative traits (the number of leaves, trunk length, and number of sylleptic laterals) were considered for validating MAppleT simulations. In 2007 climatic conditions, simulated values were close to observations, highlighting the correct simulation of genetic variability. However, in 2004 conditions which were not used for model calibration, the simulations differed from observations. This study demonstrates the possibility

  15. Combining Genome-Wide Information with a Functional Structural Plant Model to Simulate 1-Year-Old Apple Tree Architecture.

    Science.gov (United States)

    Migault, Vincent; Pallas, Benoît; Costes, Evelyne

    2016-01-01

    In crops, optimizing target traits in breeding programs can be fostered by selecting appropriate combinations of architectural traits which determine light interception and carbon acquisition. In apple tree, architectural traits were observed to be under genetic control. However, architectural traits also result from many organogenetic and morphological processes interacting with the environment. The present study aimed at combining a FSPM built for apple tree, MAppleT, with genetic determinisms of architectural traits, previously described in a bi-parental population. We focused on parameters related to organogenesis (phyllochron and immediate branching) and morphogenesis processes (internode length and leaf area) during the first year of tree growth. Two independent datasets collected in 2004 and 2007 on 116 genotypes, issued from a 'Starkrimson' × 'Granny Smith' cross, were used. The phyllochron was estimated as a function of thermal time and sylleptic branching was modeled subsequently depending on phyllochron. From a genetic map built with SNPs, marker effects were estimated on four MAppleT parameters with rrBLUP, using 2007 data. These effects were then considered in MAppleT to simulate tree development in the two climatic conditions. The genome wide prediction model gave consistent estimations of parameter values with correlation coefficients between observed values and estimated values from SNP markers ranging from 0.79 to 0.96. However, the accuracy of the prediction model following cross validation schemas was lower. Three integrative traits (the number of leaves, trunk length, and number of sylleptic laterals) were considered for validating MAppleT simulations. In 2007 climatic conditions, simulated values were close to observations, highlighting the correct simulation of genetic variability. However, in 2004 conditions which were not used for model calibration, the simulations differed from observations. This study demonstrates the possibility of

  16. Scanning electron microscopy subsequent to a combined treatment of NaOCl and EDTA in some non-collagenous calcified matrixes.

    Science.gov (United States)

    Kodaka, T; Sano, T; Mori, R

    2000-01-01

    Using backscattered electron (BSE) imaging and scanning electron microscopy, subsequent to a combined treatment of sodium hypochlorite (NaOCl) and ethylenediamine tetra-acetic acid (EDTA) or only with EDTA etching, we observed some structures of non-collagenous calcified matrixes with the aim of revealing the correlation of deposition between calcification degree and organic amount. In human tooth enamel, the NaOCl-EDTA method eroded more intensively the hypocalcified prisms of enamel tufts containing a relatively large amount of EDTA-insoluble organic matter than the hypercalcified normal prismatic enamel containing a small amount of the organic matter. Afibrillar cementum, one of the non-collagenous calcified tissues similar to the enamel, has been reported to consist of organic-rich and poor incremental lamellae. The BSE imaging showed an alternation pattern of hypocalcification and hypercalcification. The hypocalcified lamellae were retained by EDTA etching, while the hypercalcified lamellae showed a resistance against the NaOCl-EDTA method. In the non-collagenous calcareous concretions of human pineal body, organic-rich and poor, and hyper- and hypocalcified incremental lamellae have been reported. The deposition pattern of calcification degree and organic amount was similar to that in afibrillar cementum, and the hypercalcified lamellae showed a resistance against the NaOCl-EDTA method. In conclusion, the high and the lower calcified regions of non-collagenous calcified matrixes contained smaller and larger amounts of EDTA-insoluble organic matter respectively. Moreover, scanning electron microscopy subsequent to the NaOCl-EDTA method corresponding to the BSE imaging clearly showed fine calcified structures compared with the BSE imaging.

  17. Increasing Genome Sampling and Improving SNP Genotyping for Genotyping-by-Sequencing with New Combinations of Restriction Enzymes

    National Research Council Canada - National Science Library

    Fu, Yong-Bi; Peterson, Gregory W; Dong, Yibo

    2016-01-01

    .... Here we present software called IgCoverage for in silico evaluation of genomic coverage through GBS with an individual or pair of restriction enzymes on one sequenced genome, and report a new set...

  18. Renal scan

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003790.htm Renal scan To use the sharing features on this ... anaphylaxis . Alternative Names Renogram; Kidney scan Images Kidney anatomy Kidney - blood and urine flow References Chernecky CC, ...

  19. Deciphering the molecular basis of wine yeast fermentation traits using a combined genetic and genomic approach.

    Science.gov (United States)

    Ambroset, Chloé; Petit, Maud; Brion, Christian; Sanchez, Isabelle; Delobel, Pierre; Guérin, Cyprien; Chiapello, Hélène; Nicolas, Pierre; Bigey, Frédéric; Dequin, Sylvie; Blondin, Bruno

    2011-09-01

    The genetic basis of the phenotypic diversity of yeast is still poorly understood. Wine yeast strains have specific abilities to grow and ferment under stressful conditions compared with other strains, but the genetic basis underlying these traits is unknown. Understanding how sequence variation influences such phenotypes is a major challenge to address adaptation mechanisms of wine yeast. We aimed to identify the genetic basis of fermentation traits and gain insight into their relationships with variations in gene expression among yeast strains. We combined fermentation trait QTL mapping and expression profiling of fermenting cells in a segregating population from a cross between a wine yeast derivative and a laboratory strain. We report the identification of QTL for various fermentation traits (fermentation rates, nitrogen utilization, metabolites production) as well as expression QTL (eQTL). We found that many transcripts mapped to several eQTL hotspots and that two of them overlapped with QTL for fermentation traits. A QTL controlling the maximal fermentation rate and nitrogen utilization overlapping with an eQTL hotspot was dissected. We functionally demonstrated that an allele of the ABZ1 gene, localized in the hotspot and involved in p-aminobenzoate biosynthesis, controls the fermentation rate through modulation of nitrogen utilization. Our data suggest that the laboratory strain harbors a defective ABZ1 allele, which triggers strong metabolic and physiological alterations responsible for the generation of the eQTL hotspot. They also suggest that a number of gene expression differences result from some alleles that trigger major physiological disturbances.

  20. Understanding and predicting suicidality using a combined genomic and clinical risk assessment approach.

    Science.gov (United States)

    Niculescu, A B; Levey, D F; Phalen, P L; Le-Niculescu, H; Dainton, H D; Jain, N; Belanger, E; James, A; George, S; Weber, H; Graham, D L; Schweitzer, R; Ladd, T B; Learman, R; Niculescu, E M; Vanipenta, N P; Khan, F N; Mullen, J; Shankar, G; Cook, S; Humbert, C; Ballew, A; Yard, M; Gelbart, T; Shekhar, A; Schork, N J; Kurian, S M; Sandusky, G E; Salomon, D R

    2015-11-01

    Worldwide, one person dies every 40 seconds by suicide, a potentially preventable tragedy. A limiting step in our ability to intervene is the lack of objective, reliable predictors. We have previously provided proof of principle for the use of blood gene expression biomarkers to predict future hospitalizations due to suicidality, in male bipolar disorder participants. We now generalize the discovery, prioritization, validation, and testing of such markers across major psychiatric disorders (bipolar disorder, major depressive disorder, schizoaffective disorder, and schizophrenia) in male participants, to understand commonalities and differences. We used a powerful within-participant discovery approach to identify genes that change in expression between no suicidal ideation and high suicidal ideation states (n=37 participants out of a cohort of 217 psychiatric participants followed longitudinally). We then used a convergent functional genomics (CFG) approach with existing prior evidence in the field to prioritize the candidate biomarkers identified in the discovery step. Next, we validated the top biomarkers from the prioritization step for relevance to suicidal behavior, in a demographically matched cohort of suicide completers from the coroner's office (n=26). The biomarkers for suicidal ideation only are enriched for genes involved in neuronal connectivity and schizophrenia, the biomarkers also validated for suicidal behavior are enriched for genes involved in neuronal activity and mood. The 76 biomarkers that survived Bonferroni correction after validation for suicidal behavior map to biological pathways involved in immune and inflammatory response, mTOR signaling and growth factor regulation. mTOR signaling is necessary for the effects of the rapid-acting antidepressant agent ketamine, providing a novel biological rationale for its possible use in treating acute suicidality. Similarly, MAOB, a target of antidepressant inhibitors, was one of the increased

  1. Combined analysis of three genome-wide association studies on vWF and FVIII plasma levels

    Directory of Open Access Journals (Sweden)

    Cohen William

    2011-08-01

    Full Text Available Abstract Background Elevated levels of factor VIII (FVIII and von Willebrand Factor (vWF are well-established risk factors for cardiovascular diseases, in particular venous thrombosis. Although high, the heritability of these traits is poorly explained by the genetic factors known so far. The aim of this work was to identify novel single nucleotide polymorphisms (SNPs that could influence the variability of these traits. Methods Three independent genome-wide association studies for vWF plasma levels and FVIII activity were conducted and their results were combined into a meta-analysis totalling 1,624 subjects. Results No single nucleotide polymorphism (SNP reached the study-wide significance level of 1.12 × 10-7 that corresponds to the Bonferroni correction for the number of tested SNPs. Nevertheless, the recently discovered association of STXBP5, STX2, TC2N and CLEC4M genes with vWF levels and that of SCARA5 and STAB2 genes with FVIII levels were confirmed in this meta-analysis. Besides, among the fifteen novel SNPs showing promising association at p -5 with either vWF or FVIII levels in the meta-analysis, one located in ACCN1 gene also showed weak association (P = 0.0056 with venous thrombosis in a sample of 1,946 cases and 1,228 controls. Conclusions This study has generated new knowledge on genomic regions deserving further investigations in the search for genetic factors influencing vWF and FVIII plasma levels, some potentially implicated in VT, as well as providing some supporting evidence of previously identified genes.

  2. Laser-Combined Scanning Tunneling Microscopy on the Carrier Dynamics in Low-Temperature-Grown GaAs/AlGaAs/GaAs

    Directory of Open Access Journals (Sweden)

    Yasuhiko Terada

    2011-01-01

    Full Text Available We investigated carrier recombination dynamics in a low-temperature-grown GaAs (LT-GaAs/AlGaAs/GaAs heterostructure by laser-combined scanning tunneling microscopy, shaken-pulse-pair-excited STM (SPPX-STM. With the AlGaAs interlayer as a barrier against the flow of photocarriers, recombination lifetimes in LT-GaAs of 4.0 ps and GaAs of 4.8 ns were successfully observed separately. We directly demonstrated the high temporal resolution of SPPX-STM by showing the recombination lifetime of carriers in LT-GaAs (4.0 ps in the range of subpicosecond temporal resolution. In the carrier-lifetime-mapping measurement, a blurring of recombination lifetime up to 50 nm was observed at the LT-GaAs/AlGaAs boundary, which was discussed in consideration of the screening length of the electric field from the STM probe. The effect of the built-in potential on the signal, caused by the existence of LT-GaAs/AlGaAs/GaAs boundaries, was discussed in detail.

  3. Native renal function after combined liver-kidney transplant for type 1 hepatorenal syndrome: initial report on the use of postoperative Technetium-99 m-mercaptoacetyltriglycine scans.

    Science.gov (United States)

    Vagefi, Parsia A; Qian, Jesse J; Carlson, David M; Aparici, Carina Mari; Hirose, Ryutaro; Vincenti, Flavio; Wojciechowski, David

    2013-05-01

    Type 1 hepatorenal syndrome (HRS) is characterized by rapid deterioration of renal function. We sought to assess native kidney function after combined kidney-liver transplant (CLKTx) performed for type 1 HRS. We performed a retrospective, cross-sectional, single-center study. All patients with Type 1 HRS who received a CLKTx at the University of California, San Francisco from 1997 to 2007 were screened for enrollment. Patients with a baseline estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m(2) were eligible. Twenty-three patients were identified and consented to receive a Technetium-99 m-mercaptoacetyltriglycine (MAG3) nuclear scan to measure the native kidney contribution to overall renal function. Only 4 of the 23 subjects (17.4%) demonstrated native renal function that consisted of a contribution ≥50% of total renal function. Several factors and comorbidities such as age, gender, race, duration of HRS, need for and duration of renal replacement therapy, need for pressors, urine sodium, proteinuria, and use of octreotide/midodrine were analyzed and not found to be significant in predicting native renal function. The assessment of post-transplant native renal function following CLKTx may allow for improved accuracy in identifying the patients in need of CLKTx, and thus allow for greater optimization of dual-organ allocation strategies in patients with concomitant liver and renal failure. © 2013 The Authors Transplant International © 2013 European Society for Organ Transplantation. Published by Blackwell Publishing Ltd.

  4. Structure refinement of the δ1p phase in the Fe-Zn system by single-crystal X-ray diffraction combined with scanning transmission electron microscopy.

    Science.gov (United States)

    Okamoto, Norihiko L; Tanaka, Katsushi; Yasuhara, Akira; Inui, Haruyuki

    2014-04-01

    The structure of the δ1p phase in the iron-zinc system has been refined by single-crystal synchrotron X-ray diffraction combined with scanning transmission electron microscopy. The large hexagonal unit cell of the δ1p phase with the space group of P63/mmc comprises more or less regular (normal) Zn12 icosahedra, disordered Zn12 icosahedra, Zn16 icosioctahedra and dangling Zn atoms that do not constitute any polyhedra. The unit cell contains 52 Fe and 504 Zn atoms so that the compound is expressed with the chemical formula of Fe13Zn126. All Fe atoms exclusively occupy the centre of normal and disordered icosahedra. Iron-centred normal icosahedra are linked to one another by face- and vertex-sharing forming two types of basal slabs, which are bridged with each other by face-sharing with icosioctahedra, whereas disordered icosahedra with positional disorder at their vertex sites are isolated from other polyhedra. The bonding features in the δ1p phase are discussed in comparison with those in the Γ and ζ phases in the iron-zinc system.

  5. Post-therapeutic response evaluation by a combination of endoscopy and CT scan in esophagogastric adenocarcinoma after chemotherapy: better than its reputation.

    Science.gov (United States)

    Blank, Susanne; Lordick, Florian; Bader, Franz; Burian, Maria; Dobritz, Martin; Grenacher, Lars; Becker, Karen; Weichert, Wilko; Langer, Rupert; Sisic, Leila; Stange, Annika; Jäger, Dirk; Büchler, Markus; Bruckner, Thomas; Siewert, Jörg; Ott, Katja

    2015-04-01

    Neoadjuvant chemotherapy is an accepted standard of care for locally advanced esophagogastric cancer. As only a subgroup benefits, a response-based tailored treatment would be of interest. The aim of our study was the evaluation of the prognostic and predictive value of clinical response in esophagogastric adenocarcinomas. Clinical response based on a combination of endoscopy and computed tomography (CT) scan was evaluated retrospectively within a prospective database in center A and then transferred to center B. A total of 686/740 (A) and 184/210 (B) patients, staged cT3/4, cN0/1 underwent neoadjuvant chemotherapy and were then re-staged by endoscopy and CT before undergoing tumor resection. Of 184 patients, 118 (B) additionally had an interim response assessment 4-6 weeks after the start of chemotherapy. In A, 479 patients (70%) were defined as clinical nonresponders, 207 (30%) as responders. Median survival was 38 months (nonresponders: 27 months, responders: 108 months, log-rank, p value could only be confirmed in univariate analysis. The accordance with histopathological response was good in both centers, and interim clinical response evaluation showed comparable results to preoperative evaluation.

  6. A linear time algorithm for detecting long genomic regions enriched with a specific combination of epigenetic states.

    Science.gov (United States)

    Ichikawa, Kazuki; Morishita, Shinichi

    2015-01-01

    Epigenetic modifications are essential for controlling gene expression. Recent studies have shown that not only single epigenetic modifications but also combinations of multiple epigenetic modifications play vital roles in gene regulation. A striking example is the long hypomethylated regions enriched with modified H3K27me3 (called, "K27HMD" regions), which are exposed to suppress the expression of key developmental genes relevant to cellular development and differentiation during embryonic stages in vertebrates. It is thus a biologically important issue to develop an effective optimization algorithm for detecting long DNA regions (e.g., >4 kbp in size) that harbor a specific combination of epigenetic modifications (e.g., K27HMD regions). However, to date, optimization algorithms for these purposes have received little attention, and available methods are still heuristic and ad hoc. In this paper, we propose a linear time algorithm for calculating a set of non-overlapping regions that maximizes the sum of similarities between the vector of focal epigenetic states and the vectors of raw epigenetic states at DNA positions in the set of regions. The average elapsed time to process the epigenetic data of any of human chromosomes was less than 2 seconds on an Intel Xeon CPU. To demonstrate the effectiveness of the algorithm, we estimated large K27HMD regions in the medaka and human genomes using our method, ChromHMM, and a heuristic method. We confirmed that the advantages of our method over those of the two other methods. Our method is flexible enough to handle other types of epigenetic combinations. The program that implements the method is called "CSMinfinder" and is made available at: http://mlab.cb.k.u-tokyo.ac.jp/~ichikawa/Segmentation/

  7. Target selection for structural genomics based on combining fold recognition and crystallisation prediction methods: application to the human proteome.

    Science.gov (United States)

    Bray, James E

    2012-03-01

    The objective of this study is to automatically identify regions of the human proteome that are suitable for 3D structure determination by X-ray crystallography and to annotate them according to their likelihood to produce diffraction quality crystals. The results provide a powerful tool for structural genomics laboratories who wish to select human proteins based on the statistical likelihood of crystallisation success. Combining fold recognition and crystallisation prediction algorithms enables the efficient calculation of the crystallisability of the entire human proteome. This novel study estimates that there are approximately 40,000 crystallisable regions in the human proteome. Currently, only 15% of these regions (approx. 6,000 sequences) have been solved to at least 95% sequence identity. The remaining unsolved regions have been categorised into 5 crystallisation classes and an integral membrane protein (IMP) class, based on established structure prediction, crystallisation prediction and transmembrane (TM) helix prediction algorithms. Approximately 750 unsolved regions (2% of the proteome) have been identified as having a PDB fold representative (template) and an 'optimal' likelihood of crystallisation. At the other end of the spectrum, more than 10,500 non-IMP regions with a PDB template are classified as 'very difficult' to crystallise (26%) and almost 2,500 regions (6%) were predicted to contain at least 3 TM helices. The 3D-SPECS (3D Structural Proteomics Explorer with Crystallisation Scores) website contains crystallisation predictions for the entire human proteome and can be found at http://www.bioinformaticsplus.org/3dspecs.

  8. Full genomic characterization of a novel genotype combination, G4P[14], of a human rotavirus strain from Barbados.

    Science.gov (United States)

    Tam, Ka Ian; Roy, Sunando; Esona, Mathew D; Jones, Starlene; Sobers, Stephanie; Morris-Glasgow, Victoria; Rey-Benito, Gloria; Gentsch, Jon R; Bowen, Michael D

    2014-12-01

    Since 2004, the Pan American Health Organization (PAHO) has carried out rotavirus surveillance in Latin America and the Caribbean. Here we report the characterization of human rotavirus with the novel G-P combination of G4P[14], detected through PAHO surveillance in Barbados. Full genome sequencing of strain RVA/Human-wt/BRB/CDC1133/2012/G4P[14] revealed that its genotype is G4-P[14]-I1-R1-C1-M1-A8-N1-T1-E1-H1. The possession of a Genogroup 1 (Wa-like) backbone distinguishes this strain from other P[14] rotavirus strains. Phylogenetic analyses suggested that this strain was likely generated by genetic reassortment between human, porcine and possibly other animal rotavirus strains and identified 7 lineages within the P[14] genotype. The results of this study reinforce the potential role of interspecies transmission in generating human rotavirus diversity through reassortment. Continued surveillance is important to determine if rotavirus vaccines will protect against strains that express the P[14] rotavirus genotype. Published by Elsevier B.V.

  9. Molecular Determinants Underlying Binding Specificities of the ABL Kinase Inhibitors: Combining Alanine Scanning of Binding Hot Spots with Network Analysis of Residue Interactions and Coevolution.

    Directory of Open Access Journals (Sweden)

    Amanda Tse

    Full Text Available Quantifying binding specificity and drug resistance of protein kinase inhibitors is of fundamental importance and remains highly challenging due to complex interplay of structural and thermodynamic factors. In this work, molecular simulations and computational alanine scanning are combined with the network-based approaches to characterize molecular determinants underlying binding specificities of the ABL kinase inhibitors. The proposed theoretical framework unveiled a relationship between ligand binding and inhibitor-mediated changes in the residue interaction networks. By using topological parameters, we have described the organization of the residue interaction networks and networks of coevolving residues in the ABL kinase structures. This analysis has shown that functionally critical regulatory residues can simultaneously embody strong coevolutionary signal and high network centrality with a propensity to be energetic hot spots for drug binding. We have found that selective (Nilotinib and promiscuous (Bosutinib, Dasatinib kinase inhibitors can use their energetic hot spots to differentially modulate stability of the residue interaction networks, thus inhibiting or promoting conformational equilibrium between inactive and active states. According to our results, Nilotinib binding may induce a significant network-bridging effect and enhance centrality of the hot spot residues that stabilize structural environment favored by the specific kinase form. In contrast, Bosutinib and Dasatinib can incur modest changes in the residue interaction network in which ligand binding is primarily coupled only with the identity of the gate-keeper residue. These factors may promote structural adaptability of the active kinase states in binding with these promiscuous inhibitors. Our results have related ligand-induced changes in the residue interaction networks with drug resistance effects, showing that network robustness may be compromised by targeted mutations

  10. Molecular Determinants Underlying Binding Specificities of the ABL Kinase Inhibitors: Combining Alanine Scanning of Binding Hot Spots with Network Analysis of Residue Interactions and Coevolution

    Science.gov (United States)

    Tse, Amanda; Verkhivker, Gennady M.

    2015-01-01

    Quantifying binding specificity and drug resistance of protein kinase inhibitors is of fundamental importance and remains highly challenging due to complex interplay of structural and thermodynamic factors. In this work, molecular simulations and computational alanine scanning are combined with the network-based approaches to characterize molecular determinants underlying binding specificities of the ABL kinase inhibitors. The proposed theoretical framework unveiled a relationship between ligand binding and inhibitor-mediated changes in the residue interaction networks. By using topological parameters, we have described the organization of the residue interaction networks and networks of coevolving residues in the ABL kinase structures. This analysis has shown that functionally critical regulatory residues can simultaneously embody strong coevolutionary signal and high network centrality with a propensity to be energetic hot spots for drug binding. We have found that selective (Nilotinib) and promiscuous (Bosutinib, Dasatinib) kinase inhibitors can use their energetic hot spots to differentially modulate stability of the residue interaction networks, thus inhibiting or promoting conformational equilibrium between inactive and active states. According to our results, Nilotinib binding may induce a significant network-bridging effect and enhance centrality of the hot spot residues that stabilize structural environment favored by the specific kinase form. In contrast, Bosutinib and Dasatinib can incur modest changes in the residue interaction network in which ligand binding is primarily coupled only with the identity of the gate-keeper residue. These factors may promote structural adaptability of the active kinase states in binding with these promiscuous inhibitors. Our results have related ligand-induced changes in the residue interaction networks with drug resistance effects, showing that network robustness may be compromised by targeted mutations of key mediating

  11. Spontaneous combined rupture of a pelvicalyceal cyst into the collector system and retroperitoneal space during the acquisition of computed tomography scan images: a case report

    Directory of Open Access Journals (Sweden)

    Marques Diogo

    2012-11-01

    Full Text Available Abstract Introduction Pelvicalyceal cysts are common findings in autopsies and can manifest with a variety of patterns. These cystic lesions are usually a benign entity with no clinical significance unless they enlarge enough to cause compression of the adjacent collecting system and consequently obstructive uropathy. Few cases of the spontaneous rupture of pelvicalyceal renal cysts have been published and to the best of our knowledge there is no report of a combined rupture to collector system and retroperitoneal space documented during a multiphase computed tomography. Case presentation We report a case of a ‘real-time’ spontaneous rupture of a pelvicalyceal cyst into the collecting system with fistulization into the retroperitoneum. The patient was a 78-year-old Caucasian man with a previous history of renal stones and a large pelvicalyceal renal cyst who was admitted to our Emergency department with acute right flank pain. A multiphase computed tomography was performed and the pre-contrast images demonstrated a right pelvicalyceal renal cyst measuring 12.0 × 6.1cm in the lower pole causing moderate dilation of the upper right renal collection system. In addition, a partially obstructive stone on the left distal ureter with mild left hydronephrosis was noted. The nephrographic phase did not add any new information. The excretory phase (10-minute delay demonstrated a spontaneous rupture of the cyst into the pelvicalyceal system with posterior fistulization into the retroperitoneal space. Conclusion In this case study we present time-related changes of a rare pelvicalyceal cyst complication, which to the best of our knowledge has fortunately not been previously documented. Analysis of the sequential images and comparison with an earlier scan allowed us to better understand the physiopathological process of the rupture, the clinical presentation and to elaborate hypotheses for its etiopathogenesis.

  12. Genome-wide scan for seed composition provides insights into the improvement of soybean quality and the impacts of domestication and modern breeding

    Science.gov (United States)

    Soybean (Glycine max (L.) Merrill) is a world-widely grown major crop rich in both protein and oil. Improvement of seed nutrients has long been one of the most important breeding objectives in soybean. To better understand the genetic architecture of the traits for improvement, we conducted genome-w...

  13. Two are better than one: combining landscape genomics and common gardens for detecting local adaptation in forest trees.

    Science.gov (United States)

    Lepais, Olivier; Bacles, Cecile F

    2014-10-01

    Predicting likely species responses to an alteration of their local environment is key to decision-making in resource management, ecosystem restoration and biodiversity conservation practice in the face of global human-induced habitat disturbance. This is especially true for forest trees which are a dominant life form on Earth and play a central role in supporting diverse communities and structuring a wide range of ecosystems. In Europe, it is expected that most forest tree species will not be able to migrate North fast enough to follow the estimated temperature isocline shift given current predictions for rapid climate warming. In this context, a topical question for forest genetics research is to quantify the ability for tree species to adapt locally to strongly altered environmental conditions (Kremer et al. ). Identifying environmental factors driving local adaptation is, however, a major challenge for evolutionary biology and ecology in general but is particularly difficult in trees given their large individual and population size and long generation time. Empirical evaluation of local adaptation in trees has traditionally relied on fastidious long-term common garden experiments (provenance trials) now supplemented by reference genome sequence analysis for a handful of economically valuable species. However, such resources have been lacking for most tree species despite their ecological importance in supporting whole ecosystems. In this issue of Molecular Ecology, De Kort et al. () provide original and convincing empirical evidence of local adaptation to temperature in black alder, Alnus glutinosa L. Gaertn, a surprisingly understudied keystone species supporting riparian ecosystems. Here, De Kort et al. () use an innovative empirical approach complementing state-of-the-art landscape genomics analysis of A. glutinosa populations sampled in natura across a regional climate gradient with phenotypic trait assessment in a common garden experiment (Fig. ). By

  14. Cooperative scans

    NARCIS (Netherlands)

    M. Zukowski (Marcin); P.A. Boncz (Peter); M.L. Kersten (Martin)

    2004-01-01

    textabstractData mining, information retrieval and other application areas exhibit a query load with multiple concurrent queries touching a large fraction of a relation. This leads to individual query plans based on a table scan or large index scan. The implementation of this access path in most

  15. Combined Analysis of Variation in Core, Accessory and Regulatory Genome Regions Provides a Super-Resolution View into the Evolution of Bacterial Populations.

    Directory of Open Access Journals (Sweden)

    Alan McNally

    2016-09-01

    Full Text Available The use of whole-genome phylogenetic analysis has revolutionized our understanding of the evolution and spread of many important bacterial pathogens due to the high resolution view it provides. However, the majority of such analyses do not consider the potential role of accessory genes when inferring evolutionary trajectories. Moreover, the recently discovered importance of the switching of gene regulatory elements suggests that an exhaustive analysis, combining information from core and accessory genes with regulatory elements could provide unparalleled detail of the evolution of a bacterial population. Here we demonstrate this principle by applying it to a worldwide multi-host sample of the important pathogenic E. coli lineage ST131. Our approach reveals the existence of multiple circulating subtypes of the major drug-resistant clade of ST131 and provides the first ever population level evidence of core genome substitutions in gene regulatory regions associated with the acquisition and maintenance of different accessory genome elements.

  16. Efficient screening of potential cellulases and hemicellulases produced by Bosea sp. FBZP-16 using the combination of enzyme assays and genome analysis.

    Science.gov (United States)

    Houfani, Aicha Asma; Větrovský, Tomáš; Baldrian, Petr; Benallaoua, Said

    2017-02-01

    Identification of bacteria that produce carbohydrolytic enzymes is extremely important given the increased demand for these enzymes in many industries. Twenty lignocellulose-degrading bacterial isolates from Algerian compost and different soils were screened for their potential to produce different enzymes involved in biomass deconstruction. Based on 16S rRNA gene sequencing, the isolates belonged to Proteobacteria and Actinobacteria. Differences among species were reflected both as the presence/absence of enzymes or at the level of enzyme activity. Among the most active species, Bosea sp. FBZP-16 demonstrated cellulolytic activity on both amorphous cellulose (CMC) and complex lignocellulose (wheat straw) and was selected for whole-genomic sequencing. The genome sequencing revealed the presence of a complex enzymatic machinery required for organic matter decomposition. Analysis of the enzyme-encoding genes indicated that multiple genes for endoglucanase, xylanase, β-glucosidase and β-mannosidase are present in the genome with enzyme activities displayed by the bacterium, while other enzymes, such as certain cellobiohydrolases, were not detected at the genomic level. This indicates that a combination of functional screening of bacterial cultures with the use of genome-derived information is important for the prediction of potential enzyme production. These results provide insight into their possible exploitation for the production of fuels and chemicals derived from plant biomass.

  17. Development and Validation of a Gene-Based Model for Outcome Prediction in Germ Cell Tumors Using a Combined Genomic and Expression Profiling Approach.

    Directory of Open Access Journals (Sweden)

    James E Korkola

    Full Text Available Germ Cell Tumors (GCT have a high cure rate, but we currently lack the ability to accurately identify the small subset of patients who will die from their disease. We used a combined genomic and expression profiling approach to identify genomic regions and underlying genes that are predictive of outcome in GCT patients. We performed array-based comparative genomic hybridization (CGH on 53 non-seminomatous GCTs (NSGCTs treated with cisplatin based chemotherapy and defined altered genomic regions using Circular Binary Segmentation. We identified 14 regions associated with two year disease-free survival (2yDFS and 16 regions associated with five year disease-specific survival (5yDSS. From corresponding expression data, we identified 101 probe sets that showed significant changes in expression. We built several models based on these differentially expressed genes, then tested them in an independent validation set of 54 NSGCTs. These predictive models correctly classified outcome in 64-79.6% of patients in the validation set, depending on the endpoint utilized. Survival analysis demonstrated a significant separation of patients with good versus poor predicted outcome when using a combined gene set model. Multivariate analysis using clinical risk classification with the combined gene model indicated that they were independent prognostic markers. This novel set of predictive genes from altered genomic regions is almost entirely independent of our previously identified set of predictive genes for patients with NSGCTs. These genes may aid in the identification of the small subset of patients who are at high risk of poor outcome.

  18. Complete genome sequence and integrated protein localization and interaction map for alfalfa dwarf virus, which combines properties of both cytoplasmic and nuclear plant rhabdoviruses

    Energy Technology Data Exchange (ETDEWEB)

    Bejerman, Nicolás, E-mail: n.bejerman@uq.edu.au [Instituto de Patología Vegetal (IPAVE), Centro de Investigaciones Agropecuarias (CIAP), Instituto Nacional de Tecnología Agropecuaria INTA, Camino a 60 Cuadras k 5,5, Córdoba X5020ICA (Argentina); Queensland Alliance for Agriculture and Food Innovation, The University of Queensland, St Lucia, QLD 4072 (Australia); Giolitti, Fabián; Breuil, Soledad de; Trucco, Verónica; Nome, Claudia; Lenardon, Sergio [Instituto de Patología Vegetal (IPAVE), Centro de Investigaciones Agropecuarias (CIAP), Instituto Nacional de Tecnología Agropecuaria INTA, Camino a 60 Cuadras k 5,5, Córdoba X5020ICA (Argentina); Dietzgen, Ralf G. [Queensland Alliance for Agriculture and Food Innovation, The University of Queensland, St Lucia, QLD 4072 (Australia)

    2015-09-15

    Summary: We have determined the full-length 14,491-nucleotide genome sequence of a new plant rhabdovirus, alfalfa dwarf virus (ADV). Seven open reading frames (ORFs) were identified in the antigenomic orientation of the negative-sense, single-stranded viral RNA, in the order 3′-N-P-P3-M-G-P6-L-5′. The ORFs are separated by conserved intergenic regions and the genome coding region is flanked by complementary 3′ leader and 5′ trailer sequences. Phylogenetic analysis of the nucleoprotein amino acid sequence indicated that this alfalfa-infecting rhabdovirus is related to viruses in the genus Cytorhabdovirus. When transiently expressed as GFP fusions in Nicotiana benthamiana leaves, most ADV proteins accumulated in the cell periphery, but unexpectedly P protein was localized exclusively in the nucleus. ADV P protein was shown to have a homotypic, and heterotypic nuclear interactions with N, P3 and M proteins by bimolecular fluorescence complementation. ADV appears unique in that it combines properties of both cytoplasmic and nuclear plant rhabdoviruses. - Highlights: • The complete genome of alfalfa dwarf virus is obtained. • An integrated localization and interaction map for ADV is determined. • ADV has a genome sequence similarity and evolutionary links with cytorhabdoviruses. • ADV protein localization and interaction data show an association with the nucleus. • ADV combines properties of both cytoplasmic and nuclear plant rhabdoviruses.

  19. MRI Scans

    Science.gov (United States)

    Magnetic resonance imaging (MRI) uses a large magnet and radio waves to look at organs and structures inside your body. Health care professionals use MRI scans to diagnose a variety of conditions, from ...

  20. Bone Scan

    Science.gov (United States)

    ... posts Join Mayo Clinic Connect Bone scan About Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  1. Visualization for genomics: the Microbial Genome Viewer.

    NARCIS (Netherlands)

    Kerkhoven, R.; Enckevort, F.H.J. van; Boekhorst, J.; Molenaar, D.; Siezen, R.J.

    2004-01-01

    SUMMARY: A Web-based visualization tool, the Microbial Genome Viewer, is presented that allows the user to combine complex genomic data in a highly interactive way. This Web tool enables the interactive generation of chromosome wheels and linear genome maps from genome annotation data stored in a

  2. Genome-wide association scan identifies a risk locus for preeclampsia on 2q14, near the inhibin, beta B gene.

    Directory of Open Access Journals (Sweden)

    Matthew P Johnson

    Full Text Available Elucidating the genetic architecture of preeclampsia is a major goal in obstetric medicine. We have performed a genome-wide association study (GWAS for preeclampsia in unrelated Australian individuals of Caucasian ancestry using the Illumina OmniExpress-12 BeadChip to successfully genotype 648,175 SNPs in 538 preeclampsia cases and 540 normal pregnancy controls. Two SNP associations (rs7579169, p = 3.58×10(-7, OR = 1.57; rs12711941, p = 4.26×10(-7, OR = 1.56 satisfied our genome-wide significance threshold (modified Bonferroni p0.92. We attempted to provide evidence of a putative regulatory role for these SNPs using bioinformatic analyses and found that they all reside within regions of low sequence conservation and/or low complexity, suggesting functional importance is low. We also explored the mRNA expression in decidua of genes ±500 kb of INHBB and found a nominally significant correlation between a transcript encoded by the EPB41L5 gene, ∼250 kb centromeric to INHBB, and preeclampsia (p = 0.03. We were unable to replicate the associations shown by the significant GWAS SNPs in case-control cohorts from Norway and Finland, leading us to conclude that it is more likely that these SNPs are in LD with as yet unidentified causal variant(s.

  3. A genome scan for milk production traits in dairy goats reveals two new mutations in Dgat1 reducing milk fat content.

    Science.gov (United States)

    Martin, Pauline; Palhière, Isabelle; Maroteau, Cyrielle; Bardou, Philippe; Canale-Tabet, Kamila; Sarry, Julien; Woloszyn, Florent; Bertrand-Michel, Justine; Racke, Ines; Besir, Hüseyin; Rupp, Rachel; Tosser-Klopp, Gwenola

    2017-05-12

    The quantity of milk and milk fat and proteins are particularly important traits in dairy livestock. However, little is known about the regions of the genome that influence these traits in goats. We conducted a genome wide association study in French goats and identified 109 regions associated with dairy traits. For a major region on chromosome 14 closely associated with fat content, the Diacylglycerol O-Acyltransferase 1 (DGAT1) gene turned out to be a functional and positional candidate gene. The caprine reference sequence of this gene was completed and 29 polymorphisms were found in the gene sequence, including two novel exonic mutations: R251L and R396W, leading to substitutions in the protein sequence. The R251L mutation was found in the Saanen breed at a frequency of 3.5% and the R396W mutation both in the Saanen and Alpine breeds at a frequencies of 13% and 7% respectively. The R396W mutation explained 46% of the genetic variance of the trait, and the R251L mutation 6%. Both mutations were associated with a notable decrease in milk fat content. Their causality was then demonstrated by a functional test. These results provide new knowledge on the genetic basis of milk synthesis and will help improve the management of the French dairy goat breeding program.

  4. Genome-Wide Association Scan Identifies a Risk Locus for Preeclampsia on 2q14, Near the Inhibin, Beta B Gene

    Science.gov (United States)

    Johnson, Matthew P.; Brennecke, Shaun P.; East, Christine E.; Göring, Harald H. H.; Kent, Jack W.; Dyer, Thomas D.; Said, Joanne M.; Roten, Linda T.; Iversen, Ann-Charlotte; Abraham, Lawrence J.; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Kivinen, Katja; Pouta, Anneli; Laivuori, Hannele; Austgulen, Rigmor; Blangero, John; Moses, Eric K.

    2012-01-01

    Elucidating the genetic architecture of preeclampsia is a major goal in obstetric medicine. We have performed a genome-wide association study (GWAS) for preeclampsia in unrelated Australian individuals of Caucasian ancestry using the Illumina OmniExpress-12 BeadChip to successfully genotype 648,175 SNPs in 538 preeclampsia cases and 540 normal pregnancy controls. Two SNP associations (rs7579169, p = 3.58×10−7, OR = 1.57; rs12711941, p = 4.26×10−7, OR = 1.56) satisfied our genome-wide significance threshold (modified Bonferroni p0.92). We attempted to provide evidence of a putative regulatory role for these SNPs using bioinformatic analyses and found that they all reside within regions of low sequence conservation and/or low complexity, suggesting functional importance is low. We also explored the mRNA expression in decidua of genes ±500 kb of INHBB and found a nominally significant correlation between a transcript encoded by the EPB41L5 gene, ∼250 kb centromeric to INHBB, and preeclampsia (p = 0.03). We were unable to replicate the associations shown by the significant GWAS SNPs in case-control cohorts from Norway and Finland, leading us to conclude that it is more likely that these SNPs are in LD with as yet unidentified causal variant(s). PMID:22432041

  5. Using an Inbred Horse Breed in a High Density Genome-Wide Scan for Genetic Risk Factors of Insect Bite Hypersensitivity (IBH).

    Science.gov (United States)

    Velie, Brandon D; Shrestha, Merina; Franҫois, Liesbeth; Schurink, Anouk; Tesfayonas, Yohannes G; Stinckens, Anneleen; Blott, Sarah; Ducro, Bart J; Mikko, Sofia; Thomas, Ruth; Swinburne, June E; Sundqvist, Marie; Eriksson, Susanne; Buys, Nadine; Lindgren, Gabriella

    2016-01-01

    While susceptibility to hypersensitive reactions is a common problem amongst humans and animals alike, the population structure of certain animal species and breeds provides a more advantageous route to better understanding the biology underpinning these conditions. The current study uses Exmoor ponies, a highly inbred breed of horse known to frequently suffer from insect bite hypersensitivity, to identify genomic regions associated with a type I and type IV hypersensitive reaction. A total of 110 cases and 170 controls were genotyped on the 670K Axiom Equine Genotyping Array. Quality control resulted in 452,457 SNPs and 268 individuals being tested for association. Genome-wide association analyses were performed using the GenABEL package in R and resulted in the identification of two regions of interest on Chromosome 8. The first region contained the most significant SNP identified, which was located in an intron of the DCC netrin 1 receptor gene. The second region identified contained multiple top SNPs and encompassed the PIGN, KIAA1468, TNFRSF11A, ZCCHC2, and PHLPP1 genes. Although additional studies will be needed to validate the importance of these regions in horses and the relevance of these regions in other species, the knowledge gained from the current study has the potential to be a step forward in unraveling the complex nature of hypersensitive reactions.

  6. Cadaver-specific CT scans visualized at the dissection table combined with virtual dissection tables improve learning performance in general gross anatomy

    Energy Technology Data Exchange (ETDEWEB)

    Paech, Daniel [German Cancer Research Center, Department of Radiology, Heidelberg (Germany); Heidelberg University, Institute of Anatomy and Cell Biology, Heidelberg (Germany); Giesel, Frederik L. [University Hospital Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany); Unterhinninghofen, Roland [Institute of Anthropomatics, Karlsruhe Institute of Technology, Karlsruhe (Germany); Schlemmer, Heinz-Peter [German Cancer Research Center, Department of Radiology, Heidelberg (Germany); Kuner, Thomas; Doll, Sara [Heidelberg University, Institute of Anatomy and Cell Biology, Heidelberg (Germany)

    2017-05-15

    The purpose of this study was to quantify the benefit of the incorporation of radiologic anatomy (RA), in terms of student training in RA seminars, cadaver CT scans and life-size virtual dissection tables on the learning success in general anatomy. Three groups of a total of 238 students were compared in a multiple choice general anatomy exam during first-year gross anatomy: (1) a group (year 2015, n{sub 1} = 50) that received training in radiologic image interpretation (RA seminar) and additional access to cadaver CT scans (CT + seminar group); (2) a group (2011, n{sub 2} = 90) that was trained in the RA seminar only (RA seminar group); (3) a group (2011, n{sub 3} = 98) without any radiologic image interpretation training (conventional anatomy group). Furthermore, the students' perception of the new curriculum was assessed qualitatively through a survey. The average test score of the CT + seminar group (21.8 ± 5.0) was significantly higher when compared to both the RA seminar group (18.3 ± 5.0) and the conventional anatomy group (17.1 ± 4.7) (p < 0.001). The incorporation of cadaver CT scans and life-size virtual dissection tables significantly improved the performance of medical students in general gross anatomy. Medical imaging and virtual dissection should therefore be considered to be part of the standard curriculum of gross anatomy. circle Students provided with cadaver CT scans achieved 27 % higher scores in anatomy. (orig.)

  7. Combining integrated genomics and functional genomics to dissect the biology of a cancer-associated, aberrant transcription factor, the ASPSCR1–TFE3 fusion oncoprotein‡

    OpenAIRE

    Kobos, Rachel; Nagai, Makoto; Tsuda, Masumi; Merl, Man Yee; Saito, Tsuyoshi; Laé, Marick; Mo, Qianxing; Olshen, Adam; Lianoglou, Steven; Leslie, Christina; Ostrovnaya, Irina; Antczak, Christophe; Djaballah, Hakim; Ladanyi, Marc

    2013-01-01

    Oncogenic rearrangements of the TFE3 transcription factor gene are found in two distinct human cancers. These include ASPSCR1–TFE3 in all cases of alveolar soft part sarcoma (ASPS) and ASPSCR1–TFE3, PRCC-TFE3, SFPQ-TFE3 and others in a subset of paediatric and adult RCCs. Here we examined the functional properties of the ASPSCR1–TFE3 fusion oncoprotein, defined its target promoters on a genome-wide basis and performed a high-throughput RNA interference screen to identify which of its transcri...

  8. High definition colonoscopy combined with i-Scan is superior in the detection of colorectal neoplasias compared with standard video colonoscopy: a prospective randomized controlled trial.

    Science.gov (United States)

    Hoffman, A; Sar, F; Goetz, M; Tresch, A; Mudter, J; Biesterfeld, S; Galle, P R; Neurath, M F; Kiesslich, R

    2010-10-01

    Colonoscopy is the accepted gold standard for the detection of colorectal cancer. The aim of the current study was to prospectively compare high definition plus (HD+) colonoscopy with I-Scan functionality (electronic staining) vs. standard video colonoscopy. The primary endpoint was the detection of patients having colon cancer or at least one adenoma. A total of 220 patients due to undergo screening colonoscopy, postpolypectomy surveillance or with a positive occult blood test were randomized in a 1 : 1 ratio to undergo HD+ colonoscopy in conjunction with I-Scan surface enhancement (90i series, Pentax, Tokyo, Japan) or standard video colonoscopy (EC-3870FZK, Pentax). Detected colorectal lesions were judged according to type, location, and size. Lesions were characterized in the HD+ group by using further I-Scan functionality (p- and v-modes) to analyze pattern and vessel architecture. Histology was predicted and biopsies or resections were performed on all identified lesions. HD+ colonoscopy with I-Scan functionality detected significantly more patients with colorectal neoplasia (38 %) compared with standard resolution endoscopy (13 %) (200 patients finally analyzed; 100 per arm). Significantly more neoplastic (adenomatous and cancerous) lesions and more flat adenomas could be detected using high definition endoscopy with surface enhancement. Final histology could be predicted with high accuracy (98.6 %) within the HD+ group. HD+ colonoscopy with I-Scan is superior to standard video colonoscopy in detecting patients with colorectal neoplasia based on this prospective, randomized, controlled trial. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Pairagon+N-SCAN_EST: a model-based gene annotation pipeline

    DEFF Research Database (Denmark)

    Arumugam, Manimozhiyan; Wei, Chaochun; Brown, Randall H

    2006-01-01

    This paper describes Pairagon+N-SCAN_EST, a gene annotation pipeline that uses only native alignments. For each expressed sequence it chooses the best genomic alignment. Systems like ENSEMBL and ExoGean rely on trans alignments, in which expressed sequences are aligned to the genomic loci...... of putative homologs. Trans alignments contain a high proportion of mismatches, gaps, and/or apparently unspliceable introns, compared to alignments of cDNA sequences to their native loci. The Pairagon+N-SCAN_EST pipeline's first stage is Pairagon, a cDNA-to-genome alignment program based on a Pair......HMM probability model. This model relies on prior knowledge, such as the fact that introns must begin with GT, GC, or AT and end with AG or AC. It produces very precise alignments of high quality cDNA sequences. In the genomic regions between Pairagon's cDNA alignments, the pipeline combines EST alignments...

  10. Genome-wide scan of job-related exhaustion with three replication studies implicate a susceptibility variant at the UST gene locus.

    Science.gov (United States)

    Sulkava, Sonja; Ollila, Hanna M; Ahola, Kirsi; Partonen, Timo; Viitasalo, Katriina; Kettunen, Johannes; Lappalainen, Maarit; Kivimäki, Mika; Vahtera, Jussi; Lindström, Jaana; Härmä, Mikko; Puttonen, Sampsa; Salomaa, Veikko; Paunio, Tiina

    2013-08-15

    Job-related exhaustion is the core dimension of burnout, a work-related stress syndrome that has several negative health consequences. In this study, we explored the molecular genetic background of job-related exhaustion. A genome-wide analysis of job-related exhaustion was performed in the GENMETS subcohort (n = 1256) of the Finnish population-based Health 2000 study. Replication analyses included an analysis of the strongest associations in the rest of the Health 2000 sample (n = 1660 workers) and in three independent populations (the FINRISK population cohort, n = 10 753; two occupational cohorts, total n = 1451). Job-related exhaustion was ascertained using a standard self-administered questionnaire (the Maslach Burnout Inventory (MBI)-GS exhaustion scale in the Health 2000 sample and the occupational cohorts) or a single question (FINRISK). A variant located in an intron of UST, uronyl-2-sulfotransferase (rs13219957), gave the strongest statistical evidence in the initial genome-wide study (P = 1.55 × 10(-7)), and was associated with job-related exhaustion in all the replication sets (P exhaustion. However, the nominally significant signals from the allelic variant of UST in four separate samples suggest that this variant might be a weak risk factor for job-related exhaustion. Together with the previously reported associations of other dermatan/chondroitin sulfate genes with mood disorders, these results indicate a potential molecular pathway for stress-related traits and mark a candidate region for further studies of job-related and general exhaustion.

  11. Quantitative trait loci involved in sex determination and body growth in the gilthead sea bream (Sparus aurata L. through targeted genome scan.

    Directory of Open Access Journals (Sweden)

    Dimitrios Loukovitis

    Full Text Available Among vertebrates, teleost fish exhibit a considerably wide range of sex determination patterns that may be influenced by extrinsic parameters. However even for model fish species like the zebrafish Danio rerio the precise mechanisms involved in primary sex determination have not been studied extensively. The zebrafish, a gonochoristic species, is lacking discernible sex chromosomes and the sex of juvenile fish is difficult to determine. Sequential protandrous hermaphrodite species provide distinct determination of the gender and allow studying the sex determination process by looking at the mechanism of sex reversal. This is the first attempt to understand the genetic basis of phenotypic variation for sex determination and body weight in a sequential protandrous hermaphrodite species, the gilthead sea bream (Sparus aurata. This work demonstrates a fast and efficient strategy for Quantitative Trait Loci (QTL detection in the gilthead sea bream, a non-model but target hermaphrodite fish species. Therefore a comparative mapping approach was performed to query syntenies against two other Perciformes, the European sea bass (Dicentrarchus labrax, a gonochoristic species and the Asian sea bass (Lates calcarifer a protandrous hermaphrodite. In this manner two significant QTLs, one QTL affecting both body weight and sex and one QTL affecting sex, were detected on the same linkage group. The co-segregation of the two QTLs provides a genomic base to the observed genetic correlation between these two traits in sea bream as well as in other teleosts. The identification of QTLs linked to sex reversal and growth, will contribute significantly to a better understanding of the complex nature of sex determination in S. aurata where most individuals reverse to the female sex at the age of two years through development and maturation of the ovarian portion of the gonad and regression of the testicular area. [Genomic sequences reported in this manuscript have been

  12. Genetic profiles of gastroesophageal cancer: combined analysis using expression array and tiling array--comparative genomic hybridization

    DEFF Research Database (Denmark)

    Isinger-Ekstrand, Anna; Johansson, Jan; Ohlsson, Mattias

    2010-01-01

    We aimed to characterize the genomic profiles of adenocarcinomas in the gastroesophageal junction in relation to cancers in the esophagus and the stomach. Profiles of gains/losses as well as gene expression profiles were obtained from 27 gastroesophageal adenocarcinomas by means of 32k high-resolution...... array-based comparative genomic hybridization and 27k oligo gene expression arrays, and putative target genes were validated in an extended series. Adenocarcinomas in the distal esophagus and the gastroesophageal junction showed strong similarities with the most common gains at 20q13, 8q24, 1q21-23, 5p...

  13. Laser Scanning in Forests

    Directory of Open Access Journals (Sweden)

    Håkan Olsson

    2012-09-01

    Full Text Available The introduction of Airborne Laser Scanning (ALS to forests has been revolutionary during the last decade. This development was facilitated by combining earlier ranging lidar discoveries [1–5], with experience obtained from full-waveform ranging radar [6,7] to new airborne laser scanning systems which had components such as a GNSS receiver (Global Navigation Satellite System, IMU (Inertial Measurement Unit and a scanning mechanism. Since the first commercial ALS in 1994, new ALS-based forest inventory approaches have been reported feasible for operational activities [8–12]. ALS is currently operationally applied for stand level forest inventories, for example, in Nordic countries. In Finland alone, the adoption of ALS for forest data collection has led to an annual savings of around 20 M€/year, and the work is mainly done by companies instead of governmental organizations. In spite of the long implementation times and there being a limited tradition of making changes in the forest sector, laser scanning was commercially and operationally applied after about only one decade of research. When analyzing high-ranked journal papers from ISI Web of Science, the topic of laser scanning of forests has been the driving force for the whole laser scanning research society over the last decade. Thus, the topic “laser scanning in forests” has provided a significant industrial, societal and scientific impact. [...

  14. Scanning table

    CERN Multimedia

    1960-01-01

    Before the invention of wire chambers, particles tracks were analysed on scanning tables like this one. Today, the process is electronic and much faster. Bubble chamber film - currently available - (links can be found below) was used for this analysis of the particle tracks.

  15. Scan Statistics

    CERN Document Server

    Glaz, Joseph

    2009-01-01

    Suitable for graduate students and researchers in applied probability and statistics, as well as for scientists in biology, computer science, pharmaceutical science and medicine, this title brings together a collection of chapters illustrating the depth and diversity of theory, methods and applications in the area of scan statistics.

  16. SNPDelScore: combining multiple methods to score deleterious effects of noncoding mutations in the human genome.

    Science.gov (United States)

    Vera Alvarez, Roberto; Li, Shan; Landsman, David; Ovcharenko, Ivan

    2017-09-14

    Addressing deleterious effects of noncoding mutations is an essential step towards the identification of disease-causal mutations of gene regulatory elements. Several methods for quantifying the deleteriousness of noncoding mutations using artificial intelligence, deep learning, and other approaches have been recently proposed. Although the majority of the proposed methods have demonstrated excellent accuracy on different test sets, there is rarely a consensus. In addition, advanced statistical and artificial learning approaches used by these methods make it difficult porting these methods outside of the labs that have developed them. To address these challenges and to transform the methodological advances in predicting deleterious noncoding mutations into a practical resource available for the broader functional genomics and population genetics communities, we developed SNPDelScore, which uses a panel of proposed methods for quantifying deleterious effects of noncoding mutations to precompute and compare the deleteriousness scores of all common SNPs in the human genome in 44 cell lines. The panel of deleteriousness scores of a SNP computed using different methods is supplemented by functional information from the GWAS Catalog, libraries of transcription factor binding sites, and genic characteristics of mutations. SNPDelScore comes with a genome browser capable of displaying and comparing large sets of SNPs in a genomic locus and rapidly identifying consensus SNPs with the highest deleteriousness scores making those prime candidates for phenotype-causal polymorphisms. https://www.ncbi.nlm.nih.gov/research/snpdelscore/. Supplementary data are available at Bioinformatics online.

  17. Genome-wide linkage scan to identify loci associated with type 2 diabetes and blood lipid phenotypes in the Sikh Diabetes Study.

    Directory of Open Access Journals (Sweden)

    Dharambir K Sanghera

    Full Text Available In this investigation, we have carried out an autosomal genome-wide linkage analysis to map genes associated with type 2 diabetes (T2D and five quantitative traits of blood lipids including total cholesterol, high-density lipoprotein (HDL cholesterol, low-density lipoprotein (LDL cholesterol, very low-density lipoprotein (VLDL cholesterol, and triglycerides in a unique family-based cohort from the Sikh Diabetes Study (SDS. A total of 870 individuals (526 male/344 female from 321 families were successfully genotyped using 398 polymorphic microsatellite markers with an average spacing of 9.26 cM on the autosomes. Results of non-parametric multipoint linkage analysis using S(all statistics (implemented in Merlin did not reveal any chromosomal region to be significantly associated with T2D in this Sikh cohort. However, linkage analysis for lipid traits using QTL-ALL analysis revealed promising linkage signals with p≤0.005 for total cholesterol, LDL cholesterol, and HDL cholesterol at chromosomes 5p15, 9q21, 10p11, 10q21, and 22q13. The most significant signal (p = 0.0011 occurred at 10q21.2 for HDL cholesterol. We also observed linkage signals for total cholesterol at 22q13.32 (p = 0.0016 and 5p15.33 (p = 0.0031 and for LDL cholesterol at 10p11.23 (p = 0.0045. Interestingly, some of linkage regions identified in this Sikh population coincide with plausible candidate genes reported in recent genome-wide association and meta-analysis studies for lipid traits. Our study provides the first evidence of linkage for loci associated with quantitative lipid traits at four chromosomal regions in this Asian Indian population from Punjab. More detailed examination of these regions with more informative genotyping, sequencing, and functional studies should lead to rapid detection of novel targets of therapeutic importance.

  18. Multipoint genome-wide linkage scan for nonword repetition in a multigenerational family further supports chromosome 13q as a locus for verbal trait disorders.

    Science.gov (United States)

    Truong, D T; Shriberg, L D; Smith, S D; Chapman, K L; Scheer-Cohen, A R; DeMille, M M C; Adams, A K; Nato, A Q; Wijsman, E M; Eicher, J D; Gruen, J R

    2016-12-01

    Verbal trait disorders encompass a wide range of conditions and are marked by deficits in five domains that impair a person's ability to communicate: speech, language, reading, spelling, and writing. Nonword repetition is a robust endophenotype for verbal trait disorders that is sensitive to cognitive processes critical to verbal development, including auditory processing, phonological working memory, and motor planning and programming. In the present study, we present a six-generation extended pedigree with a history of verbal trait disorders. Using genome-wide multipoint variance component linkage analysis of nonword repetition, we identified a region spanning chromosome 13q14-q21 with LOD = 4.45 between 52 and 55 cM, spanning approximately 5.5 Mb on chromosome 13. This region overlaps with SLI3, a locus implicated in reading disability in families with a history of specific language impairment. Our study of a large multigenerational family with verbal trait disorders further implicates the SLI3 region in verbal trait disorders. Future studies will further refine the specific causal genetic factors in this locus on chromosome 13q that contribute to language traits.

  19. A genome-wide scan reveals important roles of DNA methylation in human longevity by regulating age-related disease genes.

    Directory of Open Access Journals (Sweden)

    Fu-Hui Xiao

    Full Text Available It is recognized that genetic factors contribute to human longevity. Besides the hypothesis of existence of longevity genes, another suggests that a lower frequency of risk alleles decreases the incidence of age-related diseases in the long-lived people. However, the latter finds no support from recent genetic studies. Considering the crucial role of epigenetic modification in gene regulation, we then hypothesize that suppressing disease-related genes in longevity individuals is likely achieved by epigenetic modification, e.g. DNA methylation. To test this hypothesis, we investigated the genome-wide methylation profile in 4 Chinese female centenarians and 4 middle-aged controls using methyl-DNA immunoprecipitation sequencing. 626 differentially methylated regions (DMRs were observed between both groups. Interestingly, genes with these DMRs were enriched in age-related diseases, including type-2 diabetes, cardiovascular disease, stroke and Alzheimer's disease. This pattern remains rather stable after including methylomes of two white individuals. Further analyses suggest that the observed DMRs likely have functional roles in regulating disease-associated gene expressions, with some genes [e.g. caspase 3 (CASP3] being down-regulated whereas the others [i.e. interleukin 1 receptor, type 2 (IL1R2] up-regulated. Therefore, our study suggests that suppressing the disease-related genes via epigenetic modification is an important contributor to human longevity.

  20. Combination analysis of genome-wide association and transcriptome sequencing of residual feed intake in quality chickens

    OpenAIRE

    Xu, Zhenqiang; Ji, Congliang; Zhang, Yan; Zhang, Zhe; Nie, Qinghua; Xu, Jiguo; Zhang, Dexiang; Zhang, Xiquan

    2016-01-01

    Background Residual feed intake (RFI) is a powerful indicator for energy utilization efficiency and responds to selection. Low RFI selection enables a reduction in feed intake without affecting growth performance. However, the effective variants or major genes dedicated to phenotypic differences in RFI in quality chickens are unclear. Therefore, a genome-wide association study (GWAS) and RNA sequencing were performed on RFI to identify genetic variants and potential candidate genes associated...

  1. Imaging genomics.

    Science.gov (United States)

    Thompson, Paul M; Martin, Nicholas G; Wright, Margaret J

    2010-08-01

    Imaging genomics is an emerging field that is rapidly identifying genes that influence the brain, cognition, and risk for disease. Worldwide, thousands of individuals are being scanned with high-throughput genotyping (genome-wide scans), and new imaging techniques [high angular resolution diffusion imaging and resting state functional magnetic resonance imaging (MRI)] that provide fine-grained measures of the brain's structural and functional connectivity. Along with clinical diagnosis and cognitive testing, brain imaging offers highly reproducible measures that can be subjected to genetic analysis. Recent studies of twin, pedigree, and population-based datasets have discovered several candidate genes that consistently show small to moderate effects on brain measures. Many studies measure single phenotypes from the images, such as hippocampal volume, but voxel-wise genomic methods can plot the profile of genetic association at each 3D point in the brain. This exploits the full arsenal of imaging statistics to discover and replicate gene effects. Imaging genomics efforts worldwide are now working together to discover and replicate many promising leads. By studying brain phenotypes closer to causative gene action, larger gene effects are detectable with realistic sample sizes obtainable from meta-analysis of smaller studies. Imaging genomics has broad applications to dementia, mental illness, and public health.

  2. Combined genome-wide linkage and targeted association analysis of head circumference in autism spectrum disorder families.

    Science.gov (United States)

    Woodbury-Smith, M; Bilder, D A; Morgan, J; Jerominski, L; Darlington, T; Dyer, T; Paterson, A D; Coon, H

    2017-01-01

    It has long been recognized that there is an association between enlarged head circumference (HC) and autism spectrum disorder (ASD), but the genetics of HC in ASD is not well understood. In order to investigate the genetic underpinning of HC in ASD, we undertook a genome-wide linkage study of HC followed by linkage signal targeted association among a sample of 67 extended pedigrees with ASD. HC measurements on members of 67 multiplex ASD extended pedigrees were used as a quantitative trait in a genome-wide linkage analysis. The Illumina 6K SNP linkage panel was used, and analyses were carried out using the SOLAR implemented variance components model. Loci identified in this way formed the target for subsequent association analysis using the Illumina OmniExpress chip and imputed genotypes. A modification of the qTDT was used as implemented in SOLAR. We identified a linkage signal spanning 6p21.31 to 6p22.2 (maximum LOD = 3.4). Although targeted association did not find evidence of association with any SNP overall, in one family with the strongest evidence of linkage, there was evidence for association (rs17586672, p = 1.72E-07). Although this region does not overlap with ASD linkage signals in these same samples, it has been associated with other psychiatric risk, including ADHD, developmental dyslexia, schizophrenia, specific language impairment, and juvenile bipolar disorder. The genome-wide significant linkage signal represents the first reported observation of a potential quantitative trait locus for HC in ASD and may be relevant in the context of complex multivariate risk likely leading to ASD.

  3. Neuronal genes for subcutaneous fat thickness in human and pig are identified by local genomic sequencing and combined SNP association study.

    Directory of Open Access Journals (Sweden)

    Kyung-Tai Lee

    Full Text Available Obesity represents a major global public health problem that increases the risk for cardiovascular or metabolic disease. The pigs represent an exceptional biomedical model related to energy metabolism and obesity in humans. To pinpoint causal genetic factors for a common form of obesity, we conducted local genomic de novo sequencing, 18.2 Mb, of a porcine QTL region affecting fatness traits, and carried out SNP association studies for backfat thickness and intramuscular fat content in pigs. In order to relate the association studies in pigs to human obesity, we performed a targeted genome wide association study for subcutaneous fat thickness in a cohort population of 8,842 Korean individuals. These combined association studies in human and pig revealed a significant SNP located in a gene family with sequence similarity 73, member A (FAM73A associated with subscapular skin-fold thickness in humans (rs4121165, GC-corrected p-value  = 0.0000175 and with backfat thickness in pigs (ASGA0029495, p-value  = 0.000031. Our combined association studies also suggest that eight neuronal genes are responsible for subcutaneous fat thickness: NEGR1, SLC44A5, PDE4B, LPHN2, ELTD1, ST6GALNAC3, ST6GALNAC5, and TTLL7. These results provide strong support for a major involvement of the CNS in the genetic predisposition to a common form of obesity.

  4. Multispecies Biofilms Transform Selenium Oxyanions into Elemental Selenium Particles: Studies Using Combined Synchrotron X-ray Fluorescence Imaging and Scanning Transmission X-ray Microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Soo In; George, Graham N.; Lawrence, John R.; Kaminskyj, Susan G. W.; Dynes, James J.; Lai, Barry; Pickering, Ingrid J.

    2016-10-04

    Selenium (Se) is an element of growing environmental concern, because low aqueous concentrations can lead to biomagnification through the aquatic food web. Biofilms, naturally occurring microbial consortia, play numerous important roles in the environment, especially in biogeochemical cycling of toxic elements in aquatic systems. The complexity of naturally forming multispecies biofilms presents challenges for characterization because conventional microscopic techniques require chemical and physical modifications of the sample. Here, multispecies biofilms biotransforming selenium oxyanions were characterized using X-ray fluorescence imaging (XFI) and scanning transmission X-ray microscopy (STXM). These complementary synchrotron techniques required minimal sample preparation and were applied correlatively to the same biofilm areas. Sub-micrometer XFI showed distributions of Se and endogenous metals, while Se K-edge X-ray absorption spectroscopy indicated the presence of elemental Se (Se0). Nanoscale carbon K-edge STXM revealed the distributions of microbial cells, extracellular polymeric substances (EPS), and lipids using the protein, saccharide, and lipid signatures, respectively, together with highly localized Se0 using the Se LIII edge. Transmission electron microscopy showed the electron-dense particle diameter to be 50–700 nm, suggesting Se0 nanoparticles. The intimate association of Se0 particles with protein and polysaccharide biofilm components has implications for the bioavailability of selenium in the environment.

  5. Comparison of fungiform taste-bud distribution among age groups using confocal laser scanning microscopy in vivo in combination with gustatory function.

    Science.gov (United States)

    Saito, Takehisa; Ito, Tetsufumi; Ito, Yumi; Manabe, Yasuhiro; Sano, Kazuo

    2016-04-01

    The aim of this study was to compare the distribution of taste buds in fungiform papillae (FP) and gustatory function between young and elderly age groups. Confocal laser scanning microscopy was used because it allows many FP to be observed non-invasively in a short period of time. The age of participants (n = 211) varied from 20 to 83 yr. The tip and midlateral region of the tongue were observed. Taste buds in an average of 10 FP in each area were counted. A total of 2,350 FP at the tongue tip and 2,592 FP in the midlateral region could be observed. The average number of taste buds was similar among all age groups both at the tongue tip and in the midlateral region. The taste function, measured by electrogustometry, among participants 20-29 yr of age was significantly lower than that in the other age groups; however, there was no difference among any other age groups in taste function. These results indicate that the peripheral gustatory system is well maintained anatomically and functionally in elderly people. © 2016 Eur J Oral Sci.

  6. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... News Physician Resources Professions Site Index A-Z Thyroid Scan and Uptake Thyroid scan and uptake uses ... the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is a ...

  7. Thyroid Scan and Uptake

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Thyroid Scan and Uptake Thyroid scan and uptake uses ... the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is a ...

  8. A novel recombinant retrovirus in the genomes of modern birds combines features of avian and mammalian retroviruses.

    Science.gov (United States)

    Henzy, Jamie E; Gifford, Robert J; Johnson, Welkin E; Coffin, John M

    2014-03-01

    Endogenous retroviruses (ERVs) represent ancestral sequences of modern retroviruses or their extinct relatives. The majority of ERVs cluster alongside exogenous retroviruses into two main groups based on phylogenetic analyses of the reverse transcriptase (RT) enzyme. Class I includes gammaretroviruses, and class II includes lentiviruses and alpha-, beta-, and deltaretroviruses. However, analyses of the transmembrane subunit (TM) of the envelope glycoprotein (env) gene result in a different topology for some retroviruses, suggesting recombination events in which heterologous env sequences have been acquired. We previously demonstrated that the TM sequences of five of the six genera of orthoretroviruses can be divided into three types, each of which infects a distinct set of vertebrate classes. Moreover, these classes do not always overlap the host range of the associated RT classes. Thus, recombination resulting in acquisition of a heterologous env gene could in theory facilitate cross-species transmissions across vertebrate classes, for example, from mammals to reptiles. Here we characterized a family of class II avian ERVs, "TgERV-F," that acquired a mammalian gammaretroviral env sequence. Although TgERV-F clusters near a sister clade to alpharetroviruses, its genome also has some features of betaretroviruses. We offer evidence that this unusual recombinant has circulated among several avian orders and may still have infectious members. In addition to documenting the infection of a nongalliform avian species by a mammalian retrovirus, TgERV-F also underscores the importance of env sequences in reconstructing phylogenies and supports a possible role for env swapping in allowing cross-species transmissions across wide taxonomic distances. Retroviruses can sometimes acquire an envelope gene (env) from a distantly related retrovirus. Since env is a key determinant of host range, such an event affects the host range of the recombinant virus and can lead to the creation

  9. Characterization of a novel Lactobacillus species closely related to Lactobacillus johnsonii using a combination of molecular and comparative genomics methods

    Science.gov (United States)

    2010-01-01

    Background Comparative genomic hybridization (CGH) constitutes a powerful tool for identification and characterization of bacterial strains. In this study we have applied this technique for the characterization of a number of Lactobacillus strains isolated from the intestinal content of rats fed with a diet supplemented with sorbitol. Results Phylogenetic analysis based on 16S rRNA gene, recA, pheS, pyrG and tuf sequences identified five bacterial strains isolated from the intestinal content of rats as belonging to the recently described Lactobacillus taiwanensis species. DNA-DNA hybridization experiments confirmed that these five strains are distinct but closely related to Lactobacillus johnsonii and Lactobacillus gasseri. A whole genome DNA microarray designed for the probiotic L. johnsonii strain NCC533 was used for CGH analysis of L. johnsonii ATCC 33200T, L. johnsonii BL261, L. gasseri ATCC 33323T and L. taiwanensis BL263. In these experiments, the fluorescence ratio distributions obtained with L. taiwanensis and L. gasseri showed characteristic inter-species profiles. The percentage of conserved L. johnsonii NCC533 genes was about 83% in the L. johnsonii strains comparisons and decreased to 51% and 47% for L. taiwanensis and L. gasseri, respectively. These results confirmed the separate status of L. taiwanensis from L. johnsonii at the level of species, and also that L. taiwanensis is closer to L. johnsonii than L. gasseri is to L. johnsonii. Conclusion Conventional taxonomic analyses and microarray-based CGH analysis have been used for the identification and characterization of the newly species L. taiwanensis. The microarray-based CGH technology has been shown as a remarkable tool for the identification and fine discrimination between phylogenetically close species, and additionally provided insight into the adaptation of the strain L. taiwanensis BL263 to its ecological niche. PMID:20849602

  10. Characterization of a novel Lactobacillus species closely related to Lactobacillus johnsonii using a combination of molecular and comparative genomics methods

    Directory of Open Access Journals (Sweden)

    Pérez-Martínez Gaspar

    2010-09-01

    Full Text Available Abstract Background Comparative genomic hybridization (CGH constitutes a powerful tool for identification and characterization of bacterial strains. In this study we have applied this technique for the characterization of a number of Lactobacillus strains isolated from the intestinal content of rats fed with a diet supplemented with sorbitol. Results Phylogenetic analysis based on 16S rRNA gene, recA, pheS, pyrG and tuf sequences identified five bacterial strains isolated from the intestinal content of rats as belonging to the recently described Lactobacillus taiwanensis species. DNA-DNA hybridization experiments confirmed that these five strains are distinct but closely related to Lactobacillus johnsonii and Lactobacillus gasseri. A whole genome DNA microarray designed for the probiotic L. johnsonii strain NCC533 was used for CGH analysis of L. johnsonii ATCC 33200T, L. johnsonii BL261, L. gasseri ATCC 33323T and L. taiwanensis BL263. In these experiments, the fluorescence ratio distributions obtained with L. taiwanensis and L. gasseri showed characteristic inter-species profiles. The percentage of conserved L. johnsonii NCC533 genes was about 83% in the L. johnsonii strains comparisons and decreased to 51% and 47% for L. taiwanensis and L. gasseri, respectively. These results confirmed the separate status of L. taiwanensis from L. johnsonii at the level of species, and also that L. taiwanensis is closer to L. johnsonii than L. gasseri is to L. johnsonii. Conclusion Conventional taxonomic analyses and microarray-based CGH analysis have been used for the identification and characterization of the newly species L. taiwanensis. The microarray-based CGH technology has been shown as a remarkable tool for the identification and fine discrimination between phylogenetically close species, and additionally provided insight into the adaptation of the strain L. taiwanensis BL263 to its ecological niche.

  11. Combining magnetic sorting of mother cells and fluctuation tests to analyze genome instability during mitotic cell aging in Saccharomyces cerevisiae.

    Science.gov (United States)

    Patterson, Melissa N; Maxwell, Patrick H

    2014-10-16

    Saccharomyces cerevisiae has been an excellent model system for examining mechanisms and consequences of genome instability. Information gained from this yeast model is relevant to many organisms, including humans, since DNA repair and DNA damage response factors are well conserved across diverse species. However, S. cerevisiae has not yet been used to fully address whether the rate of accumulating mutations changes with increasing replicative (mitotic) age due to technical constraints. For instance, measurements of yeast replicative lifespan through micromanipulation involve very small populations of cells, which prohibit detection of rare mutations. Genetic methods to enrich for mother cells in populations by inducing death of daughter cells have been developed, but population sizes are still limited by the frequency with which random mutations that compromise the selection systems occur. The current protocol takes advantage of magnetic sorting of surface-labeled yeast mother cells to obtain large enough populations of aging mother cells to quantify rare mutations through phenotypic selections. Mutation rates, measured through fluctuation tests, and mutation frequencies are first established for young cells and used to predict the frequency of mutations in mother cells of various replicative ages. Mutation frequencies are then determined for sorted mother cells, and the age of the mother cells is determined using flow cytometry by staining with a fluorescent reagent that detects bud scars formed on their cell surfaces during cell division. Comparison of predicted mutation frequencies based on the number of cell divisions to the frequencies experimentally observed for mother cells of a given replicative age can then identify whether there are age-related changes in the rate of accumulating mutations. Variations of this basic protocol provide the means to investigate the influence of alterations in specific gene functions or specific environmental conditions on

  12. Evaluation of the effects of Er:YAG laser and desensitizing paste containing 8% arginine and calcium carbonate, and their combinations on human dentine tubules: a scanning electron microscopic analysis.

    Science.gov (United States)

    Tunar, Ogul L; Gürsoy, Hare; Çakar, Gökser; Kuru, Bahar; Ipci, Sebnem Dirikan; Yılmaz, Selçuk

    2014-10-01

    The aim of this study was to evaluate the in vitro effects of Er:YAG laser and an in-office desensitizing paste alone or in combination by using scanning electron microscopic (SEM) analysis. Various treatment modalities have been proposed for dentin hypersensitivity, but to date, no single agent or form of treatment has been found effective. Forty dentine specimens obtained from freshly extracted impacted third molars were included and divided into four groups. Group I served as the control, whereas Group II, Group III, and Group IV recieved Er:YAG laser (30 Hz, 60 mJ/pulse, 10 sec), a desensitizing paste (DP) containing 8% arginine and calcium carbonate, and DP+Er:YAG laser in combination, respectively, evaluated under SEM. SEM analysis presented occlusion and narrowing of dentinal tubules in all treatment groups, but more prominent occlusion was observed in the combined treatment group. Intergroup comparisons regarding the tubule diameters and the number of the open dentinal tubules per 100 μm2 revealed statistically significant difference in favor of combined group (ptreatment procedures are effective in dentinal tubule occlusion. However, more prominent occlusion is observed in the combined treatment group.

  13. A combined tract-based spatial statistics and voxel-based morphometry study of the first MRI scan after diagnosis of amyotrophic lateral sclerosis with subgroup analysis.

    Science.gov (United States)

    Alruwaili, A R; Pannek, K; Coulthard, A; Henderson, R; Kurniawan, N D; McCombe, P

    2017-08-09

    This study aims to compare the cortical and subcortical deep gray matter (GM) and white matter (WM) of ALS subjects and controls and to compare ALS subjects with (ALScog) and without (ALSnon-cog) cognitive impairment. The study was performed in 30 ALS subjects, and 19 healthy controls. Structural T1- and diffusion-weighted MRI data were analyzed using voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS). All DTI measures and GM volume differed significantly between ALS subjects and controls. Compared to controls, greater DTI changes were present in ALScog than ALSnon-cog subjects. GM results showed reduction in the caudate nucleus volume in ALScog subjects compared to ALSnon-cog. and comparing all ALS with controls, there were changes on the right side and in a small region in the left middle frontal gyrus. This combined DTI and VBM study showed changes in motor and extra-motor regions. The DTI changes were more extensive in ALScog than ALSnon-cog subjects. It is likely that the inclusion of ALS subjects with cognitive impairment in previous studies resulted in extra-motor WM abnormalities being reported in ALS subjects. Copyright © 2017. Published by Elsevier Masson SAS.

  14. Chromosomal microarray as a primary diagnostic genomic tool for pregnancies defined as being at increased risk within a population based combined first-trimester screening program

    DEFF Research Database (Denmark)

    Vogel, Ida; Petersen, Olav Bjørn; Christensen, Rikke

    2017-01-01

    OBJECTIVE: To evaluate the impact of using high-resolution chromosomal microarray (CMA) as the standard diagnostic approach to examine for genomic imbalances in pregnancies with increased risk (≥1 in 300) defined through combined first trimester screening (cFTS). METHODS: A cohort of 575...... consecutive pregnancies that had cFTS risk ≥1:300 through a publicly funded population based screening program in the Central and Northern Regions of Denmark between September 2015 and September 2016. Women with an NT ≥3.5 mm or opting for NIPT were excluded. Comparative genomic hybridization was performed...... of aneuploidy were detected as well as 15 (15/575, 2.6%: 95% CI: 1.5-4.3%) cases with a pathogenic or likely pathogenic copy number variant (CNV). Reducing the cFTS risk threshold for invasive diagnostic testing to 1 in 100 or 1 in 50 would have led, respectively, to 60% or 100% of the pathogenic CNVs being...

  15. Combination analysis of genome-wide association and transcriptome sequencing of residual feed intake in quality chickens.

    Science.gov (United States)

    Xu, Zhenqiang; Ji, Congliang; Zhang, Yan; Zhang, Zhe; Nie, Qinghua; Xu, Jiguo; Zhang, Dexiang; Zhang, Xiquan

    2016-08-09

    Residual feed intake (RFI) is a powerful indicator for energy utilization efficiency and responds to selection. Low RFI selection enables a reduction in feed intake without affecting growth performance. However, the effective variants or major genes dedicated to phenotypic differences in RFI in quality chickens are unclear. Therefore, a genome-wide association study (GWAS) and RNA sequencing were performed on RFI to identify genetic variants and potential candidate genes associated with energy improvement. A lower average daily feed intake was found in low-RFI birds compared to high-RFI birds. The heritability of RFI measured from 44 to 83 d of age was 0.35. GWAS showed that 32 of the significant single nucleotide polymorphisms (SNPs) associated with the RFI (P energy utilization. RNA sequencing was performed to profile the liver transcriptomes of four male chickens selected from the high and low tails of the RFI. One hundred and sixteen unique genes were identified as differentially expressed genes (DEGs). Some of these genes were relevant to appetite, cell activities, and fat metabolism, such as CCKAR, HSP90B1, and PCK1. Some potential genes within the 500 Kb flanking region of the significant RFI-related SNPs detected in GWAS (i.e., MGP, HIST1H110, HIST1H2A4L3, OC3, NR0B2, PER2, ST6GALNAC2, and G0S2) were also identified as DEGs in chickens with divergent RFIs. The GWAS findings showed that the 1 Mb narrow region of GGA12 should be important because it contained genes involved in energy-consuming processes, such as lipogenesis, social behavior, and immunity. Similar results were obtained in the transcriptome sequencing experiments. In general, low-RFI birds seemed to optimize energy employment by reducing energy expenditure in cell activities, immune responses, and physical activity compared to eating.

  16. Increased genetic gains in sheep, beef and dairy breeding programs from using female reproductive technologies combined with optimal contribution selection and genomic breeding values.

    Science.gov (United States)

    Granleese, Tom; Clark, Samuel A; Swan, Andrew A; van der Werf, Julius H J

    2015-09-14

    Female reproductive technologies such as multiple ovulation and embryo transfer (MOET) and juvenile in vitro embryo production and embryo transfer (JIVET) can boost rates of genetic gain but they can also increase rates of inbreeding. Inbreeding can be managed using the principles of optimal contribution selection (OCS), which maximizes genetic gain while placing a penalty on the rate of inbreeding. We evaluated the potential benefits and synergies that exist between genomic selection (GS) and reproductive technologies under OCS for sheep and cattle breeding programs. Various breeding program scenarios were simulated stochastically including: (1) a sheep breeding program for the selection of a single trait that could be measured either early or late in life; (2) a beef breeding program with an early or late trait; and (3) a dairy breeding program with a sex limited trait. OCS was applied using a range of penalties (severe to no penalty) on co-ancestry of selection candidates, with the possibility of using multiple ovulation and embryo transfer (MOET) and/or juvenile in vitro embryo production and embryo transfer (JIVET) for females. Each breeding program was simulated with and without genomic selection. All breeding programs could be penalized to result in an inbreeding rate of 1 % increase per generation. The addition of MOET to artificial insemination or natural breeding (AI/N), without the use of GS yielded an extra 25 to 60 % genetic gain. The further addition of JIVET did not yield an extra genetic gain. When GS was used, MOET and MOET + JIVET programs increased rates of genetic gain by 38 to 76 % and 51 to 81 % compared to AI/N, respectively. Large increases in genetic gain were found across species when female reproductive technologies combined with genomic selection were applied and inbreeding was managed, especially for breeding programs that focus on the selection of traits measured late in life or that are sex-limited. Optimal contribution selection was

  17. Thyroid Scan and Uptake

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    Full Text Available ... limitations of the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is ... top of page What are some common uses of the procedure? The thyroid scan is used to ...

  18. Thyroid Scan and Uptake

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    Full Text Available ... of the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is ... of page What are some common uses of the procedure? The thyroid scan is used to determine ...

  19. Arm CT scan

    Science.gov (United States)

    CAT scan - arm; Computed axial tomography scan - arm; Computed tomography scan - arm; CT scan - arm ... stopping.) A computer creates separate images of the arm area, called slices. These images can be stored, ...

  20. Thoracic spine CT scan

    Science.gov (United States)

    CAT scan - thoracic spine; Computed axial tomography scan - thoracic spine; Computed tomography scan - thoracic spine; CT scan - ... Philadelphia, PA: Elsevier Mosby; 2013:chap 44. US Food and Drug Administration. Computed tomography (CT). Updated August ...

  1. Global Profiling and Novel Structure Discovery Using Multiple Neutral Loss/Precursor Ion Scanning Combined with Substructure Recognition and Statistical Analysis (MNPSS): Characterization of Terpene-Conjugated Curcuminoids in Curcuma longa as a Case Study.

    Science.gov (United States)

    Qiao, Xue; Lin, Xiong-hao; Ji, Shuai; Zhang, Zheng-xiang; Bo, Tao; Guo, De-an; Ye, Min

    2016-01-05

    To fully understand the chemical diversity of an herbal medicine is challenging. In this work, we describe a new approach to globally profile and discover novel compounds from an herbal extract using multiple neutral loss/precursor ion scanning combined with substructure recognition and statistical analysis. Turmeric (the rhizomes of Curcuma longa L.) was used as an example. This approach consists of three steps: (i) multiple neutral loss/precursor ion scanning to obtain substructure information; (ii) targeted identification of new compounds by extracted ion current and substructure recognition; and (iii) untargeted identification using total ion current and multivariate statistical analysis to discover novel structures. Using this approach, 846 terpecurcumins (terpene-conjugated curcuminoids) were discovered from turmeric, including a number of potentially novel compounds. Furthermore, two unprecedented compounds (terpecurcumins X and Y) were purified, and their structures were identified by NMR spectroscopy. This study extended the application of mass spectrometry to global profiling of natural products in herbal medicines and could help chemists to rapidly discover novel compounds from a complex matrix.

  2. The Effect of Antiretroviral Combination Treatment on Epstein-Barr Virus (EBV Genome Load in HIV-Infected Patients

    Directory of Open Access Journals (Sweden)

    Anna M. C. Friis

    2010-03-01

    Full Text Available We evaluated the effect of combination anti-retroviral treatment (cART on the host control of EBV infection in moderately immunosuppressed HIV-1 patients. Twenty HIV-1 infected individuals were followed for five years with repeated measurements of EBV DNA load in peripheral blood lymphocytes in relation to HIV-RNA titers and CD4+ cell counts. Individuals with optimal response, i.e. durable non-detectable HIV-RNA, showed a decline of EBV load to the level of healthy controls. Individuals with non-optimal HIV-1 control did not restore their EBV control. Long-lasting suppression of HIV-replication after early initiation of cART is a prerequisite for re-establishing the immune control of EBV.

  3. Towards an integrated food safety surveillance system: a simulation study to explore the potential of combining genomic and epidemiological metadata

    Science.gov (United States)

    Crotta, M.; Wall, B.; Good, L.; O'Brien, S. J.; Guitian, J.

    2017-01-01

    Foodborne infection is a result of exposure to complex, dynamic food systems. The efficiency of foodborne infection is driven by ongoing shifts in genetic machinery. Next-generation sequencing technologies can provide high-fidelity data about the genetics of a pathogen. However, food safety surveillance systems do not currently provide similar high-fidelity epidemiological metadata to associate with genetic data. As a consequence, it is rarely possible to transform genetic data into actionable knowledge that can be used to genuinely inform risk assessment or prevent outbreaks. Big data approaches are touted as a revolution in decision support, and pose a potentially attractive method for closing the gap between the fidelity of genetic and epidemiological metadata for food safety surveillance. We therefore developed a simple food chain model to investigate the potential benefits of combining ‘big’ data sources, including both genetic and high-fidelity epidemiological metadata. Our results suggest that, as for any surveillance system, the collected data must be relevant and characterize the important dynamics of a system if we are to properly understand risk: this suggests the need to carefully consider data curation, rather than the more ambitious claims of big data proponents that unstructured and unrelated data sources can be combined to generate consistent insight. Of interest is that the biggest influencers of foodborne infection risk were contamination load and processing temperature, not genotype. This suggests that understanding food chain dynamics would probably more effectively generate insight into foodborne risk than prescribing the hazard in ever more detail in terms of genotype. PMID:28405360

  4. Towards an integrated food safety surveillance system: a simulation study to explore the potential of combining genomic and epidemiological metadata.

    Science.gov (United States)

    Hill, A A; Crotta, M; Wall, B; Good, L; O'Brien, S J; Guitian, J

    2017-03-01

    Foodborne infection is a result of exposure to complex, dynamic food systems. The efficiency of foodborne infection is driven by ongoing shifts in genetic machinery. Next-generation sequencing technologies can provide high-fidelity data about the genetics of a pathogen. However, food safety surveillance systems do not currently provide similar high-fidelity epidemiological metadata to associate with genetic data. As a consequence, it is rarely possible to transform genetic data into actionable knowledge that can be used to genuinely inform risk assessment or prevent outbreaks. Big data approaches are touted as a revolution in decision support, and pose a potentially attractive method for closing the gap between the fidelity of genetic and epidemiological metadata for food safety surveillance. We therefore developed a simple food chain model to investigate the potential benefits of combining 'big' data sources, including both genetic and high-fidelity epidemiological metadata. Our results suggest that, as for any surveillance system, the collected data must be relevant and characterize the important dynamics of a system if we are to properly understand risk: this suggests the need to carefully consider data curation, rather than the more ambitious claims of big data proponents that unstructured and unrelated data sources can be combined to generate consistent insight. Of interest is that the biggest influencers of foodborne infection risk were contamination load and processing temperature, not genotype. This suggests that understanding food chain dynamics would probably more effectively generate insight into foodborne risk than prescribing the hazard in ever more detail in terms of genotype.

  5. Advanced Microbial Taxonomy Combined with Genome-Based-Approaches Reveals that Vibrio astriarenae sp. nov., an Agarolytic Marine Bacterium, Forms a New Clade in Vibrionaceae.

    Directory of Open Access Journals (Sweden)

    Nurhidayu Al-Saari

    Full Text Available Advances in genomic microbial taxonomy have opened the way to create a more universal and transparent concept of species but is still in a transitional stage towards becoming a defining robust criteria for describing new microbial species with minimum features obtained using both genome and classical polyphasic taxonomies. Here we performed advanced microbial taxonomies combined with both genome-based and classical approaches for new agarolytic vibrio isolates to describe not only a novel Vibrio species but also a member of a new Vibrio clade. Two novel vibrio strains (Vibrio astriarenae sp. nov. C7T and C20 showing agarolytic, halophilic and fermentative metabolic activity were isolated from a seawater sample collected in a coral reef in Okinawa. Intraspecific similarities of the isolates were identical in both sequences on the 16S rRNA and pyrH genes, but the closest relatives on the molecular phylogenetic trees on the basis of 16S rRNA and pyrH gene sequences were V. hangzhouensis JCM 15146T (97.8% similarity and V. agarivorans CECT 5085T (97.3% similarity, respectively. Further multilocus sequence analysis (MLSA on the basis of 8 protein coding genes (ftsZ, gapA, gyrB, mreB, pyrH, recA, rpoA, and topA obtained by the genome sequences clearly showed the V. astriarenae strain C7T and C20 formed a distinct new clade protruded next to V. agarivorans CECT 5085T. The singleton V. agarivorans has never been included in previous MLSA of Vibrionaceae due to the lack of some gene sequences. Now the gene sequences are completed and analysis of 100 taxa in total provided a clear picture describing the association of V. agarivorans into pre-existing concatenated network tree and concluded its relationship to our vibrio strains. Experimental DNA-DNA hybridization (DDH data showed that the strains C7T and C20 were conspecific but were separated from all of the other Vibrio species related on the basis of both 16S rRNA and pyrH gene phylogenies (e.g., V

  6. Mammographic scanning equalization radiography.

    Science.gov (United States)

    Sabol, J M; Soutar, I C; Plewes, D B

    1993-01-01

    It is well recognized that variations in breast thickness and parenchymal composition can produce a range of exposure which exceeds the latitude of high contrast mammographic film/screen combinations. Optimal imaging of the dense breast is desired since 30%-60% of women present with dense breasts, and they are believed to be at the highest relative risk of developing breast cancer. The application of scanning equalization radiography to mammography has been investigated through the construction and characterization of a prototype mammographic scanning equalization radiography (MSER) system, designed to image mammographic phantoms. The MSER system exposes a Min-R/MRH cassette by raster scanning a 2.0 x 1.6 cm beam of pulsed x-rays across the cassette. A scanning detector behind the cassette measures the local x-ray transmission of the breast. Feedback of the transmission information is used to modulate the duration of each x-ray pulse, to equalize the film exposure. The effective dynamic range of the MSER system is 25 times greater than that of conventional mammography. Artifact-free images of mammographic phantoms show that MSER effectively overcomes the latitude limitations of film/screen mammography, enabling high contrast imaging over a wide range of object x-ray transmission. Anthropomorphic phantom images show that MSER offers up to a sixfold increase in film contrast in the normally underexposed regions of conventional mammograms. Characterization of the entrance exposure shows that there is not a significant difference in exposure between MSER and conventional mammographic techniques, suggesting that both would pose comparable risk to the patient. Calculations show that the construction of a clinical multiple beam MSER system is feasible with minor changes to existing technology.

  7. Coronary Calcium Scan

    Science.gov (United States)

    ... Back To Health Topics / Coronary Calcium Scan Coronary Calcium Scan Also known as Calcium Scan Test A coronary calcium scan is a CT scan of your heart that detects and measures the amount of calcium in the walls of your coronary arteries. Overview ...

  8. The classification of mRNA expression levels by the phosphorylation state of RNAPII CTD based on a combined genome-wide approach

    Directory of Open Access Journals (Sweden)

    Tachibana Taro

    2011-10-01

    Full Text Available Abstract Background Cellular function is regulated by the balance of stringently regulated amounts of mRNA. Previous reports revealed that RNA polymerase II (RNAPII, which transcribes mRNA, can be classified into the pausing state and the active transcription state according to the phosphorylation state of RPB1, the catalytic subunit of RNAPII. However, genome-wide association between mRNA expression level and the phosphorylation state of RNAPII is unclear. While the functional importance of pausing genes is clear, such as in mouse Embryonic Stem cells for differentiation, understanding this association is critical for distinguishing pausing genes from active transcribing genes in expression profiling data, such as microarrays and RNAseq. Therefore, we examined the correlation between the phosphorylation of RNAPII and mRNA expression levels using a combined analysis by ChIPseq and RNAseq. Results We first performed a precise quantitative measurement of mRNA by performing an optimized calculation in RNAseq. We then visualized the recruitment of various phosphorylated RNAPIIs, such as Ser2P and Ser5P. A combined analysis using optimized RNAseq and ChIPseq for phosphorylated RNAPII revealed that mRNA levels correlate with the various phosphorylation states of RNAPII. Conclusions We demonstrated that the amount of mRNA is precisely reflected by the phased phosphorylation of Ser2 and Ser5. In particular, even the most "pausing" genes, for which only Ser5 is phosphorylated, were detectable at a certain level of mRNA. Our analysis indicated that the complexity of quantitative regulation of mRNA levels could be classified into three categories according to the phosphorylation state of RNAPII.

  9. Rapid detection of Salmonella in raw chicken breast using real-time PCR combined with immunomagnetic separation and whole genome amplification.

    Science.gov (United States)

    Hyeon, Ji-Yeon; Deng, Xiangyu

    2017-05-01

    We presented the first attempt to combine immunomagnetic separation (IMS), whole genome amplification by multiple displacement amplification (MDA) and real-time PCR for detecting a bacterial pathogen in a food sample. This method was effective in enabling real-time PCR detection of low levels of Salmonella enterica Serotype Enteritidis (SE) (∼10 CFU/g) in raw chicken breast without culture enrichment. In addition, it was able to detect refrigeration-stressed SE cells at lower concentrations (∼0.1 CFU/g) in raw chicken breast after a 4-h culture enrichment, shortening the detection process from days to hours and displaying no statistical difference in detection rate in comparison with a culture-based detection method. By substantially improving performance in SE detection over conventional real-time PCR, we demonstrated the potential of IMS-MDA real-time PCR as a rapid, sensitive and affordable method for detecting Salmonella in food. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Growth and Its Relationship to Individual Genetic Diversity of Mountain Hemlock (Tsuga mertensiana at Alpine Treeline in Alaska: Combining Dendrochronology and Genomics

    Directory of Open Access Journals (Sweden)

    Jeremy S. Johnson

    2017-11-01

    Full Text Available Globally, alpine treelines are characterized as temperature-limited environments with strong controls on tree growth. However, at local scales spatially heterogeneous environments generally have more variable impacts on individual patterns of tree growth. In addition to the landscape spatial heterogeneity there is local variability in individual tree genetic diversity (level of individual heterozygosity. It has been hypothesized that higher individual heterozygosity will result in more consistent patterns of growth. In this article, we combine genomics and dendrochronology to explore the relationship between individual genetic diversity and tree growth at a mountain hemlock (Tsuga mertensiana Bong. Carr alpine treeline on the Kenai Peninsula, Alaska, USA. We correlated average observed individual heterozygosity with average tree-ring width and variance in tree-ring width within individuals to test the hypothesis that trees with higher individual heterozygosity will also have more consistent growth patterns, suggesting that they may be more resilient to climate and environmental fluctuations at the alpine treeline. Our results showed that there was no significant relationship between tree growth and individual heterozygosity. However, there was a significant positive relationship between average tree-ring width and variance in tree-ring width implying that overall, fast growing trees in stressful environments, such as the alpine treeline, grow unstably regardless of the level of individual heterozygosity.

  11. Thyroid Scan and Uptake

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    Full Text Available ... of the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is ... code: Phone no: Thank you! Do you have a personal story about radiology? Share your patient story ...

  12. Heart PET scan

    Science.gov (United States)

    ... nuclear medicine scan; Heart positron emission tomography; Myocardial PET scan ... A PET scan requires a small amount of radioactive material (tracer). This tracer is given through a vein (IV), ...

  13. Thyroid Scan and Uptake

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    Full Text Available ... of the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is ... taking our brief survey: Survey Do you have a personal story about radiology? Share your patient story ...

  14. A genome scan for quantitative trait loci affecting milk somatic cell score in Israeli and Italian Holstein cows by means of selective DNA pooling with single- and multiple-marker mapping.

    Science.gov (United States)

    Tal-Stein, R; Fontanesi, L; Dolezal, M; Scotti, E; Bagnato, A; Russo, V; Canavesi, F; Friedmann, A; Soller, M; Lipkin, E

    2010-10-01

    Mastitis is an important and common dairy cattle disease affecting milk yield, quality, and consumer safety as well as cheese yields and quality. Animal welfare and residues of the antibiotics used to treat mastitis cause public concern. Considerable genetic variation may allow selection for increased resistance to mastitis. Because of high genetic correlation to milk somatic cell score (SCS), SCS can serve as a surrogate trait for mastitis resistance. The present study intended to identify quantitative trait loci (QTL) affecting SCS in Israeli and Italian Holstein dairy cattle (IsH and ItH, respectively), using selective DNA pooling with single and multiple marker mapping. Milk samples of 4,788 daughters of 6 IsH and 7 ItH sires were used to construct sire-family high- and low-tail pools, which were genotyped at 123 (IsH) and 133 (ItH) microsatellite markers. Shadow correction was used to obtain pool allele frequency estimates. Frequency difference between the tails and empirical standard error of D, SE(D), were used to obtain P-values. All markers significant by single marker mapping were also significant by multiple marker mapping, but not vice versa. Combining both populations, 22 QTL on 21 chromosomes were identified; all corresponded to previous reports in the literature. Confidence intervals were set by chi-squared drop method. Heterozygosity of QTL was estimated at 44.2%. Allele substitution effects ranged from 1,782 to 4,930 cells/mL in estimated breeding value somatic cell count units. Most (80%) of the observed variation in estimated breeding value somatic cell score could be explained by the QTL identified under the stringent criteria. The results found here can be used as a basis for further genome-wide association studies for the same trait. Copyright © 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  15. Combinations of SNP genotypes from the Wellcome Trust Case Control Study of bipolar patients

    DEFF Research Database (Denmark)

    Mellerup, Erling; Jørgensen, Martin Balslev; Dam, Henrik

    2018-01-01

    of these combinations in their genome. Conclusion: Clusters of combinations of genetic variants can be considered general risk factors for polygenic disorders, whereas accumulation of combinations from the clusters in the genome of a patient can be considered a personal risk factor....... mining tools were used to scan The Wellcome Trust data set for combinations. Results: Two clusters of combinations were significantly associated with bipolar disorder. One cluster contained 68 combinations, each of which included five SNP genotypes. Of the 1998 patients, 305 had combinations from......Objectives: Combinations of genetic variants are the basis for polygenic disorders. We examined combinations of SNP genotypes taken from the 446 729 SNPs in The Wellcome Trust Case Control Study of bipolar patients. Methods: Parallel computing by graphics processing units, cloud computing, and data...

  16. HMMerThread: detecting remote, functional conserved domains in entire genomes by combining relaxed sequence-database searches with fold recognition.

    Directory of Open Access Journals (Sweden)

    Charles Richard Bradshaw

    Full Text Available Conserved domains in proteins are one of the major sources of functional information for experimental design and genome-level annotation. Though search tools for conserved domain databases such as Hidden Markov Models (HMMs are sensitive in detecting conserved domains in proteins when they share sufficient sequence similarity, they tend to miss more divergent family members, as they lack a reliable statistical framework for the detection of low sequence similarity. We have developed a greatly improved HMMerThread algorithm that can detect remotely conserved domains in highly divergent sequences. HMMerThread combines relaxed conserved domain searches with fold recognition to eliminate false positive, sequence-based identifications. With an accuracy of 90%, our software is able to automatically predict highly divergent members of conserved domain families with an associated 3-dimensional structure. We give additional confidence to our predictions by validation across species. We have run HMMerThread searches on eight proteomes including human and present a rich resource of remotely conserved domains, which adds significantly to the functional annotation of entire proteomes. We find ∼4500 cross-species validated, remotely conserved domain predictions in the human proteome alone. As an example, we find a DNA-binding domain in the C-terminal part of the A-kinase anchor protein 10 (AKAP10, a PKA adaptor that has been implicated in cardiac arrhythmias and premature cardiac death, which upon stress likely translocates from mitochondria to the nucleus/nucleolus. Based on our prediction, we propose that with this HLH-domain, AKAP10 is involved in the transcriptional control of stress response. Further remotely conserved domains we discuss are examples from areas such as sporulation, chromosome segregation and signalling during immune response. The HMMerThread algorithm is able to automatically detect the presence of remotely conserved domains in

  17. Personal genomics services: whose genomes?

    Science.gov (United States)

    Gurwitz, David; Bregman-Eschet, Yael

    2009-07-01

    New companies offering personal whole-genome information services over the internet are dynamic and highly visible players in the personal genomics field. For fees currently ranging from US$399 to US$2500 and a vial of saliva, individuals can now purchase online access to their individual genetic information regarding susceptibility to a range of chronic diseases and phenotypic traits based on a genome-wide SNP scan. Most of the companies offering such services are based in the United States, but their clients may come from nearly anywhere in the world. Although the scientific validity, clinical utility and potential future implications of such services are being hotly debated, several ethical and regulatory questions related to direct-to-consumer (DTC) marketing strategies of genetic tests have not yet received sufficient attention. For example, how can we minimize the risk of unauthorized third parties from submitting other people's DNA for testing? Another pressing question concerns the ownership of (genotypic and phenotypic) information, as well as the unclear legal status of customers regarding their own personal information. Current legislation in the US and Europe falls short of providing clear answers to these questions. Until the regulation of personal genomics services catches up with the technology, we call upon commercial providers to self-regulate and coordinate their activities to minimize potential risks to individual privacy. We also point out some specific steps, along the trustee model, that providers of DTC personal genomics services as well as regulators and policy makers could consider for addressing some of the concerns raised below.

  18. On genome-wide association studies for family-based designs: an integrative analysis approach combining ascertained family samples with unselected controls.

    NARCIS (Netherlands)

    Lasky-Su, J.; Won, S.; Mick, E.; Anney, R.J.; Franke, B.; Neale, B.; Biederman, J.; Smalley, S.L.; Loo, S.K.; Todorov, A.; Faraone, S.V.; Weiss, S.T.; Lange, C.

    2010-01-01

    Large numbers of control individuals with genome-wide genotype data are now available through various databases. These controls are regularly used in case-control genome-wide association studies (GWAS) to increase the statistical power. Controls are often "unselected" for the disease of interest and

  19. Codification of scan path parameters and development of perimeter scan strategies for 3D bowl-shaped laser forming

    Science.gov (United States)

    Tavakoli, A.; Naeini, H. Moslemi; Roohi, Amir H.; Gollo, M. Hoseinpour; Shahabad, Sh. Imani

    2018-01-01

    In the 3D laser forming process, developing an appropriate laser scan pattern for producing specimens with high quality and uniformity is critical. This study presents certain principles for developing scan paths. Seven scan path parameters are considered, including: (1) combined linear or curved path; (2) type of combined linear path; (3) order of scan sequences; (4) the position of the start point in each scan; (5) continuous or discontinuous scan path; (6) direction of scan path; and (7) angular arrangement of combined linear scan paths. Regarding these path parameters, ten combined linear scan patterns are presented. Numerical simulations show continuous hexagonal, scan pattern, scanning from outer to inner path, is the optimized. In addition, it is observed the position of the start point and the angular arrangement of scan paths is the most effective path parameters. Also, further experimentations show four sequences due to creat symmetric condition enhance the height of the bowl-shaped products and uniformity. Finally, the optimized hexagonal pattern was compared with the similar circular one. In the hexagonal scan path, distortion value and standard deviation rather to edge height of formed specimen is very low, and the edge height despite of decreasing length of scan path increases significantly compared to the circular scan path. As a result, four-sequence hexagonal scan pattern is proposed as the optimized perimeter scan path to produce bowl-shaped product.

  20. A Novel Scan Architecture for Low Power Scan-Based Testing

    Directory of Open Access Journals (Sweden)

    Mahshid Mojtabavi Naeini

    2015-01-01

    Full Text Available Test power has been turned to a bottleneck for test considerations as the excessive power dissipation has serious negative effects on chip reliability. In scan-based designs, rippling transitions caused by test patterns shifting along the scan chain not only elevate power consumption but also introduce spurious switching activities in the combinational logic. In this paper, we propose a novel area-efficient gating scan architecture that offers an integrated solution for reducing total average power in both scan cells and combinational part during shift mode. In the proposed gating scan structure, conventional master/slave scan flip-flop has been modified into a new gating scan cell augmented with state preserving and gating logic that enables average power reduction in combinational logic during shift mode. The new gating scan cells also mitigate the number of transitions during shift and capture cycles. Thus, it contributes to average power reduction inside the scan cell during scan shifting with low impact on peak power during capture cycle. Simulation results have shown that the proposed gating scan cell saves 28.17% total average power compared to conventional scan cell that has no gating logic and up to 44.79% compared to one of the most common existing gating architectures.

  1. Application of combined SMRT and long-read pyrosequencing to produce reference genome sequences of bacteria associated with respiratory disease outbreaks in beef cattle

    Science.gov (United States)

    The effectiveness of comparing complete genomes for elucidating mechanisms of virulence in pathogenic organisms has been demonstrated recently in foodborne and waterborne human disease outbreaks. We built upon this concept to investigate virulence mechanisms in bovine respiratory disease complex (B...

  2. Evaluation of Pore Networks in Caprocks at Geologic Storage Sites: A Combined Study using High Temperature and Pressure Reaction Experiments, Small Angle Neutron Scattering, and Focused Ion Beam-Scanning Electron Microscopy

    Science.gov (United States)

    Mouzakis, K. M.; Sitchler, A.; Wang, X.; McCray, J. E.; Kaszuba, J. P.; Rother, G.; Dewers, T. A.; Heath, J. E.

    2011-12-01

    Low permeability rock units, often shales or mudstones, that overlie geologic formations under consideration for CO2 sequestration will help contain injected CO2. CO2 that does flow through these rocks will dissolve into the porewaters, creating carbonic acid lowering the pH. This perturbation of the system may result in mineral dissolution or precipitation, which can change the pore structure and impact the flow properties of the caprocks. In order to investigate the impacts that reaction can have on caprock pore structure, we performed a combination of high pressure high temperature reaction experiments, small angle neutron scattering (SANS) experiments and high resolution focused ion beam-scanning electron microscope (FIB-SEM) imaging on samples from the Gothic shale and Marine Tuscaloosa Group. Small angle neutron scattering was performed on unreacted and reacted caprocks at the High Flux Isotope Reactor at Oak Ridge National Laboratory. New precipitates and pores are observed in high-resolution images of the reacted samples. The precipitates have been preliminarily identified as gypsum or anhydrite, and sulfide minerals. Results from small angle neutron scattering, a technique that provides information about pores and pore/mineral interfaces at scales ~ 5 to 300 nm, show an increased porosity and specific surface area after reaction with brine and CO2. However, there appear to be differences in how the pore networks change between the two samples that are related to sample mineralogy and original pore network structure. Changes to pores and formation of new pores may lead to different capillary sealing behavior and permeability. This combination of controlled laboratory experiments, neutron scattering and high-resolution imaging provides detailed information about the geochemical processes that occur at the pore scale as CO2 reacts with rocks underground. Such information is integral to the evaluation of large-scale CO2 sequestration as a feasible technology

  3. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... concern for you. If you had an intravenous line inserted for the procedure, it will usually be ... procedure that same day that requires an intravenous line. Actual scanning time for a thyroid scan is ...

  4. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... the limitations of the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid ... body converts food to energy. top of page What are some common uses of the procedure? The ...

  5. RBC nuclear scan

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003835.htm RBC nuclear scan To use the sharing features on this page, please enable JavaScript. An RBC nuclear scan uses small amounts of radioactive material to ...

  6. Hyperchromatic laser scanning cytometry

    Science.gov (United States)

    Tárnok, Attila; Mittag, Anja

    2007-02-01

    In the emerging fields of high-content and high-throughput single cell analysis for Systems Biology and Cytomics multi- and polychromatic analysis of biological specimens has become increasingly important. Combining different technologies and staining methods polychromatic analysis (i.e. using 8 or more fluorescent colors at a time) can be pushed forward to measure anything stainable in a cell, an approach termed hyperchromatic cytometry. For cytometric cell analysis microscope based Slide Based Cytometry (SBC) technologies are ideal as, unlike flow cytometry, they are non-consumptive, i.e. the analyzed sample is fixed on the slide. Based on the feature of relocation identical cells can be subsequently reanalyzed. In this manner data on the single cell level after manipulation steps can be collected. In this overview various components for hyperchromatic cytometry are demonstrated for a SBC instrument, the Laser Scanning Cytometer (Compucyte Corp., Cambridge, MA): 1) polychromatic cytometry, 2) iterative restaining (using the same fluorochrome for restaining and subsequent reanalysis), 3) differential photobleaching (differentiating fluorochromes by their different photostability), 4) photoactivation (activating fluorescent nanoparticles or photocaged dyes), and 5) photodestruction (destruction of FRET dyes). With the intelligent combination of several of these techniques hyperchromatic cytometry allows to quantify and analyze virtually all components of relevance on the identical cell. The combination of high-throughput and high-content SBC analysis with high-resolution confocal imaging allows clear verification of phenotypically distinct subpopulations of cells with structural information. The information gained per specimen is only limited by the number of available antibodies and by sterical hindrance.

  7. Genome-tools: a flexible package for genome sequence analysis.

    Science.gov (United States)

    Lee, William; Chen, Swaine L

    2002-12-01

    Genome-tools is a Perl module, a set of programs, and a user interface that facilitates access to genome sequence information. The package is flexible, extensible, and designed to be accessible and useful to both nonprogrammers and programmers. Any relatively well-annotated genome available with standard GenBank genome files may be used with genome-tools. A simple Web-based front end permits searching any available genome with an intuitive interface. Flexible design choices also make it simple to handle revised versions of genome annotation files as they change. In addition, programmers can develop cross-genomic tools and analyses with minimal additional overhead by combining genome-tools modules with newly written modules. Genome-tools runs on any computer platform for which Perl is available, including Unix, Microsoft Windows, and Mac OS. By simplifying the access to large amounts of genomic data, genome-tools may be especially useful for molecular biologists looking at newly sequenced genomes, for which few informatics tools are available. The genome-tools Web interface is accessible at http://genome-tools.sourceforge.net, and the source code is available at http://sourceforge.net/projects/genome-tools.

  8. A fluorescence scanning electron microscope

    OpenAIRE

    Kanemaru, Takaaki; Hirata, Kazuho; Takasu, Shin-ichi; Isobe, Shin-Ichiro; Mizuki, Keiji; Mataka, Shuntaro; Nakamura, Kei-ichiro

    2010-01-01

    Fluorescence techniques are widely used in biological research to examine molecular localization, while electron microscopy can provide unique ultrastructural information. To date, correlative images from both fluorescence and electron microscopy have been obtained separately using two different instruments, i.e. a fluorescence microscope (FM) and an electron microscope (EM). In the current study, a scanning electron microscope (SEM) (JEOL JXA8600 M) was combined with a fluorescence digital c...

  9. Combined array-comparative genomic hybridization and single-nucleotide polymorphism-loss of heterozygosity analysis reveals complex changes and multiple forms of chromosomal instability in colorectal cancers

    DEFF Research Database (Denmark)

    Gaasenbeek, Michelle; Howarth, Kimberley; Rowan, Andrew J

    2006-01-01

    Cancers with chromosomal instability (CIN) are held to be aneuploid/polyploid with multiple large-scale gains/deletions, but the processes underlying CIN are unclear and different types of CIN might exist. We investigated colorectal cancer cell lines using array-comparative genomic hybridization ...

  10. Automated genome mining for natural products

    Directory of Open Access Journals (Sweden)

    Zajkowski James

    2009-06-01

    Full Text Available Abstract Background Discovery of new medicinal agents from natural sources has largely been an adventitious process based on screening of plant and microbial extracts combined with bioassay-guided identification and natural product structure elucidation. Increasingly rapid and more cost-effective genome sequencing technologies coupled with advanced computational power have converged to transform this trend toward a more rational and predictive pursuit. Results We have developed a rapid method of scanning genome sequences for multiple polyketide, nonribosomal peptide, and mixed combination natural products with output in a text format that can be readily converted to two and three dimensional structures using conventional software. Our open-source and web-based program can assemble various small molecules composed of twenty standard amino acids and twenty two other chain-elongation intermediates used in nonribosomal peptide systems, and four acyl-CoA extender units incorporated into polyketides by reading a hidden Markov model of DNA. This process evaluates and selects the substrate specificities along the assembly line of nonribosomal synthetases and modular polyketide synthases. Conclusion Using this approach we have predicted the structures of natural products from a diverse range of bacteria based on a limited number of signature sequences. In accelerating direct DNA to metabolomic analysis, this method bridges the interface between chemists and biologists and enables rapid scanning for compounds with potential therapeutic value.

  11. Genomic Testing

    Science.gov (United States)

    ... Counseling Genomic Testing Pathogen Genomics Epidemiology Resources Genomic Testing Recommend on Facebook Tweet Share Compartir Fact Sheet: ... Page The Need for Reliable Information on Genetic Testing In 2008, the former Secretary’s Advisory Committee on ...

  12. C-reactive protein levels in combination with abdominal CT scans is a useful tool to predict the macroscopic appearance in late-stage EPS patients prior to surgery.

    Science.gov (United States)

    Kitterer, Daniel; Segerer, Stephan; Steurer, Wolfgang; Dippon, Juergen; Geissler, Angela; Ulmer, Christoph; Braun, Niko; Alscher, Mark Dominik; Latus, Joerg

    2015-01-01

    Diagnosis of encapsulating peritoneal sclerosis (EPS) is based on clinical symptoms, radiologic findings, and macroscopic or histological criteria. Two diagnostic scores for radiologic findings in computed tomography (CT) scans of patients with EPS have been established in the past (by Tarzi et al and Vlijm et al). The macroscopic appearance of EPS has previously been separated into three types. The use of CT scan as a tool to predict different macroscopic phenotypes, leading to specific surgical techniques and different medical treatment, has not yet been investigated. We retrospectively analyzed 30 patients with late-stage EPS who underwent major surgery with peritonectomy and enterolysis. The preoperative CT scans were scored according to the two aforementioned established diagnostic CT scores. The macroscopic phenotype, surgical procedure, and laboratory values at the time of surgery were evaluated. CT findings in the different macroscopic phenotypes were analyzed. All patients had highly predictive CT scores for EPS. The macroscopic Type III had significantly higher CT scores compared with the other macroscopic phenotypes. Patients with macroscopic Type I had significantly higher C-reactive protein values compared to EPS Type III. Operation time was significantly longer, and repeated surgery and intraoperative complications were more frequent in EPS Type I compared with EPS Type III (PEPS I and III were 78% and 87% with corresponding specificities of 67% and 93%. Abdominal CT scans might help to identify patients with a higher risk of complications and provide important information for the surgical intervention prior to surgery.

  13. Protein identification from two-dimensional gel electrophoresis analysis of Klebsiella pneumoniae by combined use of mass spectrometry data and raw genome sequences

    Directory of Open Access Journals (Sweden)

    Zeng An-Ping

    2003-12-01

    Full Text Available Abstract Separation of proteins by two-dimensional gel electrophoresis (2-DE coupled with identification of proteins through peptide mass fingerprinting (PMF by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS is the widely used technique for proteomic analysis. This approach relies, however, on the presence of the proteins studied in public-accessible protein databases or the availability of annotated genome sequences of an organism. In this work, we investigated the reliability of using raw genome sequences for identifying proteins by PMF without the need of additional information such as amino acid sequences. The method is demonstrated for proteomic analysis of Klebsiella pneumoniae grown anaerobically on glycerol. For 197 spots excised from 2-DE gels and submitted for mass spectrometric analysis 164 spots were clearly identified as 122 individual proteins. 95% of the 164 spots can be successfully identified merely by using peptide mass fingerprints and a strain-specific protein database (ProtKpn constructed from the raw genome sequences of K. pneumoniae. Cross-species protein searching in the public databases mainly resulted in the identification of 57% of the 66 high expressed protein spots in comparison to 97% by using the ProtKpn database. 10 dha regulon related proteins that are essential for the initial enzymatic steps of anaerobic glycerol metabolism were successfully identified using the ProtKpn database, whereas none of them could be identified by cross-species searching. In conclusion, the use of strain-specific protein database constructed from raw genome sequences makes it possible to reliably identify most of the proteins from 2-DE analysis simply through peptide mass fingerprinting.

  14. Identification of a novel risk locus for multiple sclerosis at 13q31.3 by a pooled genome-wide scan of 500,000 single nucleotide polymorphisms.

    Directory of Open Access Journals (Sweden)

    Manuel Comabella

    Full Text Available Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system with an important genetic component and strongest association driven by the HLA genes. We performed a pooling-based genome-wide association study of 500,000 SNPs in order to find new loci associated with the disease. After applying several criteria, 320 SNPs were selected from the microarrays and individually genotyped in a first and independent Spanish Caucasian replication cohort. The 8 most significant SNPs validated in this cohort were also genotyped in a second US Caucasian replication cohort for confirmation. The most significant association was obtained for SNP rs3129934, which neighbors the HLA-DRB/DQA loci and validates our pooling-based strategy. The second strongest association signal was found for SNP rs1327328, which resides in an unannotated region of chromosome 13 but is in linkage disequilibrium with nearby functional elements that may play important roles in disease susceptibility. This region of chromosome 13 has not been previously identified in MS linkage genome screens and represents a novel risk locus for the disease.

  15. Scanning a DNA molecule for bound proteins using hybrid magnetic and optical tweezers.

    Directory of Open Access Journals (Sweden)

    Marijn T J van Loenhout

    Full Text Available The functional state of the genome is determined by its interactions with proteins that bind, modify, and move along the DNA. To determine the positions and binding strength of proteins localized on DNA we have developed a combined magnetic and optical tweezers apparatus that allows for both sensitive and label-free detection. A DNA loop, that acts as a scanning probe, is created by looping an optically trapped DNA tether around a DNA molecule that is held with magnetic tweezers. Upon scanning the loop along the λ-DNA molecule, EcoRI proteins were detected with ~17 nm spatial resolution. An offset of 33 ± 5 nm for the detected protein positions was found between back and forwards scans, corresponding to the size of the DNA loop and in agreement with theoretical estimates. At higher applied stretching forces, the scanning loop was able to remove bound proteins from the DNA, showing that the method is in principle also capable of measuring the binding strength of proteins to DNA with a force resolution of 0.1 pN/[Formula: see text]. The use of magnetic tweezers in this assay allows the facile preparation of many single-molecule tethers, which can be scanned one after the other, while it also allows for direct control of the supercoiling state of the DNA molecule, making it uniquely suitable to address the effects of torque on protein-DNA interactions.

  16. Scanning laser Doppler vibrometry

    DEFF Research Database (Denmark)

    Brøns, Marie; Thomsen, Jon Juel

    With a Scanning Laser Doppler Vibrometer (SLDV) a vibrating surface is automatically scanned over predefined grid points, and data processed for displaying vibration properties like mode shapes, natural frequencies, damping ratios, and operational deflection shapes. Our SLDV – a PSV-500H from...

  17. Frequency scanning microstrip antennas

    DEFF Research Database (Denmark)

    Danielsen, Magnus; Jørgensen, Rolf

    1979-01-01

    The principles of using radiating microstrip resonators as elements in a frequency scanning antenna array are described. The resonators are cascade-coupled. This gives a scan of the main lobe due to the phase-shift in the resonator in addition to that created by the transmission line phase...

  18. A physical map of the chicken genome

    NARCIS (Netherlands)

    Wallis, J.; Aerts, J.A.; Groenen, M.A.M.; Crooijmans, R.P.M.A.; Layman, D.; Graves, T.; Scheer, D.; Kremitzki, C.; Fedele, M.; Mudd, N.

    2004-01-01

    Strategies for assembling large, complex genomes have evolved to include a combination of whole-genome shotgun sequencing and hierarchal map-assisted sequencing1, 2. Whole-genome maps of all types can aid genome assemblies, generally starting with low-resolution cytogenetic maps and ending with the

  19. Rapid Introgression of the Fusarium Wilt Resistance Gene into an Elite Cabbage Line through the Combined Application of a Microspore Culture, Genome Background Analysis, and Disease Resistance-Specific Marker Assisted Foreground Selection.

    Science.gov (United States)

    Liu, Xing; Han, Fengqing; Kong, Congcong; Fang, Zhiyuan; Yang, Limei; Zhang, Yangyong; Zhuang, Mu; Liu, Yumei; Li, Zhansheng; Lv, Honghao

    2017-01-01

    Cabbage is an economically important vegetable worldwide. Cabbage Fusarium Wilt (CFW) is a destructive disease that results in considerable yield and quality losses in cole crops. The use of CFW-resistant varieties is the most effective strategy to mitigate the effects of CFW. 01-20 is an elite cabbage line with desirable traits and a high combining ability, but it is highly susceptible to CFW. To rapidly transfer a CFW resistance gene into 01-20 plants, we used microspore cultures to develop 230 doubled haploid (DH) lines from a cross between 01-20 (highly susceptible) and 96-100 (highly resistant). One of the generated DH lines (i.e., D134) was highly resistant to CFW and exhibited a phenotypic performance that was similar to that of line 01-20. Therefore, D134 was applied as the resistance donor parent. We generated 24 insertion-deletion markers using whole genome resequencing data for lines 01-20 and 96-100 to analyze the genomic backgrounds of backcross (BC) progenies. Based on the CFW resistance gene FOC1, a simple sequence repeat (SSR) marker (i.e., Frg13) was developed for foreground selections. We screened 240 BC1 individuals and 280 BC2 individuals with these markers and assessed their phenotypic performance. The proportion of recurrent parent genome (PRPG) of the best individuals in BC1 and BC2 were 95.8 and 99.1%. Finally, a best individual designated as YR01-20 was identified from 80 BC2F1 individuals, with homozygous FOC1 allele and genomic background and phenotype almost the same as those of 01-20. Our results may provide a rapid and efficient way of improving elite lines through the combined application of microspore culture, whole-genome background analysis, and disease resistance-specific marker selection. Additionally, the cabbage lines developed in this study represent elite materials useful for the breeding of new CFW-resistant cabbage varieties.

  20. Combined bilateral idiopathic necrosis of the humerus and femur heads: Bone scan, X-ray, CT, and MRI findings. Kombinierte beidseitige idiopathische Nekrose der Humerus- und Femurkoepfe: Skelettszintigraphie, Roentgen-, CT- und MRT-Befunde

    Energy Technology Data Exchange (ETDEWEB)

    Piepenburg, R.; Hahn, K. (Mainz Univ. (Germany). Klinik fuer Nuklearmedizin); Doll, G. (Mainz Univ. (Germany). Klinik fuer Roentgendiagnostik); Grimm, J. (Mainz Univ. (Germany). Orthopaedische Klinik)

    1992-12-01

    Untreated aseptic bone necroses close to a joint commonly leads to severe secondary arthrosis and destruction of the joint within a short time. Therefore, only a diagnosis in an early stage of the disease offers the chance of a successful joint- preserving therapy. In cases of clinically suspected aseptic bone necrosis but still negative or doubtful X-ray findings, bone scans or MRI are reliable methods of verifying the diagnosis. (orig./MG).

  1. Fungal Genomics Program

    Energy Technology Data Exchange (ETDEWEB)

    Grigoriev, Igor

    2012-03-12

    The JGI Fungal Genomics Program aims to scale up sequencing and analysis of fungal genomes to explore the diversity of fungi important for energy and the environment, and to promote functional studies on a system level. Combining new sequencing technologies and comparative genomics tools, JGI is now leading the world in fungal genome sequencing and analysis. Over 120 sequenced fungal genomes with analytical tools are available via MycoCosm (www.jgi.doe.gov/fungi), a web-portal for fungal biologists. Our model of interacting with user communities, unique among other sequencing centers, helps organize these communities, improves genome annotation and analysis work, and facilitates new larger-scale genomic projects. This resulted in 20 high-profile papers published in 2011 alone and contributing to the Genomics Encyclopedia of Fungi, which targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts). Our next grand challenges include larger scale exploration of fungal diversity (1000 fungal genomes), developing molecular tools for DOE-relevant model organisms, and analysis of complex systems and metagenomes.

  2. The genome of a Bacillus isolate causing anthrax in chimpanzees combines chromosomal properties of B. cereus with B. anthracis virulence plasmids.

    Directory of Open Access Journals (Sweden)

    Silke R Klee

    Full Text Available Anthrax is a fatal disease caused by strains of Bacillus anthracis. Members of this monophyletic species are non motile and are all characterized by the presence of four prophages and a nonsense mutation in the plcR regulator gene. Here we report the complete genome sequence of a Bacillus strain isolated from a chimpanzee that had died with clinical symptoms of anthrax. Unlike classic B. anthracis, this strain was motile and lacked the four prohages and the nonsense mutation. Four replicons were identified, a chromosome and three plasmids. Comparative genome analysis revealed that the chromosome resembles those of non-B. anthracis members of the Bacillus cereus group, whereas two plasmids were identical to the anthrax virulence plasmids pXO1 and pXO2. The function of the newly discovered third plasmid with a length of 14 kbp is unknown. A detailed comparison of genomic loci encoding key features confirmed a higher similarity to B. thuringiensis serovar konkukian strain 97-27 and B. cereus E33L than to B. anthracis strains. For the first time we describe the sequence of an anthrax causing bacterium possessing both anthrax plasmids that apparently does not belong to the monophyletic group of all so far known B. anthracis strains and that differs in important diagnostic features. The data suggest that this bacterium has evolved from a B. cereus strain independently from the classic B. anthracis strains and established a B. anthracis lifestyle. Therefore we suggest to designate this isolate as "B. cereus variety (var. anthracis".

  3. The Genome of a Bacillus Isolate Causing Anthrax in Chimpanzees Combines Chromosomal Properties of B. cereus with B. anthracis Virulence Plasmids

    Science.gov (United States)

    Nattermann, Herbert; Brüggemann, Holger; Dupke, Susann; Wollherr, Antje; Franz, Tatjana; Pauli, Georg; Appel, Bernd; Liebl, Wolfgang; Couacy-Hymann, Emmanuel; Boesch, Christophe; Meyer, Frauke-Dorothee; Leendertz, Fabian H.; Ellerbrok, Heinz; Gottschalk, Gerhard; Grunow, Roland; Liesegang, Heiko

    2010-01-01

    Anthrax is a fatal disease caused by strains of Bacillus anthracis. Members of this monophyletic species are non motile and are all characterized by the presence of four prophages and a nonsense mutation in the plcR regulator gene. Here we report the complete genome sequence of a Bacillus strain isolated from a chimpanzee that had died with clinical symptoms of anthrax. Unlike classic B. anthracis, this strain was motile and lacked the four prohages and the nonsense mutation. Four replicons were identified, a chromosome and three plasmids. Comparative genome analysis revealed that the chromosome resembles those of non-B. anthracis members of the Bacillus cereus group, whereas two plasmids were identical to the anthrax virulence plasmids pXO1 and pXO2. The function of the newly discovered third plasmid with a length of 14 kbp is unknown. A detailed comparison of genomic loci encoding key features confirmed a higher similarity to B. thuringiensis serovar konkukian strain 97-27 and B. cereus E33L than to B. anthracis strains. For the first time we describe the sequence of an anthrax causing bacterium possessing both anthrax plasmids that apparently does not belong to the monophyletic group of all so far known B. anthracis strains and that differs in important diagnostic features. The data suggest that this bacterium has evolved from a B. cereus strain independently from the classic B. anthracis strains and established a B. anthracis lifestyle. Therefore we suggest to designate this isolate as “B. cereus variety (var.) anthracis”. PMID:20634886

  4. MutScan: fast detection and visualization of target mutations by scanning FASTQ data.

    Science.gov (United States)

    Chen, Shifu; Huang, Tanxiao; Wen, Tiexiang; Li, Hong; Xu, Mingyan; Gu, Jia

    2018-01-22

    Some types of clinical genetic tests, such as cancer testing using circulating tumor DNA (ctDNA), require sensitive detection of known target mutations. However, conventional next-generation sequencing (NGS) data analysis pipelines typically involve different steps of filtering, which may cause miss-detection of key mutations with low frequencies. Variant validation is also indicated for key mutations detected by bioinformatics pipelines. Typically, this process can be executed using alignment visualization tools such as IGV or GenomeBrowse. However, these tools are too heavy and therefore unsuitable for validating mutations in ultra-deep sequencing data. We developed MutScan to address problems of sensitive detection and efficient validation for target mutations. MutScan involves highly optimized string-searching algorithms, which can scan input FASTQ files to grab all reads that support target mutations. The collected supporting reads for each target mutation will be piled up and visualized using web technologies such as HTML and JavaScript. Algorithms such as rolling hash and bloom filter are applied to accelerate scanning and make MutScan applicable to detect or visualize target mutations in a very fast way. MutScan is a tool for the detection and visualization of target mutations by only scanning FASTQ raw data directly. Compared to conventional pipelines, this offers a very high performance, executing about 20 times faster, and offering maximal sensitivity since it can grab mutations with even one single supporting read. MutScan visualizes detected mutations by generating interactive pile-ups using web technologies. These can serve to validate target mutations, thus avoiding false positives. Furthermore, MutScan can visualize all mutation records in a VCF file to HTML pages for cloud-friendly VCF validation. MutScan is an open source tool available at GitHub: https://github.com/OpenGene/MutScan.

  5. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... energy. top of page What are some common uses of the procedure? The thyroid scan is used ... gland evaluate changes in the gland following medication use, surgery, radiotherapy or chemotherapy top of page How ...

  6. Thyroid Scan and Uptake

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    Full Text Available ... nuclear medicine procedures are able to pinpoint molecular activity within the body, they offer the potential to ... tells you otherwise, you may resume your normal activities after your nuclear medicine scan. If any special ...

  7. Body CT (CAT Scan)

    Science.gov (United States)

    ... Professions Site Index A-Z Computed Tomography (CT) - Body Computed tomography (CT) of the body uses special ... the Body? What is CT Scanning of the Body? Computed tomography, more commonly known as a CT ...

  8. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... scan and uptake uses small amounts of radioactive materials called radiotracers, a special camera and a computer ... last two months that used iodine-based contrast material. Your doctor will instruct you on how to ...

  9. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... evaluate changes in the gland following medication use, surgery, radiotherapy or chemotherapy top of page How should ... such as an x-ray or CT scan, surgeries or treatments using iodinated contrast material within the ...

  10. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... imaging procedures. For many diseases, nuclear medicine scans yield the most useful information needed to make a ... any. Nuclear medicine is less expensive and may yield more precise information than exploratory surgery. Risks Because ...

  11. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... Actual scanning time for each thyroid uptake is five minutes or less. top of page What will ... diagnostic procedures have been used for more than five decades, and there are no known long-term ...

  12. Thyroid Scan and Uptake

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    Full Text Available ... A thyroid scan is a type of nuclear medicine imaging. The radioactive iodine uptake test (RAIU) is ... thyroid function, but does not involve imaging. Nuclear medicine is a branch of medical imaging that uses ...

  13. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... several hours before your exam because eating can affect the accuracy of the uptake measurement. Jewelry and ... often unattainable using other imaging procedures. For many diseases, nuclear medicine scans yield the most useful information ...

  14. Thyroid Scan and Uptake

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    Full Text Available ... iodine, medications and anesthetics. are breastfeeding. In the days prior to your examination, blood tests may be ... are scheduled for an additional procedure that same day that requires an intravenous line. Actual scanning time ...

  15. Thyroid Scan and Uptake

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    Full Text Available ... gland in the neck that controls metabolism , a chemical process that regulates the rate at which the body converts food to energy. top of page What are some common uses of the procedure? The thyroid scan is ...

  16. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... liquid or capsule form, it is typically swallowed up to 24 hours before the scan. The radiotracer given by intravenous injection is usually given up to 30 minutes prior to the test. When ...

  17. Thyroid Scan and Uptake

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    Full Text Available ... regulates the rate at which the body converts food to energy. top of page What are some ... often unattainable using other imaging procedures. For many diseases, nuclear medicine scans yield the most useful information ...

  18. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... Because nuclear medicine procedures are able to pinpoint molecular activity within the body, they offer the potential ... or imaging device that produces pictures and provides molecular information. The thyroid scan and thyroid uptake provide ...

  19. Thyroid Scan and Uptake

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    Full Text Available ... body. top of page How does the procedure work? With ordinary x-ray examinations, an image is ... with other imaging techniques, such as CT or MRI. However, nuclear medicine scans are more sensitive than ...

  20. Thyroid Scan and Uptake

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    Full Text Available ... a special camera or imaging device that produces pictures and provides molecular information. The thyroid scan and ... and with the help of a computer, create pictures offering details on both the structure and function ...

  1. Pediatric CT Scans

    Science.gov (United States)

    The Radiation Epidemiology Branch and collaborators have initiated a retrospective cohort study to evaluate the relationship between radiation exposure from CT scans conducted during childhood and adolescence and the subsequent development of cancer.

  2. Thyroid Scan and Uptake

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    Full Text Available ... abnormal was found, and should not be a cause of concern for you. If you had an ... abnormal was found, and should not be a cause of concern for you. Actual scanning time for ...

  3. Scanning Auger Electron Microscope

    Data.gov (United States)

    Federal Laboratory Consortium — A JEOL model 7830F field emission source, scanning Auger microscope.Specifications / Capabilities:Ultra-high vacuum (UHV), electron gun range from 0.1 kV to 25 kV,...

  4. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... scan and thyroid uptake provide information about the structure and function of the thyroid. The thyroid is ... computer, create pictures offering details on both the structure and function of organs and tissues in your ...

  5. The Scanning Optical Microscope.

    Science.gov (United States)

    Sheppard, C. J. R.

    1978-01-01

    Describes the principle of the scanning optical microscope and explains its advantages over the conventional microscope in the improvement of resolution and contrast, as well as the possibility of producing a picture from optical harmonies generated within the specimen.

  6. Thyroid Scan and Uptake

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    Full Text Available ... scan you are undergoing. top of page What does the equipment look like? The special camera and ... area of your body. top of page How does the procedure work? With ordinary x-ray examinations, ...

  7. Thyroid Scan and Uptake

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    Full Text Available ... eat for several hours before your exam because eating can affect the accuracy of the uptake measurement. ... often unattainable using other imaging procedures. For many diseases, nuclear medicine scans yield the most useful information ...

  8. Thyroid Scan and Uptake

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    Full Text Available ... found, and should not be a cause of concern for you. If you had an intravenous line ... found, and should not be a cause of concern for you. Actual scanning time for each thyroid ...

  9. Slow Scan Telemedicine

    Science.gov (United States)

    1984-01-01

    Originally developed under contract for NASA by Ball Bros. Research Corporation for acquiring visual information from lunar and planetary spacecraft, system uses standard closed circuit camera connected to a device called a scan converter, which slows the stream of images to match an audio circuit, such as a telephone line. Transmitted to its destination, the image is reconverted by another scan converter and displayed on a monitor. In addition to assist scans, technique allows transmission of x-rays, nuclear scans, ultrasonic imagery, thermograms, electrocardiograms or live views of patient. Also allows conferencing and consultation among medical centers, general practitioners, specialists and disease control centers. Commercialized by Colorado Video, Inc., major employment is in business and industry for teleconferencing, cable TV news, transmission of scientific/engineering data, security, information retrieval, insurance claim adjustment, instructional programs, and remote viewing of advertising layouts, real estate, construction sites or products.

  10. Thyroid Scan and Uptake

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    Full Text Available ... of page What are some common uses of the procedure? The thyroid scan is used to determine ... you are undergoing. top of page What does the equipment look like? The special camera and imaging ...

  11. Thyroid Scan and Uptake

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    Full Text Available ... to identify disease in its earliest stages as well as a patient’s immediate response to therapeutic interventions. ... but is often performed on hospitalized patients as well. Thyroid Scan You will be positioned on an ...

  12. Thyroid Scan and Uptake

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    Full Text Available ... Uptake? A thyroid scan is a type of nuclear medicine imaging. The radioactive iodine uptake test (RAIU) ... of thyroid function, but does not involve imaging. Nuclear medicine is a branch of medical imaging that ...

  13. Thyroid Scan and Uptake

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    Full Text Available ... medical tests that help physicians diagnose and evaluate medical conditions. These imaging scans use radioactive materials called radiopharmaceuticals or radiotracers . Depending on the type of nuclear medicine exam, the radiotracer is either injected into the body, ...

  14. Thyroid Scan and Uptake

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    Full Text Available ... many types of cancers, heart disease, gastrointestinal, endocrine, neurological disorders and other abnormalities within the body. Because ... with other imaging techniques, such as CT or MRI. However, nuclear medicine scans are more sensitive than ...

  15. Thyroid Scan and Uptake

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    Full Text Available ... are noninvasive and, with the exception of intravenous injections, are usually painless medical tests that help physicians ... before the scan. The radiotracer given by intravenous injection is usually given up to 30 minutes prior ...

  16. Scanning ultrafast electron microscopy

    OpenAIRE

    Yang, Ding-Shyue; Mohammed, Omar F.; Zewail, Ahmed H.

    2010-01-01

    Progress has been made in the development of four-dimensional ultrafast electron microscopy, which enables space-time imaging of structural dynamics in the condensed phase. In ultrafast electron microscopy, the electrons are accelerated, typically to 200 keV, and the microscope operates in the transmission mode. Here, we report the development of scanning ultrafast electron microscopy using a field-emission-source configuration. Scanning of pulses is made in the single-electron mode, for whic...

  17. Scan image compression-encryption hardware system

    Science.gov (United States)

    Bourbakis, Nikolaos G.; Brause, R.; Alexopoulos, C.

    1995-04-01

    This paper deals with the hardware design of an image compression/encryption scheme called SCAN. The scheme is based on the principles and ideas reflected by the specification of the SCAN language. SCAN is a fractal based context-free language which accesses sequentially the data of a 2D array, by describing and generating a wide range (near (nxn)) of space filling curves (or SCAN patterns) from a short set of simple ones. The SCAN method uses the algorithmic description of each 2D image as SCAN patterns combinations for the compression and encryption of the image data. Note that each SCAN letter or word accesses the image data with a different order (or sequence), thus the application of a variety of SCAN words associated with the compression scheme will produce various compressed versions of the same image. The compressed versions are compared in memory size and the best of them with the smallest size in bits could be used for the image compression/encryption. Note that the encryption of the image data is a result of the great number of possible space filling curves which could be generated by SCAN. Since the software implementation of the SCAN compression/encryption scheme requires some time, the hardware design and implementation of the SCAN scheme is necessary in order to reduce the image compression/encryption time to the real-time one. The development of such an image compression encryption system will have a significant impact on the transmission and storage of images. It will be applicable in multimedia and transmission of images through communication lines.

  18. Special raster scanning for reduction of charging effects in scanning electron microscopy.

    Science.gov (United States)

    Suzuki, Kazuhiko; Oho, Eisaku

    2014-01-01

    A special raster scanning (SRS) method for reduction of charging effects is developed for the field of SEM. Both a conventional fast scan (horizontal direction) and an unusual scan (vertical direction) are adopted for acquiring raw data consisting of many sub-images. These data are converted to a proper SEM image using digital image processing techniques. About sharpness of the image and reduction of charging effects, the SRS is compared with the conventional fast scan (with frame-averaging) and the conventional slow scan. Experimental results show the effectiveness of SRS images. By a successful combination of the proposed scanning method and low accelerating voltage (LV)-SEMs, it is expected that higher-quality SEM images can be more easily acquired by the considerable reduction of charging effects, while maintaining the resolution. © 2013 Wiley Periodicals, Inc.

  19. Clinical evaluation of chest x-rays, gallium-67 scans and CT scans in sarcoidosis

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, S.; Maeda, T. (Kochi Medical School (Japan)); Itoh, K.; Yamamoto, Y.; Machida, K.

    1981-10-01

    A comparative study of the accuracy of chest X-rays, Gallium-67 scans and CT scans for mediastinal lymphadenopathy of pulmonary sarcoidosis was performed. The ability of each examination to detect the lymphadenopathy of following 5 lymph node groups was evaluated, such as paratracheal, aorto-pulmonic window, subcarinal and both hilar lymph nodes. The results on 5 patients indicated that in the detection of right paratracheal and subcarinal lymphadenopathy, Gallium scans and CT scans were more sensitive than chest x-rays. Chest x-rays and Gallium scans were superior than CT in detecting bilateral hilar lymphadenopathy. In the involvement of aorto-pulmonic window nodes, Gallium scans and chest x-rays were more informative than CT. Combination of these three examination is effective in the detection of the above described lymphadenopathy.

  20. Genome-wide linkage scans for type 2 diabetes mellitus in four ethnically diverse populations; significant evidence for linkage on chromosome 4q in African Americans: the Family Investigation of Nephropathy and Diabetes (FIND) Research Group

    Science.gov (United States)

    Malhotra, Alka; Igo, Robert P.; Thameem, Farook; Kao, W.H. Linda; Abboud, Hanna E.; Adler, Sharon G.; Arar, Nedal H.; Bowden, Donald W.; Duggirala, Ravindranath; Freedman, Barry I.; Goddard, Katrina A.B.; Ipp, Eli; Iyengar, Sudha K.; Kimmel, Paul L.; Knowler, William C.; Kohn, Orly; Leehey, David; Meoni, Lucy A.; Nelson, Robert G.; Nicholas, Susanne B.; Parekh, Rulan S.; Rich, Stephen S.; Chen, Yii-Der I.; Saad, Mohammed F.; Scavini, Marina; Schelling, Jeffrey R.; Sedor, John R.; Shah, Vallabh O.; Taylor, Kent D.; Thornley-Brown, Denyse; Zager, Philip G.; Horvath, Amanda; Hanson, Robert L.

    2009-01-01

    Background Previous studies have shown that, in addition to environmental influences, type 2 diabetes mellitus (T2DM) has a strong genetic component. The goal of the current study is to identify regions of linkage for T2DM in ethnically diverse populations. Methods Phenotypic and genotypic data were obtained from African American (AA; total number of individuals (N)=1004), American Indian (AI; N=883), European American (EA; N=537), and Mexican American (MA; N=1634) individuals from the Family Investigation of Nephropathy and Diabetes. Nonparametric linkage analysis, using an average of 4,404 SNPs, was performed in relative pairs affected with T2DM in each ethnic group. In addition, family-based tests were performed to detect association with T2DM. Results Statistically significant evidence for linkage was observed on chromosomes 4q21.1 (LOD=3.13; genome-wide p=0.04) in AA. In addition, a total of eleven regions showed suggestive evidence for linkage (estimated at LOD>1.71), with the highest LOD scores on chromosomes 12q21.31 (LOD=2.02) and 22q12.3 (LOD=2.38) in AA, 2p11.1 (LOD=2.23) in AI, 6p12.3 (LOD=2.77) in EA, and 13q21.1 (LOD=2.24) in MA. While no region overlapped across all ethnic groups, at least five loci showing LOD>1.71 have been identified in previously published studies. Conclusions The results from this study provide evidence for the presence of genes affecting T2DM on chromosomes 4q, 12q, and 22q in AA, 6p in EA, 2p in AI, and 13q in MA. The strong evidence for linkage on chromosome 4q in AA provides important information given the paucity of diabetes genetic studies in this population. PMID:19795399

  1. Genome-wide linkage scans for type 2 diabetes mellitus in four ethnically diverse populations-significant evidence for linkage on chromosome 4q in African Americans: the Family Investigation of Nephropathy and Diabetes Research Group.

    Science.gov (United States)

    Malhotra, Alka; Igo, Robert P; Thameem, Farook; Kao, W H Linda; Abboud, Hanna E; Adler, Sharon G; Arar, Nedal H; Bowden, Donald W; Duggirala, Ravindranath; Freedman, Barry I; Goddard, Katrina A B; Ipp, Eli; Iyengar, Sudha K; Kimmel, Paul L; Knowler, William C; Kohn, Orly; Leehey, David; Meoni, Lucy A; Nelson, Robert G; Nicholas, Susanne B; Parekh, Rulan S; Rich, Stephen S; Chen, Yii-Der I; Saad, Mohammed F; Scavini, Marina; Schelling, Jeffrey R; Sedor, John R; Shah, Vallabh O; Taylor, Kent D; Thornley-Brown, Denyse; Zager, Philip G; Horvath, Amanda; Hanson, Robert L

    2009-11-01

    Previous studies have shown that in addition to environmental influences, type 2 diabetes mellitus (T2DM) has a strong genetic component. The goal of the current study is to identify regions of linkage for T2DM in ethnically diverse populations. Phenotypic and genotypic data were obtained from African American (AA; total number of individuals [N] = 1004), American Indian (AI; N = 883), European American (EA; N = 537), and Mexican American (MA; N = 1634) individuals from the Family Investigation of Nephropathy and Diabetes. Non-parametric linkage analysis, using an average of 4404 SNPs, was performed in relative pairs affected with T2DM in each ethnic group. In addition, family-based tests were performed to detect association with T2DM. Statistically significant evidence for linkage was observed on chromosome 4q21.1 (LOD = 3.13; genome-wide p = 0.04) in AA. In addition, a total of 11 regions showed suggestive evidence for linkage (estimated at LOD > 1.71), with the highest LOD scores on chromosomes 12q21.31 (LOD = 2.02) and 22q12.3 (LOD = 2.38) in AA, 2p11.1 (LOD = 2.23) in AI, 6p12.3 (LOD = 2.77) in EA, and 13q21.1 (LOD = . 2.24) in MA. While no region overlapped across all ethnic groups, at least five loci showing LOD > 1.71 have been identified in previously published studies. The results from this study provide evidence for the presence of genes affecting T2DM on chromosomes 4q, 12q, and 22q in AA; 6p in EA; 2p in AI; and 13q in MA. The strong evidence for linkage on chromosome 4q in AA provides important information given the paucity of diabetes genetic studies in this population.

  2. Identification of chromosomal translocation hotspots via scan statistics.

    Science.gov (United States)

    Silva, Israel T; Rosales, Rafael A; Holanda, Adriano J; Nussenzweig, Michel C; Jankovic, Mila

    2014-09-15

    The detection of genomic regions unusually rich in a given pattern is an important undertaking in the analysis of next-generation sequencing data. Recent studies of chromosomal translocations in activated B lymphocytes have identified regions that are frequently translocated to c-myc oncogene. A quantitative method for the identification of translocation hotspots was crucial to this study. Here we improve this analysis by using a simple probabilistic model and the framework provided by scan statistics to define the number and location of translocation breakpoint hotspots. A key feature of our method is that it provides a global chromosome-wide nominal control level to clustering, as opposed to previous methods based on local criteria. While being motivated by a specific application, the detection of unusual clusters is a widespread problem in bioinformatics. We expect our method to be useful in the analysis of data from other experimental approaches such as of ChIP-seq and 4C-seq. The analysis of translocations from B lymphocytes with the method described here reveals the presence of longer hotspots when compared with those defined previously. Further, we show that the hotspot size changes substantially in the absence of DNA repair protein 53BP1. When 53BP1 deficiency is combined with overexpression of activation-induced cytidine deaminase, the hotspot length increases even further. These changes are not detected by previous methods that use local significance criteria for clustering. Our method is also able to identify several exclusive translocation hotspots located in genes of known tumor supressors. The detection of translocation hotspots is done with hot_scan, a program implemented in R and Perl. Source code and documentation are freely available for download at https://github.com/itojal/hot_scan. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Laser Scanning Fluorescence Microscope

    Science.gov (United States)

    Hansen, Eric W.; Zelten, J. Peter; Wiseman, Benjamin A.

    1988-06-01

    We report on the development of a laser scanning fluorescence microscope possessing several features which facilitate its application to biological and biophysical analyses in living cells. It is built around a standard inverted microscope stand, enabling the use of standard optics, micromanipulation apparatus, and conventional (including video) microscopy in conjunction with laser scanning. The beam is scanned across the specimen by a pair of galvanometer-mounted mirrors, driven by a programmable controller which can operate in three modes: full raster scan, region of interest, and random-access. A full 512x512 pixel image can be acquired in one second. In region of interest mode, several subareas of the field can be selected for more rapid or detailed analysis. For those cases where the time scale of the observed phenomenon precludes full-field imaging, or where a full-field image is unnecessary, the random access mode enables an arbitrary pattern of isolated points to be selected and rapidly sequenced through. Via a graphical user interface implemented on the system's host computer, a user will be able to take a scout image either with video or a full-field laser scan, select regions or points on the scout image with a mouse, and set up experimental parameters such as detector integration times with a window-style menu. The instrument is designed to be a flexible testbed for investigating new techniques, without compromising its utility as a tool for biological research.

  4. A combined functional and structural genomics approach identified an EST-SSR marker with complete linkage to the Ligon lintless-2 genetic locus in cotton (Gossypium hirsutum L.).

    Science.gov (United States)

    Hinchliffe, Doug J; Turley, Rickie B; Naoumkina, Marina; Kim, Hee Jin; Tang, Yuhong; Yeater, Kathleen M; Li, Ping; Fang, David D

    2011-09-09

    Cotton fiber length is an important quality attribute to the textile industry and longer fibers can be more efficiently spun into yarns to produce superior fabrics. There is typically a negative correlation between yield and fiber quality traits such as length. An understanding of the regulatory mechanisms controlling fiber length can potentially provide a valuable tool for cotton breeders to improve fiber length while maintaining high yields. The cotton (Gossypium hirsutum L.) fiber mutation Ligon lintless-2 is controlled by a single dominant gene (Li2) that results in significantly shorter fibers than a wild-type. In a near-isogenic state with a wild-type cotton line, Li2 is a model system with which to study fiber elongation. Two near-isogenic lines of Ligon lintless-2 (Li2) cotton, one mutant and one wild-type, were developed through five generations of backcrosses (BC5). An F2 population was developed from a cross between the two Li2 near-isogenic lines and used to develop a linkage map of the Li2 locus on chromosome 18. Five simple sequence repeat (SSR) markers were closely mapped around the Li2 locus region with two of the markers flanking the Li2 locus at 0.87 and 0.52 centimorgan. No apparent differences in fiber initiation and early fiber elongation were observed between the mutant ovules and the wild-type ones. Gene expression profiling using microarrays suggested roles of reactive oxygen species (ROS) homeostasis and cytokinin regulation in the Li2 mutant phenotype. Microarray gene expression data led to successful identification of an EST-SSR marker (NAU3991) that displayed complete linkage to the Li2 locus. In the field of cotton genomics, we report the first successful conversion of gene expression data into an SSR marker that is associated with a genomic region harboring a gene responsible for a fiber trait. The EST-derived SSR marker NAU3991 displayed complete linkage to the Li2 locus on chromosome 18 and resided in a gene with similarity to a

  5. Detection of an inversion in the Ty-2 region between S. lycopersicum and S. habrochaites by a combination of de novo genome assembly and BAC cloning.

    Science.gov (United States)

    Wolters, Anne-Marie A; Caro, Myluska; Dong, Shufang; Finkers, Richard; Gao, Jianchang; Visser, Richard G F; Wang, Xiaoxuan; Du, Yongchen; Bai, Yuling

    2015-10-01

    A chromosomal inversion associated with the tomato Ty - 2 gene for TYLCV resistance is the cause of severe suppression of recombination in a tomato Ty - 2 introgression line. Among tomato and its wild relatives inversions are often observed, which result in suppression of recombination. Such inversions hamper the transfer of important traits from a related species to the crop by introgression breeding. Suppression of recombination was reported for the TYLCV resistance gene, Ty-2, which has been introgressed in cultivated tomato (Solanum lycopersicum) from the wild relative S. habrochaites accession B6013. Ty-2 was mapped to a 300-kb region on the long arm of chromosome 11. The suppression of recombination in the Ty-2 region could be caused by chromosomal rearrangements in S. habrochaites compared with S. lycopersicum. With the aim of visualizing the genome structure of the Ty-2 region, we compared the draft de novo assembly of S. habrochaites accession LYC4 with the sequence of cultivated tomato ('Heinz'). Furthermore, using populations derived from intraspecific crosses of S. habrochaites accessions, the order of markers in the Ty-2 region was studied. Results showed the presence of an inversion of approximately 200 kb in the Ty-2 region when comparing S. lycopersicum and S. habrochaites. By sequencing a BAC clone from the Ty-2 introgression line, one inversion breakpoint was identified. Finally, the obtained results are discussed with respect to introgression breeding and the importance of a priori de novo sequencing of the species involved.

  6. Performance characteristics of the AmpliSeq Cancer Hotspot panel v2 in combination with the Ion Torrent Next Generation Sequencing Personal Genome Machine.

    Science.gov (United States)

    Butler, Kimberly S; Young, Megan Y L; Li, Zhihua; Elespuru, Rosalie K; Wood, Steven C

    2016-02-01

    Next-Generation Sequencing is a rapidly advancing technology that has research and clinical applications. For many cancers, it is important to know the precise mutation(s) present, as specific mutations could indicate or contra-indicate certain treatments as well as be indicative of prognosis. Using the Ion Torrent Personal Genome Machine and the AmpliSeq Cancer Hotspot panel v2, we sequenced two pancreatic cancer cell lines, BxPC-3 and HPAF-II, alone or in mixtures, to determine the error rate, sensitivity, and reproducibility of this system. The system resulted in coverage averaging 2000× across the various amplicons and was able to reliably and reproducibly identify mutations present at a rate of 5%. Identification of mutations present at a lower rate was possible by altering the parameters by which calls were made, but with an increase in erroneous, low-level calls. The panel was able to identify known mutations in these cell lines that are present in the COSMIC database. In addition, other, novel mutations were also identified that may prove clinically useful. The system was assessed for systematic errors such as homopolymer effects, end of amplicon effects and patterns in NO CALL sequence. Overall, the system is adequate at identifying the known, targeted mutations in the panel. Published by Elsevier Inc.

  7. Scanning laser video camera/ microscope

    Science.gov (United States)

    Wang, C. P.; Bow, R. T.

    1984-10-01

    A laser scanning system capable of scanning at standard video rate has been developed. The scanning mirrors, circuit design and system performance, as well as its applications to video cameras and ultra-violet microscopes, are discussed.

  8. Calibration of scanning Lidar

    DEFF Research Database (Denmark)

    Gómez Arranz, Paula; Courtney, Michael

    This report describes the tests carried out on a scanning lidar at the DTU Test Station for large wind turbines, Høvsøre. The tests were divided in two parts. In the first part, the purpose was to obtain wind speed calibrations at two heights against two cup anemometers mounted on a mast. Additio......This report describes the tests carried out on a scanning lidar at the DTU Test Station for large wind turbines, Høvsøre. The tests were divided in two parts. In the first part, the purpose was to obtain wind speed calibrations at two heights against two cup anemometers mounted on a mast...

  9. Tomographic scanning imager.

    Science.gov (United States)

    Hovland, Harald

    2009-07-06

    In tomographic scanning (TOSCA) imaging, light from a scene is focused onto a reticle mask using conical scan optics, and collected on a single element detector. Alternatively, one or several detectors replace the reticle. Tomographic processing techniques are then applied to the one-dimensional signal to reproduce a two-dimensional image. The TOSCA technique is presented in detail, including its mathematical foundations and some of its limitations. It is shown how TOSCA imaging can be used in a multispectral configuration, and compares well with more conventional alternatives both in simplicity and performance. Examples of image reconstruction using TOSCA techniques are shown.

  10. Scanning the phenomenological MSSM

    CERN Document Server

    Wuerzinger, Jonas

    2017-01-01

    A framework to perform scans in the 19-dimensional phenomenological MSSM is developed and used to re-evaluate the ATLAS experiments' sensitivity to R-parity-conserving supersymmetry with LHC Run 2 data ($\\sqrt{s}=13$ TeV), using results from 14 separate ATLAS searches. We perform a $\\tilde{t}_1$ dedicated scan, only considering models with $m_{\\tilde{t}_1}<1$ TeV, while allowing both a neutralino ($\\tilde{\\chi}_1^0$) and a sneutrino ($\\tilde{\

  11. Molecular and clinical analyses with neuropsychological assessment of a case of del(10)(q26.2qter) without intellectual disability: Genomic and transcriptomic combined approach and review of the literature.

    Science.gov (United States)

    Laudier, Béatrice; Epiais, Tiphanie; Pâris, Arnaud; Menuet, Arnaud; Briault, Sylvain; Ozsancak, Canan; Perche, Olivier

    2016-07-01

    Terminal deletion of the long arm of the chromosome 10 is a rare but well known abnormality, with a large phenotypic variability. Very few data are available about subtelomeric deletion 10q26 patients without intellectual disability. Herein, we report the case of a young adult with a classical 10q26.2qter deletion. She exhibited mainly short stature at birth and in childhood/adulthood without intellectual disability or behavioral problems. After clinical and neuropsychological assessments, we performed genomic array and transcriptomic analysis and compared our results to the data available in the literature. The patient presents a 6.525 Mb heterozygous 10q26.2qter deletion, encompassed 48 genes. Among those genes, DOCK1, C10orf90, and CALY previously described as potential candidate genes for intellectual disability, were partially or completed deleted. Interestingly, they were not deregulated as demonstrated by transcriptomic analysis. This allowed us to suggest that the mechanism involved in the deletion 10qter phenotype is much more complex that only the haploinsufficiency of DOCK1 or other genes encompassed in the deletion. Genomic and transcriptomic combined approach has to be considered to understand this pathogenesis. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. Comparative Genomics

    Indian Academy of Sciences (India)

    tory motifs and other non-coding DNA motifs, and genome flux and dynamics. Finally the article describes how the information one can extract from a comparative analysis of genomes depends to a large extent, on the specific aspect of the genomes that is being compared and the phylogenetic distances of the organisms ...

  13. Cancer genomics

    DEFF Research Database (Denmark)

    Norrild, Bodil; Guldberg, Per; Ralfkiær, Elisabeth Methner

    2007-01-01

    Almost all cells in the human body contain a complete copy of the genome with an estimated number of 25,000 genes. The sequences of these genes make up about three percent of the genome and comprise the inherited set of genetic information. The genome also contains information that determines whe...

  14. Genomic futures of prenatal screening : Ethical reflection

    NARCIS (Netherlands)

    Dondorp, W. J.; Page-Christiaens, G. C M L; de Wert, G. M W R

    2016-01-01

    The practice of prenatal screening is undergoing important changes as a result of the introduction of genomic testing technologies at different stages of the screening trajectory. It is expected that eventually it will become possible to routinely obtain a comprehensive 'genome scan' of all fetuses.

  15. Hymenoptera Genome Database: integrating genome annotations in HymenopteraMine.

    Science.gov (United States)

    Elsik, Christine G; Tayal, Aditi; Diesh, Colin M; Unni, Deepak R; Emery, Marianne L; Nguyen, Hung N; Hagen, Darren E

    2016-01-04

    We report an update of the Hymenoptera Genome Database (HGD) (http://HymenopteraGenome.org), a model organism database for insect species of the order Hymenoptera (ants, bees and wasps). HGD maintains genomic data for 9 bee species, 10 ant species and 1 wasp, including the versions of genome and annotation data sets published by the genome sequencing consortiums and those provided by NCBI. A new data-mining warehouse, HymenopteraMine, based on the InterMine data warehousing system, integrates the genome data with data from external sources and facilitates cross-species analyses based on orthology. New genome browsers and annotation tools based on JBrowse/WebApollo provide easy genome navigation, and viewing of high throughput sequence data sets and can be used for collaborative genome annotation. All of the genomes and annotation data sets are combined into a single BLAST server that allows users to select and combine sequence data sets to search. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  16. Combining the auxin-inducible degradation system with CRISPR/Cas9-based genome editing for the conditional depletion of endogenous Drosophila melanogaster proteins.

    Science.gov (United States)

    Bence, Melinda; Jankovics, Ferenc; Lukácsovich, Tamás; Erdélyi, Miklós

    2017-04-01

    Inducible protein degradation techniques have considerable advantages over classical genetic approaches, which generate loss-of-function phenotypes at the gene or mRNA level. The plant-derived auxin-inducible degradation system (AID) is a promising technique which enables the degradation of target proteins tagged with the AID motif in nonplant cells. Here, we present a detailed characterization of this method employed during the adult oogenesis of Drosophila. Furthermore, with the help of CRISPR/Cas9-based genome editing, we improve the utility of the AID system in the conditional elimination of endogenously expressed proteins. We demonstrate that the AID system induces efficient and reversible protein depletion of maternally provided proteins both in the ovary and the early embryo. Moreover, the AID system provides a fine spatiotemporal control of protein degradation and allows for the generation of different levels of protein knockdown in a well-regulated manner. These features of the AID system enable the unraveling of the discrete phenotypes of genes with highly complex functions. We utilized this system to generate a conditional loss-of-function allele which allows for the specific degradation of the Vasa protein without affecting its alternative splice variant (solo) and the vasa intronic gene (vig). With the help of this special allele, we demonstrate that dramatic decrease of Vasa protein in the vitellarium does not influence the completion of oogenesis as well as the establishment of proper anteroposterior and dorsoventral polarity in the developing oocyte. Our study suggests that both the localization and the translation of gurken mRNA in the vitellarium is independent from Vasa. © 2017 Federation of European Biochemical Societies.

  17. Scanning transmission electron microscope

    NARCIS (Netherlands)

    Kruit, P.

    2006-01-01

    The invention relates to a scanning transmission electron microscope comprising an electron source, an electron accelerator and deflection means for directing electrons emitted by the electron source at an object to be examined, and in addition a detector for detecting electrons coming from the

  18. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... you: have had any tests, such as an x-ray or CT scan, surgeries or treatments using iodinated ... page How does the procedure work? With ordinary x-ray examinations, an image is made by passing x- ...

  19. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... may be performed to measure the level of thyroid hormones in your blood. You may be told not to eat for several hours before your exam because eating can affect the ... as well. Thyroid Scan You will be positioned on an examination ...

  20. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... or less. top of page What will I experience during and after the procedure? Most thyroid scan ... areas. Outside links: For the convenience of our users, RadiologyInfo .org provides links to relevant websites. RadiologyInfo. ...

  1. Scanning bubble chamber pictures

    CERN Multimedia

    1974-01-01

    These were taken at the 2 m hydrogen bubble chamber. The photo shows an early Shiva system where the pre-measurements needed to qualify the event were done manually (cf photo 7408136X). The scanning tables were located in bld. 12. Gilberte Saulmier sits on foreground, Inge Arents at centre.

  2. Cervical MRI scan

    Science.gov (United States)

    ... cancer in the spine Arthritis in the spine MRI works better than CT scan in diagnosing these problems ... test. The strong magnetic fields created during an MRI can cause heart pacemakers and other implants to not work as well. It can also cause a piece ...

  3. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... of page Additional Information and Resources RTAnswers.org Radiation Therapy for Head and Neck Cancer top of page ... and Neck Cancer Treatment Radioactive Iodine (I-131) Therapy Head and Neck Cancer X-ray, Interventional Radiology and Nuclear ... to Thyroid Scan and Uptake ...

  4. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... A thyroid scan is a type of nuclear medicine imaging. The radioactive iodine uptake test (RAIU) is also known as a thyroid uptake. ... a patient’s immediate response to therapeutic interventions. Nuclear ... medical tests that help physicians diagnose and evaluate medical conditions. ...

  5. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available Toggle navigation Test/Treatment Patient Type Screening/Wellness Disease/Condition Safety En Español More Info Images/Videos About Us News Physician Resources Professions Site Index A-Z Thyroid Scan and Uptake ...

  6. Terahertz scanning probe microscope

    NARCIS (Netherlands)

    Klapwijk, T.M.

    2014-01-01

    The invention provides aterahertz scanning probe microscope setup comprising (i) a terahertz radiation source configured to generate terahertz radiation; (ii) a terahertz lens configured to receive at least part of the terahertz radiation from the terahertz radiation source; (iii) a cantilever unit

  7. SPM: Scanning positron microscope

    Directory of Open Access Journals (Sweden)

    Marcel Dickmann

    2015-08-01

    Full Text Available The Munich scanning positron microscope, operated by the Universität der Bundeswehr München and the Technische Universität München, located at NEPOMUC, permits positron lifetime measurements with a lateral resolution in the µm range and within an energy range of 1 – 20 keV.

  8. Laser Beam Scanning Device.

    Science.gov (United States)

    metal mirror. Multiple thermocouple wires attached to the rear of the mirror provide temperature (and hence beam power) information at various points...on the mirror. Scanning is achieved by means of a selector switch which sequentially samples the thermocouple outputs. The thermocouple output voltages are measured and recorded as a function of laser beam power.

  9. Full cycle rapid scan EPR deconvolution algorithm

    Science.gov (United States)

    Tseytlin, Mark

    2017-08-01

    Rapid scan electron paramagnetic resonance (RS EPR) is a continuous-wave (CW) method that combines narrowband excitation and broadband detection. Sinusoidal magnetic field scans that span the entire EPR spectrum cause electron spin excitations twice during the scan period. Periodic transient RS signals are digitized and time-averaged. Deconvolution of absorption spectrum from the measured full-cycle signal is an ill-posed problem that does not have a stable solution because the magnetic field passes the same EPR line twice per sinusoidal scan during up- and down-field passages. As a result, RS signals consist of two contributions that need to be separated and postprocessed individually. Deconvolution of either of the contributions is a well-posed problem that has a stable solution. The current version of the RS EPR algorithm solves the separation problem by cutting the full-scan signal into two half-period pieces. This imposes a constraint on the experiment; the EPR signal must completely decay by the end of each half-scan in order to not be truncated. The constraint limits the maximum scan frequency and, therefore, the RS signal-to-noise gain. Faster scans permit the use of higher excitation powers without saturating the spin system, translating into a higher EPR sensitivity. A stable, full-scan algorithm is described in this paper that does not require truncation of the periodic response. This algorithm utilizes the additive property of linear systems: the response to a sum of two inputs is equal the sum of responses to each of the inputs separately. Based on this property, the mathematical model for CW RS EPR can be replaced by that of a sum of two independent full-cycle pulsed field-modulated experiments. In each of these experiments, the excitation power equals to zero during either up- or down-field scan. The full-cycle algorithm permits approaching the upper theoretical scan frequency limit; the transient spin system response must decay within the scan

  10. Identification of Major Quantitative Trait Loci for Seed Oil Content in Soybeans by Combining Linkage and Genome-Wide Association Mapping.

    Science.gov (United States)

    Cao, Yongce; Li, Shuguang; Wang, Zili; Chang, Fangguo; Kong, Jiejie; Gai, Junyi; Zhao, Tuanjie

    2017-01-01

    Soybean oil is the most widely produced vegetable oil in the world and its content in soybean seed is an important quality trait in breeding programs. More than 100 quantitative trait loci (QTLs) for soybean oil content have been identified. However, most of them are genotype specific and/or environment sensitive. Here, we used both a linkage and association mapping methodology to dissect the genetic basis of seed oil content of Chinese soybean cultivars in various environments in the Jiang-Huai River Valley. One recombinant inbred line (RIL) population (NJMN-RIL), with 104 lines developed from a cross between M8108 and NN1138-2, was planted in five environments to investigate phenotypic data, and a new genetic map with 2,062 specific-locus amplified fragment markers was constructed to map oil content QTLs. A derived F2 population between MN-5 (a line of NJMN-RIL) and NN1138-2 was also developed to confirm one major QTL. A soybean breeding germplasm population (279 lines) was established to perform a genome-wide association study (GWAS) using 59,845 high-quality single nucleotide polymorphism markers. In the NJMN-RIL population, 8 QTLs were found that explained a range of phenotypic variance from 6.3 to 26.3% in certain planting environments. Among them, qOil-5-1, qOil-10-1, and qOil-14-1 were detected in different environments, and qOil-5-1 was further confirmed using the secondary F2 population. Three loci located on chromosomes 5 and 20 were detected in a 2-year long GWAS, and one locus that overlapped with qOil-5-1 was found repeatedly and treated as the same locus. qOil-5-1 was further localized to a linkage disequilibrium block region of approximately 440 kb. These results will not only increase our understanding of the genetic control of seed oil content in soybean, but will also be helpful in marker-assisted selection for breeding high seed oil content soybean and gene cloning to elucidate the mechanisms of seed oil content.

  11. Combined genome-wide expression profiling and targeted RNA interference in primary mouse macrophages reveals perturbation of transcriptional networks associated with interferon signalling

    Directory of Open Access Journals (Sweden)

    Craigon Marie

    2009-08-01

    Full Text Available Abstract Background Interferons (IFNs are potent antiviral cytokines capable of reprogramming the macrophage phenotype through the induction of interferon-stimulated genes (ISGs. Here we have used targeted RNA interference to suppress the expression of a number of key genes associated with IFN signalling in murine macrophages prior to stimulation with interferon-gamma. Genome-wide changes in transcript abundance caused by siRNA activity were measured using exon-level microarrays in the presence or absence of IFNγ. Results Transfection of murine bone-marrow derived macrophages (BMDMs with a non-targeting (control siRNA and 11 sequence-specific siRNAs was performed using a cationic lipid transfection reagent (Lipofectamine2000 prior to stimulation with IFNγ. Total RNA was harvested from cells and gene expression measured on Affymetrix GeneChip Mouse Exon 1.0 ST Arrays. Network-based analysis of these data revealed six siRNAs to cause a marked shift in the macrophage transcriptome in the presence or absence IFNγ. These six siRNAs targeted the Ifnb1, Irf3, Irf5, Stat1, Stat2 and Nfkb2 transcripts. The perturbation of the transcriptome by the six siRNAs was highly similar in each case and affected the expression of over 600 downstream transcripts. Regulated transcripts were clustered based on co-expression into five major groups corresponding to transcriptional networks associated with the type I and II IFN response, cell cycle regulation, and NF-KB signalling. In addition we have observed a significant non-specific immune stimulation of cells transfected with siRNA using Lipofectamine2000, suggesting use of this reagent in BMDMs, even at low concentrations, is enough to induce a type I IFN response. Conclusion Our results provide evidence that the type I IFN response in murine BMDMs is dependent on Ifnb1, Irf3, Irf5, Stat1, Stat2 and Nfkb2, and that siRNAs targeted to these genes results in perturbation of key transcriptional networks associated

  12. Bos taurus genome assembly.

    Science.gov (United States)

    Liu, Yue; Qin, Xiang; Song, Xing-Zhi Henry; Jiang, Huaiyang; Shen, Yufeng; Durbin, K James; Lien, Sigbjørn; Kent, Matthew Peter; Sodeland, Marte; Ren, Yanru; Zhang, Lan; Sodergren, Erica; Havlak, Paul; Worley, Kim C; Weinstock, George M; Gibbs, Richard A

    2009-04-24

    We present here the assembly of the bovine genome. The assembly method combines the BAC plus WGS local assembly used for the rat and sea urchin with the whole genome shotgun (WGS) only assembly used for many other animal genomes including the rhesus macaque. The assembly process consisted of multiple phases: First, BACs were assembled with BAC generated sequence, then subsequently in combination with the individual overlapping WGS reads. Different assembly parameters were tested to separately optimize the performance for each BAC assembly of the BAC and WGS reads. In parallel, a second assembly was produced using only the WGS sequences and a global whole genome assembly method. The two assemblies were combined to create a more complete genome representation that retained the high quality BAC-based local assembly information, but with gaps between BACs filled in with the WGS-only assembly. Finally, the entire assembly was placed on chromosomes using the available map information.Over 90% of the assembly is now placed on chromosomes. The estimated genome size is 2.87 Gb which represents a high degree of completeness, with 95% of the available EST sequences found in assembled contigs. The quality of the assembly was evaluated by comparison to 73 finished BACs, where the draft assembly covers between 92.5 and 100% (average 98.5%) of the finished BACs. The assembly contigs and scaffolds align linearly to the finished BACs, suggesting that misassemblies are rare. Genotyping and genetic mapping of 17,482 SNPs revealed that more than 99.2% were correctly positioned within the Btau_4.0 assembly, confirming the accuracy of the assembly. The biological analysis of this bovine genome assembly is being published, and the sequence data is available to support future bovine research.

  13. Bos taurus genome assembly

    Directory of Open Access Journals (Sweden)

    Sodergren Erica

    2009-04-01

    Full Text Available Abstract Background We present here the assembly of the bovine genome. The assembly method combines the BAC plus WGS local assembly used for the rat and sea urchin with the whole genome shotgun (WGS only assembly used for many other animal genomes including the rhesus macaque. Results The assembly process consisted of multiple phases: First, BACs were assembled with BAC generated sequence, then subsequently in combination with the individual overlapping WGS reads. Different assembly parameters were tested to separately optimize the performance for each BAC assembly of the BAC and WGS reads. In parallel, a second assembly was produced using only the WGS sequences and a global whole genome assembly method. The two assemblies were combined to create a more complete genome representation that retained the high quality BAC-based local assembly information, but with gaps between BACs filled in with the WGS-only assembly. Finally, the entire assembly was placed on chromosomes using the available map information. Over 90% of the assembly is now placed on chromosomes. The estimated genome size is 2.87 Gb which represents a high degree of completeness, with 95% of the available EST sequences found in assembled contigs. The quality of the assembly was evaluated by comparison to 73 finished BACs, where the draft assembly covers between 92.5 and 100% (average 98.5% of the finished BACs. The assembly contigs and scaffolds align linearly to the finished BACs, suggesting that misassemblies are rare. Genotyping and genetic mapping of 17,482 SNPs revealed that more than 99.2% were correctly positioned within the Btau_4.0 assembly, confirming the accuracy of the assembly. Conclusion The biological analysis of this bovine genome assembly is being published, and the sequence data is available to support future bovine research.

  14. [F(18)]-fluoroethylcholine combined in-line PET-CT scan for detection of lymph-node metastasis in high risk prostate cancer patients prior to radical prostatectomy: Preliminary results from a prospective histology-based study.

    Science.gov (United States)

    Steuber, T; Schlomm, T; Heinzer, H; Zacharias, M; Ahyai, S; Chun, K F; Haese, A; Klutmann, S; Köllermann, J; Sauter, G; Mester, J; Mikecz, P; Fisch, M; Huland, H; Graefen, M; Salomon, G

    2010-01-01

    To evaluate the diagnostic potential of PET/CT using ([F(18)]fluorethylcholine (FEC) for lymph node (LN) staging in high risk prostate cancer (PCa) patients prior to radical prostatectomy (RP). Twenty patients with localised PCa and > or =20% LN risk according to a published nomogram were prospectively enrolled. FEC PET/CT was done minimum 14 d after prostate biopsy. Afterwards, open RP and extended pelvic LN dissection (ePLND) were performed. Clinical stage, Prostate Specific Antigen (PSA) and biopsy Gleason Grading were assessed and histopathological evaluation of the RP-specimens and dissected LN has been performed. The results from PET/CT were compared with LN metastasis according to their anatomical site. Overall, 285 LN have been removed with a mean number of 15 nodes per patient (7-26). Of the 20 patients, 9 men were LN positive (45%), which corresponds to 31 positive LN with a mean size of 7 mm (0.8-12 mm). Dissection of the obturator fossa, external iliac artery/vein and internal iliac artery/vein revealed 36%, 48% and 16% of positive LN, respectively. FEC PET/CT did not detect one single positive LN, thus was false-negative in 31 metastasis and true negative in 254 LN. Based on our results which confirmed experience from the previous studies, FEC PET/CT scan did not prove to be useful for LN staging in localised PCa prior to treatment and should thus not be applied if clinically occult metastatic disease is suspected. Copyright 2009 Elsevier Ltd. All rights reserved.

  15. Genetic structure of Mycobacterium avium subsp. paratuberculosis population in cattle herds in Quebec as revealed by using a combination of multilocus genomic analyses.

    Science.gov (United States)

    Sohal, Jagdip Singh; Arsenault, Julie; Labrecque, Olivia; Fairbrother, Julie-Hélène; Roy, Jean-Philippe; Fecteau, Gilles; L'Homme, Yvan

    2014-08-01

    Mycobacterium avium subsp. paratuberculosis is the etiological agent of paratuberculosis, a granulomatous enteritis affecting a wide range of domestic and wild ruminants worldwide. A variety of molecular typing tools are used to distinguish M. avium subsp. paratuberculosis strains, contributing to a better understanding of M. avium subsp. paratuberculosis epidemiology. In the present study, PCR-based typing methods, including mycobacterial interspersed repetitive units/variable-number tandem repeats (MIRU-VNTR) and small sequence repeats (SSR) in addition to IS1311 PCR-restriction enzyme analysis (PCR-REA), were used to investigate the genetic heterogeneity of 200 M. avium subsp. paratuberculosis strains from dairy herds located in the province of Quebec, Canada. The majority of strains were of the "cattle type," or type II, although 3 strains were of the "bison type." A total of 38 genotypes, including a novel one, were identified using a combination of 17 genetic markers, which generated a Simpson's index of genetic diversity of 0.876. Additional analyses revealed no differences in genetic diversity between environmental and individual strains. Of note, a spatial and spatiotemporal cluster was evidenced regarding the distribution of one of the most common genotypes. The population had an overall homogeneous genetic structure, although a few strains stemmed out of the consensus cluster, including the bison-type strains. The genetic structure of M. avium subsp. paratuberculosis populations within most herds suggested intraherd dissemination and microevolution, although evidence of interherd contamination was also revealed. The level of genetic diversity obtained by combining MIRU-VNTR and SSR markers shows a promising avenue for molecular epidemiology investigations of M. avium subsp. paratuberculosis transmission patterns. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  16. Multifunctional scanning ion conductance microscopy.

    Science.gov (United States)

    Page, Ashley; Perry, David; Unwin, Patrick R

    2017-04-01

    Scanning ion conductance microscopy (SICM) is a nanopipette-based technique that has traditionally been used to image topography or to deliver species to an interface, particularly in a biological setting. This article highlights the recent blossoming of SICM into a technique with a much greater diversity of applications and capability that can be used either standalone, with advanced control (potential-time) functions, or in tandem with other methods. SICM can be used to elucidate functional information about interfaces, such as surface charge density or electrochemical activity (ion fluxes). Using a multi-barrel probe format, SICM-related techniques can be employed to deposit nanoscale three-dimensional structures and further functionality is realized when SICM is combined with scanning electrochemical microscopy (SECM), with simultaneous measurements from a single probe opening up considerable prospects for multifunctional imaging. SICM studies are greatly enhanced by finite-element method modelling for quantitative treatment of issues such as resolution, surface charge and (tip) geometry effects. SICM is particularly applicable to the study of living systems, notably single cells, although applications extend to materials characterization and to new methods of printing and nanofabrication. A more thorough understanding of the electrochemical principles and properties of SICM provides a foundation for significant applications of SICM in electrochemistry and interfacial science.

  17. Identification of polymorphic SVA retrotransposons using a mobile element scanning method for SVA (ME-Scan-SVA).

    Science.gov (United States)

    Ha, Hongseok; Loh, Jui Wan; Xing, Jinchuan

    2016-01-01

    Mobile element insertions are a major source of human genomic variation. SVA (SINE-R/VNTR/Alu) is the youngest retrotransposon family in the human genome and a number of diseases are known to be caused by SVA insertions. However, inter-individual genomic variations generated by SVA insertions and their impacts have not been studied extensively due to the difficulty in identifying polymorphic SVA insertions. To systematically identify SVA insertions at the population level and assess their genomic impact, we developed a mobile element scanning (ME-Scan) protocol we called ME-Scan-SVA. Using a nested SVA-specific PCR enrichment method, ME-Scan-SVA selectively amplify the 5' end of SVA elements and their flanking genomic regions. To demonstrate the utility of the protocol, we constructed and sequenced a ME-Scan-SVA library of 21 individuals and analyzed the data using a new analysis pipeline designed for the protocol. Overall, the method achieved high SVA-specificity and over >90 % of the sequenced reads are from SVA insertions. The method also had high sensitivity (>90 %) for fixed SVA insertions that contain the SVA-specific primer-binding sites in the reference genome. Using candidate locus selection criteria that are expected to have a 90 % sensitivity, we identified 151 and 29 novel polymorphic SVA candidates under relaxed and stringent cutoffs, respectively (average 12 and 2 per individual). For six polymorphic SVAs that we were able to validate by PCR, the average individual genotype accuracy is 92 %, demonstrating a high accuracy of the computational genotype calling pipeline. The new approach allows identifying novel SVA insertions using high-throughput sequencing. It is cost-effective and can be applied in large-scale population study. It also can be applied for detecting potential active SVA elements, and somatic SVA retrotransposition events in different tissues or developmental stages.

  18. Scanning transmission electron microscope

    OpenAIRE

    Kruit, P.

    2006-01-01

    The invention relates to a scanning transmission electron microscope comprising an electron source, an electron accelerator and deflection means for directing electrons emitted by the electron source at an object to be examined, and in addition a detector for detecting electrons coming from the object and, connected to the detector, a device for processing the detected electrons so as to form an object image, wherein a beam splitter is provided for dividing the electron beam from the electron...

  19. Scanning micro-sclerometer

    Science.gov (United States)

    Oliver, Warren C.; Blau, Peter J.

    1994-01-01

    A scanning micro-sclerometer measures changes in contact stiffness and correlates these changes to characteristics of a scratch. A known force is applied to a contact junction between two bodies and a technique employing an oscillating force is used to generate the contact stiffness between the two bodies. As the two bodies slide relative to each other, the contact stiffness changes. The change is measured to characterize the scratch.

  20. Scanning drop sensor

    Science.gov (United States)

    Jin, Jian; Xiang, Chengxiang; Gregoire, John M.; Shinde, Aniketa A.; Guevarra, Dan W.; Jones, Ryan J.; Marcin, Martin R.; Mitrovic, Slobodan

    2017-05-09

    Electrochemical or electrochemical and photochemical experiments are performed on a collection of samples by suspending a drop of electrolyte solution between an electrochemical experiment probe and one of the samples that serves as a test sample. During the electrochemical experiment, the electrolyte solution is added to the drop and an output solution is removed from the drop. The probe and collection of samples can be moved relative to one another so the probe can be scanned across the samples.

  1. Scanning ultrafast electron microscopy.

    Science.gov (United States)

    Yang, Ding-Shyue; Mohammed, Omar F; Zewail, Ahmed H

    2010-08-24

    Progress has been made in the development of four-dimensional ultrafast electron microscopy, which enables space-time imaging of structural dynamics in the condensed phase. In ultrafast electron microscopy, the electrons are accelerated, typically to 200 keV, and the microscope operates in the transmission mode. Here, we report the development of scanning ultrafast electron microscopy using a field-emission-source configuration. Scanning of pulses is made in the single-electron mode, for which the pulse contains at most one or a few electrons, thus achieving imaging without the space-charge effect between electrons, and still in ten(s) of seconds. For imaging, the secondary electrons from surface structures are detected, as demonstrated here for material surfaces and biological specimens. By recording backscattered electrons, diffraction patterns from single crystals were also obtained. Scanning pulsed-electron microscopy with the acquired spatiotemporal resolutions, and its efficient heat-dissipation feature, is now poised to provide in situ 4D imaging and with environmental capability.

  2. Genome evolution in Reptilia, the sister group of mammals.

    Science.gov (United States)

    Janes, Daniel E; Organ, Christopher L; Fujita, Matthew K; Shedlock, Andrew M; Edwards, Scott V

    2010-01-01

    The genomes of birds and nonavian reptiles (Reptilia) are critical for understanding genome evolution in mammals and amniotes generally. Despite decades of study at the chromosomal and single-gene levels, and the evidence for great diversity in genome size, karyotype, and sex chromosome diversity, reptile genomes are virtually unknown in the comparative genomics era. The recent sequencing of the chicken and zebra finch genomes, in conjunction with genome scans and the online publication of the Anolis lizard genome, has begun to clarify the events leading from an ancestral amniote genome--predicted to be large and to possess a diverse repeat landscape on par with mammals and a birdlike sex chromosome system--to the small and highly streamlined genomes of birds. Reptilia exhibit a wide range of evolutionary rates of different subgenomes and, from isochores to mitochondrial DNA, provide a critical contrast to the genomic paradigms established in mammals.

  3. Pig genome sequence - analysis and publication strategy

    NARCIS (Netherlands)

    Archibald, A.L.; Bolund, L.; Churcher, C.; Fredholm, M.; Groenen, M.A.M.; Harlizius, B.

    2010-01-01

    Background - The pig genome is being sequenced and characterised under the auspices of the Swine Genome Sequencing Consortium. The sequencing strategy followed a hybrid approach combining hierarchical shotgun sequencing of BAC clones and whole genome shotgun sequencing. Results - Assemblies of the

  4. Overcoming Barriers to Progress in Exercise Genomics

    Science.gov (United States)

    Bouchard, Claude

    2011-01-01

    This commentary focuses on the issues of statistical power, the usefulness of hypothesis-free approaches such as in genome-wide association explorations, the necessity of expanding the research beyond common DNA variants, the advantage of combining transcriptomics with genomics, and the complexities inherent to the search for links between genotype and phenotype in exercise genomics research. PMID:21697717

  5. Combined heat and power production based on gas turbine operation with biomass by gasification or powder firing; Kraftvaermeproduktion baserad paa gasturbindrift med biobraensle genom foergasning alternativt pulvereldning

    Energy Technology Data Exchange (ETDEWEB)

    Marbe, Aasa; Colmsjoe, Linda

    2006-12-15

    Combined heat and power (CHP) technique is relatively less extended in the Swedish energy system. There is a production of 56,2 TWh in district heating meanwhile only 7,6 TWh electricity comes from CHP. This only corresponds to 6 % of all electricity produced in Sweden (132 TWh). Based on the existing district heating system the amount of electricity produced in CHP-plants could rise from today 7,6 to 20 TWh. The Swedish government has decided to reduce the amount of CO{sub 2} released to atmosphere with 4 % by the year 2012. Furthermore there is a government decision that the nuclear power in a long time perspective will be phased out, so the amount of biofuelled heat and power plants has a huge potential to increase. To be competitive, the technique is to be efficient; hence the amount electricity produced should be as high as possible. Gasification of biofuel where the gas is used in a combined-cycle provides a higher efficiency compared to the traditional steam-cycle technique. To increase the electrical efficiency, an alternative method such as integration of a gas turbine with combustion of powder shape bio fuel in an external combustion chamber could be used. The concept is known as PFBC- technique in which the coal powder is combusted in a pressurised fluidised bed, the warm flue gases are cleaned up and expanded in a gas turbine. The objectives of this project have been to investigate the technical and economical conditions for gasification of bio fuel and for powder combustion in gas turbine for production of heat and power in different districts heat systems. Respectively technique has been studied in two different cases, Boraas Energi AB and ENA Energi AB. In Boraas the existing CHP-plant has been replaced by a bio fuelled gasification plant (IGCC) meanwhile at ENA Energi the existing CHP-plant has been complemented white a powder fuelled (bio) gas turbine. The task group for this report are decision makers of Energy Companies and the report will help

  6. Combined Action of Histone Reader Modules Regulates NuA4 Local Acetyltransferase Function but Not Its Recruitment on the Genome

    Science.gov (United States)

    Steunou, Anne-Lise; Cramet, Myriam; Rossetto, Dorine; Aristizabal, Maria J.; Lacoste, Nicolas; Drouin, Simon; Côté, Valérie; Paquet, Eric; Utley, Rhea T.; Krogan, Nevan; Robert, François; Kobor, Michael S.

    2016-01-01

    Recognition of histone marks by reader modules is thought to be at the heart of epigenetic mechanisms. These protein domains are considered to function by targeting regulators to chromosomal loci carrying specific histone modifications. This is important for proper gene regulation as well as propagation of epigenetic information. The NuA4 acetyltransferase complex contains two of these reader modules, an H3K4me3-specific plant homeodomain (PHD) within the Yng2 subunit and an H3K36me2/3-specific chromodomain in the Eaf3 subunit. While each domain showed a close functional interaction with the respective histone mark that it recognizes, at the biochemical level, genetic level (as assessed with epistatic miniarray profile screens), and phenotypic level, cells with the combined loss of both readers showed greatly enhanced phenotypes. Chromatin immunoprecipitation coupled with next-generation sequencing experiments demonstrated that the Yng2 PHD specifically directs H4 acetylation near the transcription start site of highly expressed genes, while Eaf3 is important downstream on the body of the genes. Strikingly, the recruitment of the NuA4 complex to these loci was not significantly affected. Furthermore, RNA polymerase II occupancy was decreased only under conditions where both PHD and chromodomains were lost, generally in the second half of the gene coding regions. Altogether, these results argue that methylated histone reader modules in NuA4 are not responsible for its recruitment to the promoter or coding regions but, rather, are required to orient its acetyltransferase catalytic site to the methylated histone 3-bearing nucleosomes in the surrounding chromatin, cooperating to allow proper transition from transcription initiation to elongation. PMID:27550811

  7. Genomic taxonomy of vibrios

    Directory of Open Access Journals (Sweden)

    Iida Tetsuya

    2009-10-01

    Full Text Available Abstract Background Vibrio taxonomy has been based on a polyphasic approach. In this study, we retrieve useful taxonomic information (i.e. data that can be used to distinguish different taxonomic levels, such as species and genera from 32 genome sequences of different vibrio species. We use a variety of tools to explore the taxonomic relationship between the sequenced genomes, including Multilocus Sequence Analysis (MLSA, supertrees, Average Amino Acid Identity (AAI, genomic signatures, and Genome BLAST atlases. Our aim is to analyse the usefulness of these tools for species identification in vibrios. Results We have generated four new genome sequences of three Vibrio species, i.e., V. alginolyticus 40B, V. harveyi-like 1DA3, and V. mimicus strains VM573 and VM603, and present a broad analyses of these genomes along with other sequenced Vibrio species. The genome atlas and pangenome plots provide a tantalizing image of the genomic differences that occur between closely related sister species, e.g. V. cholerae and V. mimicus. The vibrio pangenome contains around 26504 genes. The V. cholerae core genome and pangenome consist of 1520 and 6923 genes, respectively. Pangenomes might allow different strains of V. cholerae to occupy different niches. MLSA and supertree analyses resulted in a similar phylogenetic picture, with a clear distinction of four groups (Vibrio core group, V. cholerae-V. mimicus, Aliivibrio spp., and Photobacterium spp.. A Vibrio species is defined as a group of strains that share > 95% DNA identity in MLSA and supertree analysis, > 96% AAI, ≤ 10 genome signature dissimilarity, and > 61% proteome identity. Strains of the same species and species of the same genus will form monophyletic groups on the basis of MLSA and supertree. Conclusion The combination of different analytical and bioinformatics tools will enable the most accurate species identification through genomic computational analysis. This endeavour will culminate in

  8. A Scanning Microwave Radar and Radiometer

    DEFF Research Database (Denmark)

    Skou, Niels

    1995-01-01

    The Scanning Microwave Radar and Radiometer (SMRR) is a line scanner featuring a combined radar and radiometer system operating around 35 and 94 GHz. The layout of the SMRR is shown. The 2 offset antenna parabolas scan in synchronism, the receiver antenna has the highest gain in order to ensure...... that footprints are identical for the radar and the radiometer. The instrument will be flown in a pod under a Gulfstream G3 normally cruising with 240 m/sec at 12500 m, and will thus be able to sense clouds and precipitation from above...

  9. Scanning radiographic apparatus

    Energy Technology Data Exchange (ETDEWEB)

    Albert, R.D.

    1980-04-01

    Visual display of dental, medical or other radiographic images is realized with an x-ray tube in which an electron beam is scanned through an x-y raster pattern on a broad anode plate, the scanning being synchronized with the x-y sweep signals of a cathode ray tube display and the intensity signal for the display being derived from a small x-ray detector which receives x-rays that have passed through the subject to be imaged. Positioning and support of the detector are provided for by disposing the detector in a probe which may be attached to the x-ray tube at any of a plurality of different locations and by providing a plurality of such probes of different configuration in order to change focal length, to accommodate to different detector placements relative to the subject, to enhance patient comfort and to enable production of both periapical images and wider angle pantomographic images. High image definition with reduced radiation dosage is provided for by a lead glass collimator situated between the x-ray tube and subject and having a large number of spaced-apart minute radiation transmissive passages convergent on the position of the detector. Releasable mounting means enable changes of collimator in conjunction with changes of the probe to change focal length. A control circuit modifies the x-y sweep signals applied to the x-ray tube and modulates electron beam energy and current in order to correct for image distortions and other undesirable effects which can otherwise be present in a scanning x-ray system.

  10. Horizon Scanning for Pharmaceuticals

    DEFF Research Database (Denmark)

    Lepage-Nefkens, Isabelle; Douw, Karla; Mantjes, GertJan

    In 2016, the Belgian, Dutch, Luxembourg and Austrian governments declared their intention to collaborate on pharmaceutical policy (BeNeLuxA Collaboration). KCE was asked to lead a task force responsible for developing a Horizon Scanning methodology for pharmaceuticals and a possible model...... and filtration of new and emerging pharmaceutical products. It will maintain and update the HS database, organise company pipeline meetings, and disseminate the HSS’s outputs.  The HS unit works closely together with the designated national HS experts in each collaborating country. The national HS experts...

  11. Surface micromachined scanning mirrors

    DEFF Research Database (Denmark)

    Mattsson, Kent Erik

    1992-01-01

    Both aluminum cantilever and torsional scanning mirrors have been fabricated and their static and dynamic properties are studied experimentally and theoretically. The experiments showed resonance frequencies in the range of 163 k-Hz - 632 kHz for cantilever beams with Q values between 5 and 11....... Torsional mirrors showed resonance frequencies in the range of 410 kHz - 667 kHz with Q values of 10 - 17. All measurements performed at atmospheric pressure. Both types of mechanical structures were deflected electrostatically at large angles (± 5°) more than 1011 times without breaking and without any...

  12. Genome Imprinting

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 5; Issue 9. Genome Imprinting - The Silencing of Genes and Genomes. H A Ranganath M T Tanuja. General Article Volume 5 Issue 9 September 2000 pp 49-57. Fulltext. Click here to view fulltext PDF. Permanent link:

  13. Baculovirus Genomics

    NARCIS (Netherlands)

    Oers, van M.M.; Vlak, J.M.

    2007-01-01

    Baculovirus genomes are covalently closed circles of double stranded-DNA varying in size between 80 and 180 kilobase-pair. The genomes of more than fourty-one baculoviruses have been sequenced to date. The majority of these (37) are pathogenic to lepidopteran hosts; three infect sawflies

  14. Confocal scanning Mueller polarimeter

    Science.gov (United States)

    Lompado, Arthur

    2009-08-01

    We describe the design, construction, calibration and testing of a confocal scanning Mueller polarimeter. A polarization state generator and polarization state analyzer have been inserted into the optical path of a conventional confocal scanning imager to collect the reflectance Muller matrix of samples measuring up to 6.26 mm on a side. Four sources are available for sample interrogation using diode lasers centered at 532 nm, 635 nm, 670 nm, and 785 nm. The device captures all required imagery to calculate the Mueller matrix of each image pixel in approximately 90 s. These matrices are then reduced into polarization imagery such as the diattenuation, retardance and depolarization index. Oftentimes this polarization imagery is quite different and potentially more informative than a conventional intensity image. There are a number of fields that can benefit from alternative/enhanced imagery, most notably in the biomedical, discrimination, and target recognition communities. The sensor has been designed for biomedical applications aimed at improving the technique of noninvasive detection of melanoma lesions.

  15. Genomic scans for selective sweeps using SNP data

    DEFF Research Database (Denmark)

    Nielsen, Rasmus; Williamson, Scott; Kim, Yuseob

    2005-01-01

    of the selection coefficient. To illustrate the method, we apply our approach to data from the Seattle SNP project and to Chromosome 2 data from the HapMap project. In Chromosome 2, the most extreme signal is found in the lactase gene, which previously has been shown to be undergoing positive selection. Evidence...

  16. A Genome-wide Breast Cancer Scan in African Americans

    Science.gov (United States)

    2012-06-01

    Vuorinen A, Kaaks R, Ko YD, Kolonel LN, Konstantopoulou I, Kosma VM, Kulkarni S, Lambrechts D, Lee AM, Marchand LL, Lesnick T, Liu J, Lindstrom S...Mannermaa A, Margolin S, Martin NG, Miron P, Montgomery GW, Nevanlinna H, Nickels S, Nyante S, Olswold C, Palmer J, Pathak H, Pectasides D, Perou CM...Vuorinen A, Kaaks R, Ko YD, Kolonel LN, Konstantopoulou I, Kosma VM, Kulkarni S, Lambrechts D, Lee AM, Marchand LL, Lesnick T, Liu J, Lindstrom S

  17. Genome scanning for identification of resistance gene analogs ...

    African Journals Online (AJOL)

    Disease resistance in plants is a desirable economic trait. Many disease resistance genes from various plants have been cloned so far. The gene products of some of these can be distinguished by the presence of an N terminal nucleotide binding site and a C-terminal stretch of leucine-rich repeats. Oligonucleotides already ...

  18. A Genome-Wide Breast Cancer Scan in African Americans

    Science.gov (United States)

    2011-06-01

    F., Palli, D., Tumino, R., Krogh, V., Panico , S., Duell, E.J., Quiros, J.R., Sanchez, M.J., Navarro, C., Ardanaz, E., Dorronsoro, 17 M., Khaw...Chapelon, F., Palli, D., 18 Tumino, R., Krogh, V., Panico , S., Gonzalez, C.A., Ramon Quiros, J., Martinez, C., Navarro, C., Ardanaz, E., Larranaga, N

  19. Conservation genetics in transition to conservation genomics

    DEFF Research Database (Denmark)

    Ouborg, N. Joop; Pertoldi, Cino; Loeschcke, Volker

    2010-01-01

    in conservation biology. This has allowed assessment of the impact of genetic drift on genetic variation, of the level of inbreeding within populations, and of the amount of gene flow between or within populations. Recent developments in genomic techniques, including next generation sequencing, whole genome scans...... and gene-expression pattern analysis, have made it possible to step up from a limited number of neutral markers to genome-wide estimates of functional genetic variation. Here, we focus on how the transition of conservation genetics to conservation genomics leads to insights into the dynamics of selectively...

  20. Genomic footprinting.

    Science.gov (United States)

    Vierstra, Jeff; Stamatoyannopoulos, John A

    2016-03-01

    The advent of DNA footprinting with DNase I more than 35 years ago enabled the systematic analysis of protein-DNA interactions, and the technique has been instrumental in the decoding of cis-regulatory elements and the identification and characterization of transcription factors and other DNA-binding proteins. The ability to analyze millions of individual genomic cleavage events via massively parallel sequencing has enabled in vivo DNase I footprinting on a genomic scale, offering the potential for global analysis of transcription factor occupancy in a single experiment. Genomic footprinting has opened unique vistas on the organization, function and evolution of regulatory DNA; however, the technology is still nascent. Here we discuss both prospects and challenges of genomic footprinting, as well as considerations for its application to complex genomes.

  1. HapMap scanning of novel human minor histocompatibility antigens.

    Science.gov (United States)

    Kamei, Michi; Nannya, Yasuhito; Torikai, Hiroki; Kawase, Takakazu; Taura, Kenjiro; Inamoto, Yoshihiro; Takahashi, Taro; Yazaki, Makoto; Morishima, Satoko; Tsujimura, Kunio; Miyamura, Koichi; Ito, Tetsuya; Togari, Hajime; Riddell, Stanley R; Kodera, Yoshihisa; Morishima, Yasuo; Takahashi, Toshitada; Kuzushima, Kiyotaka; Ogawa, Seishi; Akatsuka, Yoshiki

    2009-05-21

    Minor histocompatibility antigens (mHags) are molecular targets of allo-immunity associated with hematopoietic stem cell transplantation (HSCT) and involved in graft-versus-host disease, but they also have beneficial antitumor activity. mHags are typically defined by host SNPs that are not shared by the donor and are immunologically recognized by cytotoxic T cells isolated from post-HSCT patients. However, the number of molecularly identified mHags is still too small to allow prospective studies of their clinical importance in transplantation medicine, mostly due to the lack of an efficient method for isolation. Here we show that when combined with conventional immunologic assays, the large data set from the International HapMap Project can be directly used for genetic mapping of novel mHags. Based on the immunologically determined mHag status in HapMap panels, a target mHag locus can be uniquely mapped through whole genome association scanning taking advantage of the unprecedented resolution and power obtained with more than 3 000 000 markers. The feasibility of our approach could be supported by extensive simulations and further confirmed by actually isolating 2 novel mHags as well as 1 previously identified example. The HapMap data set represents an invaluable resource for investigating human variation, with obvious applications in genetic mapping of clinically relevant human traits.

  2. An ethnically relevant consensus Korean reference genome is a step towards personal reference genomes.

    Science.gov (United States)

    Cho, Yun Sung; Kim, Hyunho; Kim, Hak-Min; Jho, Sungwoong; Jun, JeHoon; Lee, Yong Joo; Chae, Kyun Shik; Kim, Chang Geun; Kim, Sangsoo; Eriksson, Anders; Edwards, Jeremy S; Lee, Semin; Kim, Byung Chul; Manica, Andrea; Oh, Tae-Kwang; Church, George M; Bhak, Jong

    2016-11-24

    Human genomes are routinely compared against a universal reference. However, this strategy could miss population-specific and personal genomic variations, which may be detected more efficiently using an ethnically relevant or personal reference. Here we report a hybrid assembly of a Korean reference genome (KOREF) for constructing personal and ethnic references by combining sequencing and mapping methods. We also build its consensus variome reference, providing information on millions of variants from 40 additional ethnically homogeneous genomes from the Korean Personal Genome Project. We find that the ethnically relevant consensus reference can be beneficial for efficient variant detection. Systematic comparison of human assemblies shows the importance of assembly quality, suggesting the necessity of new technologies to comprehensively map ethnic and personal genomic structure variations. In the era of large-scale population genome projects, the leveraging of ethnicity-specific genome assemblies as well as the human reference genome will accelerate mapping all human genome diversity.

  3. Scanning quantum decoherence microscopy.

    Science.gov (United States)

    Cole, Jared H; Hollenberg, Lloyd C L

    2009-12-09

    The use of qubits as sensitive nanoscale magnetometers has been studied theoretically and recently demonstrated experimentally. In this paper we propose a new concept, in which a scanning two-state quantum system is used to probe a sample through the subtle effects of decoherence. Mapping both the Hamiltonian and decoherence properties of a qubit simultaneously provides a unique image of the magnetic (or electric) field properties at the nanoscale. The resulting images are sensitive to the temporal as well as spatial variation in the fields created by the sample. As examples we theoretically study two applications; one from condensed matter physics, the other biophysics. The individual components required to realize the simplest version of this device (characterization and measurement of qubits, nanoscale positioning) have already been demonstrated experimentally.

  4. Automatic Ultrasound Scanning

    DEFF Research Database (Denmark)

    Moshavegh, Ramin

    Medical ultrasound has been a widely used imaging modality in healthcare platforms for examination, diagnostic purposes, and for real-time guidance during surgery. However, despite the recent advances, medical ultrasound remains the most operator-dependent imaging modality, as it heavily relies...... on the user adjustments on the scanner interface to optimize the scan settings. This explains the huge interest in the subject of this PhD project entitled “AUTOMATIC ULTRASOUND SCANNING”. The key goals of the project have been to develop automated techniques to minimize the unnecessary settings...... on the scanners, and to improve the computer-aided diagnosis (CAD) in ultrasound by introducing new quantitative measures. Thus, four major issues concerning automation of the medical ultrasound are addressed in this PhD project. They touch upon gain adjustments in ultrasound, automatic synthetic aperture image...

  5. Antarctic Genomics

    Directory of Open Access Journals (Sweden)

    Alex D. Rogers

    2006-03-01

    Full Text Available With the development of genomic science and its battery of technologies, polar biology stands on the threshold of a revolution, one that will enable the investigation of important questions of unprecedented scope and with extraordinary depth and precision. The exotic organisms of polar ecosystems are ideal candidates for genomic analysis. Through such analyses, it will be possible to learn not only the novel features that enable polar organisms to survive, and indeed thrive, in their extreme environments, but also fundamental biological principles that are common to most, if not all, organisms. This article aims to review recent developments in Antarctic genomics and to demonstrate the global context of such studies.

  6. Genomic Imprinting

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 5; Issue 9. Genomic Imprinting - Some Interesting Implications for the Evolution of Social Behaviour. Raghavendra Gadagkar. General Article Volume 5 Issue 9 September 2000 pp 58-68 ...

  7. Herbarium genomics

    DEFF Research Database (Denmark)

    Bakker, Freek T.; Lei, Di; Yu, Jiaying

    2016-01-01

    Herbarium genomics is proving promising as next-generation sequencing approaches are well suited to deal with the usually fragmented nature of archival DNA. We show that routine assembly of partial plastome sequences from herbarium specimens is feasible, from total DNA extracts and with specimens...... up to 146 years old. We use genome skimming and an automated assembly pipeline, Iterative Organelle Genome Assembly, that assembles paired-end reads into a series of candidate assemblies, the best one of which is selected based on likelihood estimation. We used 93 specimens from 12 different...... correlation between plastome coverage and nuclear genome size (C value) in our samples, but the range of C values included is limited. Finally, we conclude that routine plastome sequencing from herbarium specimens is feasible and cost-effective (compared with Sanger sequencing or plastome...

  8. LANL Robotic Vessel Scanning

    Energy Technology Data Exchange (ETDEWEB)

    Webber, Nels W. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-11-25

    Los Alamos National Laboratory in J-1 DARHT Operations Group uses 6ft spherical vessels to contain hazardous materials produced in a hydrodynamic experiment. These contaminated vessels must be analyzed by means of a worker entering the vessel to locate, measure, and document every penetration mark on the vessel. If the worker can be replaced by a highly automated robotic system with a high precision scanner, it will eliminate the risks to the worker and provide management with an accurate 3D model of the vessel presenting the existing damage with the flexibility to manipulate the model for better and more in-depth assessment.The project was successful in meeting the primary goal of installing an automated system which scanned a 6ft vessel with an elapsed time of 45 minutes. This robotic system reduces the total time for the original scope of work by 75 minutes and results in excellent data accumulation and transmission to the 3D model imaging program.

  9. GPR scan assessment

    Directory of Open Access Journals (Sweden)

    Abbas M. Abbas

    2015-06-01

    Full Text Available Mekaad Radwan monument is situated in the neighborhood of Bab Zuweila in the historical Cairo, Egypt. It was constructed at the middle XVII century (1635 AD. The building has a rectangle shape plan (13 × 6 m with the longitudinal sides approximately WNW-ESE. It comprises three storages namely; the ground floor; the opened floor (RADWAN Bench and the living floor with a total elevation of 15 m above the street level. The building suffers from severe deterioration phenomena with patterns of damage which have occurred over time. These deterioration and damages could be attributed to foundation problems, subsoil water and also to the earthquake that affected the entire Greater Cairo area in October 1992. Ground Penetrating Radar (GPR scan was accomplished against the walls of the opened floor (RADWAN Bench to evaluate the hazard impact on the walls textures and integrity. The results showed an anomalous feature through the southern wall of RADWAN Bench. A mathematical model has been simulated to confirm the obtained anomaly and the model response exhibited a good matching with the outlined anomaly.

  10. System and method for compressive scanning electron microscopy

    Science.gov (United States)

    Reed, Bryan W

    2015-01-13

    A scanning transmission electron microscopy (STEM) system is disclosed. The system may make use of an electron beam scanning system configured to generate a plurality of electron beam scans over substantially an entire sample, with each scan varying in electron-illumination intensity over a course of the scan. A signal acquisition system may be used for obtaining at least one of an image, a diffraction pattern, or a spectrum from the scans, the image, diffraction pattern, or spectrum representing only information from at least one of a select subplurality or linear combination of all pixel locations comprising the image. A dataset may be produced from the information. A subsystem may be used for mathematically analyzing the dataset to predict actual information that would have been produced by each pixel location of the image.

  11. Rapid and Sensitive Detection of Norovirus Genomes in Oysters by a Two-Step Isothermal Amplification Assay System Combining Nucleic Acid Sequence-Based Amplification and Reverse Transcription-Loop-Mediated Isothermal Amplification Assays▿

    Science.gov (United States)

    Fukuda, Shinji; Sasaki, Yukie; Seno, Masato

    2008-01-01

    We developed a two-step isothermal amplification assay system, which achieved the detection of norovirus (NoV) genomes in oysters with a sensitivity similar to that of reverse transcription-seminested PCR. The time taken for the amplification of NoV genomes from RNA extracts was shortened to about 3 h. PMID:18456857

  12. Rapid and Sensitive Detection of Norovirus Genomes in Oysters by a Two-Step Isothermal Amplification Assay System Combining Nucleic Acid Sequence-Based Amplification and Reverse Transcription-Loop-Mediated Isothermal Amplification Assays▿

    OpenAIRE

    Fukuda, Shinji; Sasaki, Yukie; Seno, Masato

    2008-01-01

    We developed a two-step isothermal amplification assay system, which achieved the detection of norovirus (NoV) genomes in oysters with a sensitivity similar to that of reverse transcription-seminested PCR. The time taken for the amplification of NoV genomes from RNA extracts was shortened to about 3 h.

  13. Rapid and sensitive detection of norovirus genomes in oysters by a two-step isothermal amplification assay system combining nucleic acid sequence-based amplification and reverse transcription-loop-mediated isothermal amplification assays.

    Science.gov (United States)

    Fukuda, Shinji; Sasaki, Yukie; Seno, Masato

    2008-06-01

    We developed a two-step isothermal amplification assay system, which achieved the detection of norovirus (NoV) genomes in oysters with a sensitivity similar to that of reverse transcription-seminested PCR. The time taken for the amplification of NoV genomes from RNA extracts was shortened to about 3 h.

  14. Helitrons and Retrotransposons Are Co-localized in Bos taurus Genomes.

    Science.gov (United States)

    Babii, A; Kovalchuk, S; Glazko, T; Kosovsky, G; Glazko, V

    2017-06-01

    DNA transposons helitrons are mobile genetic elements responsible for major movements of the genetic material within and across different genomes. This ability makes helitrons suitable candidate elements for the development of new approaches of multilocus genotyping of live-stock animals, along with the well-known microsatellite loci. We aimed to estimate the informativeness of helitron and microsatellite markers in assessing the consolidation and the "gene pool" standards of two commercial dairy cattle breeds (Ayrshire breed and holsteinized Black-and-White cattle) and one local breed of Kalmyk cattle, and to reveal any inter-breed difference in the organization of genomic regions flanked by helitrons in the studied cattle breeds. We used the combination of two highly-polymorphic genomic elements - helitrons and trinu-cleotide microsatellites (AGC)6G and (GAG)6C, respectively - for genome scanning of the sampled groups of cattle. Also, we pyrosequenced the genomic regions flanked by the inverted repeats of 3'-end of Heligloria family of helitron fragments. Generally, the both combinations of markers generated polymorphic spectra, based on which certain interbreed differentiation could be observed. The analysis of the identified interspersed repeats suggests that in factory and local cattle the genomic regions flanked by helitron fragments are shaped differently and contain different superfamilies of transposable elements, especially retrotransposons. Despite the well-known fact of retrotransposon-dependent microsatellite expansion, our data suggest that, in the cattle genome, the DNA transposons and microsatellites can also be found in close neighbourhood, and that helitrons and retrotransposons may form domains of increased variability - targets for factors of artificial selection.

  15. The canine genome.

    Science.gov (United States)

    Ostrander, Elaine A; Wayne, Robert K

    2005-12-01

    The dog has emerged as a premier species for the study of morphology, behavior, and disease. The recent availability of a high-quality draft sequence lifts the dog system to a new threshold. We provide a primer to use the dog genome by first focusing on its evolutionary history. We overview the relationship of dogs to wild canids and discuss their origin and domestication. Dogs clearly originated from a substantial number of gray wolves and dog breeds define distinct genetic units that can be divided into at least four hierarchical groupings. We review evidence showing that dogs have high levels of linkage disequilibrium. Consequently, given that dog breeds express specific phenotypic traits and vary in behavior and the incidence of genetic disease, genomic-wide scans for linkage disequilibrium may allow the discovery of genes influencing breed-specific characteristics. Finally, we review studies that have utilized the dog to understand the genetic underpinning of several traits, and we summarize genomic resources that can be used to advance such studies. We suggest that given these resources and the unique characteristics of breeds, that the dog is a uniquely valuable resource for studying the genetic basis of complex traits.

  16. Population Genomics of Human Adaptation

    OpenAIRE

    Lachance, Joseph; Tishkoff, Sarah A.

    2013-01-01

    Recent advances in genotyping technologies have facilitated genome-wide scans for natural selection. Identification of targets of natural selection will shed light on processes of human adaptation and evolution and could be important for identifying variation that influences both normal human phenotypic variation as well as disease susceptibility. Here we focus on studies of natural selection in modern humans who originated ~200,000 years go in Africa and migrated across the globe ~50,000 – 1...

  17. Genomes to Proteomes

    Energy Technology Data Exchange (ETDEWEB)

    Panisko, Ellen A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Grigoriev, Igor [USDOE Joint Genome Inst., Walnut Creek, CA (United States); Daly, Don S. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Webb-Robertson, Bobbie-Jo [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Baker, Scott E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2009-03-01

    Biologists are awash with genomic sequence data. In large part, this is due to the rapid acceleration in the generation of DNA sequence that occurred as public and private research institutes raced to sequence the human genome. In parallel with the large human genome effort, mostly smaller genomes of other important model organisms were sequenced. Projects following on these initial efforts have made use of technological advances and the DNA sequencing infrastructure that was built for the human and other organism genome projects. As a result, the genome sequences of many organisms are available in high quality draft form. While in many ways this is good news, there are limitations to the biological insights that can be gleaned from DNA sequences alone; genome sequences offer only a bird's eye view of the biological processes endemic to an organism or community. Fortunately, the genome sequences now being produced at such a high rate can serve as the foundation for other global experimental platforms such as proteomics. Proteomic methods offer a snapshot of the proteins present at a point in time for a given biological sample. Current global proteomics methods combine enzymatic digestion, separations, mass spectrometry and database searching for peptide identification. One key aspect of proteomics is the prediction of peptide sequences from mass spectrometry data. Global proteomic analysis uses computational matching of experimental mass spectra with predicted spectra based on databases of gene models that are often generated computationally. Thus, the quality of gene models predicted from a genome sequence is crucial in the generation of high quality peptide identifications. Once peptides are identified they can be assigned to their parent protein. Proteins identified as expressed in a given experiment are most useful when compared to other expressed proteins in a larger biological context or biochemical pathway. In this chapter we will discuss the automatic

  18. A chromosomal genomics approach to assess and validate the desi and kabuli draft chickpea genome assemblies.

    Science.gov (United States)

    Ruperao, Pradeep; Chan, Chon-Kit Kenneth; Azam, Sarwar; Karafiátová, Miroslava; Hayashi, Satomi; Cížková, Jana; Saxena, Rachit K; Simková, Hana; Song, Chi; Vrána, Jan; Chitikineni, Annapurna; Visendi, Paul; Gaur, Pooran M; Millán, Teresa; Singh, Karam B; Taran, Bunyamin; Wang, Jun; Batley, Jacqueline; Doležel, Jaroslav; Varshney, Rajeev K; Edwards, David

    2014-08-01

    With the expansion of next-generation sequencing technology and advanced bioinformatics, there has been a rapid growth of genome sequencing projects. However, while this technology enables the rapid and cost-effective assembly of draft genomes, the quality of these assemblies usually falls short of gold standard genome assemblies produced using the more traditional BAC by BAC and Sanger sequencing approaches. Assembly validation is often performed by the physical anchoring of genetically mapped markers, but this is prone to errors and the resolution is usually low, especially towards centromeric regions where recombination is limited. New approaches are required to validate reference genome assemblies. The ability to isolate individual chromosomes combined with next-generation sequencing permits the validation of genome assemblies at the chromosome level. We demonstrate this approach by the assessment of the recently published chickpea kabuli and desi genomes. While previous genetic analysis suggests that these genomes should be very similar, a comparison of their chromosome sizes and published assemblies highlights significant differences. Our chromosomal genomics analysis highlights short defined regions that appear to have been misassembled in the kabuli genome and identifies large-scale misassembly in the draft desi genome. The integration of chromosomal genomics tools within genome sequencing projects has the potential to significantly improve the construction and validation of genome assemblies. The approach could be applied both for new genome assemblies as well as published assemblies, and complements currently applied genome assembly strategies. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  19. Human Genome Variation and the Concept of Genotype Networks

    Science.gov (United States)

    Dall'Olio, Giovanni Marco; Bertranpetit, Jaume; Wagner, Andreas; Laayouni, Hafid

    2014-01-01

    Genotype networks are a concept used in systems biology to study sets of genotypes having the same phenotype, and the ability of these to bring forth novel phenotypes. In the past they have been applied to determine the genetic heterogeneity, and stability to mutations, of systems such as metabolic networks and RNA folds. Recently, they have been the base for reconciling the neutralist and selectionist views on evolution. Here, we adapted this concept to the study of population genetics data. Specifically, we applied genotype networks to the human 1000 genomes dataset, and analyzed networks composed of short haplotypes of Single Nucleotide Variants (SNV). The result is a scan of how properties related to genetic heterogeneity and stability to mutations are distributed along the human genome. We found that genes involved in acquired immunity, such as some HLA and MHC genes, tend to have the most heterogeneous and connected networks, and that coding regions tend to be more heterogeneous and stable to mutations than non-coding regions. We also found, using coalescent simulations, that regions under selection have more extended and connected networks. The application of the concept of genotype networks can provide a new opportunity to understand the evolutionary processes that shaped our genome. Learning how the genotype space of each region of our genome has been explored during the evolutionary history of the human species can lead to a better understanding on how selective pressures and neutral factors have shaped genetic diversity within populations and among individuals. Combined with the availability of larger datasets of sequencing data, genotype networks represent a new approach to the study of human genetic diversity that looks to the whole genome, and goes beyond the classical division between selection and neutrality methods. PMID:24911413

  20. Human genome variation and the concept of genotype networks.

    Science.gov (United States)

    Dall'Olio, Giovanni Marco; Bertranpetit, Jaume; Wagner, Andreas; Laayouni, Hafid

    2014-01-01

    Genotype networks are a concept used in systems biology to study sets of genotypes having the same phenotype, and the ability of these to bring forth novel phenotypes. In the past they have been applied to determine the genetic heterogeneity, and stability to mutations, of systems such as metabolic networks and RNA folds. Recently, they have been the base for reconciling the neutralist and selectionist views on evolution. Here, we adapted this concept to the study of population genetics data. Specifically, we applied genotype networks to the human 1000 genomes dataset, and analyzed networks composed of short haplotypes of Single Nucleotide Variants (SNV). The result is a scan of how properties related to genetic heterogeneity and stability to mutations are distributed along the human genome. We found that genes involved in acquired immunity, such as some HLA and MHC genes, tend to have the most heterogeneous and connected networks, and that coding regions tend to be more heterogeneous and stable to mutations than non-coding regions. We also found, using coalescent simulations, that regions under selection have more extended and connected networks. The application of the concept of genotype networks can provide a new opportunity to understand the evolutionary processes that shaped our genome. Learning how the genotype space of each region of our genome has been explored during the evolutionary history of the human species can lead to a better understanding on how selective pressures and neutral factors have shaped genetic diversity within populations and among individuals. Combined with the availability of larger datasets of sequencing data, genotype networks represent a new approach to the study of human genetic diversity that looks to the whole genome, and goes beyond the classical division between selection and neutrality methods.

  1. Scanning tunneling microscopy II further applications and related scanning techniques

    CERN Document Server

    Güntherodt, Hans-Joachim

    1995-01-01

    Scanning Tunneling Microscopy II, like its predecessor, presents detailed and comprehensive accounts of the basic principles and broad range of applications of STM and related scanning probe techniques. The applications discussed in this volume come predominantly from the fields of electrochemistry and biology. In contrast to those described in STM I, these studies may be performed in air and in liquids. The extensions of the basic technique to map other interactions are described in chapters on scanning force microscopy, magnetic force microscopy, and scanning near-field optical microscopy, together with a survey of other related techniques. Also described here is the use of a scanning proximal probe for surface modification. Together, the two volumes give a comprehensive account of experimental aspects of STM. They provide essential reading and reference material for all students and researchers involved in this field. In this second edition the text has been updated and new methods are discussed.

  2. Scanning tunneling microscopy II further applications and related scanning techniques

    CERN Document Server

    Güntherodt, Hans-Joachim

    1992-01-01

    Scanning Tunneling Microscopy II, like its predecessor, presents detailed and comprehensive accounts of the basic principles and broad range of applications of STM and related scanning probe techniques. The applications discussed in this volume come predominantly from the fields of electrochemistry and biology. In contrast to those described in Vol. I, these sudies may be performed in air and in liquids. The extensions of the basic technique to map other interactions are described inchapters on scanning force microscopy, magnetic force microscopy, scanning near-field optical microscopy, together with a survey of other related techniques. Also described here is the use of a scanning proximal probe for surface modification. Togehter, the two volumes give a comprehensive account of experimental aspcets of STM. They provide essentialreading and reference material for all students and researchers involvedin this field.

  3. Scanning Ion Conductance Microscopy of Live Keratinocytes

    Science.gov (United States)

    Hegde, V.; Mason, A.; Saliev, T.; Smith, F. J. D.; McLean, W. H. I.; Campbell, P. A.

    2012-07-01

    Scanning ion conductance microscopy (SICM) is perhaps the least well known technique from the scanning probe microscopy (SPM) family of instruments. As with its more familiar counterpart, atomic force microscopy (AFM), the technique provides high-resolution topographic imaging, with the caveat that target structures must be immersed in a conducting solution so that a controllable ion current may be utilised as the basis for feedback. In operation, this non-contact characteristic of SICM makes it ideal for the study of delicate structures, such as live cells. Moreover, the intrinsic architecture of the instrument, incorporating as it does, a scanned micropipette, lends itself to combination approaches with complementary techniques such as patch-clamp electrophysiology: SICM therefore boasts the capability for both structural and functional imaging. For the present observations, an ICnano S system (Ionscope Ltd., Melbourn, UK) operating in 'hopping mode' was used, with the objective of assessing the instrument's utility for imaging live keratinocytes under physiological buffers. In scans employing cultured HaCaT cells (spontaneously immortalised, human keratinocytes), we compared the qualitative differences of live cells imaged with SICM and AFM, and also with their respective counterparts after chemical fixation in 4% paraformaldehyde. Characteristic surface microvilli were particularly prominent in live cell imaging by SICM. Moreover, time lapse SICM imaging on live cells revealed that changes in the pattern of microvilli could be tracked over time. By comparison, AFM imaging on live cells, even at very low contact forces (monitoring the most delicate living structures with attendant high spatial resolutions.

  4. A review of genomic selection - Implications for the South African ...

    African Journals Online (AJOL)

    2013-03-09

    Mar 9, 2013 ... 1995). Genome scans were conducted for QTL associated with milk production, health and conformation ..... predictions of milk fat and protein composition generally perform better with a Bayesian approach ..... Mature weight.

  5. A genomic survey on the immune differences among Sinocyclocheilus fishes

    National Research Council Canada - National Science Library

    Qiu, Ying; Yang, Junxing; Jiang, Wansheng; Chen, Xiaoli; Bian, Chao; Shi, Qiong

    2016-01-01

    ...), the semi-cave-dewlling S. rhinocerous (Sr) and the cave-restricted S. anshuiensis (Sa). Here, we performed a genomic survey on the immunity differences among the 3 fishes by combination of the genome and transcriptome data...

  6. Enhancer Identification through Comparative Genomics

    Energy Technology Data Exchange (ETDEWEB)

    Visel, Axel; Bristow, James; Pennacchio, Len A.

    2006-10-01

    With the availability of genomic sequence from numerousvertebrates, a paradigm shift has occurred in the identification ofdistant-acting gene regulatory elements. In contrast to traditionalgene-centric studies in which investigators randomly scanned genomicfragments that flank genes of interest in functional assays, the modernapproach begins electronically with publicly available comparativesequence datasets that provide investigators with prioritized lists ofputative functional sequences based on their evolutionary conservation.However, although a large number of tools and resources are nowavailable, application of comparative genomic approaches remains far fromtrivial. In particular, it requires users to dynamically consider thespecies and methods for comparison depending on the specific biologicalquestion under investigation. While there is currently no single generalrule to this end, it is clear that when applied appropriately,comparative genomic approaches exponentially increase our power ingenerating biological hypotheses for subsequent experimentaltesting.

  7. Taxonomic classification of genomic sequences : from whole genomes to environmental genomic fragments

    OpenAIRE

    Díaz Solórzano, Naryttza Namelly

    2010-01-01

    The main goal of this dissertation is to develop a classifier for assigning environmental genomic fragments to the closest known source organism. This has been achieved by the development of a novel method for the TAxonomic COmposition Analysis - TACOA - of environmental genomic fragments using a kernelized nearest neighbor approach. A combination of machine learning techniques has been employed to realize a classifier that exploits the wealth of knowledge deposited in public databases. The d...

  8. Marine genomics

    DEFF Research Database (Denmark)

    Oliveira Ribeiro, Ângela Maria; Foote, Andrew David; Kupczok, Anne

    2017-01-01

    evolutionary biology of non-model organisms to species of commercial relevance for fishing, aquaculture and biomedicine. Instead of providing an exhaustive list of available genomic data, we rather set to present contextualized examples that best represent the current status of the field of marine genomics.......Marine ecosystems occupy 71% of the surface of our planet, yet we know little about their diversity. Although the inventory of species is continually increasing, as registered by the Census of Marine Life program, only about 10% of the estimated two million marine species are known. This lag......-throughput sequencing approaches have been helping to improve our knowledge of marine biodiversity, from the rich microbial biota that forms the base of the tree of life to a wealth of plant and animal species. In this review, we present an overview of the applications of genomics to the study of marine life, from...

  9. Listeria Genomics

    Science.gov (United States)

    Cabanes, Didier; Sousa, Sandra; Cossart, Pascale

    The opportunistic intracellular foodborne pathogen Listeria monocytogenes has become a paradigm for the study of host-pathogen interactions and bacterial adaptation to mammalian hosts. Analysis of L. monocytogenes infection has provided considerable insight into how bacteria invade cells, move intracellularly, and disseminate in tissues, as well as tools to address fundamental processes in cell biology. Moreover, the vast amount of knowledge that has been gathered through in-depth comparative genomic analyses and in vivo studies makes L. monocytogenes one of the most well-studied bacterial pathogens. This chapter provides an overview of progress in the exploration of genomic, transcriptomic, and proteomic data in Listeria spp. to understand genome evolution and diversity, as well as physiological aspects of metabolism used by bacteria when growing in diverse environments, in particular in infected hosts.

  10. Ancient genomics

    DEFF Research Database (Denmark)

    Der Sarkissian, Clio; Allentoft, Morten Erik; Avila Arcos, Maria del Carmen

    2015-01-01

    The past decade has witnessed a revolution in ancient DNA (aDNA) research. Although the field's focus was previously limited to mitochondrial DNA and a few nuclear markers, whole genome sequences from the deep past can now be retrieved. This breakthrough is tightly connected to the massive sequence...... by increasing the number of sequence reads to billions effectively means that contamination issues that have haunted aDNA research for decades, particularly in human studies, can now be efficiently and confidently quantified. At present, whole genomes have been sequenced from ancient anatomically modern humans......, archaic hominins, ancient pathogens and megafaunal species. Those have revealed important functional and phenotypic information, as well as unexpected adaptation, migration and admixture patterns. As such, the field of aDNA has entered the new era of genomics and has provided valuable information when...

  11. Cephalopod genomics

    DEFF Research Database (Denmark)

    Albertin, Caroline B.; Bonnaud, Laure; Brown, C. Titus

    2012-01-01

    The Cephalopod Sequencing Consortium (CephSeq Consortium) was established at a NESCent Catalysis Group Meeting, ``Paths to Cephalopod Genomics-Strategies, Choices, Organization,'' held in Durham, North Carolina, USA on May 24-27, 2012. Twenty-eight participants representing nine countries (Austria......, Australia, China, Denmark, France, Italy, Japan, Spain and the USA) met to address the pressing need for genome sequencing of cephalopod mollusks. This group, drawn from cephalopod biologists, neuroscientists, developmental and evolutionary biologists, materials scientists, bioinformaticians and researchers...... active in sequencing, assembling and annotating genomes, agreed on a set of cephalopod species of particular importance for initial sequencing and developed strategies and an organization (CephSeq Consortium) to promote this sequencing. The conclusions and recommendations of this meeting are described...

  12. The GLOBE-Consortium: The Next-Generation Genome Viewer

    OpenAIRE

    Knoch, Tobias; Eussen, Bert; Moorhouse, Michael

    2006-01-01

    textabstractThe GLOBE 3D Genome Viewer is the novel system-biology oriented genome browser necessary to access, present, annotate, and to simulate the holistic genome complexity in a unique gateway towards a real understanding, educative presentation and curative manipulation planning of this tremendous evolutionary information grail – genomes. This has required completely new approaches to represent the genome architecture realistically in combination with the various types of informational ...

  13. Scanning Productivity in Interlibrary Loan

    Science.gov (United States)

    Pedersen, Wayne A.; Runestad, Anders

    2009-01-01

    The authors report findings of a research study conducted at the Iowa State University Library. Data was gathered on the scanning of library materials by students working in the Interlibrary Loan (ILL) unit. The goals of the study were fourfold: (1) Develop measures of scanning productivity in ILL, (2) Determine if it is more productive to scan…

  14. Scan converting video tape recorder

    Science.gov (United States)

    Holt, N. I. (Inventor)

    1971-01-01

    A video tape recorder is disclosed of sufficient bandwidth to record monochrome television signals or standard NTSC field sequential color at current European and American standards. The system includes scan conversion means for instantaneous playback at scanning standards different from those at which the recording is being made.

  15. Detectors for scanning video imagers

    Science.gov (United States)

    Webb, Robert H.; Hughes, George W.

    1993-11-01

    In scanning video imagers, a single detector sees each pixel for only 100 ns, so the bandwidth of the detector needs to be about 10 MHz. How this fact influences the choice of detectors for scanning systems is described here. Some important parametric quantities obtained from manufacturer specifications are related and it is shown how to compare detectors when specified quantities differ.

  16. OryzaGenome: Genome Diversity Database of Wild Oryza Species

    KAUST Repository

    Ohyanagi, Hajime

    2015-11-18

    The species in the genus Oryza, encompassing nine genome types and 23 species, are a rich genetic resource and may have applications in deeper genomic analyses aiming to understand the evolution of plant genomes. With the advancement of next-generation sequencing (NGS) technology, a flood of Oryza species reference genomes and genomic variation information has become available in recent years. This genomic information, combined with the comprehensive phenotypic information that we are accumulating in our Oryzabase, can serve as an excellent genotype-phenotype association resource for analyzing rice functional and structural evolution, and the associated diversity of the Oryza genus. Here we integrate our previous and future phenotypic/habitat information and newly determined genotype information into a united repository, named OryzaGenome, providing the variant information with hyperlinks to Oryzabase. The current version of OryzaGenome includes genotype information of 446 O. rufipogon accessions derived by imputation and of 17 accessions derived by imputation-free deep sequencing. Two variant viewers are implemented: SNP Viewer as a conventional genome browser interface and Variant Table as a textbased browser for precise inspection of each variant one by one. Portable VCF (variant call format) file or tabdelimited file download is also available. Following these SNP (single nucleotide polymorphism) data, reference pseudomolecules/ scaffolds/contigs and genome-wide variation information for almost all of the closely and distantly related wild Oryza species from the NIG Wild Rice Collection will be available in future releases. All of the resources can be accessed through http://viewer.shigen.info/oryzagenome/.

  17. Optical advantages in retinal scanning displays

    Science.gov (United States)

    Urey, Hakan

    2000-06-01

    Virtual Retinal DisplayTM technology is a retinal scanning display (RSD) technology being developed at Microvision, Inc., for a variety of applications including microdisplays. An RSD scans a modulated light beam onto a viewer's retina to produce a perceived image. Red, green and blue light sources, such as lasers, laser diodes or LEDs combine with Microvision's proprietary miniaturized scanner designs to make the RSD very well suited for head-worn and helmet-mounted displays (HMD). This paper compares the features of RSD technology to other display technologies such as the cathode ray tubes or matrix-based displays for HMD and other wearable display applications, and notes important performance advantages due to the number of pixel- generating elements. Also discussed are some fundamental optical limitations for virtual displays used in the HMD applications.

  18. Laser scanning laser diode photoacoustic microscopy system.

    Science.gov (United States)

    Erfanzadeh, Mohsen; Kumavor, Patrick D; Zhu, Quing

    2018-03-01

    The development of low-cost and fast photoacoustic microscopy systems enhances the clinical applicability of photoacoustic imaging systems. To this end, we present a laser scanning laser diode-based photoacoustic microscopy system. In this system, a 905 nm, 325 W maximum output peak power pulsed laser diode with 50 ns pulsewidth is utilized as the light source. A combination of aspheric and cylindrical lenses is used for collimation of the laser diode beam. Two galvanometer scanning mirrors steer the beam across a focusing aspheric lens. The lateral resolution of the system was measured to be ∼21 μm using edge spread function estimation. No averaging was performed during data acquisition. The imaging speed is ∼370 A-lines per second. Photoacoustic microscopy images of human hairs, ex vivo mouse ear, and ex vivo porcine ovary are presented to demonstrate the feasibility and potentials of the proposed system.

  19. Solving LR Conflicts Through Context Aware Scanning

    Science.gov (United States)

    Leon, C. Rodriguez; Forte, L. Garcia

    2011-09-01

    This paper presents a new algorithm to compute the exact list of tokens expected by any LR syntax analyzer at any point of the scanning process. The lexer can, at any time, compute the exact list of valid tokens to return only tokens in this set. In the case than more than one matching token is in the valid set, the lexer can resort to a nested LR parser to disambiguate. Allowing nested LR parsing requires some slight modifications when building the LR parsing tables. We also show how LR parsers can parse conflictive and inherently ambiguous languages using a combination of nested parsing and context aware scanning. These expanded lexical analyzers can be generated from high level specifications.

  20. Genome Imprinting

    Indian Academy of Sciences (India)

    because of their maternal 'or paternal origin. Human homologies for the type of situation described above are naturally occurring placental malformation, the hydatidiform ..... drome, familial glomus tumors, psoriasis, neural tube defects, congenital heart disease and narcolepsy. Since genome imprint- ing is implicated in the ...