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Sample records for affymetrix 10k snp

  1. ACNE: a summarization method to estimate allele-specific copy numbers for Affymetrix SNP arrays

    PubMed Central

    Ortiz-Estevez, Maria; Bengtsson, Henrik; Rubio, Angel

    2010-01-01

    Motivation: Current algorithms for estimating DNA copy numbers (CNs) borrow concepts from gene expression analysis methods. However, single nucleotide polymorphism (SNP) arrays have special characteristics that, if taken into account, can improve the overall performance. For example, cross hybridization between alleles occurs in SNP probe pairs. In addition, most of the current CN methods are focused on total CNs, while it has been shown that allele-specific CNs are of paramount importance for some studies. Therefore, we have developed a summarization method that estimates high-quality allele-specific CNs. Results: The proposed method estimates the allele-specific DNA CNs for all Affymetrix SNP arrays dealing directly with the cross hybridization between probes within SNP probesets. This algorithm outperforms (or at least it performs as well as) other state-of-the-art algorithms for computing DNA CNs. It better discerns an aberration from a normal state and it also gives more precise allele-specific CNs. Availability: The method is available in the open-source R package ACNE, which also includes an add on to the aroma.affymetrix framework (http://www.aroma-project.org/). Contact: arubio@ceit.es Supplementaruy information: Supplementary data are available at Bioinformatics online. PMID:20529889

  2. DMET-Analyzer: automatic analysis of Affymetrix DMET Data

    PubMed Central

    2012-01-01

    Background Clinical Bioinformatics is currently growing and is based on the integration of clinical and omics data aiming at the development of personalized medicine. Thus the introduction of novel technologies able to investigate the relationship among clinical states and biological machineries may help the development of this field. For instance the Affymetrix DMET platform (drug metabolism enzymes and transporters) is able to study the relationship among the variation of the genome of patients and drug metabolism, detecting SNPs (Single Nucleotide Polymorphism) on genes related to drug metabolism. This may allow for instance to find genetic variants in patients which present different drug responses, in pharmacogenomics and clinical studies. Despite this, there is currently a lack in the development of open-source algorithms and tools for the analysis of DMET data. Existing software tools for DMET data generally allow only the preprocessing of binary data (e.g. the DMET-Console provided by Affymetrix) and simple data analysis operations, but do not allow to test the association of the presence of SNPs with the response to drugs. Results We developed DMET-Analyzer a tool for the automatic association analysis among the variation of the patient genomes and the clinical conditions of patients, i.e. the different response to drugs. The proposed system allows: (i) to automatize the workflow of analysis of DMET-SNP data avoiding the use of multiple tools; (ii) the automatic annotation of DMET-SNP data and the search in existing databases of SNPs (e.g. dbSNP), (iii) the association of SNP with pathway through the search in PharmaGKB, a major knowledge base for pharmacogenomic studies. DMET-Analyzer has a simple graphical user interface that allows users (doctors/biologists) to upload and analyse DMET files produced by Affymetrix DMET-Console in an interactive way. The effectiveness and easy use of DMET Analyzer is demonstrated through different case studies regarding

  3. Rawcopy: Improved copy number analysis with Affymetrix arrays

    PubMed Central

    Mayrhofer, Markus; Viklund, Björn; Isaksson, Anders

    2016-01-01

    Microarray data is subject to noise and systematic variation that negatively affects the resolution of copy number analysis. We describe Rawcopy, an R package for processing of Affymetrix CytoScan HD, CytoScan 750k and SNP 6.0 microarray raw intensities (CEL files). Noise characteristics of a large number of reference samples are used to estimate log ratio and B-allele frequency for total and allele-specific copy number analysis. Rawcopy achieves better signal-to-noise ratio and higher proportion of validated alterations than commonly used free and proprietary alternatives. In addition, Rawcopy visualizes each microarray sample for assessment of technical quality, patient identity and genome-wide absolute copy number states. Software and instructions are available at http://rawcopy.org. PMID:27796336

  4. Micro-Analyzer: automatic preprocessing of Affymetrix microarray data.

    PubMed

    Guzzi, Pietro Hiram; Cannataro, Mario

    2013-08-01

    A current trend in genomics is the investigation of the cell mechanism using different technologies, in order to explain the relationship among genes, molecular processes and diseases. For instance, the combined use of gene-expression arrays and genomic arrays has been demonstrated as an effective instrument in clinical practice. Consequently, in a single experiment different kind of microarrays may be used, resulting in the production of different types of binary data (images and textual raw data). The analysis of microarray data requires an initial preprocessing phase, that makes raw data suitable for use on existing analysis platforms, such as the TIGR M4 (TM4) Suite. An additional challenge to be faced by emerging data analysis platforms is the ability to treat in a combined way those different microarray formats coupled with clinical data. In fact, resulting integrated data may include both numerical and symbolic data (e.g. gene expression and SNPs regarding molecular data), as well as temporal data (e.g. the response to a drug, time to progression and survival rate), regarding clinical data. Raw data preprocessing is a crucial step in analysis but is often performed in a manual and error prone way using different software tools. Thus novel, platform independent, and possibly open source tools enabling the semi-automatic preprocessing and annotation of different microarray data are needed. The paper presents Micro-Analyzer (Microarray Analyzer), a cross-platform tool for the automatic normalization, summarization and annotation of Affymetrix gene expression and SNP binary data. It represents the evolution of the μ-CS tool, extending the preprocessing to SNP arrays that were not allowed in μ-CS. The Micro-Analyzer is provided as a Java standalone tool and enables users to read, preprocess and analyse binary microarray data (gene expression and SNPs) by invoking TM4 platform. It avoids: (i) the manual invocation of external tools (e.g. the Affymetrix Power

  5. Micro-Analyzer: automatic preprocessing of Affymetrix microarray data.

    PubMed

    Guzzi, Pietro Hiram; Cannataro, Mario

    2013-08-01

    A current trend in genomics is the investigation of the cell mechanism using different technologies, in order to explain the relationship among genes, molecular processes and diseases. For instance, the combined use of gene-expression arrays and genomic arrays has been demonstrated as an effective instrument in clinical practice. Consequently, in a single experiment different kind of microarrays may be used, resulting in the production of different types of binary data (images and textual raw data). The analysis of microarray data requires an initial preprocessing phase, that makes raw data suitable for use on existing analysis platforms, such as the TIGR M4 (TM4) Suite. An additional challenge to be faced by emerging data analysis platforms is the ability to treat in a combined way those different microarray formats coupled with clinical data. In fact, resulting integrated data may include both numerical and symbolic data (e.g. gene expression and SNPs regarding molecular data), as well as temporal data (e.g. the response to a drug, time to progression and survival rate), regarding clinical data. Raw data preprocessing is a crucial step in analysis but is often performed in a manual and error prone way using different software tools. Thus novel, platform independent, and possibly open source tools enabling the semi-automatic preprocessing and annotation of different microarray data are needed. The paper presents Micro-Analyzer (Microarray Analyzer), a cross-platform tool for the automatic normalization, summarization and annotation of Affymetrix gene expression and SNP binary data. It represents the evolution of the μ-CS tool, extending the preprocessing to SNP arrays that were not allowed in μ-CS. The Micro-Analyzer is provided as a Java standalone tool and enables users to read, preprocess and analyse binary microarray data (gene expression and SNPs) by invoking TM4 platform. It avoids: (i) the manual invocation of external tools (e.g. the Affymetrix Power

  6. Evaluation of genome coverage and fidelity of multiple displacement amplification from single cells by SNP array.

    PubMed

    Ling, Jiawei; Zhuang, Guanglun; Tazon-Vega, Barbara; Zhang, Chenhui; Cao, Baoqiang; Rosenwaks, Zev; Xu, Kangpu

    2009-11-01

    The scarce amount of DNA contained in a single cell is a limiting factor for clinical application of preimplantation genetic diagnosis mainly due to the risk of misdiagnosis caused by allele dropout and the difficulty in obtaining copy number variations in all 23 pairs of chromosomes. Multiple displacement amplification (MDA) has been reported to generate large quantity of products from small amount of templates. Here, we evaluated the fidelity of whole-genome amplification MDA from single or a few cells and determined the accuracy of chromosome copy number assessment on these MDA products using an Affymetrix 10K 2.0 SNP Mapping Array. An average coverage rate (86.2%) from single cells was obtained and the rates increased significantly when five or more cells were used as templates. Higher concordance for chromosome copy number from single cells could be achieved when the MDA amplified product was used as reference (93.1%) than when gDNA used as reference (82.8%). The present study indicates that satisfactory genome coverage can be obtained from single-cell MDA which may be used for studies where only a minute amount of genetic materials is available. Clinically, MDA coupled with SNP mapping array may provide a reliable and accurate method for chromosome copy number analysis and most likely for the detection of single-gene disorders as well. PMID:19671595

  7. VIZARD: analysis of Affymetrix Arabidopsis GeneChip data

    NASA Technical Reports Server (NTRS)

    Moseyko, Nick; Feldman, Lewis J.

    2002-01-01

    SUMMARY: The Affymetrix GeneChip Arabidopsis genome array has proved to be a very powerful tool for the analysis of gene expression in Arabidopsis thaliana, the most commonly studied plant model organism. VIZARD is a Java program created at the University of California, Berkeley, to facilitate analysis of Arabidopsis GeneChip data. It includes several integrated tools for filtering, sorting, clustering and visualization of gene expression data as well as tools for the discovery of regulatory motifs in upstream sequences. VIZARD also includes annotation and upstream sequence databases for the majority of genes represented on the Affymetrix Arabidopsis GeneChip array. AVAILABILITY: VIZARD is available free of charge for educational, research, and not-for-profit purposes, and can be downloaded at http://www.anm.f2s.com/research/vizard/ CONTACT: moseyko@uclink4.berkeley.edu.

  8. Affymetrix GeneChip microarray preprocessing for multivariate analyses.

    PubMed

    McCall, Matthew N; Almudevar, Anthony

    2012-09-01

    Affymetrix GeneChip microarrays are the most widely used high-throughput technology to measure gene expression, and a wide variety of preprocessing methods have been developed to transform probe intensities reported by a microarray scanner into gene expression estimates. There have been numerous comparisons of these preprocessing methods, focusing on the most common analyses-detection of differential expression and gene or sample clustering. Recently, more complex multivariate analyses, such as gene co-expression, differential co-expression, gene set analysis and network modeling, are becoming more common; however, the same preprocessing methods are typically applied. In this article, we examine the effect of preprocessing methods on some of these multivariate analyses and provide guidance to the user as to which methods are most appropriate.

  9. Practical performance evaluation of a 10k × 10k CCD for electron cryo-microscopy

    PubMed Central

    Bammes, Benjamin E.; Rochat, Ryan H.; Jakana, Joanita; Chiu, Wah

    2011-01-01

    Electron cryo-microscopy (cryo-EM) images are commonly collected using either charge-coupled devices (CCD) or photographic film. Both film and the current generation of 16 megapixel (4k × 4k) CCD cameras have yielded high-resolution structures. Yet, despite the many advantages of CCD cameras, more than two times as many structures of biological macromolecules have been published in recent years using photographic film. The continued preference to film, especially for subnanometer-resolution structures, may be partially influenced by the finer sampling and larger effective specimen imaging area offered by film. Large format digital cameras may finally allow them to overtake film as the preferred detector for cryo-EM. We have evaluated a 111-megapixel (10k × 10k) CCD camera with a 9 μm pixel size. The spectral signal-to-noise ratios of low dose images of carbon film indicate that this detector is capable of providing signal up to at least 2/5 Nyquist frequency potentially retrievable for 3-D reconstructions of biological specimens, resulting in more than double the effective specimen imaging area of existing 4k × 4k CCD cameras. We verified our estimates using frozen-hydrated ε15 bacteriophage as a biological test specimen with previously determined structure, yielding a ~7 Å resolution single particle reconstruction from only 80 CCD frames. Finally, we explored the limits of current CCD technology by comparing the performance of this detector to various CCD cameras used for recording data yielding subnanometer resolution cryo-EM structures submitted to the Electron Microscopy Data Bank (http://www.emdatabank.org/). PMID:21619932

  10. Oligonucleotide array outperforms SNP array on formalin-fixed paraffin-embedded clinical samples.

    PubMed

    Nasri, Soroush; Anjomshoaa, Ahmad; Song, Sarah; Guilford, Parry; McNoe, Les; Black, Michael; Phillips, Vicky; Reeve, Anthony; Humar, Bostjan

    2010-04-01

    Compromised quality of formalin-fixed paraffin-embedded (FFPE)-derived DNA has compounded the use of archival specimens for array-based genomic studies. Recent technological advances have led to first successes in this field; however, there is currently no general agreement on the most suitable platform for the array-based analysis of FFPE DNA. In this study, FFPE and matched fresh-frozen (FF) specimens were separately analyzed with Affymetrix single nucleotide polymorphism (SNP) 6.0 and Agilent 4x44K oligonucleotide arrays to compare the genomic profiles from the two tissue sources and to assess the relative performance of the two platforms on FFPE material. Genomic DNA was extracted from matched FFPE-FF pairs of normal intestinal epithelium from four patients and were applied to the SNP and oligonucleotide platforms according to the manufacturer-recommended protocols. On the Affymetrix platform, a substantial increase in apparent copy number alterations was observed in all FFPE tissues relative to their matched FF counterparts. In contrast, FFPE and matched FF genomic profiles obtained via the Agilent platform were very similar. Both the SNP and the oligonucleotide platform performed comparably on FF material. This study demonstrates that Agilent oligonucleotide array comparative genomic hybridization generates reliable results from FFPE extracted DNA, whereas the Affymetrix SNP-based array seems less suitable for the analysis of FFPE material.

  11. Construction of a versatile SNP array for pyramiding useful genes of rice.

    PubMed

    Kurokawa, Yusuke; Noda, Tomonori; Yamagata, Yoshiyuki; Angeles-Shim, Rosalyn; Sunohara, Hidehiko; Uehara, Kanako; Furuta, Tomoyuki; Nagai, Keisuke; Jena, Kshirod Kumar; Yasui, Hideshi; Yoshimura, Atsushi; Ashikari, Motoyuki; Doi, Kazuyuki

    2016-01-01

    DNA marker-assisted selection (MAS) has become an indispensable component of breeding. Single nucleotide polymorphisms (SNP) are the most frequent polymorphism in the rice genome. However, SNP markers are not readily employed in MAS because of limitations in genotyping platforms. Here the authors report a Golden Gate SNP array that targets specific genes controlling yield-related traits and biotic stress resistance in rice. As a first step, the SNP genotypes were surveyed in 31 parental varieties using the Affymetrix Rice 44K SNP microarray. The haplotype information for 16 target genes was then converted to the Golden Gate platform with 143-plex markers. Haplotypes for the 14 useful allele are unique and can discriminate among all other varieties. The genotyping consistency between the Affymetrix microarray and the Golden Gate array was 92.8%, and the accuracy of the Golden Gate array was confirmed in 3 F2 segregating populations. The concept of the haplotype-based selection by using the constructed SNP array was proofed. PMID:26566831

  12. SNP-VISTA

    SciTech Connect

    Shah, Nameeta; Teplitsky, Michael; Minovitsky, Simon; Dubchak, Inna

    2005-11-07

    SNP-VISTA aids in analyses of the following types of data: A. Large-scale re-sequence data of disease-related genes for discovery of associated and/or causative alleles (GeneSNP-VISTA). B. Massive amounts of ecogenomics data for studying homologous recombination in microbial populations (EcoSNP-VISTA). The main features and capabilities of SNP-VISTA are: 1) Mapping of SNPs to gene structure; 2) classification of SNPs, based on their location in the gene, frequency of occurrence in samples and allele composition; 3) clustering, based on user-defined subsets of SNPs, highlighting haplotypes as well as recombinant sequences; 4) integration of protein conservation visualization; and 5) display of automatically calculated recombination points that are user-editable. The main strength of SNP-VISTA is its graphical interface and use of visual representations, which support interactive exploration and hence better understanding of large-scale SNPs data.

  13. Power measurements on SJ-10 kE-R windmill

    SciTech Connect

    Rasmussen, F.

    1980-03-01

    This report contains results from measurements of power output for a 10 kW, 5.65-m diameter windrose. The improvements of the Windmill during the tests are described and the yearly energy output is computed for the windmill situated at different wind locations.

  14. SNP ID-info: SNP ID searching and visualization platform.

    PubMed

    Yang, Cheng-Hong; Chuang, Li-Yeh; Cheng, Yu-Huei; Wen, Cheng-Hao; Chang, Phei-Lang; Chang, Hsueh-Wei

    2008-09-01

    Many association studies provide the relationship between single nucleotide polymorphisms (SNPs), diseases and cancers, without giving a SNP ID, however. Here, we developed the SNP ID-info freeware to provide the SNP IDs within inputting genetic and physical information of genomes. The program provides an "SNP-ePCR" function to generate the full-sequence using primers and template inputs. In "SNPosition," sequence from SNP-ePCR or direct input is fed to match the SNP IDs from SNP fasta-sequence. In "SNP search" and "SNP fasta" function, information of SNPs within the cytogenetic band, contig position, and keyword input are acceptable. Finally, the SNP ID neighboring environment for inputs is completely visualized in the order of contig position and marked with SNP and flanking hits. The SNP identification problems inherent in NCBI SNP BLAST are also avoided. In conclusion, the SNP ID-info provides a visualized SNP ID environment for multiple inputs and assists systematic SNP association studies. The server and user manual are available at http://bio.kuas.edu.tw/snpid-info.

  15. The Genome 10K Project: a way forward.

    PubMed

    Koepfli, Klaus-Peter; Paten, Benedict; O'Brien, Stephen J

    2015-01-01

    The Genome 10K Project was established in 2009 by a consortium of biologists and genome scientists determined to facilitate the sequencing and analysis of the complete genomes of 10,000 vertebrate species. Since then the number of selected and initiated species has risen from ∼26 to 277 sequenced or ongoing with funding, an approximately tenfold increase in five years. Here we summarize the advances and commitments that have occurred by mid-2014 and outline the achievements and present challenges of reaching the 10,000-species goal. We summarize the status of known vertebrate genome projects, recommend standards for pronouncing a genome as sequenced or completed, and provide our present and future vision of the landscape of Genome 10K. The endeavor is ambitious, bold, expensive, and uncertain, but together the Genome 10K Consortium of Scientists and the worldwide genomics community are moving toward their goal of delivering to the coming generation the gift of genome empowerment for many vertebrate species.

  16. Development of 10kW SOFC module

    SciTech Connect

    Hisatome, N.; Nagata, K.; Kakigami, S.

    1996-12-31

    Mitsubishi Heavy industries, Ltd. (MHI) has been developing tubular type Solid Oxide Fuel Cells (SOFC) since 1984. A 1 kW module of SOFC has been continuously operated for 3,000 hours with 2 scheduled thermal cycles at Electric Power Development Co., Inc. (EPDC) Wakamatsu Power Station in 1993. We have obtained of 34% (HHV as H{sub 2}) module efficiency and deterioration rate of 2% Per 1,000 hours in this field test. As for next step, we have developed 10 kW module in 1995. The 10 kW module has been operated for 5,000 hours continuously. This module does not need heating support to maintain the operation temperature, and the module efficiency was 34% (HHV as H{sub 2}). On the other hand, we have started developing the technology of pressurized SOFC. In 1996, pressurized MW module has been tested at MHI Nagasaki Shipyard & Machinery, Works. We are now planning the development of pressurized 10 kW module.

  17. Ascertainment Biases in SNP Chips Affect Measures of Population Divergence

    PubMed Central

    Albrechtsen, Anders; Nielsen, Finn Cilius; Nielsen, Rasmus

    2010-01-01

    Chip-based high-throughput genotyping has facilitated genome-wide studies of genetic diversity. Many studies have utilized these large data sets to make inferences about the demographic history of human populations using measures of genetic differentiation such as FST or principal component analyses. However, the single nucleotide polymorphism (SNP) chip data suffer from ascertainment biases caused by the SNP discovery process in which a small number of individuals from selected populations are used as discovery panels. In this study, we investigate the effect of the ascertainment bias on inferences regarding genetic differentiation among populations in one of the common genome-wide genotyping platforms. We generate SNP genotyping data for individuals that previously have been subject to partial genome-wide Sanger sequencing and compare inferences based on genotyping data to inferences based on direct sequencing. In addition, we also analyze publicly available genome-wide data. We demonstrate that the ascertainment biases will distort measures of human diversity and possibly change conclusions drawn from these measures in some times unexpected ways. We also show that details of the genotyping calling algorithms can have a surprisingly large effect on population genetic inferences. We not only present a correction of the spectrum for the widely used Affymetrix SNP chips but also show that such corrections are difficult to generalize among studies. PMID:20558595

  18. Allelic imbalance analysis by high-density single-nucleotide polymorphic allele (SNP) array with whole genome amplified DNA

    PubMed Central

    Wong, Kwong-Kwok; Tsang, Yvonne T. M.; Shen, Jianhe; Cheng, Rita S.; Chang, Yi-Mieng; Man, Tsz-Kwong; Lau, Ching C.

    2004-01-01

    Besides their use in mRNA expression profiling, oligonucleotide microarrays have also been applied to single-nucleotide polymorphism (SNP) and loss of heterozygosity (LOH) or allelic imbalance studies. In this report, we evaluate the reliability of using whole genome amplified DNA for analysis with an oligonucleotide microarray containing 11 560 SNPs to detect allelic imbalance and chromosomal copy number abnormalities. Whole genome SNP analyses were performed with DNA extracted from osteosarcoma tissues and patient-matched blood. SNP calls were then generated by Affymetrix® GeneChip® DNA Analysis Software. In two osteosarcoma cases, using unamplified DNA, we identified 793 and 1070 SNP loci with allelic imbalance, respectively. In a parallel experiment with amplified DNA, 78% and 83% of these SNP loci with allelic imbalance was detected. The average false-positive rate is 13.8%. Furthermore, using the Affymetrix® GeneChip® Chromosome Copy Number Tool to analyze the SNP array data, we were able to detect identical chromosomal regions with gain or loss in both amplified and unamplified DNA at cytoband resolution. PMID:15148342

  19. The 10 kW power electronics for hydrogen arcjets

    NASA Technical Reports Server (NTRS)

    Hamley, John A.; Pinero, Luis R.; Hill, Gerald M.

    1992-01-01

    A combination of emerging mission considerations such as 'launch on schedule', resource limitations, and the development of higher power spacecraft busses has resulted in renewed interest in high power hydrogen arcjet systems with specific impulses greater than 1000 s for Earth-space orbit transfer and maneuver applications. Solar electric propulsion systems with about 10 kW of power appear to offer payload benefits at acceptable trip times. This work outlines the design and development of 10 kW hydrogen arcjet power electronics and results of arcjet integration testing. The power electronics incorporated a full bridge switching topology similar to that employed in state of the art 5 kW power electronics, and the output filter included an output current averaging inductor with an integral pulse generation winding for arcjet ignition. Phase shifted, pulse width modulation with current mode control was used to regulate the current delivered to arcjet, and a low inductance power stage minimized switching transients. Hybrid power Metal Oxide Semiconductor Field Effect Transistors were used to minimize conduction losses. Switching losses were minimized using a fast response, optically isolated, totem-pole gate drive circuit. The input bus voltage for the unit was 150 V, with a maximum output voltage of 225 V. The switching frequency of 20 kHz was a compromise between mass savings and higher efficiency. Power conversion efficiencies in excess of 0.94 were demonstrated, along with steady state load current regulation of 1 percent. The power electronics were successfully integrated with a 10 kW laboratory hydrogen arcjet, and reliable, nondestructive starts and transitions to steady state operation were demonstrated. The estimated specific mass for a flight packaged unit was 2 kg/kW.

  20. SNP-VISTA

    2005-11-07

    SNP-VISTA aids in analyses of the following types of data: A. Large-scale re-sequence data of disease-related genes for discovery of associated and/or causative alleles (GeneSNP-VISTA). B. Massive amounts of ecogenomics data for studying homologous recombination in microbial populations (EcoSNP-VISTA). The main features and capabilities of SNP-VISTA are: 1) Mapping of SNPs to gene structure; 2) classification of SNPs, based on their location in the gene, frequency of occurrence in samples and allele composition; 3) clustering,more » based on user-defined subsets of SNPs, highlighting haplotypes as well as recombinant sequences; 4) integration of protein conservation visualization; and 5) display of automatically calculated recombination points that are user-editable. The main strength of SNP-VISTA is its graphical interface and use of visual representations, which support interactive exploration and hence better understanding of large-scale SNPs data.« less

  1. MADS+: discovery of differential splicing events from Affymetrix exon junction array data

    PubMed Central

    Shen, Shihao; Warzecha, Claude C.; Carstens, Russ P.; Xing, Yi

    2010-01-01

    Motivation: The Affymetrix Human Exon Junction Array is a newly designed high-density exon-sensitive microarray for global analysis of alternative splicing. Contrary to the Affymetrix exon 1.0 array, which only contains four probes per exon and no probes for exon–exon junctions, this new junction array averages eight probes per probeset targeting all exons and exon–exon junctions observed in the human mRNA/EST transcripts, representing a significant increase in the probe density for alternative splicing events. Here, we present MADS+, a computational pipeline to detect differential splicing events from the Affymetrix exon junction array data. For each alternative splicing event, MADS+ evaluates the signals of probes targeting competing transcript isoforms to identify exons or splice sites with different levels of transcript inclusion between two sample groups. MADS+ is used routinely in our analysis of Affymetrix exon junction arrays and has a high accuracy in detecting differential splicing events. For example, in a study of the novel epithelial-specific splicing regulator ESRP1, MADS+ detects hundreds of exons whose inclusion levels are dependent on ESRP1, with a RT-PCR validation rate of 88.5% (153 validated out of 173 tested). Availability: MADS+ scripts, documentations and annotation files are available at http://www.medicine.uiowa.edu/Labs/Xing/MADSplus/. Contact: yi-xing@uiowa.edu PMID:19933160

  2. Diamond's elastic stiffnesses from 322 K to 10 K

    NASA Astrophysics Data System (ADS)

    Migliori, Albert; Ledbetter, Hassel; Leisure, Robert G.; Pantea, C.; Betts, J. B.

    2008-09-01

    Using resonant-ultrasound spectroscopy, we measured diamond's monocrystal elastic-stiffness coefficients C11, C12, and C44, between 322 and 10 K. Changes are small and smooth: The bulk modulus B =(C11+2C12)/3 increases about 1 part in 1000, describable by a quasiharmonic Einstein-oscillator model. Zero-temperature Cij correspond to a 2244-K Debye characteristic temperature. Using a low-temperature form of the Grüneisen-Debye model, we calculated an overall thermodynamic Grüneisen parameter of γ =1.26; using a high-temperature form we calculated 0.71; the lattice specific heat yields γ =1.10.

  3. Preliminary Evaluation of a 10 kW Hall Thruster

    NASA Technical Reports Server (NTRS)

    Jankovsky, Robert S.; McLean, Chris; McVey, John

    1999-01-01

    A 10 kW Hall thruster was characterized over a range of discharge voltages from 300-500 V and a range of discharge currents from 15-23 A. This corresponds to power levels from a low of 4.6 kW to a high of 10.7 kW. Over this range of discharge powers, thrust varied from 278 mN to 524 mN, specific impulse ranged from 1644 to 2392 seconds, and efficiency peaked at approximately 59%. A continuous 40 hour test was also undertaken in an attempt to gain insight with regard to long term operation of the engine. For this portion of the testing the thruster was operated at a discharge voltage of 500 V and a discharge current of 20 A. Steady-state temperatures were achieved after 3-5 hrs and very little variation in performance was detected.

  4. A 10 kW IRFEL Design for Jefferson Lab

    SciTech Connect

    R. Walker; R. Evans; George Biallas; James Boyce; David Douglas; H. Dylla; Kevin Jordan; Geoffrey Krafft; Rui Li; John Mammosser; George Neil; H. Phillips; Joseph Preble; Byung Yunn; Timothy Siggins; Nikolitsa Merminga; Stephen Benson; Michelle D. Shinn; Joseph Gubeli; Albert Grippo

    2001-07-01

    Recent work at Jefferson Lab has demonstrated the viability of same-cell energy recovery as a basis for a high average power free-electron laser (FEL) [1]. We are now extending this technique to lase at average powers in excess of 10 kW in the infrared. This upgrade will also produce over 1 kW in the UV and generate high brightness Thomson back-scattered X-rays. The power increase will be achieved by increasing the electron beam energy by a factor of four, and the beam current and the FEL design efficiency by a factor of two. Utilization of a near-concentric optical cavity is enabled by the use of very low loss state-of-the-art coatings. The FEL will be placed in the return leg of the electron beam transport, giving a machine footprint quite similar to that of the existing 1 kW IR device. Some features of the Upgrade are straightforward extensions of those in the present 1kW design; others break new ground and present new challenges. These will be described. The required electron beam parameters and the laser performance estimates will be summarized. Changes required in the electron beam transport will be outlined and the optical cavity design briefly reviewed.

  5. Analysis of discordant Affymetrix probesets casts serious doubt on idea of microarray data reutilization

    PubMed Central

    2014-01-01

    Background Affymetrix microarray technology allows one to investigate expression of thousands of genes simultaneously upon a variety of conditions. In a popular U133A microarray platform, the expression of 37% of genes is measured by more than one probeset. The discordant expression observed for two different probesets that match the same gene is a widespread phenomenon which is usually underestimated, ignored or disregarded. Results Here we evaluate the prevalence of discordant expression in data collected using Affymetrix HG-U133A microarray platform. In U133A, about 30% of genes annotated by two different probesets demonstrate a substantial correlation between independently measured expression values. To our surprise, sorting the probesets according to the nature of the discrepancy in their expression levels allowed the classification of the respective genes according to their fundamental functional properties, including observed enrichment by tissue-specific transcripts and alternatively spliced variants. On another hand, an absence of discrepancies in probesets that simultaneously match several different genes allowed us to pinpoint non-expressed pseudogenes and gene groups with highly correlated expression patterns. Nevertheless, in many cases, the nature of discordant expression of two probesets that match the same transcript remains unexplained. It is possible that these probesets report differently regulated sets of transcripts, or, in best case scenario, two different sets of transcripts that represent the same gene. Conclusion The majority of absolute gene expression values collected using Affymetrix microarrays may not be suitable for typical interpretative downstream analysis. PMID:25563078

  6. AffyTrees: facilitating comparative analysis of Affymetrix plant microarray chips.

    PubMed

    Frickey, Tancred; Benedito, Vagner Augusto; Udvardi, Michael; Weiller, Georg

    2008-02-01

    Microarrays measure the expression of large numbers of genes simultaneously and can be used to delve into interaction networks involving many genes at a time. However, it is often difficult to decide to what extent knowledge about the expression of genes gleaned in one model organism can be transferred to other species. This can be examined either by measuring the expression of genes of interest under comparable experimental conditions in other species, or by gathering the necessary data from comparable microarray experiments. However, it is essential to know which genes to compare between the organisms. To facilitate comparison of expression data across different species, we have implemented a Web-based software tool that provides information about sequence orthologs across a range of Affymetrix microarray chips. AffyTrees provides a quick and easy way of assigning which probe sets on different Affymetrix chips measure the expression of orthologous genes. Even in cases where gene or genome duplications have complicated the assignment, groups of comparable probe sets can be identified. The phylogenetic trees provide a resource that can be used to improve sequence annotation and detect biases in the sequence complement of Affymetrix chips. Being able to identify sequence orthologs and recognize biases in the sequence complement of chips is necessary for reliable cross-species microarray comparison. As the amount of work required to generate a single phylogeny in a nonautomated manner is considerable, AffyTrees can greatly reduce the workload for scientists interested in large-scale cross-species comparisons.

  7. Robust demographic inference from genomic and SNP data.

    PubMed

    Excoffier, Laurent; Dupanloup, Isabelle; Huerta-Sánchez, Emilia; Sousa, Vitor C; Foll, Matthieu

    2013-10-01

    We introduce a flexible and robust simulation-based framework to infer demographic parameters from the site frequency spectrum (SFS) computed on large genomic datasets. We show that our composite-likelihood approach allows one to study evolutionary models of arbitrary complexity, which cannot be tackled by other current likelihood-based methods. For simple scenarios, our approach compares favorably in terms of accuracy and speed with ∂a∂i, the current reference in the field, while showing better convergence properties for complex models. We first apply our methodology to non-coding genomic SNP data from four human populations. To infer their demographic history, we compare neutral evolutionary models of increasing complexity, including unsampled populations. We further show the versatility of our framework by extending it to the inference of demographic parameters from SNP chips with known ascertainment, such as that recently released by Affymetrix to study human origins. Whereas previous ways of handling ascertained SNPs were either restricted to a single population or only allowed the inference of divergence time between a pair of populations, our framework can correctly infer parameters of more complex models including the divergence of several populations, bottlenecks and migration. We apply this approach to the reconstruction of African demography using two distinct ascertained human SNP panels studied under two evolutionary models. The two SNP panels lead to globally very similar estimates and confidence intervals, and suggest an ancient divergence (>110 Ky) between Yoruba and San populations. Our methodology appears well suited to the study of complex scenarios from large genomic data sets.

  8. Robust Demographic Inference from Genomic and SNP Data

    PubMed Central

    Excoffier, Laurent; Dupanloup, Isabelle; Huerta-Sánchez, Emilia; Sousa, Vitor C.; Foll, Matthieu

    2013-01-01

    We introduce a flexible and robust simulation-based framework to infer demographic parameters from the site frequency spectrum (SFS) computed on large genomic datasets. We show that our composite-likelihood approach allows one to study evolutionary models of arbitrary complexity, which cannot be tackled by other current likelihood-based methods. For simple scenarios, our approach compares favorably in terms of accuracy and speed with , the current reference in the field, while showing better convergence properties for complex models. We first apply our methodology to non-coding genomic SNP data from four human populations. To infer their demographic history, we compare neutral evolutionary models of increasing complexity, including unsampled populations. We further show the versatility of our framework by extending it to the inference of demographic parameters from SNP chips with known ascertainment, such as that recently released by Affymetrix to study human origins. Whereas previous ways of handling ascertained SNPs were either restricted to a single population or only allowed the inference of divergence time between a pair of populations, our framework can correctly infer parameters of more complex models including the divergence of several populations, bottlenecks and migration. We apply this approach to the reconstruction of African demography using two distinct ascertained human SNP panels studied under two evolutionary models. The two SNP panels lead to globally very similar estimates and confidence intervals, and suggest an ancient divergence (>110 Ky) between Yoruba and San populations. Our methodology appears well suited to the study of complex scenarios from large genomic data sets. PMID:24204310

  9. 10 kW SOFC Power System Commercialization

    SciTech Connect

    Dan Norrick; Brad Palmer; Charles Vesely; Eric Barringer; John Budge; Cris DeBellis; Rich Goettler; Milind Kantak; Steve Kung; Zhien Liu; Tom Morris; Keith Rackers; Gary Roman; Greg Rush; Liang Xue

    2006-02-01

    Cummins Power Generation (CPG) as the prime contractor and SOFCo-EFS Holdings LLC (SOFCo), as their subcontractor, teamed under the Solid-state Energy Conversion Alliance (SECA) program to develop 3-10kW solid oxide fuel cell systems for use in recreational vehicles, commercial work trucks and stand-by telecommunications applications. The program goal is demonstration of power systems that meet commercial performance requirements and can be produced in volume at a cost of $400/kW. This report summarizes the team's activities during the seventh six-month period (July-December 2005) of the four-year Phase I effort. While there has been significant progress in the development of the SOFC subsystems that can support meeting the program Phase 1 goals, the SOFCo ceramic stack technology has progressed significantly slower than plan and CPG consider it unlikely that the systemic problems encountered will be overcome in the near term. SOFCo has struggled with a series of problems associated with inconsistent manufacturing, inadequate cell performance, and the achievement of consistent, durable, low resistance inter-cell connections with reduced or no precious materials. A myriad of factors have contributed to these problems, but the fact remains that progress has not kept pace with the SECA program. A contributing factor in SOFCo's technical difficulties is attributed to their significantly below plan industry cost share spending over the last four years. This has resulted in a much smaller SOFC stack development program, has contributed to SOFCo not being able to aggressively resolve core issues, and clouds their ability to continue into a commercialization phase. In view of this situation, CPG has conducted an independent assessment of the state-of-the-art in planar SOFC's stacks and have concluded that alternative technology exists offering the specific performance, durability, and low cost needed to meet the SECA objectives. We have further concluded that there is

  10. Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel.

    PubMed

    Huang, Jie; Howie, Bryan; McCarthy, Shane; Memari, Yasin; Walter, Klaudia; Min, Josine L; Danecek, Petr; Malerba, Giovanni; Trabetti, Elisabetta; Zheng, Hou-Feng; Gambaro, Giovanni; Richards, J Brent; Durbin, Richard; Timpson, Nicholas J; Marchini, Jonathan; Soranzo, Nicole

    2015-01-01

    Imputing genotypes from reference panels created by whole-genome sequencing (WGS) provides a cost-effective strategy for augmenting the single-nucleotide polymorphism (SNP) content of genome-wide arrays. The UK10K Cohorts project has generated a data set of 3,781 whole genomes sequenced at low depth (average 7x), aiming to exhaustively characterize genetic variation down to 0.1% minor allele frequency in the British population. Here we demonstrate the value of this resource for improving imputation accuracy at rare and low-frequency variants in both a UK and an Italian population. We show that large increases in imputation accuracy can be achieved by re-phasing WGS reference panels after initial genotype calling. We also present a method for combining WGS panels to improve variant coverage and downstream imputation accuracy, which we illustrate by integrating 7,562 WGS haplotypes from the UK10K project with 2,184 haplotypes from the 1000 Genomes Project. Finally, we introduce a novel approximation that maintains speed without sacrificing imputation accuracy for rare variants.

  11. 10kW SOFC POWER SYSTEM COMMERCIALIZATION

    SciTech Connect

    Dan Norrick; Charles Vesely; Todd Romine; Brad Palmer; Greg Rush; Eric Barringer; Milind Kantak; Cris DeBellis

    2003-02-01

    Participants in the SECA 10 kW SOFC Power System Commercialization project include Cummins Power Generation (CPG), the power generation arm of Cummins, Inc., SOFCo-EFS Holdings, LLC (formerly McDermott Technology, Inc.), the fuel cell and fuel processing research and development arm of McDermott International Inc., M/A-COM, the Multi-Layer Ceramics (MLC) processing and manufacturing arm of Tyco Electronics, and Ceramatec, a materials technology development company. CPG functions in the role of prime contractor and system integrator. SOFCo-EFS is responsible for the design and development of the hot box assembly, including the SOFC stack(s), heat exchanger(s), manifolding, and fuel reformer. M/A-COM and SOFCo-EFS are jointly responsible for development of the MLC manufacturing processes, and Ceramatec provides technical support in materials development. In October 2002, McDermott announced its intention to cease operations at McDermott Technology, Inc. (MTI) as of December 31, 2002. This decision was precipitated by several factors, including the announced tentative settlement of the B&W Bankruptcy which would result in all of the equity of B&W being conveyed to a trust, thereby eliminating McDermott's interest in the company, and the desire to create a separate fuel cell entity to facilitate its commercial development. The new fuel cell entity is named SOFCo-EFS Holdings, LLC. All of McDermott's solid oxide fuel cell and fuel processing work will be conducted by SOFCo-EFS, using personnel previously engaged in that work. SOFCo-EFS will continue to be located in the Alliance, OH facility and use the existing infrastructure and test facilities for its activities. While the effort needed to accomplish this reorganization has detracted somewhat from SOFCo's efficiency during the fourth quarter, we believe the improved focus on the core fuel cell and fuel reformation resulting from the reorganization will have a positive impact on the SECA project in the long run. The

  12. Using probe secondary structure information to enhance Affymetrix GeneChip background estimates

    PubMed Central

    Gharaibeh, Raad Z.; Fodor, Anthony A.; Gibas, Cynthia J.

    2007-01-01

    High-density short oligonucleotide microarrays are a primary research tool for assessing global gene expression. Background noise on microarrays comprises a significant portion of the measured raw data. A number of statistical techniques have been developed to correct for this background noise. Here, we demonstrate that probe minimum folding energy and structure can be used to enhance a previously existing model for background noise correction. We estimate that probe secondary structure accounts for up to 3% of all variation on Affymetrix microarrays. PMID:17387043

  13. Fine-scaled human genetic structure revealed by SNP microarrays.

    PubMed

    Xing, Jinchuan; Watkins, W Scott; Witherspoon, David J; Zhang, Yuhua; Guthery, Stephen L; Thara, Rangaswamy; Mowry, Bryan J; Bulayeva, Kazima; Weiss, Robert B; Jorde, Lynn B

    2009-05-01

    We report an analysis of more than 240,000 loci genotyped using the Affymetrix SNP microarray in 554 individuals from 27 worldwide populations in Africa, Asia, and Europe. To provide a more extensive and complete sampling of human genetic variation, we have included caste and tribal samples from two states in South India, Daghestanis from eastern Europe, and the Iban from Malaysia. Consistent with observations made by Charles Darwin, our results highlight shared variation among human populations and demonstrate that much genetic variation is geographically continuous. At the same time, principal components analyses reveal discernible genetic differentiation among almost all identified populations in our sample, and in most cases, individuals can be clearly assigned to defined populations on the basis of SNP genotypes. All individuals are accurately classified into continental groups using a model-based clustering algorithm, but between closely related populations, genetic and self-classifications conflict for some individuals. The 250K data permitted high-level resolution of genetic variation among Indian caste and tribal populations and between highland and lowland Daghestani populations. In particular, upper-caste individuals from Tamil Nadu and Andhra Pradesh form one defined group, lower-caste individuals from these two states form another, and the tribal Irula samples form a third. Our results emphasize the correlation of genetic and geographic distances and highlight other elements, including social factors that have contributed to population structure. PMID:19411602

  14. Fine-scaled human genetic structure revealed by SNP microarrays.

    PubMed

    Xing, Jinchuan; Watkins, W Scott; Witherspoon, David J; Zhang, Yuhua; Guthery, Stephen L; Thara, Rangaswamy; Mowry, Bryan J; Bulayeva, Kazima; Weiss, Robert B; Jorde, Lynn B

    2009-05-01

    We report an analysis of more than 240,000 loci genotyped using the Affymetrix SNP microarray in 554 individuals from 27 worldwide populations in Africa, Asia, and Europe. To provide a more extensive and complete sampling of human genetic variation, we have included caste and tribal samples from two states in South India, Daghestanis from eastern Europe, and the Iban from Malaysia. Consistent with observations made by Charles Darwin, our results highlight shared variation among human populations and demonstrate that much genetic variation is geographically continuous. At the same time, principal components analyses reveal discernible genetic differentiation among almost all identified populations in our sample, and in most cases, individuals can be clearly assigned to defined populations on the basis of SNP genotypes. All individuals are accurately classified into continental groups using a model-based clustering algorithm, but between closely related populations, genetic and self-classifications conflict for some individuals. The 250K data permitted high-level resolution of genetic variation among Indian caste and tribal populations and between highland and lowland Daghestani populations. In particular, upper-caste individuals from Tamil Nadu and Andhra Pradesh form one defined group, lower-caste individuals from these two states form another, and the tribal Irula samples form a third. Our results emphasize the correlation of genetic and geographic distances and highlight other elements, including social factors that have contributed to population structure.

  15. Improvements to previous algorithms to predict gene structure and isoform concentrations using Affymetrix Exon arrays

    PubMed Central

    2010-01-01

    Background Exon arrays provide a way to measure the expression of different isoforms of genes in an organism. Most of the procedures to deal with these arrays are focused on gene expression or on exon expression. Although the only biological analytes that can be properly assigned a concentration are transcripts, there are very few algorithms that focus on them. The reason is that previously developed summarization methods do not work well if applied to transcripts. In addition, gene structure prediction, i.e., the correspondence between probes and novel isoforms, is a field which is still unexplored. Results We have modified and adapted a previous algorithm to take advantage of the special characteristics of the Affymetrix exon arrays. The structure and concentration of transcripts -some of them possibly unknown- in microarray experiments were predicted using this algorithm. Simulations showed that the suggested modifications improved both specificity (SP) and sensitivity (ST) of the predictions. The algorithm was also applied to different real datasets showing its effectiveness and the concordance with PCR validated results. Conclusions The proposed algorithm shows a substantial improvement in the performance over the previous version. This improvement is mainly due to the exploitation of the redundancy of the Affymetrix exon arrays. An R-Package of SPACE with the updated algorithms have been developed and is freely available. PMID:21110835

  16. Study on the antiendotoxin action of Pulsatillae Decoction using an Affymetrix rat genome array.

    PubMed

    Hu, Yiyi; Chen, Xi; Lin, Hong; Hu, Yuanliang; Mu, Xiang

    2009-01-01

    A high-throughput and efficient Affymetrix rat genome array was used to investigate the pharmacological mechanism of the traditional Chinese medicine, Pulsatillae Decoction (PD), used for the treatment of diseases induced by lipopolysaccharide (LPS). Rat intestinal microvascular endothelial cells (RIMECs) were challenged with 1mug/ml LPS for 3h, and then treated with PD at a concentration of 1mg/ml for 24h. Total RNA from each treatment group was extracted from cultured RIMECs for detection by the Affymetrix Rat Genome 230 2.0 Array. The results showed that 36 genes were upregulated and 33 genes were downregulated in the LPS group vs. the blank control group; 566 genes were upregulated and 12 genes were downregulated in the PD-treated group vs. the LPS group; and 93 genes were upregulated and 29 genes were downregulated in the PD-treated group vs. the blank control group. The analysis of these data suggested that PD specifically and effectively reduce damage induced by LPS, and improved physiological and biochemical responses to counteract the effects of LPS.

  17. Evaluation of the Affymetrix CytoScan® Dx Assay for Developmental Delay

    PubMed Central

    Webb, Bryn D.; Scharf, Rebecca J.; Spear, Emily A.; Edelmann, Lisa J.; Stroustrup, Annemarie

    2015-01-01

    The goal of molecular cytogenetic testing for children presenting with developmental delay is to identify or exclude genetic abnormalities that are associated with cognitive, behavioral, and/or motor symptoms. Until 2010, chromosome analysis was the standard first-line genetic screening test for evaluation of patients with developmental delay when a specific syndrome was not suspected. In 2010, The American College of Medical Genetics and several other groups recommended chromosomal microarray (CMA) as the first-line test in children with developmental delays, multiple congenital anomalies, and/or autism. This test is able to detect regions of genomic imbalances at a much finer resolution than G-banded karyotyping. Until recently, no CMA testing had been approved by the United States Food and Drug Administration (FDA). This review will focus on the use of the Affymetrix CytoScan® Dx Assay, the first CMA to receive FDA approval for the genetic evaluation of individuals with developmental delay. PMID:25350348

  18. MAAMD: a workflow to standardize meta-analyses and comparison of affymetrix microarray data

    PubMed Central

    2014-01-01

    Background Mandatory deposit of raw microarray data files for public access, prior to study publication, provides significant opportunities to conduct new bioinformatics analyses within and across multiple datasets. Analysis of raw microarray data files (e.g. Affymetrix CEL files) can be time consuming, complex, and requires fundamental computational and bioinformatics skills. The development of analytical workflows to automate these tasks simplifies the processing of, improves the efficiency of, and serves to standardize multiple and sequential analyses. Once installed, workflows facilitate the tedious steps required to run rapid intra- and inter-dataset comparisons. Results We developed a workflow to facilitate and standardize Meta-Analysis of Affymetrix Microarray Data analysis (MAAMD) in Kepler. Two freely available stand-alone software tools, R and AltAnalyze were embedded in MAAMD. The inputs of MAAMD are user-editable csv files, which contain sample information and parameters describing the locations of input files and required tools. MAAMD was tested by analyzing 4 different GEO datasets from mice and drosophila. MAAMD automates data downloading, data organization, data quality control assesment, differential gene expression analysis, clustering analysis, pathway visualization, gene-set enrichment analysis, and cross-species orthologous-gene comparisons. MAAMD was utilized to identify gene orthologues responding to hypoxia or hyperoxia in both mice and drosophila. The entire set of analyses for 4 datasets (34 total microarrays) finished in ~ one hour. Conclusions MAAMD saves time, minimizes the required computer skills, and offers a standardized procedure for users to analyze microarray datasets and make new intra- and inter-dataset comparisons. PMID:24621103

  19. SNP-VISTA: An interactive SNP visualization tool

    PubMed Central

    Shah, Nameeta; Teplitsky, Michael V; Minovitsky, Simon; Pennacchio, Len A; Hugenholtz, Philip; Hamann, Bernd; Dubchak, Inna L

    2005-01-01

    Background Recent advances in sequencing technologies promise to provide a better understanding of the genetics of human disease as well as the evolution of microbial populations. Single Nucleotide Polymorphisms (SNPs) are established genetic markers that aid in the identification of loci affecting quantitative traits and/or disease in a wide variety of eukaryotic species. With today's technological capabilities, it has become possible to re-sequence a large set of appropriate candidate genes in individuals with a given disease in an attempt to identify causative mutations. In addition, SNPs have been used extensively in efforts to study the evolution of microbial populations, and the recent application of random shotgun sequencing to environmental samples enables more extensive SNP analysis of co-occurring and co-evolving microbial populations. The program is available at [1]. Results We have developed and present two modifications of an interactive visualization tool, SNP-VISTA, to aid in the analyses of the following types of data: A. Large-scale re-sequence data of disease-related genes for discovery of associated and/or causative alleles (GeneSNP-VISTA). B. Massive amounts of ecogenomics data for studying homologous recombination in microbial populations (EcoSNP-VISTA). The main features and capabilities of SNP-VISTA are: 1) mapping of SNPs to gene structure; 2) classification of SNPs, based on their location in the gene, frequency of occurrence in samples and allele composition; 3) clustering, based on user-defined subsets of SNPs, highlighting haplotypes as well as recombinant sequences; 4) integration of protein evolutionary conservation visualization; and 5) display of automatically calculated recombination points that are user-editable. Conclusion The main strength of SNP-VISTA is its graphical interface and use of visual representations, which support interactive exploration and hence better understanding of large-scale SNP data by the user. PMID

  20. Heat loss analysis of a 10 kA warm dielectric HTS DC cable

    NASA Astrophysics Data System (ADS)

    Dai, Shaotao; Xiao, Liye; Teng, Yuping; Song, Naihao; Gao, Zhiyuan; Zhu, Zhiqing; Liang, Xueming; Cao, Zhicheng; Zhang, Dong; Ma, Tao; Zhang, Hongen; Lin, Liangzhen

    2014-09-01

    A 10 kA/360 m warm-dielectric high-temperature superconducting direct current (DC) power cable system (10 kA cable), supported jointly the Chinese government and industrial enterprise, was developed and has been operating as a branch circuit to transmit power for a 320 kA aluminum electrolyzing production line for more than 10 months at an industrial plant in central China. Both the 10 kA cable and its supporting system of the cable system are introduced. The cryogenic system for the 10 kA cable adopts closed loop and the sub-cooled liquid nitrogen is forced to flow inside by a pump. The design of corrugated cryogenic envelope pipe is modularized and every independent module has two standardized joints, which makes it easy to integrate with the other pipes and the terminations. The heat loss sources and the structure including both the termination and the cryogenic envelope pipe of the 10 kA cable are discussed. The total heat loss of the 10 kA cable excluding the loss of cryogenic pipe for liquid nitrogen backward flowing is designed to be less than 1698 W at 10 kA, and the heat loss was compared and discussed with that of the aluminum bar. The field test and commissioning of the cable show that the 10 kA cable performs steadily and its heat loss is less than the expected value.

  1. Assessment of the functionality of genome-wide canine SNP arrays and implications for canine disease association studies.

    PubMed

    Ke, X; Kennedy, L J; Short, A D; Seppälä, E H; Barnes, A; Clements, D N; Wood, S H; Carter, S D; Happ, G M; Lohi, H; Ollier, W E R

    2011-04-01

    Domestic dogs share a wide range of important disease conditions with humans, including cancers, diabetes and epilepsy. Many of these conditions have similar or identical underlying pathologies to their human counterparts and thus dogs represent physiologically relevant natural models of human disorders. Comparative genomic approaches whereby disease genes can be identified in dog diseases and then mapped onto the human genome are now recognized as a valid method and are increasing in popularity. The majority of dog breeds have been created over the past few hundred years and, as a consequence, the dog genome is characterized by extensive linkage disequilibrium (LD), extending usually from hundreds of kilobases to several megabases within a breed, rather than tens of kilobases observed in the human genome. Genome-wide canine SNP arrays have been developed, and increasing success of using these arrays to map disease loci in dogs is emerging. No equivalent of the human HapMap currently exists for different canine breeds, and the LD structure for such breeds is far less understood than for humans. This study is a dedicated large-scale assessment of the functionalities (LD and SNP tagging performance) of canine genome-wide SNP arrays in multiple domestic dog breeds. We have used genotype data from 18 breeds as well as wolves and coyotes genotyped by the Illumina 22K canine SNP array and Affymetrix 50K canine SNP array. As expected, high tagging performance was observed with most of the breeds using both Illumina and Affymetrix arrays when multi-marker tagging was applied. In contrast, however, large differences in population structure, LD coverage and pairwise tagging performance were found between breeds, suggesting that study designs should be carefully assessed for individual breeds before undertaking genome-wide association studies (GWAS).

  2. SNP genotyping by heteroduplex analysis.

    PubMed

    Paniego, Norma; Fusari, Corina; Lia, Verónica; Puebla, Andrea

    2015-01-01

    Heteroduplex-based genotyping methods have proven to be technologically effective and economically efficient for low- to medium-range throughput single-nucleotide polymorphism (SNP) determination. In this chapter we describe two protocols that were successfully applied for SNP detection and haplotype analysis of candidate genes in association studies. The protocols involve (1) enzymatic mismatch cleavage with endonuclease CEL1 from celery, associated with fragment separation using capillary electrophoresis (CEL1 cleavage), and (2) differential retention of the homo/heteroduplex DNA molecules under partial denaturing conditions on ion pair reversed-phase liquid chromatography (dHPLC). Both methods are complementary since dHPLC is more versatile than CEL1 cleavage for identifying multiple SNP per target region, and the latter is easily optimized for sequences with fewer SNPs or small insertion/deletion polymorphisms. Besides, CEL1 cleavage is a powerful method to localize the position of the mutation when fragment resolution is done using capillary electrophoresis.

  3. Development of a 10 kW PEM fuel cell for stationary applications

    SciTech Connect

    Barthels, H.; Mergel, J.; Oetjen, H.F.

    1996-12-31

    A 10 kW Proton Exchange Membrane Fuel Cell (PEMFC) is being developed as part of a long-term energy storage path for electricity in the photovoltaic demonstration plant called PHOEBUS at the Forschungszentrum Julich.

  4. The Affymetrix DMET Plus Platform Reveals Unique Distribution of ADME-Related Variants in Ethnic Arabs

    PubMed Central

    Wakil, Salma M.; Nguyen, Cao; Muiya, Nzioka P.; Andres, Editha; Lykowska-Tarnowska, Agnieszka; Baz, Batoul; Meyer, Brian F.; Morahan, Grant

    2015-01-01

    Background. The Affymetrix Drug Metabolizing Enzymes and Transporters (DMET) Plus Premier Pack has been designed to genotype 1936 gene variants thought to be essential for screening patients in personalized drug therapy. These variants include the cytochrome P450s (CYP450s), the key metabolizing enzymes, many other enzymes involved in phase I and phase II pharmacokinetic reactions, and signaling mediators associated with variability in clinical response to numerous drugs not only among individuals, but also between ethnic populations. Materials and Methods. We genotyped 600 Saudi individuals for 1936 variants on the DMET platform to evaluate their clinical potential in personalized medicine in ethnic Arabs. Results. Approximately 49% each of the 437 CYP450 variants, 56% of the 581 transporters, 56% of 419 transferases, 48% of the 104 dehydrogenases, and 58% of the remaining 390 variants were detected. Several variants, such as rs3740071, rs6193, rs258751, rs6199, rs11568421, and rs8187797, exhibited significantly either higher or lower minor allele frequencies (MAFs) than those in other ethnic groups. Discussion. The present study revealed some unique distribution trends for several variants in Arabs, which displayed partly inverse allelic prevalence compared to other ethnic populations. The results point therefore to the need to verify and ascertain the prevalence of a variant as a prerequisite for engaging it in clinical routine screening in personalized medicine in any given population. PMID:25802476

  5. affyPara-a Bioconductor Package for Parallelized Preprocessing Algorithms of Affymetrix Microarray Data.

    PubMed

    Schmidberger, Markus; Vicedo, Esmeralda; Mansmann, Ulrich

    2009-07-22

    Microarray data repositories as well as large clinical applications of gene expression allow to analyse several hundreds of microarrays at one time. The preprocessing of large amounts of microarrays is still a challenge. The algorithms are limited by the available computer hardware. For example, building classification or prognostic rules from large microarray sets will be very time consuming. Here, preprocessing has to be a part of the cross-validation and resampling strategy which is necessary to estimate the rule's prediction quality honestly.This paper proposes the new Bioconductor package affyPara for parallelized preprocessing of Affymetrix microarray data. Partition of data can be applied on arrays and parallelization of algorithms is a straightforward consequence. The partition of data and distribution to several nodes solves the main memory problems and accelerates preprocessing by up to the factor 20 for 200 or more arrays.affyPara is a free and open source package, under GPL license, available form the Bioconductor project at www.bioconductor.org. A user guide and examples are provided with the package.

  6. ChIP-on-chip analysis methods for Affymetrix tiling arrays.

    PubMed

    Yoder, Sean J

    2015-01-01

    Although the ChIP-sequencing has gained significant attraction recently, ChIP analysis using microarrays is still an attractive option due to the low cost, ease of analysis, and access to legacy and public data sets. The analysis of ChIP-Chip data entails a multistep approach that requires several different applications to progress from the initial stages of raw data analysis to the identification and characterization of ChIP binding sites. There are multiple approaches to data analysis and there are several applications available for each stage of the analysis pipeline. Each application must be evaluated for its suitability for the particular experiment as well as the investigator's background with computational tools. This chapter is a review of the commonly available applications for Affymetrix ChIP-Chip data analysis, as well as the general workflow of a ChIP-Chip analysis approach. The purpose of the chapter is to allow the researcher to better select the appropriate applications and provide them with the direction necessary to proceed with a ChIP-Chip analysis.

  7. Identifying the impact of G-quadruplexes on Affymetrix 3' arrays using cloud computing.

    PubMed

    Memon, Farhat N; Owen, Anne M; Sanchez-Graillet, Olivia; Upton, Graham J G; Harrison, Andrew P

    2010-01-15

    A tetramer quadruplex structure is formed by four parallel strands of DNA/ RNA containing runs of guanine. These quadruplexes are able to form because guanine can Hoogsteen hydrogen bond to other guanines, and a tetrad of guanines can form a stable arrangement. Recently we have discovered that probes on Affymetrix GeneChips that contain runs of guanine do not measure gene expression reliably. We associate this finding with the likelihood that quadruplexes are forming on the surface of GeneChips. In order to cope with the rapidly expanding size of GeneChip array datasets in the public domain, we are exploring the use of cloud computing to replicate our experiments on 3' arrays to look at the effect of the location of G-spots (runs of guanines). Cloud computing is a recently introduced high-performance solution that takes advantage of the computational infrastructure of large organisations such as Amazon and Google. We expect that cloud computing will become widely adopted because it enables bioinformaticians to avoid capital expenditure on expensive computing resources and to only pay a cloud computing provider for what is used. Moreover, as well as financial efficiency, cloud computing is an ecologically-friendly technology, it enables efficient data-sharing and we expect it to be faster for development purposes. Here we propose the advantageous use of cloud computing to perform a large data-mining analysis of public domain 3' arrays.

  8. Design research on the conductor of 10 kA class HTS DC power cable

    NASA Astrophysics Data System (ADS)

    Zhang, Dong; Dai, Shaotao; Zhang, Fengyuan; Huang, Tianbin; Wang, Yinshun; Lin, Yubao; Teng, Yuping; Zhang, Guomin; Xiao, Liye; Lin, Liangzhen

    2012-12-01

    High temperature superconducting (HTS) DC power cable shows a wide application prospect in the field of power transmission for its nearly lossless and rather high capacity. A 360 m/10 kA HTS DC power cable system, which connects the rectifier output of a substation with the bus bar of an electrolytic aluminium cell, will be put into operation at Henan Zhongfu Industrial Co., Ltd. As one of the items in this project, a 5 m/10 kA HTS DC power cable was developed, which is used to investigate the conductor design, fabrication, current-carrying capacity and stability of the 360 m/10 kA HTS power cable. The HTS DC power cable core consists of five conductor layers wound with spliced Bi-2223 wires with the length of 600 m. The cable core has five layers and 23 conductors in each layer with the outer diameter of 45.42 mm. The superconducting power cable is fabricated and tested. The critical current is about 14.3 kA at 77 K. The superconducting power cable is charged to 10 kA with rate of 10 A/s and operates at steady-state for 30 min. In this paper, the 10 kA HTS DC power cable design, fabrication and test are presented. The experimental research of the performance of spliced superconducting wire and charging, steady-state operating performance of the cable was carried out.

  9. Efficiency Calculations For a Magnetic Refrigerator Operating Between 2K and 10K

    NASA Technical Reports Server (NTRS)

    Helvensteijn, Ben P. M.; Kashani, A.; Kittel, P.; Sperans, Joel (Technical Monitor)

    1994-01-01

    An adiabatic demagnetization refrigerator (ADR) is being developed at NASA-Ames Research Center. The ADR will operate between 2 K and 10 K and will provide 50 mW of cooling at 2 K. The refrigerant in the ADR is Gadolinium Gallium Garnet (GGG). Absorption of heat at 2 K and heat rejection at 10 K in this fully static refrigerator is made possible by the incorporation of 2 K and 10 K heat switches. Physical layout and experimental results are presented in a parallel paper. The present paper discusses the thermal losses associated with components of the ADR as they occur in various parts of the refrigeration cycle. The results are summarized in terms of a prediction for the ADR efficiency.

  10. Experimental investigations and improvements for the 10 K G-M refrigerator

    NASA Astrophysics Data System (ADS)

    Hao, Xihuan; Ju, Yonglin

    2012-06-01

    With the wide application of high performance cryo-pumps, high and low temperature superconducting devices, MRI, infrared detectors and cryogenic electronics, the development of high efficient and reliable 10 K G-M refrigerator is of critical importance and awaited by cryogenic industries. In the past two years, systematic studies have been carried out, and detailed experimental tests indicated that the cooling performance of the 10 K G-M refrigerator was improved by adding two additional rectification meshes inside the low temperature regenerator and by optimizing the system charge pressure. Furthermore, a new labyrinth sealing displacer was proposed and fabricated to substitute the traditional piston-ring sealing displacer for improved operating stability and reliability of the 10 K GM refrigerator. The detailed experimental results and improvements were summarized and their optimal cases were given in this paper.

  11. Ancestry informative marker panels for African Americans based on subsets of commercially available SNP arrays.

    PubMed

    Tandon, Arti; Patterson, Nick; Reich, David

    2011-01-01

    Admixture mapping is a widely used method for localizing disease genes in African Americans. Most current methods for inferring ancestry at each locus in the genome use a few thousand single nucleotide polymorphisms (SNPs) that are very different in frequency between West Africans and European Americans, and that are required to not be in linkage disequilibrium in the ancestral populations. Modern SNP arrays provide data on hundreds of thousands of SNPs per sample, and to use these to infer ancestry, using many of the standard methods, it is necessary to choose subsets of the SNPs for analysis. Here we present panels of about 4,300 ancestry informative markers (AIMs) that are subsets respectively of SNPs on the Illumina 1 M, Illumina 650, Illumina 610, Affymetrix 6.0 and Affymetrix 5.0 arrays. To validate the usefulness of these panels, we applied them to samples that are different from the ones used to select the SNPs. The panels provide about 80% of the maximum information about African or European ancestry, even with up to 10% missing data.

  12. Design, construction, and operational results of an 800-A, 10-kV hot deck amplifier

    SciTech Connect

    Reass, W.A.

    1984-06-01

    This paper describes the electrical design, implementation, and operational results of a high fidelity (feedback regulated) 800 A, 10-kV hard tube, hot deck amplifier. The amplifier can produce any linear waveform to 800-A for 30 ms and beyond (depending on main energy storage). The present use is to drive the vertical field (VF) control windings on ZT-40M, a toroidal reversed field pinch plasma physics experiment. Although our application requires only 10 kV (8 MW) of switching, anode voltage may be as high as 40 kV (32 MW).

  13. WATER FORMATION THROUGH A QUANTUM TUNNELING SURFACE REACTION, OH + H{sub 2}, AT 10 K

    SciTech Connect

    Oba, Y.; Watanabe, N.; Hama, T.; Kuwahata, K.; Hidaka, H.; Kouchi, A.

    2012-04-10

    The present study experimentally demonstrated that solid H{sub 2}O is formed through the surface reaction OH + H{sub 2} at 10 K. This is the first experimental evidence of solid H{sub 2}O formation using hydrogen in its molecular form at temperatures as low as 10 K. We further found that H{sub 2}O formation through the reaction OH + H{sub 2} is about one order of magnitude more effective than HDO formation through the reaction OH + D{sub 2}. This significant isotope effect results from differences in the effective mass of each reaction, indicating that the reactions proceed through quantum tunneling.

  14. 29 CFR 101.31 - Initiation of proceedings to hear and determine jurisdictional disputes under section 10(k).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... jurisdictional disputes under section 10(k). 101.31 Section 101.31 Labor Regulations Relating to Labor NATIONAL LABOR RELATIONS BOARD STATEMENTS OF PROCEDURES Jurisdictional Dispute Cases Under Section 10(k) of the...(k). The investigation of a jurisdictional dispute under section 10(k) is initiated by the filing...

  15. 29 CFR 101.31 - Initiation of proceedings to hear and determine jurisdictional disputes under section 10(k).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... jurisdictional disputes under section 10(k). 101.31 Section 101.31 Labor Regulations Relating to Labor NATIONAL LABOR RELATIONS BOARD STATEMENTS OF PROCEDURES Jurisdictional Dispute Cases Under Section 10(k) of the...(k). The investigation of a jurisdictional dispute under section 10(k) is initiated by the filing...

  16. 29 CFR 101.31 - Initiation of proceedings to hear and determine jurisdictional disputes under section 10(k).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... jurisdictional disputes under section 10(k). 101.31 Section 101.31 Labor Regulations Relating to Labor NATIONAL LABOR RELATIONS BOARD STATEMENTS OF PROCEDURES Jurisdictional Dispute Cases Under Section 10(k) of the...(k). The investigation of a jurisdictional dispute under section 10(k) is initiated by the filing...

  17. 29 CFR 101.31 - Initiation of proceedings to hear and determine jurisdictional disputes under section 10(k).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... jurisdictional disputes under section 10(k). 101.31 Section 101.31 Labor Regulations Relating to Labor NATIONAL LABOR RELATIONS BOARD STATEMENTS OF PROCEDURES Jurisdictional Dispute Cases Under Section 10(k) of the...(k). The investigation of a jurisdictional dispute under section 10(k) is initiated by the filing...

  18. Analysis on heat loss characteristics of a 10 kV HTS power substation

    NASA Astrophysics Data System (ADS)

    Teng, Yuping; Dai, Shaotao; Song, Naihao; Zhang, Jingye; Gao, Zhiyuan; Zhu, Zhiqin; Zhou, Weiwei; Wei, Zhourong; Lin, Liangzhen; Xiao, Liye

    2014-09-01

    A 10 kV High Temperature Superconducting power substation (10 kV HTS substation), supported by Chinese State 863 projects, was developed and has been running to supply power for several factories for more than two years at an industrial park of Baiyin, Gansu province in Northwest China. The system of the 10 kV HTS substation compositions, including a HTS cable, a HTS transformer, a SFCL, and a SMES, are introduced. The SMES works at liquid helium temperature and the other three apparatus operates under liquid nitrogen condition. There are mainly four types of heat losses existing in each HTS apparatus of the 10 kV HTS substation, including AC loss, Joule heat loss, conductive heat, and leak-in heat from cryostat. A small quantity of AC loss still exists due to the harmonic component of the current when it carries DC for HTS apparatus. The principle and basis for analysis of the heat losses are introduced and the total heat loss of each apparatus are calculated or estimated, which agree well with the test result. The analysis and result presented are of importance for the design of the refrigeration system.

  19. Identification and validation of copy number variants using SNP genotyping arrays from a large clinical cohort

    PubMed Central

    2012-01-01

    Background Genotypes obtained with commercial SNP arrays have been extensively used in many large case-control or population-based cohorts for SNP-based genome-wide association studies for a multitude of traits. Yet, these genotypes capture only a small fraction of the variance of the studied traits. Genomic structural variants (GSV) such as Copy Number Variation (CNV) may account for part of the missing heritability, but their comprehensive detection requires either next-generation arrays or sequencing. Sophisticated algorithms that infer CNVs by combining the intensities from SNP-probes for the two alleles can already be used to extract a partial view of such GSV from existing data sets. Results Here we present several advances to facilitate the latter approach. First, we introduce a novel CNV detection method based on a Gaussian Mixture Model. Second, we propose a new algorithm, PCA merge, for combining copy-number profiles from many individuals into consensus regions. We applied both our new methods as well as existing ones to data from 5612 individuals from the CoLaus study who were genotyped on Affymetrix 500K arrays. We developed a number of procedures in order to evaluate the performance of the different methods. This includes comparison with previously published CNVs as well as using a replication sample of 239 individuals, genotyped with Illumina 550K arrays. We also established a new evaluation procedure that employs the fact that related individuals are expected to share their CNVs more frequently than randomly selected individuals. The ability to detect both rare and common CNVs provides a valuable resource that will facilitate association studies exploring potential phenotypic associations with CNVs. Conclusion Our new methodologies for CNV detection and their evaluation will help in extracting additional information from the large amount of SNP-genotyping data on various cohorts and use this to explore structural variants and their impact on complex

  20. Development of a 10 kW, 2.815 GHz Klystron

    SciTech Connect

    Ives, Robert Lawrence; Read, Michael; Patrick, Ferguson

    2015-05-15

    Development of a Periodic Permanent Magnet (PPM) focused klystron is described. The klystron was designed to produce 10 kW CW at 2.815 GHz. The program developed an innovative PPM circuit that provided extremely uniform magnetic fields at the electron beam location while providing unprecedented access to the RF circuit for tuners and water cooling. Simulations indicated the klystron would produce more than 11 kW with an efficiency exceeding 65%. Problems with the mechanical design prevented successful testing of the initial prototype; however, a new design was successfully developed and implemented in a 6 MW klystron developed in a follow-on program. Funding is being pursued to rebuild the 10 kW RF circuit and complete the klystron development.

  1. BM-SNP: A Bayesian Model for SNP Calling Using High Throughput Sequencing Data.

    PubMed

    Xu, Yanxun; Zheng, Xiaofeng; Yuan, Yuan; Estecio, Marcos R; Issa, Jean-Pierre; Qiu, Peng; Ji, Yuan; Liang, Shoudan

    2014-01-01

    A single-nucleotide polymorphism (SNP) is a sole base change in the DNA sequence and is the most common polymorphism. Detection and annotation of SNPs are among the central topics in biomedical research as SNPs are believed to play important roles on the manifestation of phenotypic events, such as disease susceptibility. To take full advantage of the next-generation sequencing (NGS) technology, we propose a Bayesian approach, BM-SNP, to identify SNPs based on the posterior inference using NGS data. In particular, BM-SNP computes the posterior probability of nucleotide variation at each covered genomic position using the contents and frequency of the mapped short reads. The position with a high posterior probability of nucleotide variation is flagged as a potential SNP. We apply BM-SNP to two cell-line NGS data, and the results show a high ratio of overlap ( >95 percent) with the dbSNP database. Compared with MAQ, BM-SNP identifies more SNPs that are in dbSNP, with higher quality. The SNPs that are called only by BM-SNP but not in dbSNP may serve as new discoveries. The proposed BM-SNP method integrates information from multiple aspects of NGS data, and therefore achieves high detection power. BM-SNP is fast, capable of processing whole genome data at 20-fold average coverage in a short amount of time. PMID:26357041

  2. 'Pop-Up' Governance: developing internal governance frameworks for consortia: the example of UK10K.

    PubMed

    Kaye, Jane; Muddyman, Dawn; Smee, Carol; Kennedy, Karen; Bell, Jessica

    2015-01-01

    Innovations in information technologies have facilitated the development of new styles of research networks and forms of governance. This is evident in genomics where increasingly, research is carried out by large, interdisciplinary consortia focussing on a specific research endeavour. The UK10K project is an example of a human genomics consortium funded to provide insights into the genomics of rare conditions, and establish a community resource from generated sequence data. To achieve its objectives according to the agreed timetable, the UK10K project established an internal governance system to expedite the research and to deal with the complex issues that arose. The project's governance structure exemplifies a new form of network governance called 'pop-up' governance. 'Pop-up' because: it was put together quickly, existed for a specific period, was designed for a specific purpose, and was dismantled easily on project completion. In this paper, we use UK10K to describe how 'pop-up' governance works on the ground and how relational, hierarchical and contractual governance mechanisms are used in this new form of network governance. PMID:26412243

  3. Development of a Magnetic Refrigerator Operating Between 2K and 10K

    NASA Technical Reports Server (NTRS)

    Lane, David A.; Cooper, D. M. (Technical Monitor)

    1994-01-01

    An adiabatic demagnetization refrigerator (ADR) is under development at NASA-Ames Research Center that will operate between 2 K and 10 K and will provide 50 mW of cool ng at 2 K. Gadolinium Gallium Garnet (GGG) is selected as the refrigerant for the ADR, To minimize temperature gradients in the GGG, thick slices of GGG are sandwiched together with strips of high-purity copper in between them. The copper strips are used to exchange heat between the GGG and the 2 K and the 10 K heat switches. The heat transfer across the Cu-GGG interfaces is improved by placing thin foils of' high-purity indium at the interfaces. The heat switches employed in the ADR have no moving parts. The 10 K heat switch is a helium gas-gap heat switch; while, the 2 K heat switch is a He ll-gap heat switch. A switch is on when its gap Is filled with helium and is off' when the gap is emptied. This is accomplished with an activated carbon pump (ACP). The ACP adsorbs helium when cooled and desorbs it when heated. A superconducting magnet capable of providing 9 T at 2 K is used for the ADR cycle. A prototype of this refrigerator has been built and is currently under test. A detailed design of the ADR and preliminary test results performed on the prototype ADR will be presented.

  4. Electric propulsion options for 10 kW class earth space missions

    NASA Technical Reports Server (NTRS)

    Patterson, M. J.; Curran, Francis M.

    1989-01-01

    Five and 10 kW ion and arcjet propulsion system options for a near-term space demonstration experiment have been evaluated. Analyses were conducted to determine first-order propulsion system performance and system component mass estimates. Overall mission performance of the electric propulsion systems was quantified in terms of the maximum thrusting time, total impulse, and velocity increment capability available when integrated onto a generic spacecraft under fixed mission model assumptions. Maximum available thrusting times for the ion-propelled spacecraft options, launched on a DELTA II 6920 vehicle, range from approximately 8,600 hours for a 4-engine 10 kW system to more than 29,600 hours for a single-engine 5 kW system. Maximum total impulse values and maximum delta-v's range from 1.2x10(7) to 2.1x10(7) N-s, and 3550 to 6200 m/s, respectively. Maximum available thrusting times for the arcjet propelled spacecraft launched on the DELTA II 6920 vehicle range from approximately 528 hours for the 6-engine 10 kW hydrazine system to 2328 hours for the single-engine 5 kW system. Maximum total impulse values and maximum delta-v's range from 2.2x10(6) to 3.6x10(6) N-s, and approximately 662 to 1072 m/s, respectively.

  5. Electric Propulsion Options for 10 kW Class Earth-Space Missions

    NASA Technical Reports Server (NTRS)

    Patterson, M. J.; Curran, Francis M.

    1989-01-01

    Five and 10 kW ion and arcjet propulsion system options for a near-term space demonstration experiment were evaluated. Analyses were conducted to determine first-order propulsion system performance and system component mass estimates. Overall mission performance of the electric propulsion systems was quantified in terms of the maximum thrusting time, total impulse, and velocity increment capability available when integrated onto a generic spacecraft under fixed mission model assumptions. Maximum available thrusting times for the ion-propelled spacecraft options, launched on a DELTA 2 6920 vehicle, range from approximately 8,600 hours for a 4-engine 10 kW system to more than 29,600 hours for a single-engine 5 kW system. Maximum total impulse values and maximum delta-v's range from 1.2x10 (exp 7) to 2.1x10 (exp 7) N-s, and 3550 to 6200 m/s, respectively. Maximum available thrusting times for the arcjet propelled spacecraft launched on the DELTA 2 6920 vehicle range from approximately 528 hours for the 6-engine 10 kW hydrazine system to 2328 hours for the single-engine 5 kW system. Maximum total impulse values and maximum delta-v's range from 2.2x10 (exp 6) to 3.6x10 (exp 6) N-s, and approximately 662 to 1072 m/s, respectively.

  6. 'Pop-Up' Governance: developing internal governance frameworks for consortia: the example of UK10K.

    PubMed

    Kaye, Jane; Muddyman, Dawn; Smee, Carol; Kennedy, Karen; Bell, Jessica

    2015-01-01

    Innovations in information technologies have facilitated the development of new styles of research networks and forms of governance. This is evident in genomics where increasingly, research is carried out by large, interdisciplinary consortia focussing on a specific research endeavour. The UK10K project is an example of a human genomics consortium funded to provide insights into the genomics of rare conditions, and establish a community resource from generated sequence data. To achieve its objectives according to the agreed timetable, the UK10K project established an internal governance system to expedite the research and to deal with the complex issues that arose. The project's governance structure exemplifies a new form of network governance called 'pop-up' governance. 'Pop-up' because: it was put together quickly, existed for a specific period, was designed for a specific purpose, and was dismantled easily on project completion. In this paper, we use UK10K to describe how 'pop-up' governance works on the ground and how relational, hierarchical and contractual governance mechanisms are used in this new form of network governance.

  7. Detection of selective sweeps in cattle using genome-wide SNP data

    PubMed Central

    2013-01-01

    Background The domestication and subsequent selection by humans to create breeds and biological types of cattle undoubtedly altered the patterning of variation within their genomes. Strong selection to fix advantageous large-effect mutations underlying domesticability, breed characteristics or productivity created selective sweeps in which variation was lost in the chromosomal region flanking the selected allele. Selective sweeps have now been identified in the genomes of many animal species including humans, dogs, horses, and chickens. Here, we attempt to identify and characterise regions of the bovine genome that have been subjected to selective sweeps. Results Two datasets were used for the discovery and validation of selective sweeps via the fixation of alleles at a series of contiguous SNP loci. BovineSNP50 data were used to identify 28 putative sweep regions among 14 diverse cattle breeds. Affymetrix BOS 1 prescreening assay data for five breeds were used to identify 85 regions and validate 5 regions identified using the BovineSNP50 data. Many genes are located within these regions and the lack of sequence data for the analysed breeds precludes the nomination of selected genes or variants and limits the prediction of the selected phenotypes. However, phenotypes that we predict to have historically been under strong selection include horned-polled, coat colour, stature, ear morphology, and behaviour. Conclusions The bias towards common SNPs in the design of the BovineSNP50 assay led to the identification of recent selective sweeps associated with breed formation and common to only a small number of breeds rather than ancient events associated with domestication which could potentially be common to all European taurines. The limited SNP density, or marker resolution, of the BovineSNP50 assay significantly impacted the rate of false discovery of selective sweeps, however, we found sweeps in common between breeds which were confirmed using an ultra

  8. Protein-protein interaction and SNP analysis in intraductal papillary mucinous neoplasm.

    PubMed

    Jiang, Pu; Zang, Weidong; Wang, Lishan; Xu, Ying; Liu, Yang; Deng, Shi-Xiong

    2013-01-15

    Intraductal papillary mucinous neoplasm (IPMN) is a type of tumor that grows within the pancreatic ducts. It is a progress from hyperplasia to intraductal adenoma (IPMA), to noninvasive carcinoma, and ultimately to invasive carcinoma (IPMC). The objective of this study was to explore the molecular mechanism of the progression from IPMA to IPMC. By using the GSE19650 affymetrix microarray data accessible from Gene Expression Omnibus (GEO) database, we first identified the differentially expressed genes (DEGs) between IPMA and IPMC, followed by the protein-protein interaction and single-nucleotide polymorphism (SNP) analysis of the DEGs. Our study identified thousands of DEGs which involved regulation of cell cycle and apoptosis in this progression from IPMA to IPMC. Protein-protein interaction network construction found that MYC, IL6ST, NR3C1, CREBBP, GATA1 and LRP1 might play an important role in the progression. Furthermore, the SNP analysis confirmed the association between BRAC1 and pancreas cancer. In conclusion, our data provide a comprehensive bioinformatics analysis of genes and pathways which may be involved in the progression of IPMN from IPMA to IPMC.

  9. Adjustment of genomic waves in signal intensities from whole-genome SNP genotyping platforms.

    PubMed

    Diskin, Sharon J; Li, Mingyao; Hou, Cuiping; Yang, Shuzhang; Glessner, Joseph; Hakonarson, Hakon; Bucan, Maja; Maris, John M; Wang, Kai

    2008-11-01

    Whole-genome microarrays with large-insert clones designed to determine DNA copy number often show variation in hybridization intensity that is related to the genomic position of the clones. We found these 'genomic waves' to be present in Illumina and Affymetrix SNP genotyping arrays, confirming that they are not platform-specific. The causes of genomic waves are not well-understood, and they may prevent accurate inference of copy number variations (CNVs). By measuring DNA concentration for 1444 samples and by genotyping the same sample multiple times with varying DNA quantity, we demonstrated that DNA quantity correlates with the magnitude of waves. We further showed that wavy signal patterns correlate best with GC content, among multiple genomic features considered. To measure the magnitude of waves, we proposed a GC-wave factor (GCWF) measure, which is a reliable predictor of DNA quantity (correlation coefficient = 0.994 based on samples with serial dilution). Finally, we developed a computational approach by fitting regression models with GC content included as a predictor variable, and we show that this approach improves the accuracy of CNV detection. With the wide application of whole-genome SNP genotyping techniques, our wave adjustment method will be important for taking full advantage of genotyped samples for CNV analysis.

  10. SNP-RFLPing 2: an updated and integrated PCR-RFLP tool for SNP genotyping

    PubMed Central

    2010-01-01

    Background PCR-restriction fragment length polymorphism (RFLP) assay is a cost-effective method for SNP genotyping and mutation detection, but the manual mining for restriction enzyme sites is challenging and cumbersome. Three years after we constructed SNP-RFLPing, a freely accessible database and analysis tool for restriction enzyme mining of SNPs, significant improvements over the 2006 version have been made and incorporated into the latest version, SNP-RFLPing 2. Results The primary aim of SNP-RFLPing 2 is to provide comprehensive PCR-RFLP information with multiple functionality about SNPs, such as SNP retrieval to multiple species, different polymorphism types (bi-allelic, tri-allelic, tetra-allelic or indels), gene-centric searching, HapMap tagSNPs, gene ontology-based searching, miRNAs, and SNP500Cancer. The RFLP restriction enzymes and the corresponding PCR primers for the natural and mutagenic types of each SNP are simultaneously analyzed. All the RFLP restriction enzyme prices are also provided to aid selection. Furthermore, the previously encountered updating problems for most SNP related databases are resolved by an on-line retrieval system. Conclusions The user interfaces for functional SNP analyses have been substantially improved and integrated. SNP-RFLPing 2 offers a new and user-friendly interface for RFLP genotyping that can be used in association studies and is freely available at http://bio.kuas.edu.tw/snp-rflping2. PMID:20377871

  11. Evaluation of potential health effects of 10 kHz magnetic fields: a rodent reproductive study.

    PubMed

    Dawson, B V; Robertson, I G; Wilson, W R; Zwi, L J; Boys, J T; Green, A W

    1998-01-01

    New technology involving the use of high-frequency inductive power distribution (HID) has recently been developed for use in materials handling and personnel transfer. Sinusoidal magnetic fields at a frequency of 10 kHz with field intensities of approximately 0.2 mT are generated directly between the current-carrying coils of this equipment. Effects of 10 kHz magnetic fields on cell division, migration, and differentiation have never been previously investigated. To evaluate potential effects on these parameters, a rodent reproductive study was undertaken using Wistar rats. Exposures were at 0.095, 0.24, and 0.95 mT with a background exposure of 5-10 microT. Three sets of parental rats were exposed continuously for 20-23.5 h/day to the fields: maternal rats during gestation, paternal rats for at least 45 days prior to mating and maternal rats 1 month prior to mating. Exposure phases thus covered spermatogenesis, maturation of the ovum and ovulation, fertilization, implantation, embryogenesis, organogenesis, and maturation of the fetus immediately prior to parturition. In all experiments pregnancy outcome was assessed. These studies failed to demonstrate any reproductive toxicity resulting from maternal or fetal exposure during gestation or following paternal or maternal exposure for several weeks prior to mating. No quantitative or qualitative effects on spermatogenesis occurred after exposure, and no effects on the estrous cycle or ovulation could be demonstrably linked to the 10 kHz magnetic field exposure at 0.095, 0.25, or 0.95 mT. Where possible, parental clinical chemistry and hematology were also examined. As in mouse toxicology studies previously reported, minor differences were observed between control and treated groups. These were regarded as statistically, but not biologically, significant and could not categorically be attributed to magnetic field exposure.

  12. Development of a low noise 10 K J-T refrigeration system

    NASA Astrophysics Data System (ADS)

    Little, William A.

    1987-06-01

    This report summarizes work done on the development of a low noise Joule-Thompson, microminiature refrigeration system designed for 10 K operation. Topics discussed include: calculation of phase diagram of mixtures of certain hydrocarbon gases with nitrogen using the Benedict-Webb-Rubin equation of state, the set up of a magnetron-enhanced sputtering system to allow us to sputter a layer of adhesive on the glass substrates with a much better defined thickness than can be laid down using the older screen printing method, Redesign of H2 Refrigerator Test Stage, Redesign of Mixed Gas Heat Exchanger, Refrigerator Fabrication, Gas Cleaner.

  13. 10 kWe dual-mode space nuclear power system for military and scientific applications

    NASA Astrophysics Data System (ADS)

    Malloy, John; Westerman, Kurt; Rochow, Richard; Scoles, Stephen

    The Small Externally-fueled Heat Pipe Thermionic Reactor concept is used as the basis of a 10 kWe dual-mode space power system scheme that generates both arcjet propulsion system power and direct (hydrogen propellant-heating) thrust. This direct-thrust feature allows the nuclear-power system to move a payload from LEO to GEO in less than one month, using half as much propellant as a cryogenic-fuel chemical rocket. The nuclear reactor uses 36 thermionic heat-pipe modules, which produce electricity within the reactor and remove waste heat.

  14. Progress Toward a Compact 0.05 K Magnet Refrigerator Operating from 10 K

    NASA Technical Reports Server (NTRS)

    Canavan, Edgar; Shirron, Peter; DiPirro, Micheal; Tuttle, James; Jackson, Michael; King, Todd; Numazawa, Takenori

    2003-01-01

    Much of the most interesting information regarding our universe is hidden in the sub-millimeter, infrared, and x-rays bands of the spectrum, to which our atmosphere is largely opaque. Thus, missions exploring these bands are a very important part of NASA s Space Science program. Coincidentally, the most sensitive detectors in these spectral regions operate at extremely low temperatures, typically 0.05 - 0.10 K. Generally these temperatures will be achieved using magnetic refrigerators, also know as Adiabatic Demagnetization Refrigerators, or ADRs. Current ADRs, such as the one used in the XRS-II instrument on the Astro-E2 satellite, use a single-stage to cool detectors from 1.3 K to 0.06 K. The ADR is designed so that it can absorb the heat on the detector stage for at least 24 hours before it must stop, warm up to the helium bath temperature (1.3 K), and dump the accumulated heat. Future detector arrays will be much larger and will have higher heat dissipation. Furthermore, future missions will use mechanical cryocoolers to provide upper stage cooling, but they can only reach 4 - 10 K. Trying to scale heavy (-15 kg) single stage ADRs up to the higher heat loads and higher heat rejection temperatures required leads to unacceptably large systems. The GSFC Cryogenics Branch has developed the Continuous ADR (CADR) to solve this problem. The CADR consists of a series of ADR stages that sequentially pass heat from the load up to the high temperature heat sink. The stage connected to the load remains at a constant temperature. The continuous stage effectively decouples detector operation from ADR operation, allowing the ADR stages to be cycled much more rapidly. Rapid cycling leads to higher cooling power density. The cascading, multistage arrangement allows the magnetic refrigerant of each stage to be optimized for its own temperature swing. In the past year, we have made good progress toward a 0.05 to 10K system. A four-stage system that operates from 4.2 K was

  15. NbN A/D Conversion of IR Focal Plane Sensor Signal at 10 K

    NASA Technical Reports Server (NTRS)

    Eaton, L.; Durand, D.; Sandell, R.; Spargo, J.; Krabach, T.

    1994-01-01

    We are implementing a 12 bit SFQ counting ADC with parallel-to-serial readout using our established 10 K NbN capability. This circuit provides a key element of the analog signal processor (ASP) used in large infrared focal plane arrays. The circuit processes the signal data stream from a Si:As BIB detector array. A 10 mega samples per second (MSPS) pixel data stream flows from the chip at a 120 megabit bit rate in a format that is compatible with other superconductive time dependent processor (TDP) circuits being developed. We will discuss our planned ASP demonstration, the circuit design, and test results.

  16. A new method for class prediction based on signed-rank algorithms applied to Affymetrix® microarray experiments

    PubMed Central

    Rème, Thierry; Hose, Dirk; De Vos, John; Vassal, Aurélien; Poulain, Pierre-Olivier; Pantesco, Véronique; Goldschmidt, Hartmut; Klein, Bernard

    2008-01-01

    Background The huge amount of data generated by DNA chips is a powerful basis to classify various pathologies. However, constant evolution of microarray technology makes it difficult to mix data from different chip types for class prediction of limited sample populations. Affymetrix® technology provides both a quantitative fluorescence signal and a decision (detection call: absent or present) based on signed-rank algorithms applied to several hybridization repeats of each gene, with a per-chip normalization. We developed a new prediction method for class belonging based on the detection call only from recent Affymetrix chip type. Biological data were obtained by hybridization on U133A, U133B and U133Plus 2.0 microarrays of purified normal B cells and cells from three independent groups of multiple myeloma (MM) patients. Results After a call-based data reduction step to filter out non class-discriminative probe sets, the gene list obtained was reduced to a predictor with correction for multiple testing by iterative deletion of probe sets that sequentially improve inter-class comparisons and their significance. The error rate of the method was determined using leave-one-out and 5-fold cross-validation. It was successfully applied to (i) determine a sex predictor with the normal donor group classifying gender with no error in all patient groups except for male MM samples with a Y chromosome deletion, (ii) predict the immunoglobulin light and heavy chains expressed by the malignant myeloma clones of the validation group and (iii) predict sex, light and heavy chain nature for every new patient. Finally, this method was shown powerful when compared to the popular classification method Prediction Analysis of Microarray (PAM). Conclusion This normalization-free method is routinely used for quality control and correction of collection errors in patient reports to clinicians. It can be easily extended to multiple class prediction suitable with clinical groups, and looks

  17. A general SNP-based molecular barcode for Plasmodium falciparum identification and tracking

    PubMed Central

    Daniels, Rachel; Volkman, Sarah K; Milner, Danny A; Mahesh, Nira; Neafsey, Daniel E; Park, Daniel J; Rosen, David; Angelino, Elaine; Sabeti, Pardis C; Wirth, Dyann F; Wiegand, Roger C

    2008-01-01

    Background Single nucleotide polymorphism (SNP) genotyping provides the means to develop a practical, rapid, inexpensive assay that will uniquely identify any Plasmodium falciparum parasite using a small amount of DNA. Such an assay could be used to distinguish recrudescence from re-infection in drug trials, to monitor the frequency and distribution of specific parasites in a patient population undergoing drug treatment or vaccine challenge, or for tracking samples and determining purity of isolates in the laboratory during culture adaptation and sub-cloning, as well as routine passage. Methods A panel of twenty-four SNP markers has been identified that exhibit a high minor allele frequency (average MAF > 35%), for which robust TaqMan genotyping assays were constructed. All SNPs were identified through whole genome sequencing and MAF was estimated through Affymetrix array-based genotyping of a worldwide collection of parasites. These assays create a "molecular barcode" to uniquely identify a parasite genome. Results Using 24 such markers no two parasites known to be of independent origin have yet been found to have the same allele signature. The TaqMan genotyping assays can be performed on a variety of samples including cultured parasites, frozen whole blood, or whole blood spotted onto filter paper with a success rate > 99%. Less than 5 ng of parasite DNA is needed to complete a panel of 24 markers. The ability of this SNP panel to detect and identify parasites was compared to the standard molecular methods, MSP-1 and MSP-2 typing. Conclusion This work provides a facile field-deployable genotyping tool that can be used without special skills with standard lab equipment, and at reasonable cost that will unambiguously identify and track P. falciparum parasites both from patient samples and in the laboratory. PMID:18959790

  18. Detecting Susceptibility to Breast Cancer with SNP-SNP Interaction Using BPSOHS and Emotional Neural Networks.

    PubMed

    Wang, Xiao; Peng, Qinke; Fan, Yue

    2016-01-01

    Studies for the association between diseases and informative single nucleotide polymorphisms (SNPs) have received great attention. However, most of them just use the whole set of useful SNPs and fail to consider the SNP-SNP interactions, while these interactions have already been proven in biology experiments. In this paper, we use a binary particle swarm optimization with hierarchical structure (BPSOHS) algorithm to improve the effective of PSO for the identification of the SNP-SNP interactions. Furthermore, in order to use these SNP interactions in the susceptibility analysis, we propose an emotional neural network (ENN) to treat SNP interactions as emotional tendency. Different from the normal architecture, just as the emotional brain, this architecture provides a specific path to treat the emotional value, by which the SNP interactions can be considered more quickly and directly. The ENN helps us use the prior knowledge about the SNP interactions and other influence factors together. Finally, the experimental results prove that the proposed BPSOHS_ENN algorithm can detect the informative SNP-SNP interaction and predict the breast cancer risk with a much higher accuracy than existing methods. PMID:27294121

  19. Detecting Susceptibility to Breast Cancer with SNP-SNP Interaction Using BPSOHS and Emotional Neural Networks

    PubMed Central

    Wang, Xiao; Fan, Yue

    2016-01-01

    Studies for the association between diseases and informative single nucleotide polymorphisms (SNPs) have received great attention. However, most of them just use the whole set of useful SNPs and fail to consider the SNP-SNP interactions, while these interactions have already been proven in biology experiments. In this paper, we use a binary particle swarm optimization with hierarchical structure (BPSOHS) algorithm to improve the effective of PSO for the identification of the SNP-SNP interactions. Furthermore, in order to use these SNP interactions in the susceptibility analysis, we propose an emotional neural network (ENN) to treat SNP interactions as emotional tendency. Different from the normal architecture, just as the emotional brain, this architecture provides a specific path to treat the emotional value, by which the SNP interactions can be considered more quickly and directly. The ENN helps us use the prior knowledge about the SNP interactions and other influence factors together. Finally, the experimental results prove that the proposed BPSOHS_ENN algorithm can detect the informative SNP-SNP interaction and predict the breast cancer risk with a much higher accuracy than existing methods. PMID:27294121

  20. Design and performance of a 4He-evaporator at <1.0 K

    NASA Astrophysics Data System (ADS)

    Das, N. K.; Pradhan, J.; Naser, Md. Z. A.; Roy, A.; Mandal, B. Ch.; Mallik, C.; Bhandari, R. K.

    2012-12-01

    A helium evaporator for obtaining 1 K temperature has been built and tested in laboratory. This will function primarily as the precooling stage for the circulating helium isotopic gas mixture. This works on evaporative cooling by way of pumping out the vapour from the top of the pot. A precision needle valve is used initially to fill up the pot and subsequently a permanent flow impedance maintains the helium flow from the bath into the pot to replenish the evaporative loss of helium. Considering the cooling power of 10 mW @1.0 K, a 99.0 cm3 helium evaporator was designed, fabricated from OFE copper and tested in the laboratory. A pumping station comprising of a roots pump backed by a dry pump was used for evacuation. The calibrated RuO thermometer and kapton film heater were used for measuring the temperature and cooling power of the system respectively. The continuously filled 1 K bath is tested in the laboratory and found to offer a temperature less than 1.0 K by withdrawing vapour from the evaporator. In order to minimize the heat load and to prevent film creep across the pumping tube, size optimization of the pumping line and pump-out port has been performed. The results of test run along with relevant analysis, mechanical fabrication of flow impedance are presented here.

  1. 1 MeV, 10 kW DC electron accelerator for industrial applications

    NASA Astrophysics Data System (ADS)

    Nayak, B.; Acharya, S.; Bhattacharjee, D.; Bakhtsingh, R. I.; Rajan, R.; Sharma, D. K.; Dewangan, S.; Sharma, V.; Patel, R.; Tiwari, R.; Benarjee, S.; Srivastava, S. K.

    2016-03-01

    Several modern applications of radiation processing like medical sterilization, rubber vulcanization, polymerization, cross-linking and pollution control from thermal power stations etc. require D.C. electron accelerators of energy ranging from a few hundred keVs to few MeVs and power from a few kilowatts to hundreds of kilowatts. To match these requirements, a 3 MeV, 30 kW DC electron linac has been developed at BARC, Mumbai and current operational experience of 1 MeV, 10 kW beam power will be described in this paper. The LINAC composed mainly of Electron Gun, Accelerating Tubes, Magnets, High Voltage source and provides 10 kW beam power at the Ti beam window stably after the scanning section. The control of the LINAC is fully automated. Here Beam Optics study is carried out to reach the preferential parameters of Accelerating as well as optical elements. Beam trials have been conducted to find out the suitable operation parameters of the system.

  2. inSilicoDb: an R/Bioconductor package for accessing human Affymetrix expert-curated datasets from GEO.

    PubMed

    Taminau, Jonatan; Steenhoff, David; Coletta, Alain; Meganck, Stijn; Lazar, Cosmin; de Schaetzen, Virginie; Duque, Robin; Molter, Colin; Bersini, Hugues; Nowé, Ann; Weiss Solís, David Y

    2011-11-15

    Microarray technology has become an integral part of biomedical research and increasing amounts of datasets become available through public repositories. However, re-use of these datasets is severely hindered by unstructured, missing or incorrect biological samples information; as well as the wide variety of preprocessing methods in use. The inSilicoDb R/Bioconductor package is a command-line front-end to the InSilico DB, a web-based database currently containing 86 104 expert-curated human Affymetrix expression profiles compiled from 1937 GEO repository series. The use of this package builds on the Bioconductor project's focus on reproducibility by enabling a clear workflow in which not only analysis, but also the retrieval of verified data is supported.

  3. Managing large SNP datasets with SNPpy.

    PubMed

    Mitha, Faheem

    2013-01-01

    Using relational databases to manage SNP datasets is a very useful technique that has significant advantages over alternative methods, including the ability to leverage the power of relational databases to perform data validation, and the use of the powerful SQL query language to export data. SNPpy is a Python program which uses the PostgreSQL database and the SQLAlchemy Python library to automate SNP data management. This chapter shows how to use SNPpy to store and manage large datasets.

  4. SNP Arrays for Species Identification in Salmonids.

    PubMed

    Wenne, Roman; Drywa, Agata; Kent, Matthew; Sundsaasen, Kristil Kindem; Lien, Sigbjørn

    2016-01-01

    The use of SNP genotyping microarrays, developed in one species to analyze a closely related species for which genomic sequence information is scarce, enables the rapid development of a genomic resource (SNP information) without the need to develop new species-specific markers. Using large numbers of microarray SNPs offers the best chance to detect informative markers in nontarget species, markers that can very often be assayed using a lower throughput platform as is described in this paper. PMID:27460372

  5. EXPERIMENTAL EVIDENCE FOR WATER FORMATION VIA OZONE HYDROGENATION ON DUST GRAINS AT 10 K

    SciTech Connect

    Mokrane, H.; Chaabouni, H.; Accolla, M.; Congiu, E.; Dulieu, F.; Chehrouri, M.; Lemaire, J. L.

    2009-11-10

    The formation of water molecules from the reaction between ozone (O{sub 3}) and D-atoms is studied experimentally for the first time. Ozone is deposited on non-porous amorphous solid water ice (H{sub 2}O), and D-atoms are then sent onto the sample held at 10 K. HDO molecules are detected during the desorption of the whole substrate where isotope mixing takes place, indicating that water synthesis has occurred. The efficiency of water formation via hydrogenation of ozone is of the same order of magnitude as that found for reactions involving O-atoms or O{sub 2} molecules and exhibits no apparent activation barrier. These experiments validate the assumption made by models using ozone as one of the precursors of water formation via solid-state chemistry on interstellar dust grains.

  6. Design considerations for a 10-kW integrated hydrogen-oxygen regenerative fuel cell system

    NASA Technical Reports Server (NTRS)

    Hoberecht, M. A.; Miller, T. B.; Rieker, L. L.; Gonzalez-Sanabria, O. D.

    1984-01-01

    Integration of an alkaline fuel cell subsystem with an alkaline electrolysis subsystem to form a regenerative fuel cell (RFC) system for low earth orbit (LEO) applications characterized by relatively high overall round trip electrical efficiency, long life, and high reliability is possible with present state of the art technology. A hypothetical 10 kW system computer modeled and studied based on data from ongoing contractual efforts in both the alkaline fuel cell and alkaline water electrolysis areas. The alkaline fuel cell technology is under development utilizing advanced cell components and standard Shuttle Orbiter system hardware. The alkaline electrolysis technology uses a static water vapor feed technique and scaled up cell hardware is developed. The computer aided study of the performance, operating, and design parameters of the hypothetical system is addressed.

  7. Fast Ignition Research and 10 kJ Petawatt Laser System

    NASA Astrophysics Data System (ADS)

    Tanaka, Kazuo A.

    2004-05-01

    Our integrated exeriment to model fast ignition has been succesful to show thousand times increase of neutrons by enforcing fast heating to a highly compressed core. This experiment is reviewed first. Then we show our basic studies relevant to fast ignition such as hot electron production, implosion detailed study, relativisitic self focusing. The hot electron production was increased with use of Au guiding cone. Imploded core with plastic shell inserted with a Au cone shows rapid flow out of the hot central area toward the Au cone tip. PW laser pulse was injected into an overdense plasma and showed a clear evidence of super penetration. Ignition requirement is discussed using simulation results. Based on the results 10 kJ petawatt laser system will be constructed and its status will be reported.

  8. Thermodynamic design of 10 kW Brayton cryocooler for HTS cable

    NASA Astrophysics Data System (ADS)

    Chang, Ho-Myung; Park, C. W.; Yang, H. S.; Sohn, Song Ho; Lim, Ji Hyun; Oh, S. R.; Hwang, Si Dole

    2012-06-01

    Thermodynamic design of Brayton cryocooler is presented as part of an ongoing governmental project in Korea, aiming at 1 km HTS power cable in the transmission grid. The refrigeration requirement is 10 kW for continuously sub-cooling liquid nitrogen from 72 K to 65 K. An ideal Brayton cycle for this application is first investigated to examine the fundamental features. Then a practical cycle for a Brayton cryocooler is designed, taking into account the performance of compressor, expander, and heat exchangers. Commercial software (Aspen HYSYS) is used for simulating the refrigeration cycle with real fluid properties of refrigerant. Helium is selected as a refrigerant, as it is superior to neon in thermodynamic efficiency. The operating pressure and flow rate of refrigerant are decided with a constraint to avoid the freezing of liquid nitrogen

  9. Large-aperture, tapered fiber-coupled, 10-kHz particle-image velocimetry.

    PubMed

    Hsu, Paul S; Roy, Sukesh; Jiang, Naibo; Gord, James R

    2013-02-11

    We demonstrate the design and implementation of a fiber-optic beam-delivery system using a large-aperture, tapered step-index fiber for high-speed particle-image velocimetry (PIV) in turbulent combustion flows. The tapered fiber in conjunction with a diffractive-optical-element (DOE) fiber-optic coupler significantly increases the damage threshold of the fiber, enabling fiber-optic beam delivery of sufficient nanosecond, 532-nm, laser pulse energy for high-speed PIV measurements. The fiber successfully transmits 1-kHz and 10-kHz laser pulses with energies of 5.3 mJ and 2 mJ, respectively, for more than 25 min without any indication of damage. It is experimentally demonstrated that the tapered fiber possesses the high coupling efficiency (~80%) and moderate beam quality for PIV. Additionally, the nearly uniform output-beam profile exiting the fiber is ideal for PIV applications. Comparative PIV measurements are made using a conventionally (bulk-optic) delivered light sheet, and a similar order of measurement accuracy is obtained with and without fiber coupling. Effective use of fiber-coupled, 10-kHz PIV is demonstrated for instantaneous 2D velocity-field measurements in turbulent reacting flows. Proof-of-concept measurements show significant promise for the performance of fiber-coupled, high-speed PIV using a tapered optical fiber in harsh laser-diagnostic environments such as those encountered in gas-turbine test beds and the cylinder of a combustion engine. PMID:23481818

  10. Large-aperture, tapered fiber-coupled, 10-kHz particle-image velocimetry.

    PubMed

    Hsu, Paul S; Roy, Sukesh; Jiang, Naibo; Gord, James R

    2013-02-11

    We demonstrate the design and implementation of a fiber-optic beam-delivery system using a large-aperture, tapered step-index fiber for high-speed particle-image velocimetry (PIV) in turbulent combustion flows. The tapered fiber in conjunction with a diffractive-optical-element (DOE) fiber-optic coupler significantly increases the damage threshold of the fiber, enabling fiber-optic beam delivery of sufficient nanosecond, 532-nm, laser pulse energy for high-speed PIV measurements. The fiber successfully transmits 1-kHz and 10-kHz laser pulses with energies of 5.3 mJ and 2 mJ, respectively, for more than 25 min without any indication of damage. It is experimentally demonstrated that the tapered fiber possesses the high coupling efficiency (~80%) and moderate beam quality for PIV. Additionally, the nearly uniform output-beam profile exiting the fiber is ideal for PIV applications. Comparative PIV measurements are made using a conventionally (bulk-optic) delivered light sheet, and a similar order of measurement accuracy is obtained with and without fiber coupling. Effective use of fiber-coupled, 10-kHz PIV is demonstrated for instantaneous 2D velocity-field measurements in turbulent reacting flows. Proof-of-concept measurements show significant promise for the performance of fiber-coupled, high-speed PIV using a tapered optical fiber in harsh laser-diagnostic environments such as those encountered in gas-turbine test beds and the cylinder of a combustion engine.

  11. Gradient Boosting as a SNP Filter: an Evaluation Using Simulated and Hair Morphology Data.

    PubMed

    Lubke, Gh; Laurin, C; Walters, R; Eriksson, N; Hysi, P; Spector, Td; Montgomery, Gw; Martin, Ng; Medland, Se; Boomsma, DI

    2013-10-20

    Typically, genome-wide association studies consist of regressing the phenotype on each SNP separately using an additive genetic model. Although statistical models for recessive, dominant, SNP-SNP, or SNP-environment interactions exist, the testing burden makes an evaluation of all possible effects impractical for genome-wide data. We advocate a two-step approach where the first step consists of a filter that is sensitive to different types of SNP main and interactions effects. The aim is to substantially reduce the number of SNPs such that more specific modeling becomes feasible in a second step. We provide an evaluation of a statistical learning method called "gradient boosting machine" (GBM) that can be used as a filter. GBM does not require an a priori specification of a genetic model, and permits inclusion of large numbers of covariates. GBM can therefore be used to explore multiple GxE interactions, which would not be feasible within the parametric framework used in GWAS. We show in a simulation that GBM performs well even under conditions favorable to the standard additive regression model commonly used in GWAS, and is sensitive to the detection of interaction effects even if one of the interacting variables has a zero main effect. The latter would not be detected in GWAS. Our evaluation is accompanied by an analysis of empirical data concerning hair morphology. We estimate the phenotypic variance explained by increasing numbers of highest ranked SNPs, and show that it is sufficient to select 10K-20K SNPs in the first step of a two-step approach. PMID:24404405

  12. SNPMeta: SNP annotation and SNP metadata collection without a reference genome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The increase in availability of resequencing data is greatly accelerating SNP discovery and has facilitated the development of SNP genotyping assays. This, in turn, is increasing interest in annotation of individual SNPs. Currently, these data are only available through curation, or comparison to a ...

  13. Genome-wide SNP detection, validation, and development of an 8K SNP array for apple

    Technology Transfer Automated Retrieval System (TEKTRAN)

    As high-throughput genetic marker screening systems are essential for a range of genetics studies and plant breeding applications, the International RosBREED SNP Consortium (IRSC) has utilized the Illumina Infinium® II system to develop a medium- to high-throughput SNP screening tool for genome-wide...

  14. SNP Discovery Using Next Generation Transcriptomic Sequencing.

    PubMed

    De Wit, Pierre

    2016-01-01

    In this chapter, I will guide the user through methods to find new SNP markers from expressed sequence (RNA-Seq) data, focusing on the sample preparation and also on the bioinformatic analyses needed to sort through the immense flood of data from high-throughput sequencing machines. The general steps included are as follows: sample preparation, sequencing, quality control of data, assembly, mapping, SNP discovery, filtering, validation. The first few steps are traditional laboratory protocols, whereas steps following the sequencing are of bioinformatic nature. The bioinformatics described herein are by no means exhaustive, rather they serve as one example of a simple way of analyzing high-throughput sequence data to find SNP markers. Ideally, one would like to run through this protocol several times with a new dataset, while varying software parameters slightly, in order to determine the robustness of the results. The final validation step, although not described in much detail here, is also quite critical as that will be the final test of the accuracy of the assumptions made in silico.There is a plethora of downstream applications of a SNP dataset, not covered in this chapter. For an example of a more thorough protocol also including differential gene expression and functional enrichment analyses, BLAST annotation and downstream applications of SNP markers, a good starting point could be the "Simple Fool's Guide to population genomics via RNA-Seq," which is available at http://sfg.stanford.edu . PMID:27460371

  15. Multi objective SNP selection using pareto optimality.

    PubMed

    Gumus, Ergun; Gormez, Zeliha; Kursun, Olcay

    2013-04-01

    Biomarker discovery is a challenging task of bioinformatics especially when targeting high dimensional problems such as SNP (single nucleotide polymorphism) datasets. Various types of feature selection methods can be applied to accomplish this task. Typically, using features versus class labels of samples in the training dataset, these methods aim at selecting feature subsets with maximal classification accuracies. Although finding such class-discriminative features is crucial, selection of relevant SNPs for maximizing other properties that exist in the nature of population genetics such as the correlation between genetic diversity and geographical distance of ethnic groups can also be equally important. In this work, a methodology using a multi objective optimization technique called Pareto Optimal is utilized for selecting SNP subsets offering both high classification accuracy and correlation between genomic and geographical distances. In this method, discriminatory power of an SNP is determined using mutual information and its contribution to the genomic-geographical correlation is estimated using its loadings on principal components. Combining these objectives, the proposed method identifies SNP subsets that can better discriminate ethnic groups than those obtained with sole mutual information and yield higher correlation than those obtained with sole principal components on the Human Genome Diversity Project (HGDP) SNP dataset.

  16. Preliminary Results of a 10 kJ Z-Pinch

    SciTech Connect

    Cortazar, O. D.; Piriz, A. R.; Prieto, G. Rodriguez; Hoffmann, D. H. H.; Tahir, N. A.

    2008-04-07

    Preliminary results obtained on 10 kJ Z-pinch device developed at the Plasma and Electrical Discharge Laboratory in the University of Castilla-La Mancha are presented. The device called ENERGU-1 is composed by 8 capacitors (0.5 {mu}F, 75 kV, 20 nH) connected in parallel to a discharge chamber by means of one high power plane transmission line by mean of 8 spark-gaps switches triggered by a 100 kV, 13 ns trigger pulse. The discharge chamber is a cylindrical Pyrex glass tube externally surrounded by a SF{sub 6} isolation atmosphere with the electrodes at the ends. Two different chambers have been studied by discharging the capacitor bank energy in deuterium for optimizing the D-D nuclear fusion reactions: one of 100 mm long by 100 mm inner diameter and the other of the same length and 70 mm inner diameter. Several sequences of ultrahigh speed converter camera photography (5 ns) are presented showing the implosion of plasma columns for different deuterium pressure and currents. Preliminary measurements of integrated 2.45 MeV neutron emissions by a silver activated neutron counter are analyzed as a function of electrical and constructive parameters. A yield of 10{sup 7}-10{sup 8} D-D fusion reactions by shot is reported when the optimum conditions are reached conducting currents of 400-600 kA with a plasma column lifetime above 100 ns.

  17. Dynamic simulation of 10 kW Brayton cryocooler for HTS cable

    NASA Astrophysics Data System (ADS)

    Chang, Ho-Myung; Park, Chan Woo; Yang, Hyung Suk; Hwang, Si Dole

    2014-01-01

    Dynamic simulation of a Brayton cryocooler is presented as a partial effort of a Korean governmental project to develop 1˜3 km HTS cable systems at transmission level in Jeju Island. Thermodynamic design of a 10 kW Brayton cryocooler was completed, and a prototype construction is underway with a basis of steady-state operation. This study is the next step to investigate the transient behavior of cryocooler for two purposes. The first is to simulate and design the cool-down process after scheduled or unscheduled stoppage. The second is to predict the transient behavior following the variation of external conditions such as cryogenic load or outdoor temperature. The detailed specifications of key components, including plate-fin heat exchangers and cryogenic turbo-expanders are incorporated into a commercial software (Aspen HYSYS) to estimate the temporal change of temperature and flow rate over the cryocooler. An initial cool-down scenario and some examples on daily variation of cryocooler are presented and discussed, aiming at stable control schemes of a long cable system.

  18. Dynamic simulation of 10 kW Brayton cryocooler for HTS cable

    SciTech Connect

    Chang, Ho-Myung; Park, Chan Woo; Yang, Hyung Suk; Hwang, Si Dole

    2014-01-29

    Dynamic simulation of a Brayton cryocooler is presented as a partial effort of a Korean governmental project to develop 1∼3 km HTS cable systems at transmission level in Jeju Island. Thermodynamic design of a 10 kW Brayton cryocooler was completed, and a prototype construction is underway with a basis of steady-state operation. This study is the next step to investigate the transient behavior of cryocooler for two purposes. The first is to simulate and design the cool-down process after scheduled or unscheduled stoppage. The second is to predict the transient behavior following the variation of external conditions such as cryogenic load or outdoor temperature. The detailed specifications of key components, including plate-fin heat exchangers and cryogenic turbo-expanders are incorporated into a commercial software (Aspen HYSYS) to estimate the temporal change of temperature and flow rate over the cryocooler. An initial cool-down scenario and some examples on daily variation of cryocooler are presented and discussed, aiming at stable control schemes of a long cable system.

  19. Progress Towards a 6-10 K Turbo-Brayton Cryocooler

    NASA Astrophysics Data System (ADS)

    Zagarola, M. V.; Cragin, K. J.; Breedlove, J. J.; Davis, T. M.

    2006-04-01

    Turbomachine-based Brayton (turbo-Brayton) cryocoolers are an ideal option for long-duration space missions. Key attributes inherent to the technology are high reliability, extremely low vibration emittance, and flexible packaging and integration with instruments and spacecraft systems. The first space implementation of the technology was the NICMOS Cryocooler, which is a single-stage unit that was installed on the Hubble Space Telescope in March 2002. This cryocooler provides 7 W of cooling at 70 K and has been operating for 3.3 years (July 2005) without degradation in performance. New developments at Creare are focused on two-stage configurations with load temperatures as low as 6 K. The lower temperatures and loads have required advances in component technologies to meet aggressive targets for cryocooler mass, size and performance. The development of the electronics, compressors and intermediate turboalternator for a 6-10 K cryocooler are complete. This paper summarizes our accomplishments on the completed components, and reviews our progress towards the development of the remaining critical components, a lightweight recuperator and a high performance low temperature turboalternator.

  20. Pipeline design and thermal stress analysis of a 10kW@20K helium refrigerator

    NASA Astrophysics Data System (ADS)

    Xu, D.; Gong, L. H.; Xu, P.; Liu, H. M.; Li, L. F.; Xu, X. D.

    2014-01-01

    This paper is based on the devices and pipeline in the horizontal cryogenic cold-box of a 10kW@20K helium refrigerator developed by Technical Institute of Physics and Chemistry, Chinese Academy of Sciences. Four devices, six valves, supporting components and pipe lines are positioned in the cold-box. At operating state, the temperature of these devices and pipeline is far below the room temperature, and the lowest temperature is 14K. Due to different material and temperature, the shrinkage of devices and pipes is different. Finite element analysis software SOLIDWORKS SIMULATION was used to numerically simulate the thermal stress and deformation. The results show that the thermal stress of pipe A is a little large. So we should change the pipe route or use a bellows expansion joint. Bellows expansion joints should also be used in the pipes connected to three of the six valves to protect them by decreasing the deformation. At last, the effect of diameter, thickness and bend radius on the thermal stress was analyzed. The results show that the thermal stress of the pipes increases with the increase of the diameter and the decrease of the bend radius.

  1. Ferromagnetism below 10K in Mn-doped BiTe

    NASA Astrophysics Data System (ADS)

    Bos, J. W. G.; Lee, M.; Morosan, E.; Zandbergen, H. W.; Lee, W. L.; Ong, N. P.; Cava, R. J.

    2006-11-01

    Ferromagnetism is observed below 10K in [Bi0.75Te0.125Mn0.125]Te . This material has the BiTe structure, which is made from the stacking of two Te-Bi-Te-Bi-Te blocks and one Bi-Bi block per unit cell. Crystal structure analysis shows that Mn is localized in the Bi2 blocks, and is accompanied by an equal amount of TeBi antisite occupancy in the Bi2Te3 blocks. These TeBi antisite defects greatly enhance the Mn solubility. This is demonstrated by comparison of the [Bi1-xMnx]Te and [Bi1-2xTexMnx]Te series; in the former, the solubility is limited to x=0.067 , while the latter has xmax=0.125 . The magnetism in [Bi1-xMnx]Te changes little with x , while that for [Bi1-2xTexMnx]Te shows a clear variation, leading to ferromagnetism for x>0.067 . Magnetic hysteresis and the anomalous Hall effect are observed for the ferromagnetic samples.

  2. Internal erosion rates of a 10-kW xenon ion thruster

    NASA Technical Reports Server (NTRS)

    Rawlin, Vincent K.

    1988-01-01

    A 30 cm diameter divergent magnetic field ion thruster, developed for mercury operation at 2.7 kW, was modified and operated with xenon propellant at a power level of 10 kW for 567 h to evaluate thruster performance and lifetime. The major differences between this thruster and its baseline configuration were elimination of the three mercury vaporizers, use of a main discharge cathode with a larger orifice, reduction in discharge baffle diameter, and use of an ion accelerating system with larger acceleration grid holes. Grid thickness measurement uncertainties, combined with estimates of the effects of reactive residual facility background gases gave a minimum screen grid lifetime of 7000 h. Discharge cathode orifice erosion rates were measured with three different cathodes with different initial orifice diameters. Three potential problems were identified during the wear test: the upstream side of the discharge baffle eroded at an unacceptable rate; two of the main cathode tubes experienced oxidation, deformation, and failure; and the accelerator grid impingement current was more than an order of magnitude higher than that of the baseline mercury thruster. The charge exchange ion erosion was not quantified in this test. There were no measurable changes in the accelerator grid thickness or the accelerator grid hole diameters.

  3. Electronic Spectra of Protonated Fluoranthene in a Neon Matrix and Gas Phase at 10 K.

    PubMed

    Chakraborty, A; Rice, C A; Hardy, F-X; Fulara, J; Maier, J P

    2016-07-14

    Four electronic systems with origin bands at 759.5, 559.3, 476.3, and 385.5 nm are detected in a 6 K neon matrix following deposition of mass-selected protonated fluoranthene C16H11(+) produced from a reaction of neutral vapor and ethanol in a hot-cathode ion source. Two cationic isomers are identified as the carriers of these band systems. The 559.3, 476.3, and 385.5 nm absorptions are assigned to 4,3,2 (1)A' ← X (1)A' transitions of isomer E(+) (γ-) and the 2 (1)A' ← X (1)A' system at 759.5 nm is of isomer C(+) (α-) of protonated fluoranthene on the basis of theoretical predictions. The electronic spectrum of E(+) was also recorded in the gas phase using a resonant 1 + 1 two-photon excitation-dissociation technique in an ion trap at vibrational and rotational temperatures of 10 K. The 3,2 (1)A' ← X (1)A' transitions have origin band maxima at 558.28 ± 0.01 and 474.92 ± 0.01 nm. Both the 2 (1)A' and 3 (1)A' excited states have a distinct vibrational pattern with lifetimes on the order of 1 ps. PMID:26837823

  4. Field Test Results from a 10 kW Wind Turbine with Active Flow Control

    NASA Astrophysics Data System (ADS)

    Rice, Thomas; Bychkova, Veronika; Taylor, Keith; Clingman, Dan; Amitay, Michael

    2015-11-01

    Active flow control devices including synthetic jets and dynamic vortex generators were tested on a 10 kW wind turbine at RPI. Previous work has shown that load oscillations caused by dynamic stall could be modified through the use of active flow control by injecting momentum into the flow field near the leading edge of a dynamically pitching model. In this study, this work has been extended to its logical conclusion, field-testing active flow control on a real wind turbine. The blades in the current study have a 0.28m chord and 3.05m span, no twist or taper, and were retrofitted with six synthetic jets on one blade and ten dynamic vortex generators on a second blade. The third blade of this turbine was not modified, in order to serve as a control. Strain gauges were installed on each blade to measure blades' deflection. A simple closed loop control was demonstrated and preliminary results indicate reduced vibrational amplitude. Future testing will be conducted on a larger scale, 600kW machine at NREL, incorporating information collected during this study.

  5. Electronic Spectra of Protonated Fluoranthene in a Neon Matrix and Gas Phase at 10 K.

    PubMed

    Chakraborty, A; Rice, C A; Hardy, F-X; Fulara, J; Maier, J P

    2016-07-14

    Four electronic systems with origin bands at 759.5, 559.3, 476.3, and 385.5 nm are detected in a 6 K neon matrix following deposition of mass-selected protonated fluoranthene C16H11(+) produced from a reaction of neutral vapor and ethanol in a hot-cathode ion source. Two cationic isomers are identified as the carriers of these band systems. The 559.3, 476.3, and 385.5 nm absorptions are assigned to 4,3,2 (1)A' ← X (1)A' transitions of isomer E(+) (γ-) and the 2 (1)A' ← X (1)A' system at 759.5 nm is of isomer C(+) (α-) of protonated fluoranthene on the basis of theoretical predictions. The electronic spectrum of E(+) was also recorded in the gas phase using a resonant 1 + 1 two-photon excitation-dissociation technique in an ion trap at vibrational and rotational temperatures of 10 K. The 3,2 (1)A' ← X (1)A' transitions have origin band maxima at 558.28 ± 0.01 and 474.92 ± 0.01 nm. Both the 2 (1)A' and 3 (1)A' excited states have a distinct vibrational pattern with lifetimes on the order of 1 ps.

  6. Development of a 10 kW hydrogen/air PEM fuel cell stack

    SciTech Connect

    Barbir, F.; Marken, F.; Bahar, B.; Kolde, J.A.

    1996-12-31

    PEM fuel cells have potential for meeting automotive industry`s power density and cost requirements, such as 0.8 kW/kg, 0.8 kW/1 and $30/kW. For automotive applications, the fuel cell power requirements are in the 10-100 kW range. As the first phase in reaching this power output, a 10 kW PEM fuel cell stack has been developed at Energy Partners. The stack consists of 50 cells with relatively large active area of 780 cm{sup 2}. The main feature of the stack is the advanced membrane electrode assembly (MEA) developed by W.L. Gore & Associates, Inc. These novel MEAs consist of a thin composite perfluorinated polymer membrane with a catalyst layer with platinum loading of 0.3 Mg/cm{sup 2} on each side. The combination of reinforcement and thinness provides high membrane conductance and improved water distribution in the operating cell. In addition, the membrane has excellent mechanical properties (particularly when it is hydrated) and dimensional stability.

  7. Study of the 100 fs 10 kA X-band linac

    NASA Astrophysics Data System (ADS)

    Takeshita, A.; Uesaka, M.; Watanabe, Tomoyuki; Yamamoto, Masashi; Kaneko, Namio

    1999-01-01

    Design and numerical analysis of an X-band femtosecond electron linear accelerator (linac) is presented. We aim to generate a 100 fs (full width at half maxium: FWHM) electron single bunch with more than 1 nC at the X-band femtosecond linac. The simulation of electron dynamics including magnetic pulse compression is carried out by using PARMELA and SUPERFISH. It is found that the 700 ps (tail-to-tail) electron emission from a 150 kV thermionic gun can be bunched and compressed to 100 fs (FWHM) electron single bunch with the charge of 1 nC which gives 10 kA. We plan to use one high power X-band klystron which can supply 60 MW with more than 200 ns pulse duration. The flatness of plateau of the RF pulse should be 0.2% for stable ultrashort bunch generation. The influence of the klystron voltage fluctuation on the accelerating voltage is quantitatively evaluated and the vacuum design is also done. We have confirmed the feasibility of the linac from viewpoints of state-of the-art technologies.

  8. Gene expression in the rat brain during sleep deprivation and recovery sleep: an Affymetrix GeneChip study.

    PubMed

    Terao, A; Wisor, J P; Peyron, C; Apte-Deshpande, A; Wurts, S W; Edgar, D M; Kilduff, T S

    2006-01-01

    Previous studies have demonstrated that macromolecular synthesis in the brain is modulated in association with the occurrence of sleep and wakefulness. Similarly, the spectral composition of electroencephalographic activity that occurs during sleep is dependent on the duration of prior wakefulness. Since this homeostatic relationship between wake and sleep is highly conserved across mammalian species, genes that are truly involved in the electroencephalographic response to sleep deprivation might be expected to be conserved across mammalian species. Therefore, in the rat cerebral cortex, we have studied the effects of sleep deprivation on the expression of immediate early gene and heat shock protein mRNAs previously shown to be upregulated in the mouse brain in sleep deprivation and in recovery sleep after sleep deprivation. We find that the molecular response to sleep deprivation and recovery sleep in the brain is highly conserved between these two mammalian species, at least in terms of expression of immediate early gene and heat shock protein family members. Using Affymetrix Neurobiology U34 GeneChips , we also screened the rat cerebral cortex, basal forebrain, and hypothalamus for other genes whose expression may be modulated by sleep deprivation or recovery sleep. We find that the response of the basal forebrain to sleep deprivation is more similar to that of the cerebral cortex than to the hypothalamus. Together, these results suggest that sleep-dependent changes in gene expression in the cerebral cortex are similar across rodent species and therefore may underlie sleep history-dependent changes in sleep electroencephalographic activity.

  9. Development of a brushless HTS exciter for a 10 kW HTS synchronous generator

    NASA Astrophysics Data System (ADS)

    Bumby, Chris W.; Badcock, Rodney A.; Sung, Hae-Jin; Kim, Kwang-Min; Jiang, Zhenan; Pantoja, Andres E.; Bernardo, Patrick; Park, Minwon; Buckley, Robert G.

    2016-02-01

    HTS synchronous generators, in which the rotor coils are wound from high-T c superconducting wire, are exciting attention due to their potential to deliver very high torque and power densities. However, injection of the large DC currents required by the HTS rotor coils presents a technical challenge. In this paper we discuss the development of a brushless HTS exciter which operates across the cryostat wall to inject a superconducting DC current into the rotor coil circuit. This approach fundamentally alters the thermal load upon the cryogenic system by removing the need for thermally inefficient normal-conducting current leads. We report results from an experimental laboratory device and show that it operates as a constant voltage source with an effective internal resistance. We then discuss the design of a prototype HTS-PM exciter based on our experimental device, and describe its integration with a demonstration HTS generator. This 200 RPM, 10 kW synchronous generator comprises eight double pancake HTS rotor coils which are operated at 30 K, and are energised to 1.5 T field through the injection of 85 A per pole. We show how this excitation can be achieved using an HTS-PM exciter consisting of 12 stator poles of 12 mm YBCO coated-conductor wire and an external permanent magnet rotor. We demonstrate that such an exciter can excite the rotor windings of this generator without forming a thermal-bridge across the cryostat wall. Finally, we provide estimates of the thermal load imposed by our prototype HTS-PM exciter on the rotor cryostat. We show that duty cycle operation of the device ensures that this heat load can be minimised, and that it is substantially lower than that of equivalently-rated conventional current leads.

  10. Demonstration of 10 K Superconducting Electronics in an Infrared Imaging System

    NASA Astrophysics Data System (ADS)

    Ressler, Michael E.

    1997-04-01

    We report the successful operation of a superconducting niobium nitride (NbN) Josephson Junction-based analog-to-digital converter (ADC) in an infrared imaging system. This system is a flexible testbed which will allow the evaluation of a large variety of cryogenic components (e.g. detector arrays, ADC's, etc.), while still following the general architecture of a scientific instrument, permitting us to determine how well the component will perform in the ``real world''. The testbed is currently composed of a Rockwell International HF-16 128x128 pixel Si:As BIB array, a JPL-developed GaAs 16-to-1 analog multiplexer, and a TRW 12-bit, 10 mega-samples per second, NbN ADC. All three components are located inside a pour/fill liquid helium dewar and operated at 10 K. Simple cold optics along with an 8.5 micron filter image objects onto the focal plane. The images are read out at rates up to 600 frames per second; data can either be stored to hard disk at this rate or every 20th frame can be displayed on a monitor providing ``real-time'' video. We describe the layout and operation of the testbed, with particular emphasis on the lessons learned about operating superconducting electronics as merely another component in a system. We also discuss images and other data comparing the performance of the NbN ADC with a commercially available, equal speed and resolution, silicon ADC. Finally, we explore the future of superconducting electronics; potential products as well as their impact on instrument and spacecraft design.

  11. Lattice constants and expansivities of gas hydrates from 10 K up to the stability limit.

    PubMed

    Hansen, T C; Falenty, A; Kuhs, W F

    2016-02-01

    The lattice constants of hydrogenated and deuterated CH4-, CO2-, Xe- (clathrate structure type I) and N2-hydrates (clathrate structure type II) from 10 K up to the stability limit were established in neutron- and synchrotron diffraction experiments and were used to derive the related thermal expansivities. The following results emerge from this analysis: (1) The differences of expansivities of structure type I and II hydrates are fairly small. (2) Despite the larger guest-size of CO2 as compared to methane, CO2-hydrate has the smaller lattice constants at low temperatures, which is ascribed to the larger attractive guest-host interaction of the CO2-water system. (3) The expansivity of CO2-hydrate is larger than for CH4-hydrate which leads to larger lattice constants for the former at temperatures above ∼150 K; this is likely due to the higher motional degrees of freedom of the CO2 guest molecules. (4) The cage occupancies of Xe- and CO2-hydrates affect significantly the lattice constants. (5) Similar to ice Ih, the deuterated compounds have generally slightly larger lattice constants which can be ascribed to the somewhat weaker H-bonding. (6) Compared to ice Ih, the high temperature expansivities are about 50% larger; in contrast to ice Ih and the empty hydrate, there is no negative thermal expansion at low temperature. (7) A comparison of the experimental results with lattice dynamical work, with models based on an Einstein oscillator model, and results from inelastic neutron scattering suggest that the contribution of the guest atoms' vibrational energy to thermal expansion is important, most prominently for CO2- and Xe-hydrates. PMID:26851915

  12. Lattice constants and expansivities of gas hydrates from 10 K up to the stability limit

    NASA Astrophysics Data System (ADS)

    Hansen, T. C.; Falenty, A.; Kuhs, W. F.

    2016-02-01

    The lattice constants of hydrogenated and deuterated CH4-, CO2-, Xe- (clathrate structure type I) and N2-hydrates (clathrate structure type II) from 10 K up to the stability limit were established in neutron- and synchrotron diffraction experiments and were used to derive the related thermal expansivities. The following results emerge from this analysis: (1) The differences of expansivities of structure type I and II hydrates are fairly small. (2) Despite the larger guest-size of CO2 as compared to methane, CO2-hydrate has the smaller lattice constants at low temperatures, which is ascribed to the larger attractive guest-host interaction of the CO2-water system. (3) The expansivity of CO2-hydrate is larger than for CH4-hydrate which leads to larger lattice constants for the former at temperatures above ˜150 K; this is likely due to the higher motional degrees of freedom of the CO2 guest molecules. (4) The cage occupancies of Xe- and CO2-hydrates affect significantly the lattice constants. (5) Similar to ice Ih, the deuterated compounds have generally slightly larger lattice constants which can be ascribed to the somewhat weaker H-bonding. (6) Compared to ice Ih, the high temperature expansivities are about 50% larger; in contrast to ice Ih and the empty hydrate, there is no negative thermal expansion at low temperature. (7) A comparison of the experimental results with lattice dynamical work, with models based on an Einstein oscillator model, and results from inelastic neutron scattering suggest that the contribution of the guest atoms' vibrational energy to thermal expansion is important, most prominently for CO2- and Xe-hydrates.

  13. Continuous Cooling from 10 K to 4 K Using a Toroidal ADR

    NASA Technical Reports Server (NTRS)

    DiPirro, Michael J.; Canavan, Edgar R.; Shirron, Peter J.; Tuttle, James G.

    2003-01-01

    Future large infrared space telescopes will require cooling to 4K to achieve background limited performance for submillimeter wavelengths. These observatories will require lifetimes of many years and will have relatively large cooling requirements making stored helium dewars impractical. We have designed and are building an adiabatic demagnetization refrigerator (ADR) for use in cooling relatively large loads (10- 100 mW) at 4K and rejecting that heat to a cryocooler operating at 1 OK. Cryocoolers below 1 OK have poor thermodynamic efficiency and ADRs can operate in this temperature range with an efficiency of 75% of Carnot or better. Overall, this can save as much as 2/3 of the input power required to operate a 4K cryocooler. The ADR magnet consists of 8 short coils wired in series and arranged in a toroid to provide self shielding of its magnetic field. This will save mass (about 30% of the mass or about 1.5 kg in our small version, higher percentages in higher cooling power, larger versions) that would have been used for passive or active shields in an ordinary solenoid. The toroid has a 100 mm outer diameter and will produce an approximately 3T average field. In the initial demonstration model the toroid coils will be wound with ordinary NbTi wire and operated at 4K. A second version will then use Nb3Sn wire to provide complete 10K operation. As a refrigerant for this temperature range we will use either GdLiF4 or GdF3 crystals, pending tests of these crystals' cooling capacity per field and thermal conductance. Preliminary indications are that these materials are superior to GGG. We will use gas gap heat switches to alternately connect the toroid to the cold load and the warm heat sink. A small continuous stage will maintain the cold end at 4K while the main toroid is recycled.

  14. SNP-SNP Interaction Analysis on Soybean Oil Content under Multi-Environments

    PubMed Central

    Yin, Zhengong; Leng, Yue; Yu, Hongxiao; Jia, Huiying; Jiang, Shanshan; Ni, Zhongqiu; Jiang, Hongwei; Han, Xue; Liu, Chunyan; Hu, Zhenbang; Wu, Xiaoxia; Hu, Guohua; Xin, Dawei; Qi, Zhaoming

    2016-01-01

    Soybean oil content is one of main quality traits. In this study, we used the multifactor dimensionality reduction (MDR) method and a soybean high-density genetic map including 5,308 markers to identify stable single nucleotide polymorphism (SNP)—SNP interactions controlling oil content in soybean across 23 environments. In total, 36,442,756 SNP-SNP interaction pairs were detected, 1865 of all interaction pairs associated with soybean oil content were identified under multiple environments by the Bonferroni correction with p <3.55×10−11. Two and 1863 SNP-SNP interaction pairs detected stable across 12 and 11 environments, respectively, which account around 50% of total environments. Epistasis values and contribution rates of stable interaction (the SNP interaction pairs were detected in more than 2 environments) pairs were detected by the two way ANOVA test, the available interaction pairs were ranged 0.01 to 0.89 and from 0.01 to 0.85, respectively. Some of one side of the interaction pairs were identified with previously research as a major QTL without epistasis effects. The results of this study provide insights into the genetic architecture of soybean oil content and can serve as a basis for marker-assisted selection breeding. PMID:27668866

  15. SNP discovery by amplicon sequencing and multiplex SNP genotyping in the allopolyploid species Brassica napus.

    PubMed

    Durstewitz, G; Polley, A; Plieske, J; Luerssen, H; Graner, E M; Wieseke, R; Ganal, M W

    2010-11-01

    Oilseed rape (Brassica napus) is an allotetraploid species consisting of two genomes, derived from B. rapa (A genome) and B. oleracea (C genome). The presence of these two genomes makes single nucleotide polymorphism (SNP) marker identification and SNP analysis more challenging than in diploid species, as for a given locus usually two versions of a DNA sequence (based on the two ancestral genomes) have to be analyzed simultaneously during SNP identification and analysis. One hundred amplicons derived from expressed sequence tag (ESTs) were analyzed to identify SNPs in a panel of oilseed rape varieties and within two sister species representing the ancestral genomes. A total of 604 SNPs were identified, averaging one SNP in every 42 bp. It was possible to clearly discriminate SNPs that are polymorphic between different plant varieties from SNPs differentiating the two ancestral genomes. To validate the identified SNPs for their use in genetic analysis, we have developed Illumina GoldenGate assays for some of the identified SNPs. Through the analysis of a number of oilseed rape varieties and mapping populations with GoldenGate assays, we were able to identify a number of different segregation patterns in allotetraploid oilseed rape. The majority of the identified SNP markers can be readily used for genetic mapping, showing that amplicon sequencing and Illumina GoldenGate assays can be used to reliably identify SNP markers in tetraploid oilseed rape and to convert them into successful SNP assays that can be used for genetic analysis.

  16. Next generation genome-wide association tool: Design and coverage of a high-throughput European-optimized SNP array

    PubMed Central

    Hoffmann, Thomas J.; Kvale, Mark N.; Hesselson, Stephanie E.; Zhan, Yiping; Aquino, Christine; Cao, Yang; Cawley, Simon; Chung, Elaine; Connell, Sheryl; Eshragh, Jasmin; Ewing, Marcia; Gollub, Jeremy; Henderson, Mary; Hubbell, Earl; Iribarren, Carlos; Kaufman, Jay; Lao, Richard Z.; Lu, Yontao; Ludwig, Dana; Mathauda, Gurpreet K.; McGuire, William; Mei, Gangwu; Miles, Sunita; Purdy, Matthew M.; Quesenberry, Charles; Ranatunga, Dilrini; Rowell, Sarah; Sadler, Marianne; Shapero, Michael H.; Shen, Ling; Shenoy, Tanushree R.; Smethurst, David; Van den Eeden, Stephen K.; Walter, Larry; Wan, Eunice; Wearley, Reid; Webster, Teresa; Wen, Christopher C.; Weng, Li; Whitmer, Rachel A.; Williams, Alan; Wong, Simon C.; Zau, Chia; Finn, Andrea; Schaefer, Catherine; Kwok, Pui-Yan; Risch, Neil

    2011-01-01

    The success of genome-wide association studies has paralleled the development of efficient genotyping technologies. We describe the development of a next-generation microarray based on the new highly-efficient Affymetrix Axiom genotyping technology that we are using to genotype individuals of European ancestry from the Kaiser Permanente Research Program on Genes, Environment and Health (RPGEH). The array contains 674,517 SNPs, and provides excellent genome-wide as well as gene-based and candidate-SNP coverage. Coverage was calculated using an approach based on imputation and cross validation. Preliminary results for the first 80,301 saliva-derived DNA samples from the RPGEH demonstrate very high quality genotypes, with sample success rates above 94% and over 98% of successful samples having SNP call rates exceeding 98%. At steady state, we have produced 462 million genotypes per week for each Axiom system. The new array provides a valuable addition to the repertoire of tools for large scale genome-wide association studies. PMID:21565264

  17. SNP Array in Hematopoietic Neoplasms: A Review

    PubMed Central

    Song, Jinming; Shao, Haipeng

    2015-01-01

    Cytogenetic analysis is essential for the diagnosis and prognosis of hematopoietic neoplasms in current clinical practice. Many hematopoietic malignancies are characterized by structural chromosomal abnormalities such as specific translocations, inversions, deletions and/or numerical abnormalities that can be identified by karyotype analysis or fluorescence in situ hybridization (FISH) studies. Single nucleotide polymorphism (SNP) arrays offer high-resolution identification of copy number variants (CNVs) and acquired copy-neutral loss of heterozygosity (LOH)/uniparental disomy (UPD) that are usually not identifiable by conventional cytogenetic analysis and FISH studies. As a result, SNP arrays have been increasingly applied to hematopoietic neoplasms to search for clinically-significant genetic abnormalities. A large numbers of CNVs and UPDs have been identified in a variety of hematopoietic neoplasms. CNVs detected by SNP array in some hematopoietic neoplasms are of prognostic significance. A few specific genes in the affected regions have been implicated in the pathogenesis and may be the targets for specific therapeutic agents in the future. In this review, we summarize the current findings of application of SNP arrays in a variety of hematopoietic malignancies with an emphasis on the clinically significant genetic variants. PMID:27600067

  18. SNP Array in Hematopoietic Neoplasms: A Review

    PubMed Central

    Song, Jinming; Shao, Haipeng

    2015-01-01

    Cytogenetic analysis is essential for the diagnosis and prognosis of hematopoietic neoplasms in current clinical practice. Many hematopoietic malignancies are characterized by structural chromosomal abnormalities such as specific translocations, inversions, deletions and/or numerical abnormalities that can be identified by karyotype analysis or fluorescence in situ hybridization (FISH) studies. Single nucleotide polymorphism (SNP) arrays offer high-resolution identification of copy number variants (CNVs) and acquired copy-neutral loss of heterozygosity (LOH)/uniparental disomy (UPD) that are usually not identifiable by conventional cytogenetic analysis and FISH studies. As a result, SNP arrays have been increasingly applied to hematopoietic neoplasms to search for clinically-significant genetic abnormalities. A large numbers of CNVs and UPDs have been identified in a variety of hematopoietic neoplasms. CNVs detected by SNP array in some hematopoietic neoplasms are of prognostic significance. A few specific genes in the affected regions have been implicated in the pathogenesis and may be the targets for specific therapeutic agents in the future. In this review, we summarize the current findings of application of SNP arrays in a variety of hematopoietic malignancies with an emphasis on the clinically significant genetic variants.

  19. Compression and fast retrieval of SNP data

    PubMed Central

    Sambo, Francesco; Di Camillo, Barbara; Toffolo, Gianna; Cobelli, Claudio

    2014-01-01

    Motivation: The increasing interest in rare genetic variants and epistatic genetic effects on complex phenotypic traits is currently pushing genome-wide association study design towards datasets of increasing size, both in the number of studied subjects and in the number of genotyped single nucleotide polymorphisms (SNPs). This, in turn, is leading to a compelling need for new methods for compression and fast retrieval of SNP data. Results: We present a novel algorithm and file format for compressing and retrieving SNP data, specifically designed for large-scale association studies. Our algorithm is based on two main ideas: (i) compress linkage disequilibrium blocks in terms of differences with a reference SNP and (ii) compress reference SNPs exploiting information on their call rate and minor allele frequency. Tested on two SNP datasets and compared with several state-of-the-art software tools, our compression algorithm is shown to be competitive in terms of compression rate and to outperform all tools in terms of time to load compressed data. Availability and implementation: Our compression and decompression algorithms are implemented in a C++ library, are released under the GNU General Public License and are freely downloadable from http://www.dei.unipd.it/~sambofra/snpack.html. Contact: sambofra@dei.unipd.it or cobelli@dei.unipd.it. PMID:25064564

  20. Genome-wide identification of copy number variations in Holstein cattle from Baja California, Mexico, using high-density SNP genotyping arrays.

    PubMed

    Salomón-Torres, R; González-Vizcarra, V M; Medina-Basulto, G E; Montaño-Gómez, M F; Mahadevan, P; Yaurima-Basaldúa, V H; Villa-Angulo, C; Villa-Angulo, R

    2015-10-02

    Copy number variations (CNVs) are an important source of genomic structural variation, and can be used as markers to investigate phenotypic and economic traits. CNVs also have functional effects on gene expression and can contribute to disease susceptibility in mammals. Currently, single nucleotide polymorphism genotyping arrays (SNP chips) are the technology of choice for identifying CNV variations. Microarray technologies have recently been used to study the bovine genome. The objective of the present study was to develop CNVs in Holstein cows from the Northwest of Mexico using the Affymetrix Axiom Genome-Wide BOS 1 Array, which assays 648,315 SNPs and provides a wide coverage for genome-wide studies. We applied the two most widely used algorithms for the discovery of CNVs (PennCNV and QuantiSNP) and found 56 CNV regions (CNVRs) representing 0.33% of the bovine genome (8.46 Mb). These CNVRs ranged from 1.5 to 970.8 kb with an average length of 151 kb. They involved 103 genes and showed a 28% overlap with CNVRs already reported. Of the 56 CNVRs found, 20 were novel. In this study we present the first genomic analysis of CNVs in Mexican cattle using high-density SNP data. Our results provide a new reference basis for future genomic variation and association studies between CNVs and phenotypes, especially in Mexican cattle.

  1. 2002 Monthly Carbon Dioxide Emissions from Mexico at a 10x10k Spatial Resolution

    NASA Astrophysics Data System (ADS)

    Mendoza, D. L.; Gurney, K. R.; Geethakumar, S.; Zhou, Y.; Sahni, N.

    2009-12-01

    The contribution of fossil fuel CO2 emissions to the total measured amount of CO2 in the Earth’s atmosphere remains an important component of carbon cycle science, particularly as efforts to understand the net exchange of carbon at the surface move to smaller scales. In order to reduce the uncertainty of this flux, researchers led by Purdue University have built a high-resolution fossil fuel CO2 flux inventory for the United States, called “Vulcan”. The Vulcan inventory quantifies emissions for the United States at 10km resolution every hour for the year 2002 and can be seen as a key component of a national assessment and verification system for greenhouse gas emissions and emissions mitigation. As part of the North American Carbon Project, the 2002 carbon dioxide emissions from Mexico are presented at the monthly temporal and municipality spatial scale. Mexico is of particular importance because of the scientific integration under the North American Carbon Program. Furthermore, Mexico has seen a notable growth in its population as well as migration toward urban centers and increasing energy requirements due in part to industrial intensification. The native resolution of the emissions is geolocated (lat/lon) for point sources, such as power plants, airports, and large industry. The emissions are estimated at the municipality level for residential and commercial sources, and allocated to roads for the mobile transport sector. Data sources include the National Emissions Inventory (NEI), Commission for Environmental Cooperation (CEC), and Carbon Monitoring for Action (CARMA). CO2 emissions are calculated from the 1999 NEI data by converting CO emissions using sector and process-dependent emission factors, and is scaled up to 2002 using statistics obtained from the Carbon Dioxide Information Analysis Center CDIAC. CEC and CARMA data, which encompass power plant emissions, are already in units of CO2. Emissions are regridded to 10x10k and 0.1x0.1 deg grids to

  2. 1?10 kW Stationary Combined Heat and Power Systems Status and Technical Potential: Independent Review

    SciTech Connect

    Maru, H. C.; Singhal, S. C.; Stone, C.; Wheeler, D.

    2010-11-01

    This independent review examines the status and technical potential of 1-10 kW stationary combined heat and power fuel cell systems and analyzes the achievability of the DOE cost, efficiency, and durability targets for 2012, 2015, and 2020.

  3. A 10 kW dc-dc converter using IGBTs with active snubbers. [Insulated Gate Bipolar Transistor

    NASA Technical Reports Server (NTRS)

    Masserant, Brian J.; Shriver, Jeffrey L.; Stuart, Thomas A.

    1993-01-01

    This full bridge dc-dc converter employs zero voltage switching (ZVS) on one leg and zero current switching (ZCS) on the other. This technique produces exceptionally low IGBT switching losses through the use of an active snubber that recycles energy back to the source. Experimental results are presented for a 10 kW, 20 kHz converter.

  4. ENVIRONMENTAL TECHNOLOGY VERIFICATION REPORT: STORMWATER SOURCE AREA TREATMENT DEVICE — BAYSAVER TECHNOLOGIES, INC. BAYSAVER SEPARATION SYSTEM, MODEL 10K

    EPA Science Inventory

    Verification testing of the BaySaver Separation System, Model 10K was conducted on a 10 acre drainage basin near downtown Griffin, Georgia. The system consists of two water tight pre-cast concrete manholes and a high-density polyethylene BaySaver Separator Unit. The BaySaver Mod...

  5. Exhaustive Genome-Wide Search for SNP-SNP Interactions Across 10 Human Diseases

    PubMed Central

    Murk, William; DeWan, Andrew T.

    2016-01-01

    The identification of statistical SNP-SNP interactions may help explain the genetic etiology of many human diseases, but exhaustive genome-wide searches for these interactions have been difficult, due to a lack of power in most datasets. We aimed to use data from the Resource for Genetic Epidemiology Research on Adult Health and Aging (GERA) study to search for SNP-SNP interactions associated with 10 common diseases. FastEpistasis and BOOST were used to evaluate all pairwise interactions among approximately N = 300,000 single nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) ≥ 0.15, for the dichotomous outcomes of allergic rhinitis, asthma, cardiac disease, depression, dermatophytosis, type 2 diabetes, dyslipidemia, hemorrhoids, hypertensive disease, and osteoarthritis. A total of N = 45,171 subjects were included after quality control steps were applied. These data were divided into discovery and replication subsets; the discovery subset had > 80% power, under selected models, to detect genome-wide significant interactions (P < 10−12). Interactions were also evaluated for enrichment in particular SNP features, including functionality, prior disease relevancy, and marginal effects. No interaction in any disease was significant in both the discovery and replication subsets. Enrichment analysis suggested that, for some outcomes, interactions involving SNPs with marginal effects were more likely to be nominally replicated, compared to interactions without marginal effects. If SNP-SNP interactions play a role in the etiology of the studied conditions, they likely have weak effect sizes, involve lower-frequency variants, and/or involve complex models of interaction that are not captured well by the methods that were utilized. PMID:27185397

  6. Exhaustive Genome-Wide Search for SNP-SNP Interactions Across 10 Human Diseases.

    PubMed

    Murk, William; DeWan, Andrew T

    2016-01-01

    The identification of statistical SNP-SNP interactions may help explain the genetic etiology of many human diseases, but exhaustive genome-wide searches for these interactions have been difficult, due to a lack of power in most datasets. We aimed to use data from the Resource for Genetic Epidemiology Research on Adult Health and Aging (GERA) study to search for SNP-SNP interactions associated with 10 common diseases. FastEpistasis and BOOST were used to evaluate all pairwise interactions among approximately N = 300,000 single nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) ≥ 0.15, for the dichotomous outcomes of allergic rhinitis, asthma, cardiac disease, depression, dermatophytosis, type 2 diabetes, dyslipidemia, hemorrhoids, hypertensive disease, and osteoarthritis. A total of N = 45,171 subjects were included after quality control steps were applied. These data were divided into discovery and replication subsets; the discovery subset had > 80% power, under selected models, to detect genome-wide significant interactions (P < 10(-12)). Interactions were also evaluated for enrichment in particular SNP features, including functionality, prior disease relevancy, and marginal effects. No interaction in any disease was significant in both the discovery and replication subsets. Enrichment analysis suggested that, for some outcomes, interactions involving SNPs with marginal effects were more likely to be nominally replicated, compared to interactions without marginal effects. If SNP-SNP interactions play a role in the etiology of the studied conditions, they likely have weak effect sizes, involve lower-frequency variants, and/or involve complex models of interaction that are not captured well by the methods that were utilized.

  7. Exhaustive Genome-Wide Search for SNP-SNP Interactions Across 10 Human Diseases.

    PubMed

    Murk, William; DeWan, Andrew T

    2016-01-01

    The identification of statistical SNP-SNP interactions may help explain the genetic etiology of many human diseases, but exhaustive genome-wide searches for these interactions have been difficult, due to a lack of power in most datasets. We aimed to use data from the Resource for Genetic Epidemiology Research on Adult Health and Aging (GERA) study to search for SNP-SNP interactions associated with 10 common diseases. FastEpistasis and BOOST were used to evaluate all pairwise interactions among approximately N = 300,000 single nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) ≥ 0.15, for the dichotomous outcomes of allergic rhinitis, asthma, cardiac disease, depression, dermatophytosis, type 2 diabetes, dyslipidemia, hemorrhoids, hypertensive disease, and osteoarthritis. A total of N = 45,171 subjects were included after quality control steps were applied. These data were divided into discovery and replication subsets; the discovery subset had > 80% power, under selected models, to detect genome-wide significant interactions (P < 10(-12)). Interactions were also evaluated for enrichment in particular SNP features, including functionality, prior disease relevancy, and marginal effects. No interaction in any disease was significant in both the discovery and replication subsets. Enrichment analysis suggested that, for some outcomes, interactions involving SNPs with marginal effects were more likely to be nominally replicated, compared to interactions without marginal effects. If SNP-SNP interactions play a role in the etiology of the studied conditions, they likely have weak effect sizes, involve lower-frequency variants, and/or involve complex models of interaction that are not captured well by the methods that were utilized. PMID:27185397

  8. Genome-wide SNP detection, validation, and development of an 8K SNP array for apple.

    PubMed

    Chagné, David; Crowhurst, Ross N; Troggio, Michela; Davey, Mark W; Gilmore, Barbara; Lawley, Cindy; Vanderzande, Stijn; Hellens, Roger P; Kumar, Satish; Cestaro, Alessandro; Velasco, Riccardo; Main, Dorrie; Rees, Jasper D; Iezzoni, Amy; Mockler, Todd; Wilhelm, Larry; Van de Weg, Eric; Gardiner, Susan E; Bassil, Nahla; Peace, Cameron

    2012-01-01

    As high-throughput genetic marker screening systems are essential for a range of genetics studies and plant breeding applications, the International RosBREED SNP Consortium (IRSC) has utilized the Illumina Infinium® II system to develop a medium- to high-throughput SNP screening tool for genome-wide evaluation of allelic variation in apple (Malus×domestica) breeding germplasm. For genome-wide SNP discovery, 27 apple cultivars were chosen to represent worldwide breeding germplasm and re-sequenced at low coverage with the Illumina Genome Analyzer II. Following alignment of these sequences to the whole genome sequence of 'Golden Delicious', SNPs were identified using SoapSNP. A total of 2,113,120 SNPs were detected, corresponding to one SNP to every 288 bp of the genome. The Illumina GoldenGate® assay was then used to validate a subset of 144 SNPs with a range of characteristics, using a set of 160 apple accessions. This validation assay enabled fine-tuning of the final subset of SNPs for the Illumina Infinium® II system. The set of stringent filtering criteria developed allowed choice of a set of SNPs that not only exhibited an even distribution across the apple genome and a range of minor allele frequencies to ensure utility across germplasm, but also were located in putative exonic regions to maximize genotyping success rate. A total of 7867 apple SNPs was established for the IRSC apple 8K SNP array v1, of which 5554 were polymorphic after evaluation in segregating families and a germplasm collection. This publicly available genomics resource will provide an unprecedented resolution of SNP haplotypes, which will enable marker-locus-trait association discovery, description of the genetic architecture of quantitative traits, investigation of genetic variation (neutral and functional), and genomic selection in apple.

  9. A Bayesian Framework for SNP Identification

    SciTech Connect

    Webb-Robertson, Bobbie-Jo M.; Havre, Susan L.; Payne, Deborah A.

    2005-07-01

    Current proteomics techniques, such as mass spectrometry, focus on protein identification, usually ignoring most types of modifications beyond post-translational modifications, with the assumption that only a small number of peptides have to be matched to a protein for a positive identification. However, not all proteins are being identified with current techniques and improved methods to locate points of mutation are becoming a necessity. In the case when single-nucleotide polymorphisms (SNPs) are observed, brute force is the most common method to locate them, quickly becoming computationally unattractive as the size of the database associated with the model organism grows. We have developed a Bayesian model for SNPs, BSNP, incorporating evolutionary information at both the nucleotide and amino acid levels. Formulating SNPs as a Bayesian inference problem allows probabilities of interest to be easily obtained, for example the probability of a specific SNP or specific type of mutation over a gene or entire genome. Three SNP databases were observed in the evaluation of the BSNP model; the first SNP database is a disease specific gene in human, hemoglobin, the second is also a disease specific gene in human, p53, and the third is a more general SNP database for multiple genes in mouse. We validate that the BSNP model assigns higher posterior probabilities to the SNPs defined in all three separate databases than can be attributed to chance under specific evolutionary information, for example the amino acid model described by Majewski and Ott in conjunction with either the four-parameter nucleotide model by Bulmer or seven-parameter nucleotide model by Majewski and Ott.

  10. eSNPO: An eQTL-based SNP Ontology and SNP functional enrichment analysis platform

    PubMed Central

    Li, Jin; Wang, Limei; Jiang, Tao; Wang, Jizhe; Li, Xue; Liu, Xiaoyan; Wang, Chunyu; Teng, Zhixia; Zhang, Ruijie; Lv, Hongchao; Guo, Maozu

    2016-01-01

    Genome-wide association studies (GWASs) have mined many common genetic variants associated with human complex traits like diseases. After that, the functional annotation and enrichment analysis of significant SNPs are important tasks. Classic methods are always based on physical positions of SNPs and genes. Expression quantitative trait loci (eQTLs) are genomic loci that contribute to variation in gene expression levels and have been proven efficient to connect SNPs and genes. In this work, we integrated the eQTL data and Gene Ontology (GO), constructed associations between SNPs and GO terms, then performed functional enrichment analysis. Finally, we constructed an eQTL-based SNP Ontology and SNP functional enrichment analysis platform. Taking Parkinson Disease (PD) as an example, the proposed platform and method are efficient. We believe eSNPO will be a useful resource for SNP functional annotation and enrichment analysis after we have got significant disease related SNPs. PMID:27470167

  11. eSNPO: An eQTL-based SNP Ontology and SNP functional enrichment analysis platform.

    PubMed

    Li, Jin; Wang, Limei; Jiang, Tao; Wang, Jizhe; Li, Xue; Liu, Xiaoyan; Wang, Chunyu; Teng, Zhixia; Zhang, Ruijie; Lv, Hongchao; Guo, Maozu

    2016-01-01

    Genome-wide association studies (GWASs) have mined many common genetic variants associated with human complex traits like diseases. After that, the functional annotation and enrichment analysis of significant SNPs are important tasks. Classic methods are always based on physical positions of SNPs and genes. Expression quantitative trait loci (eQTLs) are genomic loci that contribute to variation in gene expression levels and have been proven efficient to connect SNPs and genes. In this work, we integrated the eQTL data and Gene Ontology (GO), constructed associations between SNPs and GO terms, then performed functional enrichment analysis. Finally, we constructed an eQTL-based SNP Ontology and SNP functional enrichment analysis platform. Taking Parkinson Disease (PD) as an example, the proposed platform and method are efficient. We believe eSNPO will be a useful resource for SNP functional annotation and enrichment analysis after we have got significant disease related SNPs. PMID:27470167

  12. Design and characterization of the ePix10k: a high dynamic range integrating pixel ASIC for LCLS detectors

    NASA Astrophysics Data System (ADS)

    Caragiulo, P.; Dragone, A.; Markovic, B.; Herbst, R.; Nishimura, K.; Reese, B.; Herrmann, S.; Hart, P.; Blaj, G.; Segal, J.; Tomada, A.; Hasi, J.; Carini, G.; Kenney, C.; Haller, G.

    2015-05-01

    ePix10k is a variant of a novel class of integrating pixel ASICs architectures optimized for the processing of signals in second generation LINAC Coherent Light Source (LCLS) X-Ray cameras. The ASIC is optimized for high dynamic range application requiring high spatial resolution and fast frame rates. ePix ASICs are based on a common platform composed of a random access analog matrix of pixel with global shutter, fast parallel column readout, and dedicated sigma-delta analog to digital converters per column. The ePix10k variant has 100um×100um pixels arranged in a 176×192 matrix, a resolution of 140e- r.m.s. and a signal range of 3.5pC (10k photons at 8keV). In its final version it will be able to sustain a frame rate of 2kHz. A first prototype has been fabricated and characterized. Performance in terms of noise, linearity, uniformity, cross-talk, together with preliminary measurements with bump bonded sensors are reported here.

  13. Linkage mapping bovine EST-based SNP

    PubMed Central

    Snelling, Warren M; Casas, Eduardo; Stone, Roger T; Keele, John W; Harhay, Gregory P; Bennett, Gary L; Smith, Timothy PL

    2005-01-01

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

  14. pfSNP: An integrated potentially functional SNP resource that facilitates hypotheses generation through knowledge syntheses.

    PubMed

    Wang, Jingbo; Ronaghi, Mostafa; Chong, Samuel S; Lee, Caroline G L

    2011-01-01

    Currently, >14,000,000 single nucleotide polymorphisms (SNPs) are reported. Identifying phenotype-affecting SNPs among these many SNPs pose significant challenges. Although several Web resources are available that can inform about the functionality of SNPs, these resources are mainly annotation databases and are not very comprehensive. In this article, we present a comprehensive, well-annotated, integrated pfSNP (potentially functional SNPs) Web resource (http://pfs.nus.edu.sg/), which is aimed to facilitate better hypothesis generation through knowledge syntheses mediated by better data integration and a user-friendly Web interface. pfSNP integrates >40 different algorithms/resources to interrogate >14,000,000 SNPs from the dbSNP database for SNPs of potential functional significance based on previous published reports, inferred potential functionality from genetic approaches as well as predicted potential functionality from sequence motifs. Its query interface has the user-friendly "auto-complete, prompt-as-you-type" feature and is highly customizable, facilitating different combination of queries using Boolean-logic. Additionally, to facilitate better understanding of the results and aid in hypotheses generation, gene/pathway-level information with text clouds highlighting enriched tissues/pathways as well as detailed-related information are also provided on the results page. Hence, the pfSNP resource will be of great interest to scientists focusing on association studies as well as those interested to experimentally address the functionality of SNPs.

  15. Methods comparison for high-resolution transcriptional analysis of archival material on Affymetrix Plus 2.0 and Exon 1.0 microarrays.

    PubMed

    Linton, Kim; Hey, Yvonne; Dibben, Sian; Miller, Crispin; Freemont, Anthony; Radford, John; Pepper, Stuart

    2009-07-01

    Microarray gene expression profiling of formalin-fixed paraffin-embedded (FFPE) tissues is a new and evolving technique. This report compares transcript detection rates on Affymetrix U133 Plus 2.0 and Human Exon 1.0 ST GeneChips across several RNA extraction and target labeling protocols, using routinely collected archival FFPE samples. All RNA extraction protocols tested (Ambion-Optimum, Ambion-RecoverAll, and Qiagen-RNeasy FFPE) provided extracts suitable for microarray hybridization. Compared with Affymetrix One-Cycle labeled extracts, NuGEN system protocols utilizing oligo(dT) and random hexamer primers, and cDNA target preparations instead of cRNA, achieved percent present rates up to 55% on Plus 2.0 arrays. Based on two paired-sample analyses, at 90% specificity this equalled an average 30 percentage-point increase (from 50% to 80%) in FFPE transcript sensitivity relative to fresh frozen tissues, which we have assumed to have 100% sensitivity and specificity. The high content of Exon arrays, with multiple probe sets per exon, improved FFPE sensitivity to 92% at 96% specificity, corresponding to an absolute increase of ~600 genes over Plus 2.0 arrays. While larger series are needed to confirm high correspondence between fresh-frozen and FFPE expression patterns, these data suggest that both Plus 2.0 and Exon arrays are suitable platforms for FFPE microarray expression analyses.

  16. SNP marker detection and genotyping in tilapia.

    PubMed

    Van Bers, N E M; Crooijmans, R P M A; Groenen, M A M; Dibbits, B W; Komen, J

    2012-09-01

    We have generated a unique resource consisting of nearly 175 000 short contig sequences and 3569 SNP markers from the widely cultured GIFT (Genetically Improved Farmed Tilapia) strain of Nile tilapia (Oreochromis niloticus). In total, 384 SNPs were selected to monitor the wider applicability of the SNPs by genotyping tilapia individuals from different strains and different geographical locations. In all strains and species tested (O. niloticus, O. aureus and O. mossambicus), the genotyping assay was working for a similar number of SNPs (288-305 SNPs). The actual number of polymorphic SNPs was, as expected, highest for individuals from the GIFT population (255 SNPs). In the individuals from an Egyptian strain and in individuals caught in the wild in the basin of the river Volta, 197 and 163 SNPs were polymorphic, respectively. A pairwise calculation of Nei's genetic distance allowed the discrimination of the individual strains and species based on the genotypes determined with the SNP set. We expect that this set will be widely applicable for use in tilapia aquaculture, e.g. for pedigree reconstruction. In addition, this set is currently used for assaying the genetic diversity of native Nile tilapia in areas where tilapia is, or will be, introduced in aquaculture projects. This allows the tracing of escapees from aquaculture and the monitoring of effects of introgression and hybridization. PMID:22524158

  17. SNP marker detection and genotyping in tilapia.

    PubMed

    Van Bers, N E M; Crooijmans, R P M A; Groenen, M A M; Dibbits, B W; Komen, J

    2012-09-01

    We have generated a unique resource consisting of nearly 175 000 short contig sequences and 3569 SNP markers from the widely cultured GIFT (Genetically Improved Farmed Tilapia) strain of Nile tilapia (Oreochromis niloticus). In total, 384 SNPs were selected to monitor the wider applicability of the SNPs by genotyping tilapia individuals from different strains and different geographical locations. In all strains and species tested (O. niloticus, O. aureus and O. mossambicus), the genotyping assay was working for a similar number of SNPs (288-305 SNPs). The actual number of polymorphic SNPs was, as expected, highest for individuals from the GIFT population (255 SNPs). In the individuals from an Egyptian strain and in individuals caught in the wild in the basin of the river Volta, 197 and 163 SNPs were polymorphic, respectively. A pairwise calculation of Nei's genetic distance allowed the discrimination of the individual strains and species based on the genotypes determined with the SNP set. We expect that this set will be widely applicable for use in tilapia aquaculture, e.g. for pedigree reconstruction. In addition, this set is currently used for assaying the genetic diversity of native Nile tilapia in areas where tilapia is, or will be, introduced in aquaculture projects. This allows the tracing of escapees from aquaculture and the monitoring of effects of introgression and hybridization.

  18. Development and validation of the Axiom(®) Apple480K SNP genotyping array.

    PubMed

    Bianco, Luca; Cestaro, Alessandro; Linsmith, Gareth; Muranty, Hélène; Denancé, Caroline; Théron, Anthony; Poncet, Charles; Micheletti, Diego; Kerschbamer, Emanuela; Di Pierro, Erica A; Larger, Simone; Pindo, Massimo; Van de Weg, Eric; Davassi, Alessandro; Laurens, François; Velasco, Riccardo; Durel, Charles-Eric; Troggio, Michela

    2016-04-01

    Cultivated apple (Malus × domestica Borkh.) is one of the most important fruit crops in temperate regions, and has great economic and cultural value. The apple genome is highly heterozygous and has undergone a recent duplication which, combined with a rapid linkage disequilibrium decay, makes it difficult to perform genome-wide association (GWA) studies. Single nucleotide polymorphism arrays offer highly multiplexed assays at a relatively low cost per data point and can be a valid tool for the identification of the markers associated with traits of interest. Here, we describe the development and validation of a 487K SNP Affymetrix Axiom(®) genotyping array for apple and discuss its potential applications. The array has been built from the high-depth resequencing of 63 different cultivars covering most of the genetic diversity in cultivated apple. The SNPs were chosen by applying a focal points approach to enrich genic regions, but also to reach a uniform coverage of non-genic regions. A total of 1324 apple accessions, including the 92 progenies of two mapping populations, have been genotyped with the Axiom(®) Apple480K to assess the effectiveness of the array. A large majority of SNPs (359 994 or 74%) fell in the stringent class of poly high resolution polymorphisms. We also devised a filtering procedure to identify a subset of 275K very robust markers that can be safely used for germplasm surveys in apple. The Axiom(®) Apple480K has now been commercially released both for public and proprietary use and will likely be a reference tool for GWA studies in apple. PMID:26919684

  19. 17 CFR 249.310 - Form 10-K, for annual and transition reports pursuant to sections 13 or 15(d) of the Securities...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Form 10-K, for annual and transition reports pursuant to sections 13 or 15(d) of the Securities Exchange Act of 1934. 249.310 Section... 15(d) of the Securities Exchange Act of 1934 § 249.310 Form 10-K, for annual and transition...

  20. Conceptual design of a 0.1 W magnetic refrigerator for operation between 10 K and 2 K

    NASA Technical Reports Server (NTRS)

    Helvensteijn, Ben P. M.; Kashani, Ali

    1990-01-01

    The design of a magnetic refrigerator for space applications is discussed. The refrigerator is to operate in the temperature range of 10 K-2 K, at a 2 K cooling power of 0.10 W. As in other magnetic refrigerators operating in this temperature range GGG has been selected as the refrigerant. Crucial to the design of the magnetic refrigerator are the heat switches at both the hot and cold ends of the GGG pill. The 2 K heat switch utilizes a narrow He II filled gap. The 10 K heat switch is based on a narrow helium gas gap. For each switch, the helium in the gap is cycled by means of activated carbon pumps. The design concentrates on reducing the switching times of the pumps and the switches as a whole. A single stage system (one magnet; one refrigerant pill) is being developed. Continuous cooling requires the fully stationary system to have at least two stages running parallel/out of phase with each other. In order to conserve energy, it is intended to recycle the magnetic energy between the magnets. To this purpose, converter networks designed for superconducting magnetic energy storage are being studied.

  1. Fiber-coupled, 10 kHz simultaneous OH planar laser-induced fluorescence/particle-image velocimetry.

    PubMed

    Hsu, Paul S; Jiang, Naibo; Gord, James R; Roy, Sukesh

    2013-01-15

    Planar laser-induced fluorescence (PLIF) and particle-image velocimetry (PIV) techniques that employ free-standing optics face severe challenges when implemented in harsh environments associated with practical combustion facilities because of limited optical access and restrictions on operation of sensitive laser systems. To circumvent this problem, we have developed and implemented a fiber-coupled, high-speed ultraviolet (UV) PLIF/PIV system for measuring hydroxyl radical (OH) concentration and velocity in a realistic 4 MW combustion rig. This system permits delivery of high-power, 10 kHz, nanosecond-duration OH-PLIF excitation pulses (283 nm) and PIV pulses (532 nm) through a common 6 m long, 600 μm core, deep-UV-enhanced multimode fiber. Simultaneous OH-PLIF and PIV imaging at a data-acquisition rate of 10 kHz is demonstrated in turbulent premixed flames behind a bluff body. The effects of delivering high-repetition-rate, intense UV and visible beams through a long optical fiber are investigated, and potential system improvements are discussed.

  2. SNPConvert: SNP Array Standardization and Integration in Livestock Species

    PubMed Central

    Nicolazzi, Ezequiel Luis; Marras, Gabriele; Stella, Alessandra

    2016-01-01

    One of the main advantages of single nucleotide polymorphism (SNP) array technology is providing genotype calls for a specific number of SNP markers at a relatively low cost. Since its first application in animal genetics, the number of available SNP arrays for each species has been constantly increasing. However, conversely to that observed in whole genome sequence data analysis, SNP array data does not have a common set of file formats or coding conventions for allele calling. Therefore, the standardization and integration of SNP array data from multiple sources have become an obstacle, especially for users with basic or no programming skills. Here, we describe the difficulties related to handling SNP array data, focusing on file formats, SNP allele coding, and mapping. We also present SNPConvert suite, a multi-platform, open-source, and user-friendly set of tools to overcome these issues. This tool, which can be integrated with open-source and open-access tools already available, is a first step towards an integrated system to standardize and integrate any type of raw SNP array data. The tool is available at: https://github. com/nicolazzie/SNPConvert.git.

  3. SNPConvert: SNP Array Standardization and Integration in Livestock Species

    PubMed Central

    Nicolazzi, Ezequiel Luis; Marras, Gabriele; Stella, Alessandra

    2016-01-01

    One of the main advantages of single nucleotide polymorphism (SNP) array technology is providing genotype calls for a specific number of SNP markers at a relatively low cost. Since its first application in animal genetics, the number of available SNP arrays for each species has been constantly increasing. However, conversely to that observed in whole genome sequence data analysis, SNP array data does not have a common set of file formats or coding conventions for allele calling. Therefore, the standardization and integration of SNP array data from multiple sources have become an obstacle, especially for users with basic or no programming skills. Here, we describe the difficulties related to handling SNP array data, focusing on file formats, SNP allele coding, and mapping. We also present SNPConvert suite, a multi-platform, open-source, and user-friendly set of tools to overcome these issues. This tool, which can be integrated with open-source and open-access tools already available, is a first step towards an integrated system to standardize and integrate any type of raw SNP array data. The tool is available at: https://github. com/nicolazzie/SNPConvert.git. PMID:27600083

  4. SNPConvert: SNP Array Standardization and Integration in Livestock Species.

    PubMed

    Nicolazzi, Ezequiel Luis; Marras, Gabriele; Stella, Alessandra

    2016-01-01

    One of the main advantages of single nucleotide polymorphism (SNP) array technology is providing genotype calls for a specific number of SNP markers at a relatively low cost. Since its first application in animal genetics, the number of available SNP arrays for each species has been constantly increasing. However, conversely to that observed in whole genome sequence data analysis, SNP array data does not have a common set of file formats or coding conventions for allele calling. Therefore, the standardization and integration of SNP array data from multiple sources have become an obstacle, especially for users with basic or no programming skills. Here, we describe the difficulties related to handling SNP array data, focusing on file formats, SNP allele coding, and mapping. We also present SNPConvert suite, a multi-platform, open-source, and user-friendly set of tools to overcome these issues. This tool, which can be integrated with open-source and open-access tools already available, is a first step towards an integrated system to standardize and integrate any type of raw SNP array data. The tool is available at: https://github. com/nicolazzie/SNPConvert.git. PMID:27600083

  5. Atomic Force Microscopy for DNA SNP Identification

    NASA Astrophysics Data System (ADS)

    Valbusa, Ugo; Ierardi, Vincenzo

    The knowledge of the effects of single-nucleotide polymorphisms (SNPs) in the human genome greatly contributes to better comprehension of the relation between genetic factors and diseases. Sequence analysis of genomic DNA in different individuals reveals positions where variations that involve individual base substitutions can occur. Single-nucleotide polymorphisms are highly abundant and can have different consequences at phenotypic level. Several attempts were made to apply atomic force microscopy (AFM) to detect and map SNP sites in DNA strands. The most promising approach is the study of DNA mutations producing heteroduplex DNA strands and identifying the mismatches by means of a protein that labels the mismatches. MutS is a protein that is part of a well-known complex of mismatch repair, which initiates the process of repairing when the MutS binds to the mismatched DNA filament. The position of MutS on the DNA filament can be easily recorded by means of AFM imaging.

  6. High-resolution copy number analysis of paraffin-embedded archival tissue using SNP BeadArrays.

    PubMed

    Oosting, Jan; Lips, Esther H; van Eijk, Ronald; Eilers, Paul H C; Szuhai, Károly; Wijmenga, Cisca; Morreau, Hans; van Wezel, Tom

    2007-03-01

    High-density SNP microarrays provide insight into the genomic events that occur in diseases like cancer through their capability to measure both LOH and genomic copy numbers. Where currently available methods are restricted to the use of fresh frozen tissue, we now describe the design and validation of copy number measurements using the Illumina BeadArray platform and the application of this technique to formalin-fixed, paraffin-embedded (FFPE) tissue. In fresh frozen tissue from a set of colorectal tumors with numerous chromosomal aberrations, our method measures copy number patterns that are comparable to values from established platforms, like Affymetrix GeneChip and BAC array-CGH. Moreover, paired comparisons of fresh frozen and FFPE tissues showed nearly identical patterns of genomic change. We conclude that this method enables the use of paraffin-embedded material for research into both LOH and numerical chromosomal abnormalities. These findings make the large pathological archives available for genomic analysis, which could be especially relevant for hereditary disease where fresh material from affected relatives is rarely available.

  7. Effects of the MDM2 promoter SNP285 and SNP309 on Sp1 transcription factor binding and cancer risk.

    PubMed

    Knappskog, Stian; Lønning, Per E

    2011-01-01

    The proto-oncogene MDM2 inhibits p53 and plays a key role in cell growth control and apoptosis. Identification of two antagonizing MDM2 polymorphisms, SNP285 and SNP309, affecting cancer risk through modulation of Sp1 transcription factor binding, shed new light on the biological activity and phylogeny of this gene.

  8. Vibrational population dynamics in liquids and glasses: IR pump-probe experiments from 10 K to 300 K

    SciTech Connect

    Kwok, A.S.; Francis, R.S.; Rector, K.D.

    1995-12-31

    The temperature dependent vibrational relaxation of the CO stretching mode of Rhodium dicarbonyl acetylacetonate (Rh(CO){sub 2}(acac)) and tungsten hexacarbonyl (W(CO){sub 6}) in dibutylphthalate (DBP) and 2-methylpentane (2-MP) were measured with IR pump and probe (P-P) experiments. The experiments were performed with {approximately}1.5 ps pulses generated by the Stanford superconducting accelerator pumped free electron laser (FEL). Measurements were performed on the Rh(CO){sub 2}(acac) CO asymmetric stretching mode at {lambda} = 4.98{mu}m from 10 K to 300 K. Both the parallel and magic angle probe polarizations decay curves are biexponential over the entire temperature range. The slow component (ranging from 40 ps at 300 K to 55 ps at 10K) is attributed to the population relaxations. For the fast component (ranging from 4-5 ps at 300 K to 13-15 ps at 10K), we propose a mechanism of spectral diffusion, in contrast to the previously proposed mechanisms of scattering between closely spaced vibrational levels. Support for this assignment is given by the lack of a steep temperature dependence consistent with the Boltzmann factor for the separation of the levels and the detection of spectral diffusion using multi-bandwidth P-P measurements and associated vibrational photon echo experiments done on W(CO){sub 6} in 2 MP by Tokmakoff and co-workers. For the W(CO){sub 6} in DBP, preliminary data were taken at {lambda}= 5.06 {mu}m in the temperature range 75-300 K. The data are again bi-exponential both with parallel and magic angle probing. The decay time of the slow component increases as the temperature increase: going from 55 ps at 75 K to 70-80 ps at room temperature. For the fast component, instead, the decay time decreases with increasing temperature, changing form 15 ps at 75 K to 5 ps at 300 K in a manner very similar to that observed for Rh(CO){sub 2}(acac).

  9. Identification of biomarkers regulated by rexinoids (LGD1069, LG100268 and Ro25-7386) in human breast cells using Affymetrix microarray.

    PubMed

    Seo, Hye-Sook; Woo, Jong-Kyu; Shin, Yong Cheol; Ko, Seong-Gyu

    2015-07-01

    Retinoids possess anti-proliferative properties, which suggests that they possess chemopreventive and therapeutic potential against cancer. In the current study, genes modulated by rexinoids (retinoid X receptor (RXR)-pan agonists, LGD1069 and LG100268; and the RXRα agonist, Ro25-7386) were identified using an Affymetrix microarray in normal and malignant breast cells. It was observed that LGD1069, LG100268 and Ro25-7386 suppressed the growth of breast cells. Secondly, several rexinoid-regulated genes were identified, which are involved in cell death, cell growth/maintenance, signal transduction and response to stimulus. These genes may be associated with the growth-suppressive activity of rexinoids. Therefore, the identified genes may serve as biomarkers and novel molecular targets for the prevention and treatment of breast cancer.

  10. Performance of a 10-kJ SMES model cooled by liquid hydrogen thermo-siphon flow for ASPCS study

    NASA Astrophysics Data System (ADS)

    Makida, Y.; Shintomi, T.; Hamajima, T.; Ota, N.; Katsura, M.; Ando, K.; Takao, T.; Tsuda, M.; Miyagi, D.; Tsujigami, H.; Fujikawa, S.; Hirose, J.; Iwaki, K.; Komagome, T.

    2015-12-01

    We propose a new electrical power storage and stabilization system, called an Advanced Superconducting Power Conditioning System (ASPCS), which consists of superconducting magnetic energy storage (SMES) and hydrogen energy storage, converged on a liquid hydrogen station for fuel cell vehicles. A small 10- kJ SMES system, in which a BSCCO coil cooled by liquid hydrogen was installed, was developed to create an experimental model of an ASPCS. The SMES coil is conductively cooled by liquid hydrogen flow through a thermo-siphon line under a liquid hydrogen buffer tank. After fabrication of the system, cooldown tests were carried out using liquid hydrogen. The SMES coil was successfully charged up to a nominal current of 200 A. An eddy current loss, which was mainly induced in pure aluminum plates pasted onto each pancake coils for conduction cooling, was also measured.

  11. Plate-fin Heat-exchangers for a 10 kW Brayton Cryocooler and a 1 km HTS Cable

    NASA Astrophysics Data System (ADS)

    Chang, Ho-Myung; Gwak, Kyung Hyun; Jung, Seyong; Yang, Hyung Suk; Hwang, Si-Dole

    Plate-fin heat exchangers (PFHX) are designed and fabricated for a cryogenic cooling system, serving for a 10 kW Brayton cryocooler and a 1 km HTS transmission cable under development in Korea. To achieve compactness and thermal efficiency at the same time, a recuperative HX for Brayton cycle and a sub-cooling HX of liquid nitrogen for HTS cable are designed as integrated parts. A key design feature is focused on the coldest part of sub-cooling HX, where the streams of liquid nitrogen and refrigerant (helium gas) are arranged as two-pass cross-flow so that the risk of freeze-out of liquid nitrogen can be reduced. Details of hardware PFHX design are presented and discussed towards its immediate application to the HTS cable system.

  12. Two year performance of a 10 kW CPV system installed in two areas of Saudi Arabia

    NASA Astrophysics Data System (ADS)

    Khonkar, Hussam; Alowais, Abdullah; Sheikho, Ayman; Alyahya, Abdulaziz; Alghamdi, Ahmed; Alsaedan, Abdullah; Eugenio, Nunilo N.; Alalweet, Fahad; Halawani, Mohammad; Alsaferan, Abdulrahman

    2014-09-01

    The three year KACST/IBM collaboration in solar technology research led to the design and development of a 10kW CPV system. The system is comprised of 81 PV modules, inverters and a tracking system and is grid connected. A primary and secondary optics were employed to reach 1600x concentration on multijunction solar cells. Two CPV trackers were installed in the city of Riyadh and one in the eastern coastal city of Al Khafji. These two areas differ in climatic conditions. Riyadh is mostly dry and very often hit by very strong sand storms while Al Khafji is very humid with sand storms. Very fine dusts and dirt carried by the storms hits the surface of the primary optics, Fresnel lens, of the system. In Riyadh, the particles stick to the lenses but accumulation in the surface is not much since it is blown away by wind. However, the humid condition of the coastal areas wets the dusts and makes it sticky, cumulating more dusts and dirt. This paper discusses in details the parts of the 10kW CPV system. It presents a comprehensive analysis of the system's performance since the time they were installed and operated. CPV systems are operated with the least number of personnel and supervision. However, dust and dirt lessens the amount of sunlight passing through the primary optics. It requires periodic cleaning of the Fresnel lens. Different methods of cleaning were tried to identify the efficient way to clean the system that results to a higher power generation. Corrections and modifications of the system to further increase power production are presented.

  13. Viability of Cladosporium herbarum spores under 157 nm laser and vacuum ultraviolet irradiation, low temperature (10 K) and vacuum

    SciTech Connect

    Sarantopoulou, E. Stefi, A.; Kollia, Z.; Palles, D.; Cefalas, A. C.; Petrou, P. S.; Bourkoula, A.; Koukouvinos, G.; Kakabakos, S.; Velentzas, A. D.

    2014-09-14

    Ultraviolet photons can damage microorganisms, which rarely survive prolonged irradiation. In addition to the need for intact DNA, cell viability is directly linked to the functionality of the cell wall and membrane. In this work, Cladosporium herbarum spore monolayers exhibit high viability (7%) when exposed to 157 nm laser irradiation (412 kJm⁻²) or vacuum-ultraviolet irradiation (110–180 nm) under standard pressure and temperature in a nitrogen atmosphere. Spore viability can be determined by atomic-force microscopy, nano-indentation, mass, μ-Raman and attenuated reflectance Fourier-transform far-infrared spectroscopies and DNA electrophoresis. Vacuum ultraviolet photons cause molecular damage to the cell wall, but radiation resistance in spores arises from the activation of a photon-triggered signaling reaction, expressed via the exudation of intracellular substances, which, in combination with the low penetration depth of vacuum-ultraviolet photons, shields DNA from radiation. Resistance to phototoxicity under standard conditions was assessed, as was resistance to additional environmental stresses, including exposure in a vacuum, under different rates of change of pressure during pumping time and low (10 K) temperatures. Vacuum conditions were far more destructive to spores than vacuum-ultraviolet irradiation, and UV-B photons were two orders of magnitude more damaging than vacuum-ultraviolet photons. The viability of irradiated spores was also enhanced at 10 K. This work, in addition to contributing to the photonic control of the viability of microorganisms exposed under extreme conditions, including decontamination of biological warfare agents, outlines the basis for identifying bio-signaling in vivo using physical methodologies.

  14. Evaluation of potential health effects of 10 kHz magnetic fields: A short-term mouse toxicology study

    SciTech Connect

    Robertson, I.G.C.; Wilson, W.R.; Dawson, B.V.; Zwi, L.J.; Green, A.W.; Boys, J.T.

    1996-05-01

    A high-frequency inductive power distribution (HID) technology has been developed that generates sinusoidal magnetic fields at a frequency of 10 kHz. In typical industrial applications, field intensities in the order of 0.2 mT can be expected between the current-carrying coils. Because the possible health effects of 10 kHz sinusoidal magnetic fields of this type had never been investigated, a broad evaluation of possible effects on animal health was made in a preliminary 14 day acute study and in a 90 day subchromic study using male and female B6C3F1 mice. Exposures were at 0.08, 0.28, and 1.0 mT vs a background exposure of 3.7 {micro}T and were essentially continuous. These studies failed to demonstrate any health effects that can be clearly related to the magnetic field exposure. No changes in animal behavior or indications of morbidity were detected during the initial exposure to the fields. There were no significant differences in body weight between exposed and unexposed (control) mice at any time int h study, and the clinical chemistry and hematology parameters were essentially unchanged. Although minor differences in some clinical chemistry and hematology parameters were seen between control and exposure groups, the lack of exposure dependence, the lack of consistency between sexes, and the lack of correspondence with the results of the two studies all suggest that these were chance associations. Even if the changes were real, the magnitude of the changes was very small and does not indicate serious biological effects. Finally, all organs were macroscopically and microscopically normal except for isolated, generally mild, histological lesions and lesions that were ascribed to fighting among males. There was no obvious association with field intensity.

  15. Viability of Cladosporium herbarum spores under 157 nm laser and vacuum ultraviolet irradiation, low temperature (10 K) and vacuum

    NASA Astrophysics Data System (ADS)

    Sarantopoulou, E.; Stefi, A.; Kollia, Z.; Palles, D.; Petrou, P. S.; Bourkoula, A.; Koukouvinos, G.; Velentzas, A. D.; Kakabakos, S.; Cefalas, A. C.

    2014-09-01

    Ultraviolet photons can damage microorganisms, which rarely survive prolonged irradiation. In addition to the need for intact DNA, cell viability is directly linked to the functionality of the cell wall and membrane. In this work, Cladosporium herbarum spore monolayers exhibit high viability (7%) when exposed to 157 nm laser irradiation (412 kJm-2) or vacuum-ultraviolet irradiation (110-180 nm) under standard pressure and temperature in a nitrogen atmosphere. Spore viability can be determined by atomic-force microscopy, nano-indentation, mass, μ-Raman and attenuated reflectance Fourier-transform far-infrared spectroscopies and DNA electrophoresis. Vacuum ultraviolet photons cause molecular damage to the cell wall, but radiation resistance in spores arises from the activation of a photon-triggered signaling reaction, expressed via the exudation of intracellular substances, which, in combination with the low penetration depth of vacuum-ultraviolet photons, shields DNA from radiation. Resistance to phototoxicity under standard conditions was assessed, as was resistance to additional environmental stresses, including exposure in a vacuum, under different rates of change of pressure during pumping time and low (10 K) temperatures. Vacuum conditions were far more destructive to spores than vacuum-ultraviolet irradiation, and UV-B photons were two orders of magnitude more damaging than vacuum-ultraviolet photons. The viability of irradiated spores was also enhanced at 10 K. This work, in addition to contributing to the photonic control of the viability of microorganisms exposed under extreme conditions, including decontamination of biological warfare agents, outlines the basis for identifying bio-signaling in vivo using physical methodologies.

  16. A Whole-Genome SNP Association Study of NCI60 Cell Line Panel Indicates a Role of Ca2+ Signaling in Selenium Resistance

    PubMed Central

    Savas, Sevtap; Briollais, Laurent; Ibrahim-zada, Irada; Jarjanazi, Hamdi; Choi, Yun Hee; Musquera, Mireia; Fleshner, Neil; Venkateswaran, Vasundara; Ozcelik, Hilmi

    2010-01-01

    Epidemiological studies have suggested an association between selenium intake and protection from a variety of cancer. Considering this clinical importance of selenium, we aimed to identify the genes associated with resistance to selenium treatment. We have applied a previous methodology developed by our group, which is based on the genetic and pharmacological data publicly available for the NCI60 cancer cell line panel. In short, we have categorized the NCI60 cell lines as selenium resistant and sensitive based on their growth inhibition (GI50) data. Then, we have utilized the Affymetrix 125K SNP chip data available and carried out a genome-wide case-control association study for the selenium sensitive and resistant NCI60 cell lines. Our results showed statistically significant association of four SNPs in 5q33–34, 10q11.2, 10q22.3 and 14q13.1 with selenium resistance. These SNPs were located in introns of the genes encoding for a kinase-scaffolding protein (AKAP6), a membrane protein (SGCD), a channel protein (KCNMA1), and a protein kinase (PRKG1). The knock-down of KCNMA1 by siRNA showed increased sensitivity to selenium in both LNCaP and PC3 cell lines. Furthermore, SNP-SNP interaction (epistasis) analysis indicated the interactions of the SNPs in AKAP6 with SGCD as well as SNPs in AKAP6 with KCNMA1 with each other, assuming additive genetic model. These genes were also all involved in the Ca2+ signaling, which has a direct role in induction of apoptosis and induction of apoptosis in tumor cells is consistent with the chemopreventive action of selenium. Once our findings are further validated, this knowledge can be translated into clinics where individuals who can benefit from the chemopreventive characteristics of the selenium supplementation will be easily identified using a simple DNA analysis. PMID:20830292

  17. Epistatic effects on abdominal fat content in chickens: results from a genome-wide SNP-SNP interaction analysis.

    PubMed

    Li, Fangge; Hu, Guo; Zhang, Hui; Wang, Shouzhi; Wang, Zhipeng; Li, Hui

    2013-01-01

    We performed a pairwise epistatic interaction test using the chicken 60 K single nucleotide polymorphism (SNP) chip for the 11(th) generation of the Northeast Agricultural University broiler lines divergently selected for abdominal fat content. A linear mixed model was used to test two dimensions of SNP interactions affecting abdominal fat weight. With a threshold of P<1.2×10(-11) by a Bonferroni 5% correction, 52 pairs of SNPs were detected, comprising 45 pairs showing an Additive×Additive and seven pairs showing an Additive×Dominance epistatic effect. The contribution rates of significant epistatic interactive SNPs ranged from 0.62% to 1.54%, with 47 pairs contributing more than 1%. The SNP-SNP network affecting abdominal fat weight constructed using the significant SNP pairs was analyzed, estimated and annotated. On the basis of the network's features, SNPs Gga_rs14303341 and Gga_rs14988623 at the center of the subnet should be important nodes, and an interaction between GGAZ and GGA8 was suggested. Twenty-two quantitative trait loci, 97 genes (including nine non-coding genes), and 50 pathways were annotated on the epistatic interactive SNP-SNP network. The results of the present study provide insights into the genetic architecture underlying broiler chicken abdominal fat weight.

  18. SNP-SNP interaction analysis of NF-κB signaling pathway on breast cancer survival

    PubMed Central

    Jamshidi, Maral; Fagerholm, Rainer; Khan, Sofia; Aittomäki, Kristiina; Czene, Kamila; Darabi, Hatef; Li, Jingmei; Andrulis, Irene L.; Chang-Claude, Jenny; Devilee, Peter; Fasching, Peter A.; Michailidou, Kyriaki; Bolla, Manjeet K.; Dennis, Joe; Wang, Qin; Guo, Qi; Rhenius, Valerie; Cornelissen, Sten; Rudolph, Anja; Knight, Julia A.; Loehberg, Christian R.; Burwinkel, Barbara; Marme, Frederik; Hopper, John L.; Southey, Melissa C.; Bojesen, Stig E.; Flyger, Henrik; Brenner, Hermann; Holleczek, Bernd; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Dyck, Laurien Van; Nevelsteen, Ines; Couch, Fergus J.; Olson, Janet E.; Giles, Graham G.; McLean, Catriona; Haiman, Christopher A.; Henderson, Brian E.; Winqvist, Robert; Pylkäs, Katri; Tollenaar, Rob A.E.M.; García-Closas, Montserrat; Figueroa, Jonine; Hooning, Maartje J.; Martens, John W.M.; Cox, Angela; Cross, Simon S.; Simard, Jacques; Dunning, Alison M.; Easton, Douglas F.; Pharoah, Paul D.P.; Hall, Per; Blomqvist, Carl; Schmidt, Marjanka K.; Nevanlinna, Heli

    2015-01-01

    In breast cancer, constitutive activation of NF-κB has been reported, however, the impact of genetic variation of the pathway on patient prognosis has been little studied. Furthermore, a combination of genetic variants, rather than single polymorphisms, may affect disease prognosis. Here, in an extensive dataset (n = 30,431) from the Breast Cancer Association Consortium, we investigated the association of 917 SNPs in 75 genes in the NF-κB pathway with breast cancer prognosis. We explored SNP-SNP interactions on survival using the likelihood-ratio test comparing multivariate Cox’ regression models of SNP pairs without and with an interaction term. We found two interacting pairs associating with prognosis: patients simultaneously homozygous for the rare alleles of rs5996080 and rs7973914 had worse survival (HRinteraction 6.98, 95% CI=3.3-14.4, P = 1.42E-07), and patients carrying at least one rare allele for rs17243893 and rs57890595 had better survival (HRinteraction 0.51, 95% CI=0.3-0.6, P = 2.19E-05). Based on in silico functional analyses and literature, we speculate that the rs5996080 and rs7973914 loci may affect the BAFFR and TNFR1/TNFR3 receptors and breast cancer survival, possibly by disturbing both the canonical and non-canonical NF-κB pathways or their dynamics, whereas, rs17243893-rs57890595 interaction on survival may be mediated through TRAF2-TRAIL-R4 interplay. These results warrant further validation and functional analyses. PMID:26317411

  19. Monitoring Thermodynamic Equilibrium Processes at 10 K: Conformational Isomerization and Photochromism of O4+ in Argon Matrices.

    NASA Astrophysics Data System (ADS)

    Ludwig, Ryan M.; Moore, David T.

    2014-06-01

    Bands corresponding to structural isomers of matrix-isolated O4+ are observed upon deposition of ions into argon matrices doped with moderate (0.1-1%) concentrations of O2. These bands have been assigned based on previous matrix isolation spectroscopy, as well as high-level computational studies. In the current work, these bands are observed upon co-deposition of Cu- and Ar+ ions at low-energies. The Cu- is present only as a non-interacting counter-ion, as is verified by studies using exclusively high-energy Ar+ beams; in this case, the spectroscopy of the O4+ species is completely equivalent, however there is now also an intense peak corresponding to O4- counter-ion species. Following deposition at 20 K, the matrices are cooled to 10 K, where the FTIR spectra show a band at 1119 wn for the trans-O4+ isomer, and a doublet at 1329/1331 wn, corresponding to the cyclic-O4+ isomer, based on earlier work. There is also a band at 1186 wn that was previously assigned to a larger O6+ complex. A temperature series taken in 1 K increments between 10 and 20 K reveal two reversible interconversion processes: the 1119 wn band decreases between 10 and 14 K while a new band grows in at 1242 wn, and the 1186 band shows a similar interconversion between 11 and 16 K with the 1331 wn peak of the cyclic-O4+ doublet, while the 1329 wn peak diminishes and broadens over the same temperature range. The interconverting peak pairs can be converted into equilibrium constants based on relative changes in integrated intensities, and the associated van't Hoff plots show linear trends with ΔH values in the range expected based on computational work. Finally, the 1186 wn and 1331 wn peak pair exhibit strong photochromism at 10 K: irradiation with red light converts 1186 to 1331, while irradiation with blue light shifts the equilibrium in the other direction. In both cases the phenomena is completely reversible and reproducible, with the original intensity ratio being restored after a few minutes

  20. MALDI-TOF mass spectrometry-based SNP genotyping.

    PubMed

    Pusch, Wolfgang; Wurmbach, Jan-Henner; Thiele, Herbert; Kostrzewa, Markus

    2002-07-01

    In recent years a growing demand for simple and robust SNP genotyping platforms has arisen from the widespread use of SNPs in industrial and public research. The resulting knowledge about genotype/phenotype correlations is of special interest for the identification of potential new drug targets and in the field of pharmacogenomics. However, full exploitation of the available genomic information requires vast numbers of SNP analyses, as large cohorts of patients have to be screened for a large number of markers. Only very few of the current SNP genotyping techniques can cope with the resulting demands concerning sample throughput, automation, accuracy and cost-effectiveness. MALDI-TOF mass spectrometry has the potential to develop into a 'Gold Standard' for high-throughput SNP genotyping - if it has not already done so. This review will focus on the latest developments of this technology.

  1. Genomic position mapping discrepancies of commercial SNP chips.

    PubMed

    Fadista, João; Bendixen, Christian

    2012-01-01

    The field of genetics has come to rely heavily on commercial genotyping arrays and accompanying annotations for insights into genotype-phenotype associations. However, in order to avoid errors and false leads, it is imperative that the annotation of SNP chromosomal positions is accurate and unambiguous. We report on genomic positional discrepancies of various SNP chips for human, cattle and mouse species, and discuss their causes and consequences.

  2. Profiling of the Tox21 10K compound library for agonists and antagonists of the estrogen receptor alpha signaling pathway

    PubMed Central

    Huang, Ruili; Sakamuru, Srilatha; Martin, Matt T.; Reif, David M.; Judson, Richard S.; Houck, Keith A.; Casey, Warren; Hsieh, Jui-Hua; Shockley, Keith R.; Ceger, Patricia; Fostel, Jennifer; Witt, Kristine L.; Tong, Weida; Rotroff, Daniel M.; Zhao, Tongan; Shinn, Paul; Simeonov, Anton; Dix, David J.; Austin, Christopher P.; Kavlock, Robert J.; Tice, Raymond R.; Xia, Menghang

    2014-01-01

    The U.S. Tox21 program has screened a library of approximately 10,000 (10K) environmental chemicals and drugs in three independent runs for estrogen receptor alpha (ERα) agonist and antagonist activity using two types of ER reporter gene cell lines, one with an endogenous full length ERα (ER-luc; BG1 cell line) and the other with a transfected partial receptor consisting of the ligand binding domain (ER-bla; ERα β-lactamase cell line), in a quantitative high-throughput screening (qHTS) format. The ability of the two assays to correctly identify ERα agonists and antagonists was evaluated using a set of 39 reference compounds with known ERα activity. Although both assays demonstrated adequate (i.e. >80%) predictivity, the ER-luc assay was more sensitive and the ER-bla assay more specific. The qHTS assay results were compared with results from previously published ERα binding assay data and showed >80% consistency. Actives identified from both the ER-bla and ER-luc assays were analyzed for structure-activity relationships (SARs) revealing known and potentially novel ERα active structure classes. The results demonstrate the feasibility of qHTS to identify environmental chemicals with the potential to interact with the ERα signaling pathway and the two different assay formats improve the confidence in correctly identifying these chemicals. PMID:25012808

  3. Alternating current calorimeter for specific heat capacity measurements at temperatures below 10 K and pressures up to 10 GPa

    NASA Astrophysics Data System (ADS)

    Umeo, Kazunori

    2016-06-01

    A developed alternating current calorimeter for measuring the absolute value of specific heat C of a very small sample under a pressure up to 10 GPa and low temperature below 10 K is described. A Bridgman anvil cell made of tungsten carbide with a top diameter of 3 mm is used. A hollow at the top prevents expansion of the sample space over the anvil top. Two chip resistors, which act as a thermometer and a heater, are mounted on the outer part of a copper-beryllium gasket with a frying pan-like shape. Thus, the thermometer is not pressurized. In order to isolate the gasket from the anvil thermally, diamond powder with a grain size of 0.25 μm is placed on the anvil top. Two jumps of C at the superconducting transitions of Pb (3.3 mg) and In (5.0 mg) are observed under various pressures up to 9 GPa, as clearly as those at the ambient pressure.

  4. Studies of Adsorption Characteristics of Activated Carbons in between 4.5 to 10 K for Cryopump Applications

    NASA Astrophysics Data System (ADS)

    Krishnamoorthy, V.; Swarup Udgata, Satya; Shankar Tripathi, Vijai; Gangradey, Ranjana; Kasthurirengan, Srinivasan; Behera, Upendra

    2012-11-01

    Cryosorption pump is the only solution to pump helium, hydrogen and its isotopes in fusion devices. To design such pumps, knowledge of adsorption characteristics of activated carbons in the temperature range from 4.5 to 77 K is needed, but is very scarce in the open literature. Hence an experimental setup is designed and developed to measure adsorption characteristics of activated carbons down to 4.5 K. For this purpose, a commercial micropore analyzer operating down to 77K is coupled to a two-stage GM cryocooler, to enable cooling the sample temperature down to 4.5 K. A heat switch is mounted in between the second stage cold head and the sample chamber helps to vary the sample temperature from 4.5 K to 77K without affecting the performance of the cryocooler. The details of the experimental setup is presented elsewhere. We present here the experimental results of adsorption of different types of activated carbons in the temperature range 4.5K to 10 K using Helium gas as adsorbate. These results are evaluated in terms of surface area, pore sizes and their distributions. Also the effect of epoxy based adhesive used in bonding the activated carbons to the panels is evaluated. These results will be useful towards the selection of the right activated carbons for the development of cryosorption pumps.

  5. Comparison of 10kHz TR-PIV and LES near-field data in high speed jets

    NASA Astrophysics Data System (ADS)

    Lewalle, Jacques; Kan, Pinqing

    2012-11-01

    The identification of the sources of noise in high-speed jets may help formulate control strategies, an important unsolved problem. We report on the existence of large intermittent and localized relative phase velocities for near-jet fluctuations, and on the flow patterns that are associated with them (see companion abstract by P. Kan). Here we analyze two data sets. Experimentally, 10 kHz TR-PIV in a Ma = 0 . 6 cold jet (Re = 700,000) yielded two components of velocity, from which we calculate the phase velocities for various indicators (see related abstracts by Z.P. Berger and by M.G. Berry; data provided by Spectral Energies LLC). Similar results are obtained for Ma=0.9 LES results (Re = 400,000, sampling at 80 kHz). The comparison of algorithms and flow patterns vindicates our approach. Correlations with far-field events will also be attempted. Thanks to Guillaume Daviller (Institut PPrime, France) for the LES data, and to the Glauser group at Syracuse University. Thanks for partial support from Spectral Energies LLC (under SBIR grant from AFOSR), Syracuse University and the LCS College.

  6. Genome 10K: A Proposal to Obtain Whole-Genome Sequence for 10 000 Vertebrate Species

    PubMed Central

    2009-01-01

    The human genome project has been recently complemented by whole-genome assessment sequence of 32 mammals and 24 nonmammalian vertebrate species suitable for comparative genomic analyses. Here we anticipate a precipitous drop in costs and increase in sequencing efficiency, with concomitant development of improved annotation technology and, therefore, propose to create a collection of tissue and DNA specimens for 10 000 vertebrate species specifically designated for whole-genome sequencing in the very near future. For this purpose, we, the Genome 10K Community of Scientists (G10KCOS), will assemble and allocate a biospecimen collection of some 16 203 representative vertebrate species spanning evolutionary diversity across living mammals, birds, nonavian reptiles, amphibians, and fishes (ca. 60 000 living species). In this proposal, we present precise counts for these 16 203 individual species with specimens presently tagged and stipulated for DNA sequencing by the G10KCOS. DNA sequencing has ushered in a new era of investigation in the biological sciences, allowing us to embark for the first time on a truly comprehensive study of vertebrate evolution, the results of which will touch nearly every aspect of vertebrate biological enquiry. PMID:19892720

  7. Computer simulation of the CSPAD, ePix10k, and RayonixMX170HS X-ray detectors

    SciTech Connect

    Tina, Adrienne

    2015-08-21

    The invention of free-electron lasers (FELs) has opened a door to an entirely new level of scientific research. The Linac Coherent Light Source (LCLS) at SLAC National Accelerator Laboratory is an X-ray FEL that houses several instruments, each with its own unique X-ray applications. This light source is revolutionary in that while its properties allow for a whole new range of scientific opportunities, it also poses numerous challenges. For example, the intensity of a focused X-ray beam is enough to damage a sample in one mere pulse; however, the pulse speed and extreme brightness of the source together are enough to obtain enough information about that sample, so that no further measurements are necessary. An important device in the radiation detection process, particularly for X-ray imaging, is the detector. The power of the LCLS X-rays has instigated a need for better performing detectors. The research conducted for this project consisted of the study of X-ray detectors to imitate their behaviors in a computer program. The analysis of the Rayonix MX170-HS, CSPAD, and ePix10k in particular helped to understand their properties. This program simulated the interaction of X-ray photons with these detectors to discern the patterns of their responses. A scientist’s selection process of a detector for a specific experiment is simplified from the characterization of the detectors in the program.

  8. Alternating current calorimeter for specific heat capacity measurements at temperatures below 10 K and pressures up to 10 GPa.

    PubMed

    Umeo, Kazunori

    2016-06-01

    A developed alternating current calorimeter for measuring the absolute value of specific heat C of a very small sample under a pressure up to 10 GPa and low temperature below 10 K is described. A Bridgman anvil cell made of tungsten carbide with a top diameter of 3 mm is used. A hollow at the top prevents expansion of the sample space over the anvil top. Two chip resistors, which act as a thermometer and a heater, are mounted on the outer part of a copper-beryllium gasket with a frying pan-like shape. Thus, the thermometer is not pressurized. In order to isolate the gasket from the anvil thermally, diamond powder with a grain size of 0.25 μm is placed on the anvil top. Two jumps of C at the superconducting transitions of Pb (3.3 mg) and In (5.0 mg) are observed under various pressures up to 9 GPa, as clearly as those at the ambient pressure. PMID:27370464

  9. Alternating current calorimeter for specific heat capacity measurements at temperatures below 10 K and pressures up to 10 GPa.

    PubMed

    Umeo, Kazunori

    2016-06-01

    A developed alternating current calorimeter for measuring the absolute value of specific heat C of a very small sample under a pressure up to 10 GPa and low temperature below 10 K is described. A Bridgman anvil cell made of tungsten carbide with a top diameter of 3 mm is used. A hollow at the top prevents expansion of the sample space over the anvil top. Two chip resistors, which act as a thermometer and a heater, are mounted on the outer part of a copper-beryllium gasket with a frying pan-like shape. Thus, the thermometer is not pressurized. In order to isolate the gasket from the anvil thermally, diamond powder with a grain size of 0.25 μm is placed on the anvil top. Two jumps of C at the superconducting transitions of Pb (3.3 mg) and In (5.0 mg) are observed under various pressures up to 9 GPa, as clearly as those at the ambient pressure.

  10. Genome 10K: a proposal to obtain whole-genome sequence for 10,000 vertebrate species.

    PubMed

    2009-01-01

    The human genome project has been recently complemented by whole-genome assessment sequence of 32 mammals and 24 nonmammalian vertebrate species suitable for comparative genomic analyses. Here we anticipate a precipitous drop in costs and increase in sequencing efficiency, with concomitant development of improved annotation technology and, therefore, propose to create a collection of tissue and DNA specimens for 10,000 vertebrate species specifically designated for whole-genome sequencing in the very near future. For this purpose, we, the Genome 10K Community of Scientists (G10KCOS), will assemble and allocate a biospecimen collection of some 16,203 representative vertebrate species spanning evolutionary diversity across living mammals, birds, nonavian reptiles, amphibians, and fishes (ca. 60,000 living species). In this proposal, we present precise counts for these 16,203 individual species with specimens presently tagged and stipulated for DNA sequencing by the G10KCOS. DNA sequencing has ushered in a new era of investigation in the biological sciences, allowing us to embark for the first time on a truly comprehensive study of vertebrate evolution, the results of which will touch nearly every aspect of vertebrate biological enquiry.

  11. 10 kHz repetitive high-resolution TV Thomson scattering on TEXTOR: Design and performance (invited)

    NASA Astrophysics Data System (ADS)

    van der Meiden, H. J.; Varshney, S. K.; Barth, C. J.; Oyevaar, T.; Jaspers, R.; Donné, A. J. H.; Kantor, M. Yu.; Kouprienko, D. V.; Uzgel, E.; Biel, W.; Pospieszczyk, A.; Textor Team

    2006-10-01

    In late 2003 a 10kHz multiposition Thomson scattering diagnostic with high spatial resolution became operational on the TEXTOR tokamak. In the initial phase of operation, one burst of 18 pulses of 12J each with a repetition rate of 5kHz could be extracted from the laser system. The installation of a low-dope ruby rod (spring 2005) resulted in a system, which can deliver higher pulse energy and moreover a divergence of better than 0.7mrad, leading to a big improvement in the detection of Thomson scattering photons. Furthermore, the number of laser pulses in one burst could be extended to even more than 30. The achieved laser energy of more than 15J/pulse makes it possible to measure electron temperature and density profiles with an observational error of 8% on the electron temperature (Te) and 4% on the electron density (ne) at ne=2.5×1019m-3, per spatial element of 7.5mm. The viewing optics enables sampling of either the full plasma diameter of 900mm with 120 spatial channels of 7.5mm each or a 160mm long edge chord with 98 spatial channels of 1.7mm each. The system, which has recently become available for physics exploration, has already been used to study the structure of m =2 magnetic islands and the response of the plasma to off-axis electron cyclotron resonance heating.

  12. Comparison of 250 MHz R10K Origin 2000 and 400 MHz Origin 2000 Using NAS Parallel Benchmarks

    NASA Technical Reports Server (NTRS)

    Turney, Raymond D.; Thigpen, William W. (Technical Monitor)

    2001-01-01

    This report describes results of benchmark tests on Steger, a 250 MHz Origin 2000 system with R10K processors, currently installed at the NASA Ames National Advanced Supercomputing (NAS) facility. For comparison purposes, the tests were also run on Lomax, a 400 MHz Origin 2000 with R12K processors. The BT, LU, and SP application benchmarks in the NAS Parallel Benchmark Suite and the kernel benchmark FT were chosen to measure system performance. Having been written to measure performance on Computational Fluid Dynamics applications, these benchmarks are assumed appropriate to represent the NAS workload. Since the NAS runs both message passing (MPI) and shared-memory, compiler directive type codes, both MPI and OpenMP versions of the benchmarks were used. The MPI versions used were the latest official release of the NAS Parallel Benchmarks, version 2.3. The OpenMP versions used were PBN3b2, a beta version that is in the process of being released. NPB 2.3 and PBN3b2 are technically different benchmarks, and NPB results are not directly comparable to PBN results.

  13. Performance of new 10 kW class MCFC using Li/K and Li/Na electrolyte

    SciTech Connect

    Mugikura, Yoshihiro; Yoshiba, Fumihiko; Izaki, Yoshiyuki; Watanabe, Takao

    1996-12-31

    The molten carbonate fuel cell (MCFC) uses generally mixture of lithium carbonate and potassium carbonate (Li/K) as the electrolyte. NiO cathode dissolution is one of serious problems for MCFC life. The NiO cathode has been found to dissolve into the electrolyte as Ni{sup 2+} ion which is reduced to metallic Ni by H{sub 2} in the fuel gas and bridges the anode and the cathode. The bridges short circuit and degrade cell performance and shorten cell life. Since solubility of NiO in mixture of lithium carbonate and sodium carbonate (Li/Na) is lower than in Li/K, it takes longer time to take place slowing by NiO cathode dissolution in Li/Na compared with in Li/K. The ionic conductivity of Li/Na is higher than of Li/K, however, oxygen solubility in Li/Na is lower 9 than in Li/K. A new 10 kW class MCFC stack composed of Li/K cells and Li/Na cells, was tested. Basic performance of the Li/K cells and Li/Na cells of the stack was reported.

  14. Identification of null alleles and deletions from SNP genotypes for an intercross between domestic and wild chickens.

    PubMed

    Crooks, Lucy; Carlborg, Örjan; Marklund, Stefan; Johansson, Anna M

    2013-08-01

    We analyzed genotypes from ~10K single-nucleotide polymorphisms (SNPs) in two families of an F2 intercross between Red Junglefowl and White Leghorn chickens. Possible null alleles were found by patterns of incompatible and missing genotypes. We estimated that 2.6% of SNPs had null alleles compared with 2.3% with genotyping errors and that 40% of SNPs in which a parent and offspring were genotyped as different homozygotes had null alleles. Putative deletions were identified by null alleles at adjacent markers. We found two candidate deletions that were supported by fluorescence intensity data from a 60K SNP chip. One of the candidate deletions was from the Red Junglefowl, and one was present in both the Red Junglefowl and White Leghorn. Both candidate deletions spanned protein-coding regions and were close to a previously detected quantitative trait locus affecting body weight in this population. This study demonstrates that the ~50K SNP genotyping arrays now available for several agricultural species can be used to identify null alleles and deletions in data from large families. We suggest that our approach could be a useful complement to linkage analysis in experimental crosses. PMID:23708300

  15. Identification of null alleles and deletions from SNP genotypes for an intercross between domestic and wild chickens.

    PubMed

    Crooks, Lucy; Carlborg, Örjan; Marklund, Stefan; Johansson, Anna M

    2013-08-07

    We analyzed genotypes from ~10K single-nucleotide polymorphisms (SNPs) in two families of an F2 intercross between Red Junglefowl and White Leghorn chickens. Possible null alleles were found by patterns of incompatible and missing genotypes. We estimated that 2.6% of SNPs had null alleles compared with 2.3% with genotyping errors and that 40% of SNPs in which a parent and offspring were genotyped as different homozygotes had null alleles. Putative deletions were identified by null alleles at adjacent markers. We found two candidate deletions that were supported by fluorescence intensity data from a 60K SNP chip. One of the candidate deletions was from the Red Junglefowl, and one was present in both the Red Junglefowl and White Leghorn. Both candidate deletions spanned protein-coding regions and were close to a previously detected quantitative trait locus affecting body weight in this population. This study demonstrates that the ~50K SNP genotyping arrays now available for several agricultural species can be used to identify null alleles and deletions in data from large families. We suggest that our approach could be a useful complement to linkage analysis in experimental crosses.

  16. Laboratory measurements of H-D substitution rates in solid methanol-dn (n=0-2) at 10 K

    NASA Astrophysics Data System (ADS)

    Nagaoka, Akihiro; Watanabe, Naoki; Kouchi, Akira

    The deuterium fractionation of interstellar methanol is investigated experimentally using the ASURA (Apparatus for SUrface Reactions in Astrophysics) system. Recent observations toward the low-mass protostars IRAS16293 found the very high D/H ratios in formaldehyde and methanol up to 0.2 and 0.4, respectively (Loinard et al. 2000; Parise et al. 2004; Aikawa et al. 2005). To date, several models have been proposed to explain D-fractionation mechanism. Pure gas-phase models are difficult to reproduce the D-fractionation, particularly, for multideuterated species, while the results of some gas-grain models can achieve the observed fractionation levels fairly well (Stantcheva & Herbst 2003). However, the gas-grain models require many assumptions regarding the grain surface reactions. Then, the experiments on the surface reaction have been highly desirable. In this context, we performed the experiments on the formation of deuterated formaldehyde and methanol on cold (10 K) interstellar grain analogues and revealed that a key route for the D-fractionation is not successive addition of H and D to CO as previously considered (e.g., Charnley, Tielens, & Rodgers 1997) but H-D substitution in solid CH3OH on icy grains (Nagaoka, Watanabe, & Kouchi 2005). We report the results of further experiments on the deuteration of CH3OH using a cold (30 K) atomic D beam. The relative rates of H-D substitution reactions; CH3OH → CH2DOH, CH2DOH → CHD2OH, CHD2OH → CD3OH, were measured. Experiments were performed using the ASURA system described previously (Watanabe et al. 2004; Nagaoka, Watanabe, & Kouchi 2005). The experimental procedure is as follows. An aluminum substrate was placed in the centre of an ultra-high vacuum chamber (10-10 Torr) and cooled to 10 K by a helium refrigerator. The solid samples of normal and deuterated methanol (CH3OH, CH2DOH, CHD2OH) were vapor-deposited on the substrate. The D atoms produced by dissociation of D2 molecules by microwave discharge were

  17. GISMO: A Giant (30m) cold (10K) far-Ir and Submm space Observatory using Fresnel optics

    NASA Astrophysics Data System (ADS)

    Hawarden, T. G.; Stevens, J. A.; Cliffe, M. R.; Henry, D. M.

    2004-12-01

    We have examined the possibility of applying difractive Fresnel optical concepts developed at Lawrence Livermore National Laboratory for a possible O/NIR space telescope to the much more relaxed tolerance regimes of the far-IR and sub-millimetre. We conclude that the approach is indeed applicable and that a powerful FIR-submm observatory (GISMO) could be built around a 30m primary lens of ultra-high molecular weight polyethylene (UHMW-PE) 2.3mm thick.This would be the main component of a "Lens" Spacecraft (LSC) which would be located 3 km from a second "Instrument" spacecraft (ISC) carrying field optics, a Fresnel corrector lens, re-imaging optics and focal plane instruments. In its Sun-Earth L2 halo orbit, the Lens would cool by radiation to 10K; the ISC optics would be actively cooled to a few K and would resemble a simplified version of current plans for SAFIR, the Single-Aperture Far-IR mission under study by NASA. GISMO could be a good deal cheaper to build than the current 10m, 4K SAFIR concept. Relative positioning of the two spaceraft needs to be accurate to a few millimetres laterally and a tens of centimetres in separation (focus). We highlight some technical uncertainties. For most observations at wavelengths between 20 and 600 microns GISMO should be between 3 and 10 times more sensitive than the 10m, 4K SAFIR concept. The possible exception is spectroscopy betwen 250 and 450 microns, where its sensitivity should be about the same. GISMO's 30m aperture would of course offer a three-fold improvement in spatial resolution at all wavelengths. As a result GISMO is expected to achieve almost complete resolution of the FIR background, reaching sources below 100 micro-Jansky in seconds, and would be an immensely powerful facility throughout its wavelength range of operation.

  18. Local heat treatment of high strength steels with zoom-optics and 10kW-diode laser

    NASA Astrophysics Data System (ADS)

    Baumann, Markus; Krause, Volker; Bergweiler, Georg; Flaischerowitz, Martin; Banik, Janko

    2012-03-01

    High strength steels enable new solutions for weight optimized car bodies without sacrificing crash safety. However, cold forming of these steels is limited due to the need of high press capacity, increased tool wear, and limitations in possible geometries. One can compensate for these drawbacks by local heat treatment of the blanks. In high-deformation areas the strength of the material is reduced and the plasticity is increased by diode laser irradiation. Local heat treatment with diode laser radiation could also yield key benefits for the applicability of press hardened parts. High strength is not desired all over the part. Joint areas or deformation zones for requested crash properties require locally reduced strength. In the research project "LOKWAB" funded by the German Federal Ministry of Education and Research (BMBF), heat treatment of high strength steels was investigated in cooperation with Audi, BMW, Daimler, ThyssenKrupp, Fraunhofer- ILT, -IWU and others. A diode laser with an output power of 10 kW was set up to achieve acceptable process speed. Furthermore a homogenizing zoom-optics was developed, providing a rectangular focus with homogeneous power density. The spot size in x- and y-direction can be changed independently during operation. With pyrometer controlled laser power the surface temperature is kept constant, thus the laser treated zone can be flexibly adapted to the needs. Deep-drawing experiments show significant improvement in formability. With this technique, parts can be manufactured, which can conventionally only be made of steel with lower strength. Locally reduced strength of press hardened serial parts was demonstrated.

  19. Cell-Based High-Throughput Screening for Aromatase Inhibitors in the Tox21 10K Library

    PubMed Central

    Chen, Shiuan; Hsieh, Jui-Hua; Huang, Ruili; Sakamuru, Srilatha; Hsin, Li-Yu; Xia, Menghang; Shockley, Keith R.; Auerbach, Scott; Kanaya, Noriko; Lu, Hannah; Svoboda, Daniel; Witt, Kristine L.; Merrick, B. Alex; Teng, Christina T.; Tice, Raymond R.

    2015-01-01

    Multiple mechanisms exist for endocrine disruption; one nonreceptor-mediated mechanism is via effects on aromatase, an enzyme critical for maintaining the normal in vivo balance of androgens and estrogens. We adapted the AroER tri-screen 96-well assay to 1536-well format to identify potential aromatase inhibitors (AIs) in the U.S. Tox21 10K compound library. In this assay, screening with compound alone identifies estrogen receptor alpha (ERα) agonists, screening in the presence of testosterone (T) identifies AIs and/or ERα antagonists, and screening in the presence of 17β-estradiol (E2) identifies ERα antagonists. Screening the Tox-21 library in the presence of T resulted in finding 302 potential AIs. These compounds, along with 31 known AI actives and inactives, were rescreened using all 3 assay formats. Of the 333 compounds tested, 113 (34%; 63 actives, 50 marginal actives) were considered to be potential AIs independent of cytotoxicity and ER antagonism activity. Structure-activity analysis suggested the presence of both conventional (eg, 1, 2, 4, - triazole class) and novel AI structures. Due to their novel structures, 14 of the 63 potential AI actives, including both drugs and fungicides, were selected for confirmation in the biochemical tritiated water-release aromatase assay. Ten compounds were active in the assay; the remaining 4 were only active in high-throughput screen assay, but with low efficacy. To further characterize these 10 novel AIs, we investigated their binding characteristics. The AroER tri-screen, in high-throughput format, accurately and efficiently identified chemicals in a large and diverse chemical library that selectively interact with aromatase. PMID:26141389

  20. Global Expression Patterns of Three Festuca Species Exposed to Different Doses of Glyphosate Using the Affymetrix GeneChip Wheat Genome Array.

    PubMed

    Cebeci, Ozge; Budak, Hikmet

    2009-01-01

    Glyphosate has been shown to act as an inhibitor of an aromatic amino acid biosynthetic pathway, while other pathways that may be affected by glyphosate are not known. Cross species hybridizations can provide a tool for elucidating biological pathways conserved among organisms. Comparative genome analyses have indicated a high level of colinearity among grass species and Festuca, on which we focus here, and showed rearrangements common to the Pooideae family. Based on sequence conservation among grass species, we selected the Affymetrix GeneChip Wheat Genome Array as a tool for the analysis of expression profiles of three Festuca (fescue) species with distinctly different tolerances to varying levels of glyphosate. Differences in transcript expression were recorded upon foliar glyphosate application at 1.58 mM and 6.32 mM, representing 5% and 20%, respectively, of the recommended rate. Differences highlighted categories of general metabolic processes, such as photosynthesis, protein synthesis, stress responses, and a larger number of transcripts responded to 20% glyphosate application. Differential expression of genes encoding proteins involved in the shikimic acid pathway could not be identified by cross hybridization. Microarray data were confirmed by RT-PCR and qRT-PCR analyses. This is the first report to analyze the potential of cross species hybridization in Fescue species and the data and analyses will help extend our knowledge on the cellular processes affected by glyphosate.

  1. RASSF1A and the rs2073498 Cancer Associated SNP

    PubMed Central

    Donninger, Howard; Barnoud, Thibaut; Nelson, Nick; Kassler, Suzanna; Clark, Jennifer; Cummins, Timothy D.; Powell, David W.; Nyante, Sarah; Millikan, Robert C.; Clark, Geoffrey J.

    2011-01-01

    RASSF1A is one of the most frequently inactivated tumor suppressors yet identified in human cancer. It is pro-apoptotic and appears to function as a scaffolding protein that interacts with a variety of other tumor suppressors to modulate their function. It can also complex with the Ras oncoprotein and may serve to integrate pro-growth and pro-death signaling pathways. A SNP has been identified that is present in approximately 29% of European populations [rs2073498, A(133)S]. Several studies have now presented evidence that this SNP is associated with an enhanced risk of developing breast cancer. We have used a proteomics based approach to identify multiple differences in the pattern of protein/protein interactions mediated by the wild type compared to the SNP variant protein. We have also identified a significant difference in biological activity between wild type and SNP variant protein. However, we have found only a very modest association of the SNP with breast cancer predisposition. PMID:22649770

  2. DoGSD: the dog and wolf genome SNP database

    PubMed Central

    Bai, Bing; Zhao, Wen-Ming; Tang, Bi-Xia; Wang, Yan-Qing; Wang, Lu; Zhang, Zhang; Yang, He-Chuan; Liu, Yan-Hu; Zhu, Jun-Wei; Irwin, David M.; Wang, Guo-Dong; Zhang, Ya-Ping

    2015-01-01

    The rapid advancement of next-generation sequencing technology has generated a deluge of genomic data from domesticated dogs and their wild ancestor, grey wolves, which have simultaneously broadened our understanding of domestication and diseases that are shared by humans and dogs. To address the scarcity of single nucleotide polymorphism (SNP) data provided by authorized databases and to make SNP data more easily/friendly usable and available, we propose DoGSD (http://dogsd.big.ac.cn), the first canidae-specific database which focuses on whole genome SNP data from domesticated dogs and grey wolves. The DoGSD is a web-based, open-access resource comprising ∼19 million high-quality whole-genome SNPs. In addition to the dbSNP data set (build 139), DoGSD incorporates a comprehensive collection of SNPs from two newly sequenced samples (1 wolf and 1 dog) and collected SNPs from three latest dog/wolf genetic studies (7 wolves and 68 dogs), which were taken together for analysis with the population genetic statistics, Fst. In addition, DoGSD integrates some closely related information including SNP annotation, summary lists of SNPs located in genes, synonymous and non-synonymous SNPs, sampling location and breed information. All these features make DoGSD a useful resource for in-depth analysis in dog-/wolf-related studies. PMID:25404132

  3. DoGSD: the dog and wolf genome SNP database.

    PubMed

    Bai, Bing; Zhao, Wen-Ming; Tang, Bi-Xia; Wang, Yan-Qing; Wang, Lu; Zhang, Zhang; Yang, He-Chuan; Liu, Yan-Hu; Zhu, Jun-Wei; Irwin, David M; Wang, Guo-Dong; Zhang, Ya-Ping

    2015-01-01

    The rapid advancement of next-generation sequencing technology has generated a deluge of genomic data from domesticated dogs and their wild ancestor, grey wolves, which have simultaneously broadened our understanding of domestication and diseases that are shared by humans and dogs. To address the scarcity of single nucleotide polymorphism (SNP) data provided by authorized databases and to make SNP data more easily/friendly usable and available, we propose DoGSD (http://dogsd.big.ac.cn), the first canidae-specific database which focuses on whole genome SNP data from domesticated dogs and grey wolves. The DoGSD is a web-based, open-access resource comprising ∼ 19 million high-quality whole-genome SNPs. In addition to the dbSNP data set (build 139), DoGSD incorporates a comprehensive collection of SNPs from two newly sequenced samples (1 wolf and 1 dog) and collected SNPs from three latest dog/wolf genetic studies (7 wolves and 68 dogs), which were taken together for analysis with the population genetic statistics, Fst. In addition, DoGSD integrates some closely related information including SNP annotation, summary lists of SNPs located in genes, synonymous and non-synonymous SNPs, sampling location and breed information. All these features make DoGSD a useful resource for in-depth analysis in dog-/wolf-related studies. PMID:25404132

  4. DoGSD: the dog and wolf genome SNP database.

    PubMed

    Bai, Bing; Zhao, Wen-Ming; Tang, Bi-Xia; Wang, Yan-Qing; Wang, Lu; Zhang, Zhang; Yang, He-Chuan; Liu, Yan-Hu; Zhu, Jun-Wei; Irwin, David M; Wang, Guo-Dong; Zhang, Ya-Ping

    2015-01-01

    The rapid advancement of next-generation sequencing technology has generated a deluge of genomic data from domesticated dogs and their wild ancestor, grey wolves, which have simultaneously broadened our understanding of domestication and diseases that are shared by humans and dogs. To address the scarcity of single nucleotide polymorphism (SNP) data provided by authorized databases and to make SNP data more easily/friendly usable and available, we propose DoGSD (http://dogsd.big.ac.cn), the first canidae-specific database which focuses on whole genome SNP data from domesticated dogs and grey wolves. The DoGSD is a web-based, open-access resource comprising ∼ 19 million high-quality whole-genome SNPs. In addition to the dbSNP data set (build 139), DoGSD incorporates a comprehensive collection of SNPs from two newly sequenced samples (1 wolf and 1 dog) and collected SNPs from three latest dog/wolf genetic studies (7 wolves and 68 dogs), which were taken together for analysis with the population genetic statistics, Fst. In addition, DoGSD integrates some closely related information including SNP annotation, summary lists of SNPs located in genes, synonymous and non-synonymous SNPs, sampling location and breed information. All these features make DoGSD a useful resource for in-depth analysis in dog-/wolf-related studies.

  5. Laser beam welding quality monitoring system based in high-speed (10 kHz) uncooled MWIR imaging sensors

    NASA Astrophysics Data System (ADS)

    Linares, Rodrigo; Vergara, German; Gutiérrez, Raúl; Fernández, Carlos; Villamayor, Víctor; Gómez, Luis; González-Camino, Maria; Baldasano, Arturo; Castro, G.; Arias, R.; Lapido, Y.; Rodríguez, J.; Romero, Pablo

    2015-05-01

    The combination of flexibility, productivity, precision and zero-defect manufacturing in future laser-based equipment are a major challenge that faces this enabling technology. New sensors for online monitoring and real-time control of laserbased processes are necessary for improving products quality and increasing manufacture yields. New approaches to fully automate processes towards zero-defect manufacturing demand smarter heads where lasers, optics, actuators, sensors and electronics will be integrated in a unique compact and affordable device. Many defects arising in laser-based manufacturing processes come from instabilities in the dynamics of the laser process. Temperature and heat dynamics are key parameters to be monitored. Low cost infrared imagers with high-speed of response will constitute the next generation of sensors to be implemented in future monitoring and control systems for laser-based processes, capable to provide simultaneous information about heat dynamics and spatial distribution. This work describes the result of using an innovative low-cost high-speed infrared imager based on the first quantum infrared imager monolithically integrated with Si-CMOS ROIC of the market. The sensor is able to provide low resolution images at frame rates up to 10 KHz in uncooled operation at the same cost as traditional infrared spot detectors. In order to demonstrate the capabilities of the new sensor technology, a low-cost camera was assembled on a standard production laser welding head, allowing to register melting pool images at frame rates of 10 kHz. In addition, a specific software was developed for defect detection and classification. Multiple laser welding processes were recorded with the aim to study the performance of the system and its application to the real-time monitoring of laser welding processes. During the experiments, different types of defects were produced and monitored. The classifier was fed with the experimental images obtained. Self

  6. Population distribution and ancestry of the cancer protective MDM2 SNP285 (rs117039649).

    PubMed

    Knappskog, Stian; Gansmo, Liv B; Dibirova, Khadizha; Metspalu, Andres; Cybulski, Cezary; Peterlongo, Paolo; Aaltonen, Lauri; Vatten, Lars; Romundstad, Pål; Hveem, Kristian; Devilee, Peter; Evans, Gareth D; Lin, Dongxin; Van Camp, Guy; Manolopoulos, Vangelis G; Osorio, Ana; Milani, Lili; Ozcelik, Tayfun; Zalloua, Pierre; Mouzaya, Francis; Bliznetz, Elena; Balanovska, Elena; Pocheshkova, Elvira; Kučinskas, Vaidutis; Atramentova, Lubov; Nymadawa, Pagbajabyn; Titov, Konstantin; Lavryashina, Maria; Yusupov, Yuldash; Bogdanova, Natalia; Koshel, Sergey; Zamora, Jorge; Wedge, David C; Charlesworth, Deborah; Dörk, Thilo; Balanovsky, Oleg; Lønning, Per E

    2014-09-30

    The MDM2 promoter SNP285C is located on the SNP309G allele. While SNP309G enhances Sp1 transcription factor binding and MDM2 transcription, SNP285C antagonizes Sp1 binding and reduces the risk of breast-, ovary- and endometrial cancer. Assessing SNP285 and 309 genotypes across 25 different ethnic populations (>10.000 individuals), the incidence of SNP285C was 6-8% across European populations except for Finns (1.2%) and Saami (0.3%). The incidence decreased towards the Middle-East and Eastern Russia, and SNP285C was absent among Han Chinese, Mongolians and African Americans. Interhaplotype variation analyses estimated SNP285C to have originated about 14,700 years ago (95% CI: 8,300 - 33,300). Both this estimate and the geographical distribution suggest SNP285C to have arisen after the separation between Caucasians and modern day East Asians (17,000 - 40,000 years ago). We observed a strong inverse correlation (r = -0.805; p < 0.001) between the percentage of SNP309G alleles harboring SNP285C and the MAF for SNP309G itself across different populations suggesting selection and environmental adaptation with respect to MDM2 expression in recent human evolution. In conclusion, we found SNP285C to be a pan-Caucasian variant. Ethnic variation regarding distribution of SNP285C needs to be taken into account when assessing the impact of MDM2 SNPs on cancer risk.

  7. Whole genome SNP scanning of snow sheep (Ovis nivicola).

    PubMed

    Deniskova, T E; Okhlopkov, I M; Sermyagin, A A; Gladyr', E A; Bagirov, V A; Sölkner, J; Mamaev, N V; Brem, G; Zinov'eva, N A

    2016-07-01

    This is the first report performing the whole genome SNP scanning of snow sheep (Ovis nivicola). Samples of snow sheep (n = 18) collected in six different regions of the Republic of Sakha (Yakutia) from 64° to 71° N. For SNP genotyping, we applied Ovine 50K SNP BeadChip (Illumina, United States), designed for domestic sheep. The total number of genotyped SNPs (call rate 90%) was 47796 (88.1% of total SNPs), wherein 1006 SNPs were polymorphic (2.1%). Principal component analysis (PCA) showed the clear differentiation within the species O. nivicola: studied individuals were distributed among five distinct arrays corresponding to the geographical locations of sampling points. Our results demonstrate that the DNA chip designed for domestic sheep can be successfully used to study the allele pool and the genetic structure of snow sheep populations. PMID:27599514

  8. Exhaustive search of the SNP-SNP interactome identifies epistatic effects on brain volume in two cohorts

    PubMed Central

    Hibar, Derrek P.; Stein, Jason L.; Jahanshad, Neda; Kohannim, Omid; Toga, Arthur W.; McMahon, Katie L.; de Zubicaray, Greig I.; Montgomery, Grant W.; Martin, Nicholas G.; Wright, Margaret J.; Weiner, Michael W.; Thompson, Paul M.

    2014-01-01

    The SNP-SNP interactome has rarely been explored in the context of neuroimaging genetics mainly due to the complexity of conducting ∼1011 pairwise statistical tests. However, recent advances in machine learning, specifically the iterative sure independence screening (SIS) method, have enabled the analysis of datasets where the number of predictors is much larger than the number of observations. Using an implementation of the SIS algorithm (called EPISIS), we used exhaustive search of the genome-wide, SNP-SNP interactome to identify and prioritize SNPs for interaction analysis. We identified a significant SNP pair, rs1345203 and rs1213205, associated with temporal lobe volume. We further examined the full-brain, voxelwise effects of the interaction in the ADNI dataset and separately in an independent dataset of healthy twins (QTIM). We found that each additional loading in the epistatic effect was associated with ∼5% greater brain regional brain volume (a protective effect) in both the ADNI and QTIM samples. PMID:24505811

  9. A 48 SNP set for grapevine cultivar identification

    PubMed Central

    2011-01-01

    Background Rapid and consistent genotyping is an important requirement for cultivar identification in many crop species. Among them grapevine cultivars have been the subject of multiple studies given the large number of synonyms and homonyms generated during many centuries of vegetative multiplication and exchange. Simple sequence repeat (SSR) markers have been preferred until now because of their high level of polymorphism, their codominant nature and their high profile repeatability. However, the rapid application of partial or complete genome sequencing approaches is identifying thousands of single nucleotide polymorphisms (SNP) that can be very useful for such purposes. Although SNP markers are bi-allelic, and therefore not as polymorphic as microsatellites, the high number of loci that can be multiplexed and the possibilities of automation as well as their highly repeatable results under any analytical procedure make them the future markers of choice for any type of genetic identification. Results We analyzed over 300 SNP in the genome of grapevine using a re-sequencing strategy in a selection of 11 genotypes. Among the identified polymorphisms, we selected 48 SNP spread across all grapevine chromosomes with allele frequencies balanced enough as to provide sufficient information content for genetic identification in grapevine allowing for good genotyping success rate. Marker stability was tested in repeated analyses of a selected group of cultivars obtained worldwide to demonstrate their usefulness in genetic identification. Conclusions We have selected a set of 48 stable SNP markers with a high discrimination power and a uniform genome distribution (2-3 markers/chromosome), which is proposed as a standard set for grapevine (Vitis vinifera L.) genotyping. Any previous problems derived from microsatellite allele confusion between labs or the need to run reference cultivars to identify allele sizes disappear using this type of marker. Furthermore, because SNP

  10. Sniper: improved SNP discovery by multiply mapping deep sequenced reads.

    PubMed

    Simola, Daniel F; Kim, Junhyong

    2011-06-20

    SNP (single nucleotide polymorphism) discovery using next-generation sequencing data remains difficult primarily because of redundant genomic regions, such as interspersed repetitive elements and paralogous genes, present in all eukaryotic genomes. To address this problem, we developed Sniper, a novel multi-locus Bayesian probabilistic model and a computationally efficient algorithm that explicitly incorporates sequence reads that map to multiple genomic loci. Our model fully accounts for sequencing error, template bias, and multi-locus SNP combinations, maintaining high sensitivity and specificity under a broad range of conditions. An implementation of Sniper is freely available at http://kim.bio.upenn.edu/software/sniper.shtml.

  11. Demonstration of correlations between the 8 and 10 kHz atmospherics and the inflammatory reaction of rats after carrageenan injection

    NASA Astrophysics Data System (ADS)

    Ruhenstroth-Bauer, Gerhard; Rösing, Olga; Baumer, Hans; Sönning, Walter; Lehmacher, Walter

    1988-09-01

    Between the mean daily density of 28 kHz atmospherics and the onset of epileptic fits there is a highly significant correlation coefficient ( r) of 0.30; there is a negative coefficient of -0.20 between the fits and the mean daily density of 10 kHz atmospherics. The onset of heart infarction is correlated with 28 kHz atmospherics ( r=0.15). Furthermore, we have discovered that sudden deafness is also correlated with certain configurations of atmospherics. In this paper we report the following correlation coefficients between the inflammatory reaction of rats to a carrageenan injection (rci) into a hind paw and the mean daily pulse rate of atmospherics of the same day: r=0.49 for the 8 kHz atmospherics ( P<0.02) and r=0.44 for the 10 kHz atmospherics ( P<0.04). The correlations between rci reaction and other atmospherics (12 and 28 kHz) are smaller and not significant. By the method of multiple linear regression we found a multiple R=0.54 between rci reaction and the 8 and 10 kHz atmospherics (the regression function for the rci reaction is 0.15+0.004×8 kHz+0.002×10 kHz, P<0.05).

  12. SNP marker diversity in common bean (Phaseolus vulgaris L.).

    PubMed

    Cortés, Andrés J; Chavarro, Martha C; Blair, Matthew W

    2011-09-01

    Single nucleotide polymorphism (SNP) markers have become a genetic technology of choice because of their automation and high precision of allele calls. In this study, our goal was to develop 94 SNPs and test them across well-chosen common bean (Phaseolus vulgaris L.) germplasm. We validated and accessed SNP diversity at 84 gene-based and 10 non-genic loci using KASPar technology in a panel of 70 genotypes that have been used as parents of mapping populations and have been previously evaluated for SSRs. SNPs exhibited high levels of genetic diversity, an excess of middle frequency polymorphism, and a within-genepool mismatch distribution as expected for populations affected by sudden demographic expansions after domestication bottlenecks. This set of markers was useful for distinguishing Andean and Mesoamerican genotypes but less useful for distinguishing within each gene pool. In summary, slightly greater polymorphism and race structure was found within the Andean gene pool than within the Mesoamerican gene pool but polymorphism rate between genotypes was consistent with genepool and race identity. Our survey results represent a baseline for the choice of SNP markers for future applications because gene-associated SNPs could themselves be causative SNPs for traits. Finally, we discuss that the ideal genetic marker combination with which to carry out diversity, mapping and association studies in common bean should consider a mix of both SNP and SSR markers.

  13. Do you really know where this SNP goes?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The release of build 10.2 of the swine genome was a marked improvement over previous builds and has proven extremely useful. However, as most know, there are regions of the genome that this particular build does not accurately represent. For instance, nearly 25% of the 62,162 SNP on the Illumina Por...

  14. Software solutions for the livestock genomics SNP array revolution.

    PubMed

    Nicolazzi, E L; Biffani, S; Biscarini, F; Orozco Ter Wengel, P; Caprera, A; Nazzicari, N; Stella, A

    2015-08-01

    Since the beginning of the genomic era, the number of available single nucleotide polymorphism (SNP) arrays has grown considerably. In the bovine species alone, 11 SNP chips not completely covered by intellectual property are currently available, and the number is growing. Genomic/genotype data are not standardized, and this hampers its exchange and integration. In addition, software used for the analyses of these data usually requires not standard (i.e. case specific) input files which, considering the large amount of data to be handled, require at least some programming skills in their production. In this work, we describe a software toolkit for SNP array data management, imputation, genome-wide association studies, population genetics and genomic selection. However, this toolkit does not solve the critical need for standardization of the genotypic data and software input files. It only highlights the chaotic situation each researcher has to face on a daily basis and gives some helpful advice on the currently available tools in order to navigate the SNP array data complexity. PMID:25907889

  15. SNP Discovery through Next-Generation Sequencing and Its Applications

    PubMed Central

    Kumar, Santosh; Banks, Travis W.; Cloutier, Sylvie

    2012-01-01

    The decreasing cost along with rapid progress in next-generation sequencing and related bioinformatics computing resources has facilitated large-scale discovery of SNPs in various model and nonmodel plant species. Large numbers and genome-wide availability of SNPs make them the marker of choice in partially or completely sequenced genomes. Although excellent reviews have been published on next-generation sequencing, its associated bioinformatics challenges, and the applications of SNPs in genetic studies, a comprehensive review connecting these three intertwined research areas is needed. This paper touches upon various aspects of SNP discovery, highlighting key points in availability and selection of appropriate sequencing platforms, bioinformatics pipelines, SNP filtering criteria, and applications of SNPs in genetic analyses. The use of next-generation sequencing methodologies in many non-model crops leading to discovery and implementation of SNPs in various genetic studies is discussed. Development and improvement of bioinformatics software that are open source and freely available have accelerated the SNP discovery while reducing the associated cost. Key considerations for SNP filtering and associated pipelines are discussed in specific topics. A list of commonly used software and their sources is compiled for easy access and reference. PMID:23227038

  16. Software solutions for the livestock genomics SNP array revolution.

    PubMed

    Nicolazzi, E L; Biffani, S; Biscarini, F; Orozco Ter Wengel, P; Caprera, A; Nazzicari, N; Stella, A

    2015-08-01

    Since the beginning of the genomic era, the number of available single nucleotide polymorphism (SNP) arrays has grown considerably. In the bovine species alone, 11 SNP chips not completely covered by intellectual property are currently available, and the number is growing. Genomic/genotype data are not standardized, and this hampers its exchange and integration. In addition, software used for the analyses of these data usually requires not standard (i.e. case specific) input files which, considering the large amount of data to be handled, require at least some programming skills in their production. In this work, we describe a software toolkit for SNP array data management, imputation, genome-wide association studies, population genetics and genomic selection. However, this toolkit does not solve the critical need for standardization of the genotypic data and software input files. It only highlights the chaotic situation each researcher has to face on a daily basis and gives some helpful advice on the currently available tools in order to navigate the SNP array data complexity.

  17. Amerindians show association to obesity with adiponectin gene SNP45 and SNP276: population genetics of a food intake control and "thrifty" gene.

    PubMed

    Arnaiz-Villena, Antonio; Fernández-Honrado, Mercedes; Rey, Diego; Enríquez-de-Salamanca, Mercedes; Abd-El-Fatah-Khalil, Sedeka; Arribas, Ignacio; Coca, Carmen; Algora, Manuel; Areces, Cristina

    2013-02-01

    Adiponectin gene polymorphisms SNP45 and SNP276 have been related to metabolic syndrome (MS) and related pathologies, including obesity. However results of associations are contradictory depending on which population is studied. In the present study, these adiponectin SNPs are for the first time studied in Amerindians. Allele frequencies are obtained and comparison with obesity and other MS related parameters are performed. Amerindians were also defined by characteristic HLA genes. Our main results are: (1) SNP276 T is associated to low diastolic blood pressure in Amerindians, (2) SNP45 G allele is correlated with obesity in female but not in male Amerindians, (3) SNP45/SNP276 T/G haplotype in total obese/non-obese subjects tends to show a linkage with non-obese Amerindians, (4) SNP45/SNP276 T/T haplotype is linked to obese Amerindian males. Also, a world population study is carried out finding that SNP45 T and SNP276 T alleles are the most frequent in African Blacks and are found significantly in lower frequencies in Europeans and Asians. This together with the fact that there is a linkage of this haplotype to obese Amerindian males suggest that evolutionary forces related to famine (or population density in relation with available food) may have shaped world population adiponectin polymorphism frequencies. PMID:23108996

  18. Development and application of a 6.5 million feature Affymetrix Genechip® for massively parallel discovery of single position polymorphisms in lettuce (Lactuca spp.)

    PubMed Central

    2012-01-01

    Background High-resolution genetic maps are needed in many crops to help characterize the genetic diversity that determines agriculturally important traits. Hybridization to microarrays to detect single feature polymorphisms is a powerful technique for marker discovery and genotyping because of its highly parallel nature. However, microarrays designed for gene expression analysis rarely provide sufficient gene coverage for optimal detection of nucleotide polymorphisms, which limits utility in species with low rates of polymorphism such as lettuce (Lactuca sativa). Results We developed a 6.5 million feature Affymetrix GeneChip® for efficient polymorphism discovery and genotyping, as well as for analysis of gene expression in lettuce. Probes on the microarray were designed from 26,809 unigenes from cultivated lettuce and an additional 8,819 unigenes from four related species (L. serriola, L. saligna, L. virosa and L. perennis). Where possible, probes were tiled with a 2 bp stagger, alternating on each DNA strand; providing an average of 187 probes covering approximately 600 bp for each of over 35,000 unigenes; resulting in up to 13 fold redundancy in coverage per nucleotide. We developed protocols for hybridization of genomic DNA to the GeneChip® and refined custom algorithms that utilized coverage from multiple, high quality probes to detect single position polymorphisms in 2 bp sliding windows across each unigene. This allowed us to detect greater than 18,000 polymorphisms between the parental lines of our core mapping population, as well as numerous polymorphisms between cultivated lettuce and wild species in the lettuce genepool. Using marker data from our diversity panel comprised of 52 accessions from the five species listed above, we were able to separate accessions by species using both phylogenetic and principal component analyses. Additionally, we estimated the diversity between different types of cultivated lettuce and distinguished morphological types

  19. Large-Scale SNP Discovery through RNA Sequencing and SNP Genotyping by Targeted Enrichment Sequencing in Cassava (Manihot esculenta Crantz)

    PubMed Central

    Pootakham, Wirulda; Shearman, Jeremy R.; Ruang-areerate, Panthita; Sonthirod, Chutima; Sangsrakru, Duangjai; Jomchai, Nukoon; Yoocha, Thippawan; Triwitayakorn, Kanokporn; Tragoonrung, Somvong; Tangphatsornruang, Sithichoke

    2014-01-01

    Cassava (Manihot esculenta Crantz) is one of the most important crop species being the main source of dietary energy in several countries. Marker-assisted selection has become an essential tool in plant breeding. Single nucleotide polymorphism (SNP) discovery via transcriptome sequencing is an attractive strategy for genome complexity reduction in organisms with large genomes. We sequenced the transcriptome of 16 cassava accessions using the Illumina HiSeq platform and identified 675,559 EST-derived SNP markers. A subset of those markers was subsequently genotyped by capture-based targeted enrichment sequencing in 100 F1 progeny segregating for starch viscosity phenotypes. A total of 2,110 non-redundant SNP markers were used to construct a genetic map. This map encompasses 1,785 cM and consists of 19 linkage groups. A major quantitative trait locus (QTL) controlling starch pasting properties was identified and shown to coincide with the QTL previously reported for this trait. With a high-density SNP-based linkage map presented here, we also uncovered a novel QTL associated with starch pasting time on LG 10. PMID:25551642

  20. Large-scale SNP discovery through RNA sequencing and SNP genotyping by targeted enrichment sequencing in cassava (Manihot esculenta Crantz).

    PubMed

    Pootakham, Wirulda; Shearman, Jeremy R; Ruang-Areerate, Panthita; Sonthirod, Chutima; Sangsrakru, Duangjai; Jomchai, Nukoon; Yoocha, Thippawan; Triwitayakorn, Kanokporn; Tragoonrung, Somvong; Tangphatsornruang, Sithichoke

    2014-01-01

    Cassava (Manihot esculenta Crantz) is one of the most important crop species being the main source of dietary energy in several countries. Marker-assisted selection has become an essential tool in plant breeding. Single nucleotide polymorphism (SNP) discovery via transcriptome sequencing is an attractive strategy for genome complexity reduction in organisms with large genomes. We sequenced the transcriptome of 16 cassava accessions using the Illumina HiSeq platform and identified 675,559 EST-derived SNP markers. A subset of those markers was subsequently genotyped by capture-based targeted enrichment sequencing in 100 F1 progeny segregating for starch viscosity phenotypes. A total of 2,110 non-redundant SNP markers were used to construct a genetic map. This map encompasses 1,785 cM and consists of 19 linkage groups. A major quantitative trait locus (QTL) controlling starch pasting properties was identified and shown to coincide with the QTL previously reported for this trait. With a high-density SNP-based linkage map presented here, we also uncovered a novel QTL associated with starch pasting time on LG 10.

  1. Multiple SNP Set Analysis for Genome-Wide Association Studies Through Bayesian Latent Variable Selection.

    PubMed

    Lu, Zhao-Hua; Zhu, Hongtu; Knickmeyer, Rebecca C; Sullivan, Patrick F; Williams, Stephanie N; Zou, Fei

    2015-12-01

    The power of genome-wide association studies (GWAS) for mapping complex traits with single-SNP analysis (where SNP is single-nucleotide polymorphism) may be undermined by modest SNP effect sizes, unobserved causal SNPs, correlation among adjacent SNPs, and SNP-SNP interactions. Alternative approaches for testing the association between a single SNP set and individual phenotypes have been shown to be promising for improving the power of GWAS. We propose a Bayesian latent variable selection (BLVS) method to simultaneously model the joint association mapping between a large number of SNP sets and complex traits. Compared with single SNP set analysis, such joint association mapping not only accounts for the correlation among SNP sets but also is capable of detecting causal SNP sets that are marginally uncorrelated with traits. The spike-and-slab prior assigned to the effects of SNP sets can greatly reduce the dimension of effective SNP sets, while speeding up computation. An efficient Markov chain Monte Carlo algorithm is developed. Simulations demonstrate that BLVS outperforms several competing variable selection methods in some important scenarios. PMID:26515609

  2. A compact 10 kW, 476 MHz solid state radio frequency amplifier for pre-buncher cavity of free electron laser injector linear accelerator

    SciTech Connect

    Mohania, Praveen; Mahawar, Ashish; Shrivastava, Purushottam; Gupta, P. D.

    2013-09-15

    A 10 kW, 476 MHz, 0.1% duty cycle solid state RF amplifier system for driving sub-harmonic, pre-buncher cavity of IR-FEL injector LINAC, has been developed at RRCAT. The 10 kW power is achieved by combining output of eight 1400 W amplifier modules using 8-way planar corporate combiner. The solid state amplifier modules have been developed using 50 V RF LDMOS transistors which although meant for push-pull operation are being used in single ended configuration with matching circuit developed on a thin (25 mils), high dielectric constant (9.7), low loss microwave laminate with an aim to have a compact structure. Ease of fabrication, modularity, small size, and low cost are the important features of this design which could be used as a template for low duty cycle medium to high pulsed power UHF amplifier system.

  3. Design and performance of the 10-kV, 5-MA pulsed-power system for the FRX-C compression experiment

    SciTech Connect

    Rej, D.J.; Barnes, G.A.; Gribble, R.J.; Hinckley, J.E.; Kreider, T.W.; Waganaar, W.J.

    1989-05-01

    The design and performance of the pulsed-power system for the FRX-C compact toroid compression heating experiment are reviewed. Two inductively-isolated, 10-kV capacitor banks (total energy = 1.5 MJ) are discharged through a common, low-inductance load. The 5-MA currents are switched and crowbarred with parallel arrays of size-D ignitrons. Power supplies are constructed in simple 25 and 50 kJ modules, each capable of supplying 100 kA at 10 kV. Non-negligible source inductance and the addition of high-power resistors maintain module isolation and protect the system during fault modes. 21 refs., 31 figs.

  4. Development of a 10 kW High Temperature High Power Density Three-Phase AC-DC-AC SiC Converter

    SciTech Connect

    Ning, Puqi

    2012-01-01

    This paper presents the development and experimental performance of a 10 kW, all SiC, 250 C junction temperature high-power-density three-phase ac-dc-ac converter. The electromagnetic interference filter, thermal system, high temperature package, and gate drive design are discussed in detail. Finally, tests confirming the feasibility and validating the theoretical basis of the prototype converter system are described.

  5. 17 CFR 240.12b-25 - Notification of inability to timely file all or any required portion of a Form 10-K, 20-F, 11-K...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., annual or transition report on Form N-CSR (17 CFR 249.331; 17 CFR 274.128) or Form N-SAR (17 CFR 249.330... all or any required portion of an annual or transition report on Form 10-K, 20-F or 11-K (17 CFR 249.310, 249.220f or 249.311), a quarterly or transition report on Form 10-Q (17 CFR 249.308a), or...

  6. SNP genotyping using single-tube fluorescent bidirectional PCR.

    PubMed

    Waterfall, Christy M; Cobb, Benjamin D

    2002-07-01

    SNP genotyping is a well-populatedfield with a large number of assay formats offering accurate allelic discrimination. However, there remains a discord between the ultimate goal of rapid, inexpensive assays that do not require complex design considerations and involved optimization strategies. We describe the first integration of bidirectional allele-specific amplification, SYBR Green I, and rapid-cycle PCR to provide a homogeneous SNP-typing assay. Wild-type, mutant, and heterozygous alleles were easily discriminated in a single tube using melt curve profiling of PCR products alone. We demonstrate the effectiveness and reliability of this assay with a blinded trial using clinical samples from individuals with sickle cell anemia, sickle cell trait, or unaffected individuals. The tests were completed in less than 30 min without expensive fluorogenic probes, prohibiting design rules, or lengthy downstream processing for product analysis.

  7. Detection of homologous horizontal gene transfer in SNP data

    2012-07-23

    We study the detection of mutations, sequencing errors, and homologous horizontal gene transfers (HGT) in a set of closely related microbial genomes. We base the model on single nucleotide polymorphisms (SNP's) and break the genomes into blocks to handle the rearrangement problem. Then we apply a synamic programming algorithm to model whether changes within each block are likely a result of mutations, sequencing errors, or HGT.

  8. SNP Haplotype Mapping in a Small ALS Family

    PubMed Central

    Krueger, Katherine A. Dick; Tsuji, Shoji; Fukuda, Yoko; Takahashi, Yuji; Goto, Jun; Mitsui, Jun; Ishiura, Hiroyuki; Dalton, Joline C.; Miller, Michael B.; Day, John W.; Ranum, Laura P. W.

    2009-01-01

    The identification of genes for monogenic disorders has proven to be highly effective for understanding disease mechanisms, pathways and gene function in humans. Nevertheless, while thousands of Mendelian disorders have not yet been mapped there has been a trend away from studying single-gene disorders. In part, this is due to the fact that many of the remaining single-gene families are not large enough to map the disease locus to a single site in the genome. New tools and approaches are needed to allow researchers to effectively tap into this genetic gold-mine. Towards this goal, we have used haploid cell lines to experimentally validate the use of high-density single nucleotide polymorphism (SNP) arrays to define genome-wide haplotypes and candidate regions, using a small amyotrophic lateral sclerosis (ALS) family as a prototype. Specifically, we used haploid-cell lines to determine if high-density SNP arrays accurately predict haplotypes across entire chromosomes and show that haplotype information significantly enhances the genetic information in small families. Panels of haploid-cell lines were generated and a 5 centimorgan (cM) short tandem repeat polymorphism (STRP) genome scan was performed. Experimentally derived haplotypes for entire chromosomes were used to directly identify regions of the genome identical-by-descent in 5 affected individuals. Comparisons between experimentally determined and in silico haplotypes predicted from SNP arrays demonstrate that SNP analysis of diploid DNA accurately predicted chromosomal haplotypes. These methods precisely identified 12 candidate intervals, which are shared by all 5 affected individuals. Our study illustrates how genetic information can be maximized using readily available tools as a first step in mapping single-gene disorders in small families. PMID:19479031

  9. Introgression browser: high-throughput whole-genome SNP visualization.

    PubMed

    Aflitos, Saulo Alves; Sanchez-Perez, Gabino; de Ridder, Dick; Fransz, Paul; Schranz, Michael E; de Jong, Hans; Peters, Sander A

    2015-04-01

    Breeding by introgressive hybridization is a pivotal strategy to broaden the genetic basis of crops. Usually, the desired traits are monitored in consecutive crossing generations by marker-assisted selection, but their analyses fail in chromosome regions where crossover recombinants are rare or not viable. Here, we present the Introgression Browser (iBrowser), a bioinformatics tool aimed at visualizing introgressions at nucleotide or SNP (Single Nucleotide Polymorphisms) accuracy. The software selects homozygous SNPs from Variant Call Format (VCF) information and filters out heterozygous SNPs, multi-nucleotide polymorphisms (MNPs) and insertion-deletions (InDels). For data analysis iBrowser makes use of sliding windows, but if needed it can generate any desired fragmentation pattern through General Feature Format (GFF) information. In an example of tomato (Solanum lycopersicum) accessions we visualize SNP patterns and elucidate both position and boundaries of the introgressions. We also show that our tool is capable of identifying alien DNA in a panel of the closely related S. pimpinellifolium by examining phylogenetic relationships of the introgressed segments in tomato. In a third example, we demonstrate the power of the iBrowser in a panel of 597 Arabidopsis accessions, detecting the boundaries of a SNP-free region around a polymorphic 1.17 Mbp inverted segment on the short arm of chromosome 4. The architecture and functionality of iBrowser makes the software appropriate for a broad set of analyses including SNP mining, genome structure analysis, and pedigree analysis. Its functionality, together with the capability to process large data sets and efficient visualization of sequence variation, makes iBrowser a valuable breeding tool.

  10. Investigating single nucleotide polymorphism (SNP) density in the human genome and its implications for molecular evolution.

    PubMed

    Zhao, Zhongming; Fu, Yun-Xin; Hewett-Emmett, David; Boerwinkle, Eric

    2003-07-17

    We investigated the single nucleotide polymorphism (SNP) density across the human genome and in different genic categories using two SNP databases: Celera's CgsSNP, which includes SNPs identified by comparing genomic sequences, and Celera's RefSNP, which includes SNPs from a variety of sources and is biased toward disease-associated genes. Based on CgsSNP, the average numbers of SNPs per 10 kb was 8.33, 8.44, and 8.09 in the human genome, in intergenic regions, and in genic regions, respectively. In genic regions, the SNP density in intronic, exonic and adjoining untranslated regions was 8.21, 5.28, and 7.51 SNPs per 10 kb, respectively. The pattern of SNP density based on RefSNP was different from that based on CgsSNP, emphasizing its utility for genotype-phenotype association studies but not for most population genetic studies. The number of SNPs per chromosome was correlated with chromosome length, but the density of SNPs estimated by CgsSNP was not significantly correlated with the GC content of the chromosome. Based on CgsSNP, the ratio of nonsense to missense mutations (0.027), the ratio of missense to silent mutations (1.15), and the ratio of non-synonymous to synonymous mutations (1.18) was less than half of that expected in a human protein coding sequence under the neutral mutation theory, reflecting a role for natural selection, especially purifying selection. PMID:12909357

  11. Population distribution and ancestry of the cancer protective MDM2 SNP285 (rs117039649).

    PubMed

    Knappskog, Stian; Gansmo, Liv B; Dibirova, Khadizha; Metspalu, Andres; Cybulski, Cezary; Peterlongo, Paolo; Aaltonen, Lauri; Vatten, Lars; Romundstad, Pål; Hveem, Kristian; Devilee, Peter; Evans, Gareth D; Lin, Dongxin; Van Camp, Guy; Manolopoulos, Vangelis G; Osorio, Ana; Milani, Lili; Ozcelik, Tayfun; Zalloua, Pierre; Mouzaya, Francis; Bliznetz, Elena; Balanovska, Elena; Pocheshkova, Elvira; Kučinskas, Vaidutis; Atramentova, Lubov; Nymadawa, Pagbajabyn; Titov, Konstantin; Lavryashina, Maria; Yusupov, Yuldash; Bogdanova, Natalia; Koshel, Sergey; Zamora, Jorge; Wedge, David C; Charlesworth, Deborah; Dörk, Thilo; Balanovsky, Oleg; Lønning, Per E

    2014-09-30

    The MDM2 promoter SNP285C is located on the SNP309G allele. While SNP309G enhances Sp1 transcription factor binding and MDM2 transcription, SNP285C antagonizes Sp1 binding and reduces the risk of breast-, ovary- and endometrial cancer. Assessing SNP285 and 309 genotypes across 25 different ethnic populations (>10.000 individuals), the incidence of SNP285C was 6-8% across European populations except for Finns (1.2%) and Saami (0.3%). The incidence decreased towards the Middle-East and Eastern Russia, and SNP285C was absent among Han Chinese, Mongolians and African Americans. Interhaplotype variation analyses estimated SNP285C to have originated about 14,700 years ago (95% CI: 8,300 - 33,300). Both this estimate and the geographical distribution suggest SNP285C to have arisen after the separation between Caucasians and modern day East Asians (17,000 - 40,000 years ago). We observed a strong inverse correlation (r = -0.805; p < 0.001) between the percentage of SNP309G alleles harboring SNP285C and the MAF for SNP309G itself across different populations suggesting selection and environmental adaptation with respect to MDM2 expression in recent human evolution. In conclusion, we found SNP285C to be a pan-Caucasian variant. Ethnic variation regarding distribution of SNP285C needs to be taken into account when assessing the impact of MDM2 SNPs on cancer risk. PMID:25327560

  12. Population distribution and ancestry of the cancer protective MDM2 SNP285 (rs117039649)

    PubMed Central

    Knappskog, Stian; Gansmo, Liv B.; Dibirova, Khadizha; Metspalu, Andres; Cybulski, Cezary; Peterlongo, Paolo; Aaltonen, Lauri; Vatten, Lars; Romundstad, Pål; Hveem, Kristian; Devilee, Peter; Evans, Gareth D.; Lin, Dongxin; Camp, Guy Van; Manolopoulos, Vangelis G.; Osorio, Ana; Milani, Lili; Ozcelik, Tayfun; Zalloua, Pierre; Mouzaya, Francis; Bliznetz, Elena; Balanovska, Elena; Pocheshkova, Elvira; Kučinskas, Vaidutis; Atramentova, Lubov; Nymadawa, Pagbajabyn; Titov, Konstantin; Lavryashina, Maria; Yusupov, Yuldash; Bogdanova, Natalia; Koshel, Sergey; Zamora, Jorge; Wedge, David C.; Charlesworth, Deborah; Dörk, Thilo; Balanovsky, Oleg; Lønning, Per E.

    2014-01-01

    The MDM2 promoter SNP285C is located on the SNP309G allele. While SNP309G enhances Sp1 transcription factor binding and MDM2 transcription, SNP285C antagonizes Sp1 binding and reduces the risk of breast-, ovary- and endometrial cancer. Assessing SNP285 and 309 genotypes across 25 different ethnic populations (>10.000 individuals), the incidence of SNP285C was 6-8% across European populations except for Finns (1.2%) and Saami (0.3%). The incidence decreased towards the Middle-East and Eastern Russia, and SNP285C was absent among Han Chinese, Mongolians and African Americans. Interhaplotype variation analyses estimated SNP285C to have originated about 14,700 years ago (95% CI: 8,300 – 33,300). Both this estimate and the geographical distribution suggest SNP285C to have arisen after the separation between Caucasians and modern day East Asians (17,000 - 40,000 years ago). We observed a strong inverse correlation (r = -0.805; p < 0.001) between the percentage of SNP309G alleles harboring SNP285C and the MAF for SNP309G itself across different populations suggesting selection and environmental adaptation with respect to MDM2 expression in recent human evolution. In conclusion, we found SNP285C to be a pan-Caucasian variant. Ethnic variation regarding distribution of SNP285C needs to be taken into account when assessing the impact of MDM2 SNPs on cancer risk. PMID:25327560

  13. Both a nicotinic single nucleotide polymorphism (SNP) and a noradrenergic SNP modulate working memory performance when attention is manipulated.

    PubMed

    Greenwood, Pamela M; Sundararajan, Ramya; Lin, Ming-Kuan; Kumar, Reshma; Fryxell, Karl J; Parasuraman, Raja

    2009-11-01

    We investigated the relation between the two systems of visuospatial attention and working memory by examining the effect of normal variation in cholinergic and noradrenergic genes on working memory performance under attentional manipulation. We previously reported that working memory for location was impaired following large location precues, indicating the scale of visuospatial attention has a role in forming the mental representation of the target. In one of the first studies to compare effects of two single nucleotide polymorphisms (SNPs) on the same cognitive task, we investigated the neurotransmission systems underlying interactions between attention and memory. Based on our previous report that the CHRNA4 rs#1044396 C/T nicotinic receptor SNP affected visuospatial attention, but not working memory, and the DBH rs#1108580 G/A noradrenergic enzyme SNP affected working memory, but not attention, we predicted that both SNPs would modulate performance when the two systems interacted and working memory was manipulated by attention. We found the scale of visuospatial attention deployed around a target affected memory for location of that target. Memory performance was modulated by the two SNPs. CHRNA4 C/C homozygotes and DBH G allele carriers showed the best memory performance but also the greatest benefit of visuospatial attention on memory. Overall, however, the CHRNA4 SNP exerted a stronger effect than the DBH SNP on memory performance when visuospatial attention was manipulated. This evidence of an integrated cholinergic influence on working memory performance under attentional manipulation is consistent with the view that working memory and visuospatial attention are separate systems which can interact.

  14. Relative biological effectiveness of 25 and 10 kV X-rays for the induction of chromosomal aberrations in two human mammary epithelial cell lines.

    PubMed

    Beyreuther, Elke; Dörr, Wolfgang; Lehnert, Anna; Lessmann, Elisabeth; Pawelke, Jörg

    2009-08-01

    Administration of ionizing radiation for diagnostic purposes can be associated with a risk for the induction of tumors. Therefore, particularly with regard to general screening programs, e.g. with mammography, cost-benefit considerations must be discussed including risk estimation depending upon the radiation quality administered. The present study was initiated to investigate the in vitro X-ray energy dependence for the induction of chromosomal aberrations in the two mammary epithelial cell lines, 184A1 and MCF-12A. The induced excess fragments, dicentric chromosomes and centric rings were analyzed and the relative biological effectiveness (RBE) was determined for 10 and 25 kV X-rays relative to 200 kV X-rays. The assumed energy dependence with higher values for 10 kV X-rays was confirmed for the excess fragments, with RBE(M) values of 1.92 +/- 0.26 and 1.40 +/- 0.12 for 10 kV X-rays and 1.17 +/- 0.12 and 0.97 +/- 0.10 for 25 kV photons determined for cell lines 184A1 and MCF-12A, respectively. Meaningful results for the induction of dicentric chromosomes and centric rings were obtained only for higher doses with RBE values of 1.31 +/- 0.21 and 1.70 +/- 0.29 for 184A1 and 1.08 +/- 0.08 and 1.43 +/- 0.12 for MCF-12A irradiated with 25 and 10 kV X-rays, respectively.

  15. Time dependent chemistry in dense molecular clouds. III - Infrared band cross sections of molecules in the solid state at 10 K

    NASA Technical Reports Server (NTRS)

    Dhendecourt, L. B.; Allamandola, L. J.

    1986-01-01

    Thin film transmission infrared spectra and a list of integrated absorbance values (band strengths) of bands in the 2.5 to 20 micron range of various molecular solids deposited on a CsI window cooled to 10 K are presented. These solids include molecules known or suspected to be present on interstellar grains such as H2O, CO, NH3 and CH4 and mixtures of these molecules as well as various hydrocarbons. The method is described by which the absorbance values derived can be used to estimate column densities of species adsorbed on interstellar grains and other solids associated with celestial IR sources.

  16. A 10-kW SiC Inverter with A Novel Printed Metal Power Module With Integrated Cooling Using Additive Manufacturing

    SciTech Connect

    Chinthavali, Madhu Sudhan; Ayers, Curtis William; Campbell, Steven L; Wiles, Randy H; Ozpineci, Burak

    2014-01-01

    With efforts to reduce the cost, size, and thermal management systems for the power electronics drivetrain in hybrid electric vehicles (HEVs) and plug-in hybrid electric vehicles (PHEVs), wide band gap semiconductors including silicon carbide (SiC) have been identified as possibly being a partial solution. This paper focuses on the development of a 10-kW all SiC inverter using a high power density, integrated printed metal power module with integrated cooling using additive manufacturing techniques. This is the first ever heat sink printed for a power electronics application. About 50% of the inverter was built using additive manufacturing techniques.

  17. Force Euramet supplementary comparison EURAMET.M.F-S4 (Euramet Project 1311)10 kN and 20 kN

    NASA Astrophysics Data System (ADS)

    Averlant, P.; Duflon, C.

    2016-01-01

    This report details the results of a bilateral force comparison carried out between the KIM-LIPI (Indonesia) and the LNE (France), for force values of 10 kN and 20 kN. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  18. Transposed stimuli improve sensitivity to envelope-based interaural timing information for stimuli having center frequencies of up to 10 kHz

    NASA Astrophysics Data System (ADS)

    Bernstein, Leslie R.; Trahiotis, Constantine

    2002-05-01

    Threshold interaural temporal disparities (ITDs) at high frequencies are larger than threshold ITDs obtained at low frequencies. Colburn and Esquissaud [J. Acoust. Soc. Am. Suppl. 1 59, S23 (1976)], hypothesized that this reflects differences in peripheral processing of the stimuli rather than in binaural mechanisms that mediate performance. Previously [L. R. Bernstein and C. Trahiotis, J. Acoust. Soc. Am. 109, 2485 (2001)] this hypothesis was supported in ITD-discrimination experiments employing high-frequency ``transposed stimuli'' centered at 4 kHz that were designed to provide high-frequency channels with envelope-based information mimicking that normally available only in low-frequency channels. Here, we report new results using stimuli centered at 4, 6, and 10 kHz. It was found that (1) transposed stimuli can yield relatively small threshold ITDs, even at 6 and 10 kHz, (2) the data could be well accounted for in terms of a constant-criterion change in normalized interaural correlation computed subsequent to bandpass filtering, compression, rectification, and low-pass filtering. In addition, it was found necessary to incorporate a specific limitation to capture the inability of the auditory system to follow envelope fluctuations greater than 150 Hz. [Work supported by NIH DC 04147.

  19. Force supplementary comparison EURAMET.M.F-S3 (1 kN, 2 kN, 5 kN, and 10 kN)

    NASA Astrophysics Data System (ADS)

    Knott, A.; Machado, R. R.

    2016-01-01

    This report describes EURAMET supplementary comparison EURAMET.M.F-S3, a comparison between the 20 kN force standard machine of NPL and the 10 kN force standard machine of INMETRO, at generated forces of 1 kN, 2 kN, 5 kN, and 10 kN, in both tension and compression, with both incremental and decremental loading. Two different transducers were used and the force-time profile was strictly controlled, to minimise effects of creep. At all four force levels, the results demonstrate that there is no evidence that either machine fails to generate forces in accordance with its CMC. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  20. Copy number and loss of heterozygosity detected by SNP array of formalin-fixed tissues using whole-genome amplification.

    PubMed

    Stokes, Angela; Drozdov, Ignat; Guerra, Eliete; Ouzounis, Christos A; Warnakulasuriya, Saman; Gleeson, Michael J; McGurk, Mark; Tavassoli, Mahvash; Odell, Edward W

    2011-01-01

    The requirement for large amounts of good quality DNA for whole-genome applications prohibits their use for small, laser capture micro-dissected (LCM), and/or rare clinical samples, which are also often formalin-fixed and paraffin-embedded (FFPE). Whole-genome amplification of DNA from these samples could, potentially, overcome these limitations. However, little is known about the artefacts introduced by amplification of FFPE-derived DNA with regard to genotyping, and subsequent copy number and loss of heterozygosity (LOH) analyses. Using a ligation adaptor amplification method, we present data from a total of 22 Affymetrix SNP 6.0 experiments, using matched paired amplified and non-amplified DNA from 10 LCM FFPE normal and dysplastic oral epithelial tissues, and an internal method control. An average of 76.5% of SNPs were called in both matched amplified and non-amplified DNA samples, and concordance was a promising 82.4%. Paired analysis for copy number, LOH, and both combined, showed that copy number changes were reduced in amplified DNA, but were 99.5% concordant when detected, amplifications were the changes most likely to be 'missed', only 30% of non-amplified LOH changes were identified in amplified pairs, and when copy number and LOH are combined ∼50% of gene changes detected in the unamplified DNA were also detected in the amplified DNA and within these changes, 86.5% were concordant for both copy number and LOH status. However, there are also changes introduced as ∼20% of changes in the amplified DNA are not detected in the non-amplified DNA. An integrative network biology approach revealed that changes in amplified DNA of dysplastic oral epithelium localize to topologically critical regions of the human protein-protein interaction network, suggesting their functional implication in the pathobiology of this disease. Taken together, our results support the use of amplification of FFPE-derived DNA, provided sufficient samples are used to increase power

  1. PCR amplification of SNP loci from crude DNA for large-scale genotyping of oomycetes.

    PubMed

    Hu, Jian; Lyon, Rebecca; Zhou, Yuxin; Lamour, Kurt

    2014-01-01

    Similar to other eukaryotes, single nucleotide polymorphism (SNP) markers are abundant in many oomycete plant pathogen genomes. High resolution DNA melting analysis (HR-DMA) is a cost-effective method for SNP genotyping, but like many SNP marker technologies, is limited by the amount and quality of template DNA. We describe PCR preamplification of Phytophthora and Peronospora SNP loci from crude DNA extracted from a small amount of mycelium and/or infected plant tissue to produce sufficient template to genotype at least 10 000 SNPs. The approach is fast, inexpensive, requires minimal biological material and should be useful for many organisms in a variety of contexts. PMID:24871597

  2. Accuracy of direct genomic values in Holstein bulls and cows using subsets of SNP markers

    PubMed Central

    2010-01-01

    Background At the current price, the use of high-density single nucleotide polymorphisms (SNP) genotyping assays in genomic selection of dairy cattle is limited to applications involving elite sires and dams. The objective of this study was to evaluate the use of low-density assays to predict direct genomic value (DGV) on five milk production traits, an overall conformation trait, a survival index, and two profit index traits (APR, ASI). Methods Dense SNP genotypes were available for 42,576 SNP for 2,114 Holstein bulls and 510 cows. A subset of 1,847 bulls born between 1955 and 2004 was used as a training set to fit models with various sets of pre-selected SNP. A group of 297 bulls born between 2001 and 2004 and all cows born between 1992 and 2004 were used to evaluate the accuracy of DGV prediction. Ridge regression (RR) and partial least squares regression (PLSR) were used to derive prediction equations and to rank SNP based on the absolute value of the regression coefficients. Four alternative strategies were applied to select subset of SNP, namely: subsets of the highest ranked SNP for each individual trait, or a single subset of evenly spaced SNP, where SNP were selected based on their rank for ASI, APR or minor allele frequency within intervals of approximately equal length. Results RR and PLSR performed very similarly to predict DGV, with PLSR performing better for low-density assays and RR for higher-density SNP sets. When using all SNP, DGV predictions for production traits, which have a higher heritability, were more accurate (0.52-0.64) than for survival (0.19-0.20), which has a low heritability. The gain in accuracy using subsets that included the highest ranked SNP for each trait was marginal (5-6%) over a common set of evenly spaced SNP when at least 3,000 SNP were used. Subsets containing 3,000 SNP provided more than 90% of the accuracy that could be achieved with a high-density assay for cows, and 80% of the high-density assay for young bulls

  3. Personalized Medicine Through SNP Testing for Breast Cancer Risk: Clinical Implementation.

    PubMed

    Howe, Rebecca; Miron-Shatz, Talya; Hanoch, Yaniv; Omer, Zehra B; O'Donoghue, Cristina; Ozanne, Elissa M

    2015-10-01

    Single nucleotide polymorphisms (SNPs) have the potential to improve personalized medicine in breast cancer care. As new SNPs are discovered, further enhancing risk classification, SNP testing may serve to complement family history and phenotypic risk factors when assessed in a clinical setting. SNP analysis is particularly relevant to high-risk women who may seek out such information to guide their decision-making around risk-reduction. However, little is known about how high-risk women may respond to SNP testing with regard to clinical decision-making. We examined high-risk women's interest in SNP testing for breast cancer risk through an online survey of hypothetical testing scenarios. Women stated their preferences for sharing test results and selected the most likely follow-up action they would pursue in each of the test result scenarios (above average and below average risk for breast cancer). Four hundred seventy-eight women participated. Most women (89 %) did not know what a SNP was prior to the study. Once SNP testing was described, 75 % were interested in SNP testing. Participants stated an interest in lifestyle interventions for risk-reduction and wanted to discuss their testing results with their doctor or a genetic counselor. Women are interested in SNP testing and are prepared to make lifestyle changes based on testing results. Women's preference for discussing testing results with a healthcare provider aligns with the current trend towards SNP testing in a clinical setting.

  4. RNASEL and MIR146A SNP-SNP Interaction as a Susceptibility Factor for Non-Melanoma Skin Cancer

    PubMed Central

    Farzan, Shohreh F.; Karagas, Margaret R.; Christensen, Brock C.; Li, Zhongze; Kuriger, Jacquelyn K.; Nelson, Heather H.

    2014-01-01

    Immunity and inflammatory pathways are important in the genesis of non-melanoma skin cancers (NMSC). Functional genetic variation in immune modulators has the potential to affect disease etiology. We investigated associations between common variants in two key regulators, MIR146A and RNASEL, and their relation to NMSCs. Using a large population-based case-control study of basal cell (BCC) and squamous cell carcinoma (SCC), we investigated the impact of MIR146A SNP rs2910164 on cancer risk, and interaction with a SNP in one of its putative targets (RNASEL, rs486907). To examine associations between genotype and BCC and SCC, occurrence odds ratios (OR) and 95% confidence intervals (95%CI) were calculated using unconditional logistic regression, accounting for multiple confounding factors. We did not observe an overall change in the odds ratios for SCC or BCC among individuals carrying either of the RNASEL or MIR146A variants compared with those who were wild type at these loci. However, there was a sex-specific association between BCC and MIR146A in women (ORGC = 0.73, [95%CI = 0.52–1.03]; ORCC = 0.29, [95% CI = 0.14–0.61], p-trend<0.001), and a reduction in risk, albeit not statistically significant, associated with RNASEL and SCC in men (ORAG = 0.88, [95%CI = 0.65–1.19]; ORAA = 0.68, [95%CI = 0.43–1.08], p-trend = 0.10). Most striking was the strong interaction between the two genes. Among individuals carrying variant alleles of both rs2910164 and rs486907, we observed inverse relationships with SCC (ORSCC = 0.56, [95%CI = 0.38–0.81], p-interaction = 0.012) and BCC (ORBCC = 0.57, [95%CI = 0.40–0.80], p-interaction = 0.005). Our results suggest that genetic variation in immune and inflammatory regulators may influence susceptibility to NMSC, and novel SNP-SNP interaction for a microRNA and its target. These data suggest that RNASEL, an enzyme involved in RNA turnover, is controlled by miR-146a

  5. Structural Architecture of SNP Effects on Complex Traits

    PubMed Central

    Gamazon, Eric R.; Cox, Nancy J.; Davis, Lea K.

    2014-01-01

    Despite the discovery of copy-number variation (CNV) across the genome nearly 10 years ago, current SNP-based analysis methodologies continue to collapse the homozygous (i.e., A/A), hemizygous (i.e., A/0), and duplicative (i.e., A/A/A) genotype states, treating the genotype variable as irreducible or unaltered by other colocalizing forms of genetic (e.g., structural) variation. Our understanding of common, genome-wide CNVs suggests that the canonical genotype construct might belie the enormous complexity of the genome. Here we present multiple analyses of several phenotypes and provide methods supporting a conceptual shift that embraces the structural dimension of genotype. We comprehensively investigate the impact of the structural dimension of genotype on (1) GWAS methods, (2) interpretation of rare LOF variants, (3) characterization of genomic architecture, and (4) implications for mapping loci involved in complex disease. Taken together, these results argue for the inclusion of a structural dimension and suggest that some portion of the “missing” heritability might be recovered through integration of the structural dimension of SNP effects on complex traits. PMID:25307299

  6. Dielectric behavior of wild-type yeast and vacuole-deficient mutant over a frequency range of 10 kHz to 10 GHz.

    PubMed Central

    Asami, K; Yonezawa, T

    1996-01-01

    Dielectric behavior of Saccharomyces cerevisiae wild-type and vacuole-deficient mutant cells has been studied over a frequency range of 10 kHz to 10 GHz. Both types of cells harvested at the early stationary growth phase showed dielectric dispersion that was phenomenologically formulated by a sum of three separate dispersion terms: beta 1-dispersion (main dispersion) and beta 2-dispersion (additional dispersion) and gamma-dispersion due to orientation of water molecules. The beta 1-dispersion centered at a few MHz, which has been extensively studied so far, is due to interfacial polarization (or the Maxwell-Wagner effect) related to the plasma membrane. The beta 2-dispersion for the vacuole-deficient mutant centered at approximately 50 MHz was explained by taking the cell wall into account, whereas, for the wild-type cells, the beta 2-dispersion around a few tens MHz involved the contributions from the vacuole and cell wall. PMID:8889195

  7. Design a 10 kJ IS Mather Type Plasma Focus for Solid Target Activation to Produce Short-Lived Radioisotopes 12C(d,n)13N

    NASA Astrophysics Data System (ADS)

    Sadat Kiai, S. M.; Adlparvar, S.; Sheibani, S.; Elahi, M.; Safarien, A.; Farhangi, S.; Zirak, A. R.; Alhooie, S.; Mortazavi, B. N.; Khalaj, M. M.; Khanchi, A. R.; Dabirzadeh, A. A.; Kashani, A.; Zahedi, F.

    2010-10-01

    A 10 kJ (15 kV, 88 μF) IS (Iranian Sun) Mather type plasma focus device has been studied to determine the activity of a compound exogenous carbon solid target through 12C(d,n)13N nuclear reaction. The produced 13N is a short-lived radioisotope with a half-life of 9.97 min and threshold energy of 0.28 MeV. The results indicate that energetic deuterons impinging on the solid target can produce yield of = 6.7 × 10-5 with an activity of A = 6.8 × 104 Bq for one plasma focus shut and A ν = 4 × 105 Bq for 6 shut per mint when the projectile maximum deuterons energy is E max = 3 MeV.

  8. Balance of plant for SOFC experiences with the planning, engineering, construction and testing of a 10 kW planar SOFC pilot plant

    SciTech Connect

    Klov, K.; Sundal, P.; Monsen, T.; Vik, A.

    1996-12-31

    The Statoil Solide Oxide Fuel Cell Research Program was started in January 1991. Some results from this Program were presented to the 1994 Fuel Cell Seminar in San Diego. The final technical milestone for the program was to design, engineer, construct and test a 10 kW pilot plant. From the very beginning, the importance of coordination and integration in the development of components, subsystems and systems, combined with basic research on cell and stack performance, were established as the guidelines for the program. In this way the progress towards the final goal was not a matter of making the best individual cell, the best stack or a superior balance of plant, but to build an efficient, reliable and operative pilot plant system, and thus make a further step towards a verification of commercial SOFC system technology.

  9. Experimental study on the sealing clearance between the labyrinth sealing displacer and cylinder in the 10 K G-M refrigerator

    NASA Astrophysics Data System (ADS)

    Hao, X. H.; Ju, Y. L.; Lu, Y. J.

    2011-05-01

    The labyrinth sealing displacer has been optimal designed to improve the operating stability and life-time of 10 K G-M refrigerator. The displacer was made of stainless steel 304 or inconel 718, coated with PTFE on its outer surface. Compared to the traditional piston-ring sealing displacer, the sealing clearance between the ridge of the labyrinth sealing displacer and cylinder is critical to the cooling performance of the G-M refrigerator. The displacers with different sealing clearances were experimentally studied, and the optimal clearance was given. The effects of the materials of the displacers and the system charge pressures on the performance of the labyrinth sealing were also tested and analyzed.

  10. Conjugation of 10 kDa Linear PEG onto Trastuzumab Fab' Is Sufficient to Significantly Enhance Lymphatic Exposure while Preserving in Vitro Biological Activity.

    PubMed

    Chan, Linda J; Ascher, David B; Yadav, Rajbharan; Bulitta, Jürgen B; Williams, Charlotte C; Porter, Christopher J H; Landersdorfer, Cornelia B; Kaminskas, Lisa M

    2016-04-01

    The lymphatic system is a major conduit by which many diseases spread and proliferate. There is therefore increasing interest in promoting better lymphatic drug targeting. Further, antibody fragments such as Fabs have several advantages over full length monoclonal antibodies but are subject to rapid plasma clearance, which can limit the lymphatic exposure and activity of Fabs against lymph-resident diseases. This study therefore explored ideal PEGylation strategies to maximize biological activity and lymphatic exposure using trastuzumab Fab' as a model. Specifically, the Fab' was conjugated with single linear 10 or 40 kDa PEG chains at the hinge region. PEGylation led to a 3-4-fold reduction in binding affinity to HER2, but antiproliferative activity against HER2-expressing BT474 cells was preserved. Lymphatic pharmacokinetics were then examined in thoracic lymph duct cannulated rats after intravenous and subcutaneous dosing at 2 mg/kg, and the data were evaluated via population pharmacokinetic modeling. The Fab' displayed limited lymphatic exposure, but conjugation of 10 kDa PEG improved exposure by approximately 11- and 5-fold after intravenous (15% dose collected in thoracic lymph over 30 h) and subcutaneous (9%) administration, respectively. Increasing the molecular weight of the PEG to 40 kDa, however, had no significant impact on lymphatic exposure after intravenous (14%) administration and only doubled lymphatic exposure after subcutaneous administration (18%) when compared to 10 kDa PEG-Fab'. The data therefore suggests that minimal PEGylation has the potential to enhance the exposure and activity of Fab's against lymph-resident diseases, while no significant benefit is achieved with very large PEGs.

  11. Comparing the efficacy of SNP filtering methods for identifying a single causal SNP in a known association region.

    PubMed

    Spencer, Amy Victoria; Cox, Angela; Walters, Kevin

    2014-01-01

    Genome-wide association studies have successfully identified associations between common diseases and a large number of single nucleotide polymorphisms (SNPs) across the genome. We investigate the effectiveness of several statistics, including p-values, likelihoods, genetic map distance and linkage disequilibrium between SNPs, in filtering SNPs in several disease-associated regions. We use simulated data to compare the efficacy of filters with different sample sizes and for causal SNPs with different minor allele frequencies (MAFs) and effect sizes, focusing on the small effect sizes and MAFs likely to represent the majority of unidentified causal SNPs. In our analyses, of all the methods investigated, filtering on the ranked likelihoods consistently retains the true causal SNP with the highest probability for a given false positive rate. This was the case for all the local linkage disequilibrium patterns investigated. Our results indicate that when using this method to retain only the top 5% of SNPs, even a causal SNP with an odds ratio of 1.1 and MAF of 0.08 can be retained with a probability exceeding 0.9 using an overall sample size of 50,000.

  12. Molecular cloning and SNP association analysis of chicken PMCH gene.

    PubMed

    Sun, Guirong; Li, Ming; Li, Hong; Tian, Yadong; Chen, Qixin; Bai, Yichun; Kang, Xiangtao

    2013-08-01

    The pre-melanin-concentrating hormone (PMCH) gene is an important gene functionally concerning the regulations of body fat content, feeding behavior and energy balance. In this study, the full-length cDNA of chicken PMCH gene was amplified by SMART RACE method. The single nucleotide polymorphisms (SNPs) in the PMCH gene were screened by comparative sequence analysis. The obtained non-synonymous coding SNPs (ncSNPs) were designed for genotyping firstly. Its effects on growth, carcass characteristics and meat quality traits were investigated employing the F2 resource population of Gushi chicken crossed with Anak broiler by AluI CRS-PCR-RFLP. Our results indicated that the cDNA of chicken PMCH shared 67.25 and 66.47% homology with that of human and bovine PMCH, respectively. The deduced amino acid sequence of chicken PMCH (163 amino acids) were 52.07 and 50.89% identical to those of human and bovine PMCH, respectively. The PMCH protein sequence is predicted to have several functional domains, including pro-MCH, CSP, IL7, XPGI and some low complexity sequence. It has 8 phosphorylation sites and no signal peptide sequence. gga-miR-18a, gga-miR-18b, gga-miR-499 microRNA targeting site was predicted in the 3' untranslated region of chicken PMCH mRNA. In addition, a total of seven SNPs including an ncSNP and a synonymous coding SNP, were identified in the PMCH gene. The ncSNP c.81 A>T was found to be in moderate polymorphic state (polymorphic index=0.365), and the frequencies for genotype AA, AB and BB were 0.3648, 0.4682 and 0.1670, respectively. Significant associations between the locus and shear force of breast and leg were observed. This polymorphic site may serve as a useful target for the marker assisted selection of the growth and meat quality traits in chicken.

  13. Approaches for identifying multiple-SNP haplotype blocks for use in human identification.

    PubMed

    Hiroaki, Nakahara; Koji, Fujii; Tetsushi, Kitayama; Kazumasa, Sekiguchi; Hiroaki, Nakanishi; Kazuyuki, Saito

    2015-09-01

    Single nucleotide polymorphism (SNP) discrimination effectiveness is low due to the bi-allelic nature of SNPs, and large numbers of loci must be analyzed for human identification in forensic casework. To resolve these issues, the authors support the use of multiple SNP haplotypes that will generate many haplotypes based on the combination of SNP alleles. First, 27 regions were selected from the JSNP database (http://snp.ims.u-tokyo.ac.jp) according to the following criteria: (1) 3 or more SNP loci within 100bp; (2) on-intron or out-of-gene location; and (3) frequency of more than 40% for each SNP allele. PCR amplification and high-resolution melting curve (HRM) analysis were then carried out for all selected regions to determine variation in the haplotypes of each. HRM analysis indicated that 7 regions (1q25, 1q42.2, 3p24, 10p13, 11p15.1, 14q12-q13, and 20q12) containing 3 SNP loci had more than 2 haplotypes. The frequencies of the haplotypes for each region were observed via direct sequencing of more than 100 individuals. Not only haplotyping increases the effectiveness of individual identification but also the analysis region is shorter than in common short tandem repeat analysis, representing a further advantage for fragmented DNA samples in SNP typing.

  14. A Coordinated Approach to Peach SNP Discovery in RosBREED

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the USDA-funded multi-institutional and trans-disciplinary project, “RosBREED”, crop-specific SNP genome scan platforms are being developed for peach, apple, strawberry, and cherry at a resolution of at least one polymorphic SNP marker every 5 cM in any random cross, for use in Pedigree-Based Ana...

  15. Genome-wide copy number variations using SNP genotyping in a mixed breed swine population

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Copy number variations (CNVs) are increasingly understood to affect phenotypic variation. This study uses SNP genotyping of trios of mixed breed swine to add to the catalog of known genotypic variation in an important agricultural animal. Porcine SNP60 BeadChip genotypes were collected from 1802 pi...

  16. Development and Applications of a Bovine 50,000 SNP Chip

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To develop an Illumina iSelect high density single nucleotide polymorphism (SNP) assay for cattle, the collaborative iBMC (Illumina, USDA ARS Beltsville, University of Missouri, USDA ARS Clay Center) Consortium first performed a de novo SNP discovery project in which genomic reduced representation l...

  17. A new SNP panel for evaluating genetic diversity in a composite cattle breed

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A custom 60K SNP panel, extracted from Bovine HD SNP chip was used to evaluate genotypic frequency changes in Braford (BF, a composite breed) when compared to progenitor breeds: Hereford (HF), Brahman (BR), and Nelore (NE). Samples from both the U. S. and Brazil were used. The new panel differentiat...

  18. The development and characterization of a 60K SNP chip for chicken

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In livestock species like the chicken, high throughput SNP genotyping assays are increasingly being used for whole genome association studies and as a tool in breeding (referred to as genomic selection). We describe the design of a moderate density (60K) Illumina SNP BeadChip in chicken consisting o...

  19. SNP discovery and allele frequency estimation by deep sequencing of reduced representation libraries

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genome projects routinely produce draft sequences for species from diverse evolutionary clades, but generally do not create single nucleotide polymorphism (SNP) resources. We present an approach for de novo SNP discovery based on short-read sequencing of reduced representation libraries (RRL) to ge...

  20. SNP-VISTA: An Interactive SNPs Visualization Tool

    SciTech Connect

    Shah, Nameeta; Teplitsky, Michael V.; Pennacchio, Len A.; Hugenholtz, Philip; Hamann, Bernd; Dubchak, Inna L.

    2005-07-05

    Recent advances in sequencing technologies promise better diagnostics for many diseases as well as better understanding of evolution of microbial populations. Single Nucleotide Polymorphisms(SNPs) are established genetic markers that aid in the identification of loci affecting quantitative traits and/or disease in a wide variety of eukaryotic species. With today's technological capabilities, it is possible to re-sequence a large set of appropriate candidate genes in individuals with a given disease and then screen for causative mutations.In addition, SNPs have been used extensively in efforts to study the evolution of microbial populations, and the recent application of random shotgun sequencing to environmental samples makes possible more extensive SNP analysis of co-occurring and co-evolving microbial populations. The program is available at http://genome.lbl.gov/vista/snpvista.

  1. SNPsyn: detection and exploration of SNP–SNP interactions

    PubMed Central

    Curk, Tomaz; Rot, Gregor; Zupan, Blaz

    2011-01-01

    SNPsyn (http://snpsyn.biolab.si) is an interactive software tool for the discovery of synergistic pairs of single nucleotide polymorphisms (SNPs) from large genome-wide case-control association studies (GWAS) data on complex diseases. Synergy among SNPs is estimated using an information-theoretic approach called interaction analysis. SNPsyn is both a stand-alone C++/Flash application and a web server. The computationally intensive part is implemented in C++ and can run in parallel on a dedicated cluster or grid. The graphical user interface is written in Adobe Flash Builder 4 and can run in most web browsers or as a stand-alone application. The SNPsyn web server hosts the Flash application, receives GWAS data submissions, invokes the interaction analysis and serves result files. The user can explore details on identified synergistic pairs of SNPs, perform gene set enrichment analysis and interact with the constructed SNP synergy network. PMID:21576219

  2. Expression and SNP association analysis of porcine FBXL4 gene.

    PubMed

    Li, Y; Yang, S L; Tang, Z L; Cui, W T; Mu, Y L; Chu, M X; Zhao, S H; Wu, Z F; Li, K; Peng, K M

    2010-01-01

    As a kind of E3 ligase, the product of FBXL4 gene belongs to a member of FBLs which is the biggest eukaryotic subfamily of F-BOX proteins, it can recognize some substrate through particular protein-protein interaction domains. To investigate its functions, the polymorphism and association analysis was analyzed. The partial cDNA of porcine FBXL4 with 2384 bp long was first cloned; the deduced protein comprises a conserved F-BOX domain at position from the 277th to 332nd amino acid. The phylogenetic tree indicated porcine FBXL4 has the closest genetic relationship with bovine FBXL4 than other selected animal species. Ten tissue expression level of porcine FBXL4 mRNA fluctuated remarkably in a large range by quantitative RT-PCR analysis. For two identified SNPs, the genotyping analysis of Tail showed TT genotype owned dominance in introduced Landrace pig and miniature Guizhou and Wuzhishan breeds, but CC genotype was more than two other genotypes in miniature Laiwu breed. While in another genotyping analysis of BsaJI, CC genotype was obviously more than other genotypes in two kinds of Chinese miniature pig breeds and introduced Landrace pig breeds. Furthermore, the association analysis with immune traits and blood parameters revealed that SNP Tail was significantly associated with the lymphocyte percentage (P = 0.0166) and the antibody levels for pseudorabies virus vaccination (P = 0.0001) of neonate piglets at 0 day. Meanwhile, SNP BsaJI was significantly associated with lymphocyte percentage of individuals at 32 days (P = 0.0351), neutrophil percentage (P = 0.0005), the absolute lymphocyte count (P = 0.0458), and the mixed cells (P = 0.0010) of neonate piglets at 0 day. PMID:19768576

  3. TNF-alpha SNP haplotype frequencies in equidae.

    PubMed

    Brown, J J; Ollier, W E R; Thomson, W; Matthews, J B; Carter, S D; Binns, M; Pinchbeck, G; Clegg, P D

    2006-05-01

    Tumour necrosis factor alpha (TNF-alpha) is a pro-inflammatory cytokine that plays a crucial role in the regulation of inflammatory and immune responses. In all vertebrate species the genes encoding TNF-alpha are located within the major histocompatability complex. In the horse TNF-alpha has been ascribed a role in a variety of important disease processes. Previously two single nucleotide polymorphisms (SNPs) have been reported within the 5' un-translated region of the equine TNF-alpha gene. We have examined the equine TNF-alpha promoter region further for additional SNPs by analysing DNA from 131 horses (Equus caballus), 19 donkeys (E. asinus), 2 Grant's zebras (E. burchellii boehmi) and one onager (E. hemionus). Two further SNPs were identified at nucleotide positions 24 (T/G) and 452 (T/C) relative to the first nucleotide of the 522 bp polymerase chain reaction product. A sequence variant at position 51 was observed between equidae. SNaPSHOT genotyping assays for these and the two previously reported SNPs were performed on 457 horses comprising seven different breeds and 23 donkeys to determine the gene frequencies. SNP frequencies varied considerably between different horse breeds and also between the equine species. In total, nine different TNF-alpha promoter SNP haplotypes and their frequencies were established amongst the various equidae examined, with some haplotypes being found only in horses and others only in donkeys or zebras. The haplotype frequencies observed varied greatly between different horse breeds. Such haplotypes may relate to levels of TNF-alpha production and disease susceptibility and further investigation is required to identify associations between particular haplotypes and altered risk of disease.

  4. New aQTL SNPs for the CYP2D6 Identified by a Novel Mediation Analysis of Genome-Wide SNP Arrays, Gene Expression Arrays, and CYP2D6 Activity

    PubMed Central

    Wang, Zhiping; Boustani, Malaz; Liu, Yunlong; Skaar, Todd; Li, Lang

    2013-01-01

    Background. The genome-wide association studies (GWAS) have been successful during the last few years. A key challenge is that the interpretation of the results is not straightforward, especially for transacting SNPs. Integration of transcriptome data into GWAS may provide clues elucidating the mechanisms by which a genetic variant leads to a disease. Methods. Here, we developed a novel mediation analysis approach to identify new expression quantitative trait loci (eQTL) driving CYP2D6 activity by combining genotype, gene expression, and enzyme activity data. Results. 389,573 and 1,214,416 SNP-transcript-CYP2D6 activity trios are found strongly associated (P < 10−5, FDR = 16.6% and 11.7%) for two different genotype platforms, namely, Affymetrix and Illumina, respectively. The majority of eQTLs are trans-SNPs. A single polymorphism leads to widespread downstream changes in the expression of distant genes by affecting major regulators or transcription factors (TFs), which would be visible as an eQTL hotspot and can lead to large and consistent biological effects. Overlapped eQTL hotspots with the mediators lead to the discovery of 64 TFs. Conclusions. Our mediation analysis is a powerful approach in identifying the trans-QTL-phenotype associations. It improves our understanding of the functional genetic variations for the liver metabolism mechanisms. PMID:24232670

  5. Genotyping NAT2 with only two SNPs (rs1041983 and rs1801280) outperforms the tagging SNP rs1495741 and is equivalent to the conventional 7-SNP NAT2 genotype.

    PubMed

    Selinski, Silvia; Blaszkewicz, Meinolf; Lehmann, Marie-Louise; Ovsiannikov, Daniel; Moormann, Oliver; Guballa, Christoph; Kress, Alexander; Truss, Michael C; Gerullis, Holger; Otto, Thomas; Barski, Dimitri; Niegisch, Günter; Albers, Peter; Frees, Sebastian; Brenner, Walburgis; Thüroff, Joachim W; Angeli-Greaves, Miriam; Seidel, Thilo; Roth, Gerhard; Dietrich, Holger; Ebbinghaus, Rainer; Prager, Hans M; Bolt, Hermann M; Falkenstein, Michael; Zimmermann, Anna; Klein, Torsten; Reckwitz, Thomas; Roemer, Hermann C; Löhlein, Dietrich; Weistenhöfer, Wobbeke; Schöps, Wolfgang; Hassan Rizvi, Syed Adibul; Aslam, Muhammad; Bánfi, Gergely; Romics, Imre; Steffens, Michael; Ekici, Arif B; Winterpacht, Andreas; Ickstadt, Katja; Schwender, Holger; Hengstler, Jan G; Golka, Klaus

    2011-10-01

    Genotyping N-acetyltransferase 2 (NAT2) is of high relevance for individualized dosing of antituberculosis drugs and bladder cancer epidemiology. In this study we compared a recently published tagging single nucleotide polymorphism (SNP) (rs1495741) to the conventional 7-SNP genotype (G191A, C282T, T341C, C481T, G590A, A803G and G857A haplotype pairs) and systematically analysed if novel SNP combinations outperform the latter. For this purpose, we studied 3177 individuals by PCR and phenotyped 344 individuals by the caffeine test. Although the tagSNP and the 7-SNP genotype showed a high degree of correlation (R=0.933, P<0.0001) the 7-SNP genotype nevertheless outperformed the tagging SNP with respect to specificity (1.0 vs. 0.9444, P=0.0065). Considering all possible SNP combinations in a receiver operating characteristic analysis we identified a 2-SNP genotype (C282T, T341C) that outperformed the tagging SNP and was equivalent to the 7-SNP genotype. The 2-SNP genotype predicted the correct phenotype with a sensitivity of 0.8643 and a specificity of 1.0. In addition, it predicted the 7-SNP genotype with sensitivity and specificity of 0.9993 and 0.9880, respectively. The prediction of the NAT2 genotype by the 2-SNP genotype performed similar in populations of Caucasian, Venezuelan and Pakistani background. A 2-SNP genotype predicts NAT2 phenotypes with similar sensitivity and specificity as the conventional 7-SNP genotype. This procedure represents a facilitation in individualized dosing of NAT2 substrates without losing sensitivity or specificity.

  6. Design and characterization of a 52K SNP chip for goats.

    PubMed

    Tosser-Klopp, Gwenola; Bardou, Philippe; Bouchez, Olivier; Cabau, Cédric; Crooijmans, Richard; Dong, Yang; Donnadieu-Tonon, Cécile; Eggen, André; Heuven, Henri C M; Jamli, Saadiah; Jiken, Abdullah Johari; Klopp, Christophe; Lawley, Cynthia T; McEwan, John; Martin, Patrice; Moreno, Carole R; Mulsant, Philippe; Nabihoudine, Ibouniyamine; Pailhoux, Eric; Palhière, Isabelle; Rupp, Rachel; Sarry, Julien; Sayre, Brian L; Tircazes, Aurélie; Jun Wang; Wang, Wen; Zhang, Wenguang

    2014-01-01

    The success of Genome Wide Association Studies in the discovery of sequence variation linked to complex traits in humans has increased interest in high throughput SNP genotyping assays in livestock species. Primary goals are QTL detection and genomic selection. The purpose here was design of a 50-60,000 SNP chip for goats. The success of a moderate density SNP assay depends on reliable bioinformatic SNP detection procedures, the technological success rate of the SNP design, even spacing of SNPs on the genome and selection of Minor Allele Frequencies (MAF) suitable to use in diverse breeds. Through the federation of three SNP discovery projects consolidated as the International Goat Genome Consortium, we have identified approximately twelve million high quality SNP variants in the goat genome stored in a database together with their biological and technical characteristics. These SNPs were identified within and between six breeds (meat, milk and mixed): Alpine, Boer, Creole, Katjang, Saanen and Savanna, comprising a total of 97 animals. Whole genome and Reduced Representation Library sequences were aligned on >10 kb scaffolds of the de novo goat genome assembly. The 60,000 selected SNPs, evenly spaced on the goat genome, were submitted for oligo manufacturing (Illumina, Inc) and published in dbSNP along with flanking sequences and map position on goat assemblies (i.e. scaffolds and pseudo-chromosomes), sheep genome V2 and cattle UMD3.1 assembly. Ten breeds were then used to validate the SNP content and 52,295 loci could be successfully genotyped and used to generate a final cluster file. The combined strategy of using mainly whole genome Next Generation Sequencing and mapping on a contig genome assembly, complemented with Illumina design tools proved to be efficient in producing this GoatSNP50 chip. Advances in use of molecular markers are expected to accelerate goat genomic studies in coming years.

  7. A Customized Pigmentation SNP Array Identifies a Novel SNP Associated with Melanoma Predisposition in the SLC45A2 Gene

    PubMed Central

    Alonso, Santos; Boyano, M. Dolores; Peña-Chilet, Maria; Pita, Guillermo; Aviles, Jose A.; Mayor, Matias; Gomez-Fernandez, Cristina; Casado, Beatriz; Martin-Gonzalez, Manuel; Izagirre, Neskuts; De la Rua, Concepcion; Asumendi, Aintzane; Perez-Yarza, Gorka; Arroyo-Berdugo, Yoana; Boldo, Enrique; Lozoya, Rafael; Torrijos-Aguilar, Arantxa; Pitarch, Ana; Pitarch, Gerard; Sanchez-Motilla, Jose M.; Valcuende-Cavero, Francisca; Tomas-Cabedo, Gloria; Perez-Pastor, Gemma; Diaz-Perez, Jose L.; Gardeazabal, Jesus; de Lizarduy, Iñigo Martinez; Sanchez-Diez, Ana; Valdes, Carlos; Pizarro, Angel; Casado, Mariano; Carretero, Gregorio; Botella-Estrada, Rafael; Nagore, Eduardo; Lazaro, Pablo; Lluch, Ana; Benitez, Javier; Martinez-Cadenas, Conrado; Ribas, Gloria

    2011-01-01

    As the incidence of Malignant Melanoma (MM) reflects an interaction between skin colour and UV exposure, variations in genes implicated in pigmentation and tanning response to UV may be associated with susceptibility to MM. In this study, 363 SNPs in 65 gene regions belonging to the pigmentation pathway have been successfully genotyped using a SNP array. Five hundred and ninety MM cases and 507 controls were analyzed in a discovery phase I. Ten candidate SNPs based on a p-value threshold of 0.01 were identified. Two of them, rs35414 (SLC45A2) and rs2069398 (SILV/CKD2), were statistically significant after conservative Bonferroni correction. The best six SNPs were further tested in an independent Spanish series (624 MM cases and 789 controls). A novel SNP located on the SLC45A2 gene (rs35414) was found to be significantly associated with melanoma in both phase I and phase II (P<0.0001). None of the other five SNPs were replicated in this second phase of the study. However, three SNPs in TYR, SILV/CDK2 and ADAMTS20 genes (rs17793678, rs2069398 and rs1510521 respectively) had an overall p-value<0.05 when considering the whole DNA collection (1214 MM cases and 1296 controls). Both the SLC45A2 and the SILV/CDK2 variants behave as protective alleles, while the TYR and ADAMTS20 variants seem to function as risk alleles. Cumulative effects were detected when these four variants were considered together. Furthermore, individuals carrying two or more mutations in MC1R, a well-known low penetrance melanoma-predisposing gene, had a decreased MM risk if concurrently bearing the SLC45A2 protective variant. To our knowledge, this is the largest study on Spanish sporadic MM cases to date. PMID:21559390

  8. The Analysis of Particles at Low Accelerating Voltages (≤ 10 kV) With Energy Dispersive X-Ray Spectroscopy (EDS).

    PubMed

    Small, J A

    2002-01-01

    In recent years, there have been a series of advancements in electron beam instruments and x-ray detectors which may make it possible to improve significantly the quality of results from the quantitative electron-probe analysis of individual particles. These advances include: (1) field-emission gun electron beam instruments such as scanning electron microscopes (FEG-SEMs) that have high brightness electron guns with excellent performance at low beam energies, E 0 ≤ 10 keV and (2) high-resolution energy-dispersive x-ray spectrometers, like the microcalorimeter detector, that provide high-resolution (< 10 eV) parallel x-ray collection. These devices make it possible to separate low energy (< 4 keV) x-ray lines including the K lines of carbon, nitrogen and oxygen and the L and M lines for elements with atomic numbers in the range of 25 to 83. In light of these advances, this paper investigates the possibility of using accelerating voltages ≤ 10 kV, as a method to improve the accuracy of elemental analysis for micrometer-sized particles.

  9. 10kHz TRPIV near-field velocity and far-field noise: experimental results of a Mach 0.6 jet

    NASA Astrophysics Data System (ADS)

    Kan, Pinqing; Lewalle, Jacques

    2012-11-01

    Last year, we extracted footprints of sources from far-field pressure data of high speed jet. In this paper, we focus on processing 10kHz TR-PIV data in the near-field region. The velocity and pressure data were collected in the jet experiment of Kerwin Low, et al. in 2011. From the PIV snapshots, we extract kinematic indicators, construct their histories over the sequence of snapshots, and select the most promising diagnostics by cross-correlation with far-field pressure. For these indicators, including mass flux, we map out their fluctuations and their downstream propagation. In particular, the phase velocity of fluctuations is compared to the local convective speed. Events with large relative phase velocity are identified, and the corresponding velocity and vorticity fields are mapped out. Our goal is to correlate such events to the far-field footprints of sources. For more info and results related to the experiment, please refer to abstracts by Z.P. Berger and by M.G. Berry at this meeting. This work is supported by Glauser group of Syracuse University, Spectral Energies LLC under AFOSR SBIR grant, and by a Syracuse University Graduate Fellowship. Thanks for partial support from Spectral Energies LLC (under SBIR grant from AFOSR), Syracuse University and the LCS College.

  10. Infrared optical properties of the 10-K organic superconductor (BEDT-TTF) sub 2 (Cu(NCS) sub 2 ) (where (BEDT-TTF) is bis(ethylenedithio)tetrathiafulvalene)

    SciTech Connect

    Kornelsen, K.; Eldridge, J.E. ); Wang, H.H.; Williams, J.M. )

    1991-09-01

    Low-temperature polarized bolometric absorption measurements have been performed on the {ital T}{sub {ital c}}=10.4 K organic superconductor {kappa}-(BEDT-TTF){sub 2}(Cu(NCS){sub 2}), where BEDT-TTF is bis(ethylenedithio)tetrathiafulvalene. The ratio of the absorption at 5.3 K to that at 10.5 K from 10 to 40 cm{sup {minus}1} showed no evidence of a conventional BCS gap. Polarized-reflectivity measurements at temperatures between 10 and 295 K are also reported for both the protonated and deuterated compounds, between 200 and 8000 cm{sup {minus}1}. The 10-K spectra were calibrated by a technique of simultaneously measuring the reflectivity {ital R} and the absorptance, 1{minus}{ital R}. The resulting conductivities display vibrational features superimposed on an electronic background. This background shifts from mid-infrared interband transitions, when the dc conductivity is low, to far-infrared intraband transitions as the dc conductivity increases. The vibrations have been assigned to a mixture of normally inactive {ital a}{sub {ital g}} modes and normally active {ital b}{sub 2{ital u}} modes of the BEDT-TTF molecule. A few of both types couple strongly to the charge carriers. One in particular has a very temperature-dependent frequency due to the changing intensity of the mid-infrared band.

  11. Report on key comparison COOMET.AUV.A-K5: pressure calibration of laboratory standard microphones in the frequency range 2 Hz to 10 kHz

    NASA Astrophysics Data System (ADS)

    Dobrowolska, D.; Kosterov, A.

    2016-01-01

    This is the final report for regional key comparison COOMET.AUV.A-K5 on the pressure calibration of laboratory standard microphones in the frequency range from 2 Hz to 10 kHz. Two laboratories—Central Office of Measures (GUM)—the national metrology institute for Poland and the State Enterprise Scientific-Research Institute for Metrology of Measurement and Control Systems (DP NDI Systema)— the designated institute for acoustics in Ukraine took part in this comparison with the GUM as a pilot. One travelling type LS1P microphone was circulated to the participants and results in the form of regular calibration certificates were collected. The results of the DP NDI Systema obtained in this comparison were linked to the CCAUV.A-K5 key comparison through the joint participation of the GUM. The degrees of equivalence were computed for DP NDI Systema with respect to the CCAUV.A-K5 key comparison reference value. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCAUV, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  12. Sequential sentinel SNP Regional Association Plots (SSS-RAP): an approach for testing independence of SNP association signals using meta-analysis data.

    PubMed

    Zheng, Jie; Gaunt, Tom R; Day, Ian N M

    2013-01-01

    Genome-Wide Association Studies (GWAS) frequently incorporate meta-analysis within their framework. However, conditional analysis of individual-level data, which is an established approach for fine mapping of causal sites, is often precluded where only group-level summary data are available for analysis. Here, we present a numerical and graphical approach, "sequential sentinel SNP regional association plot" (SSS-RAP), which estimates regression coefficients (beta) with their standard errors using the meta-analysis summary results directly. Under an additive model, typical for genes with small effect, the effect for a sentinel SNP can be transformed to the predicted effect for a possibly dependent SNP through a 2×2 2-SNP haplotypes table. The approach assumes Hardy-Weinberg equilibrium for test SNPs. SSS-RAP is available as a Web-tool (http://apps.biocompute.org.uk/sssrap/sssrap.cgi). To develop and illustrate SSS-RAP we analyzed lipid and ECG traits data from the British Women's Heart and Health Study (BWHHS), evaluated a meta-analysis for ECG trait and presented several simulations. We compared results with existing approaches such as model selection methods and conditional analysis. Generally findings were consistent. SSS-RAP represents a tool for testing independence of SNP association signals using meta-analysis data, and is also a convenient approach based on biological principles for fine mapping in group level summary data.

  13. High-Throughput DNA Array for SNP Detection of KRAS Gene Using a Centrifugal Microfluidic Device.

    PubMed

    Sedighi, Abootaleb; Li, Paul C H

    2016-01-01

    Here, we describe detection of single nucleotide polymorphism (SNP) in genomic DNA samples using a NanoBioArray (NBA) chip. Fast DNA hybridization is achieved in the chip when target DNAs are introduced to the surface-arrayed probes using centrifugal force. Gold nanoparticles (AuNPs) are used to assist SNP detection at room temperature. The parallel setting of sample introduction in the spiral channels of the NBA chip enables multiple analyses on many samples, resulting in a technique appropriate for high-throughput SNP detection. The experimental procedure, including chip fabrication, probe array printing, DNA amplification, hybridization, signal detection, and data analysis, is described in detail.

  14. Expression of a low-molecular-weight (10 kDa) calcium binding protein in glial cells of the brain of the trout (Teleostei).

    PubMed

    Manso, M J; Becerra, M; Becerra, M; Anadón, R

    1997-11-01

    Calcium-binding proteins of the EF-hand family are widely distributed in the vertebrate central nervous system. In the present study of the trout brain, immunocytochemistry with a monoclonal antibody against chick gut calbindin-28k and a polyclonal antibody against bovine S100 protein specifically stained ependymocytes and radial glia cells with identical patterns. Western blot analysis of trout brain extracts with the antibodies to S100 and calbindin stained the same low-molecular-weight (10 kDa) protein band. In rat brain extracts, however, the monoclonal antibody to calbindin recognized a major protein band with molecular weight corresponding to that of calbindin-28k. This indicates that the trout protein is a new calcium-binding-like (calbindin-like) molecule that is immunologically related to both S100 and calbindin. Immunocytochemical studies of the trout brain using the antibodies to CaB and S100 showed that ependymocytes were stained in most ventricular regions, except in a few specialized ependymal areas of the ventral telencephalon, epithalamus, hypothalamus (including the paraventricular organ and saccus vasculosus) and brain stem. Immunocytochemistry also indicated the presence of calbindin-like protein in radial glia cells of several regions of the brain (thalamus, pretectal region, optic tectum, and rhombencephalon). Differences in immunoreactivity between neighbouring ependymal areas suggest that this protein may be a useful marker of different territories. All immunoreactive glial cells were nicotin-adenin-dinucleotide-phosphate diaphorase-positive, although this enzymohistochemical reaction is not specific for these glial cells since it reveals oligodendrocytes and some neurons. Immunoreactivity appears at different developmental stages in the different brain regions, with a broadly caudorostral gradient, suggesting that the expression of this protein is developmentally regulated. Comparison of the distribution of the calbindin-like protein with

  15. Summary of measured radiofrequency electric and magnetic fields (10 kHz to 30 GHz) in the general and work environment.

    PubMed

    Mantiply, E D; Pohl, K R; Poppell, S W; Murphy, J A

    1997-01-01

    We have plotted data from a number of studies on the range of radiofrequency (RF) field levels associated with a variety of environmental and occupational sources. Field intensity is shown in units of volts/meter (V/m) for electric field strength and amps/meter (A/m) for magnetic field strength. Duty factors, modulation frequencies, and modulation indices are also reported for some sources. This paper is organized into seven sections, each cataloging sources into appropriate RF frequency bands from very-low frequency (VLF) to super-high frequency (SHF), and covers frequencies from 10 kHz to 30 GHz. Sources included in this summary are the following: Coast Guard navigational transmitters, a Navy VLF transmitter, computer visual display terminals (VDTs), induction stoves or range tops, industrial induction and dielectric heaters, radio and television broadcast transmitters, amateur and citizens band (CB) transmitters, medical diathermy and electrosurgical units, mobile and handheld transmitters, cordless and cellular telephones, microwave ovens, microwave terrestrial relay and satellite uplinks, and police, air traffic, and aircraft onboard radars. For the sources included in this summary, the strongest fields are found near industrial induction and dielectric heaters, and close to the radiating elements or transmitter leads of high power antenna systems. Handheld transmitters can produce near fields of about 500 V/m at the antenna. Fields in the general urban environment are principally associated with radio and TV broadcast services and measure about 0.1 V/m root-mean-square (rms). Peak fields from air traffic radars sampled in one urban environment were about 10 V/m, 300 times greater than the rms value of 0.03 V/m when the duty factor associated with antenna rotation and pulsing are factored in.

  16. Support of NASA ADR/ Cross-Enterprise NRA Advanced Adiabatic Demagnetization Refrigerators for Continuous Cooling from 10K to 50mK, Development of a Heat Switch

    NASA Technical Reports Server (NTRS)

    Richards, Paul L.

    2005-01-01

    Mechanical heat switches are used in conjunction with sorption refrigerators, adiabatic demagnetization refrigerators and for other cryogenic tasks including the pre-cooling cryogenic systems. They use a mechanical actuator which closes Au plated Cu jaws on an Au plated Cu bar. The thermal conductance in the closed position is essentially independent of the area of the jaws and proportional to the force applied. It varies linearly with T. It is approximately 10mW/K for 200 N at 1.5K. In some applications, the heat switch can be driven from outside the cryostat by a rotating rod and a screw. Such heat switches are available commercially from several sources. In other applications, including systems for space, it is desirable to drive the switch using a cold linear motor, or solenoid. Superconducting windings are used at temperatures s 4.2K to minimize power dissipation, but are not appropriate for pre-cooling a system at higher temperatures. This project was intended to improve the design of solenoid activated mechanical heat switches and to provide such switches as required to support the development of Advanced Adiabatic Demagnetization Refrigerators for Continuous Cooling from 10 K to 50 mK at GSFC. By the time funding began in 5/1/01, the immediate need for mechanical heat switches at GSFC had subsided but, at the same time, the opportunity had arisen to improve the design of mechanical heat switching by incorporating a "latching solenoid". In this device, the solenoid current is required only for changing the state of the switch and not during the whole time that the switch is closed.

  17. Three-year aging of prototype flight laser at 10 kHz and 1 ns pulses with external frequency doubler for ICESat-2 mission

    NASA Astrophysics Data System (ADS)

    Konoplev, Oleg A.; Chiragh, Furqan L.; Vasilyev, Aleksey A.; Edwards, Ryan; Stephen, Mark A.; Troupaki, Elisavet; Yu, Anthony W.; Krainak, Michael A.; Sawruk, Nick; Hovis, Floyd; Culpepper, Charles F.; Strickler, Kathy

    2016-05-01

    We present the results of a three-year operational-aging test of a specially designed prototype flight laser operating at 1064 nm, 10 kHz, 1ns, 15W average power and externally frequency-doubled. Fibertek designed and built the q-switched, 1064nm laser and this laser was in a sealed container of dry air pressurized to 1.3 atm. The external frequency doubler was in a clean room at a normal air pressure. The goal of the experiment was to measure degradation modes at 1064 and 532 nm separately. The external frequency doubler consisted of a Lithium triborate, LiB3O5, non-critically phase-matched crystal. After some 1064 nm light was diverted for diagnostics, 13.7W of fundamental power was available to pump the doubling crystal. Between 8.5W and 10W of 532nm power was generated, depending on the level of stress and degradation. The test consisted of two stages, the first at 0.3 J/cm2 for almost 1 year, corresponding to expected operational conditions, and the second at 0.93 J/cm2 for the remainder of the experiment, corresponding to accelerated optical stress testing. We observed no degradation at the first stress-level and linear degradation at the second stress-level. The linear degradation was linked to doubler crystal output surface changes from laser-assisted contamination. We estimate the expected lifetime for the flight laser at 532 nm using fluence as the stress parameter. This work was done for NASA's Ice, Cloud, and land Elevation Satellite-2 (ICESat-2) LIDAR at Goddard Space Flight Center in Greenbelt, MD with the goal of 1 trillion shots lifetime.

  18. Three Three-Year Aging of Prototype Flight Laser at 10 kHz and 1 ns Pulses With External Frequency Doubler for ICESat-2 Mission

    NASA Technical Reports Server (NTRS)

    Konoplev, Oleg A.; Chiragh, Furqan L.; Vasilyev, Aleksey A.; Edwards, Ryan; Stephen, Mark A.; Troupaki, Elisavet; Yu, Anthony W.; Krainak, Michael A.; Sawruk, Nick; Hovis, Floyd; Culpepper, Charles F.; Strickler, Kathy

    2016-01-01

    We present the results of three year life-aging of a specially designed prototype flight source laser operating at 1064 nm, 10 kHz, 1ns, 15W average power and external frequency doubler. The Fibertek-designed, slightly pressurized air, enclosed-container source laser operated at 1064 nm in active Q-switching mode. The external frequency doubler was set in a clean room at a normal air pressure. The goal of the experiment was to measure degradation modes at 1064 and 532 nm discreetly. The external frequency doubler consisted of a Lithium triborate, LiB3O5, crystal operated at non-critical phase-matching. Due to 1064 nm diagnostic needs, the amount of fundamental frequency power available for doubling was 13.7W. The power generated at 532 nm was between 8.5W and 10W, depending on the level of stress and degradation. The life-aging consisted of double stress-step operation for doubler crystal, at 0.35 Jcm2 for almost 1 year, corresponding to normal conditions, and then at 0.93 Jcm2 for the rest of the experiment, corresponding to accelerated testing. We observed no degradation at the first step and linear degradation at the second step. The linear degradation at the second stress-step was related to doubler crystal output surface changes and linked to laser-assisted contamination. We discuss degradation model and estimate the expected lifetime for the flight laser at 532 nm. This work was done within the laser testing for NASAs Ice, Cloud, and land Elevation Satellite-2 (ICESat-2) LIDAR at Goddard Space Flight Center in Greenbelt, MD with the goal of 1 trillion shots lifetime.

  19. Experimental Investigation of a Direct-drive Hall Thruster and Solar Array System at Power Levels up to 10 kW

    NASA Technical Reports Server (NTRS)

    Snyder, John S.; Brophy, John R.; Hofer, Richard R.; Goebel, Dan M.; Katz, Ira

    2012-01-01

    As NASA considers future exploration missions, high-power solar-electric propulsion (SEP) plays a prominent role in achieving many mission goals. Studies of high-power SEP systems (i.e. tens to hundreds of kilowatts) suggest that significant mass savings may be realized by implementing a direct-drive power system, so NASA recently established the National Direct-Drive Testbed to examine technical issues identified by previous investigations. The testbed includes a 12-kW solar array and power control station designed to power single and multiple Hall thrusters over a wide range of voltages and currents. In this paper, single Hall thruster operation directly from solar array output at discharge voltages of 200 to 450 V and discharge powers of 1 to 10 kW is reported. Hall thruster control and operation is shown to be simple and no different than for operation on conventional power supplies. Thruster and power system electrical oscillations were investigated over a large range of operating conditions and with different filter capacitances. Thruster oscillations were the same as for conventional power supplies, did not adversely affect solar array operation, and were independent of filter capacitance from 8 to 80 ?F. Solar array current and voltage oscillations were very small compared to their mean values and showed a modest dependence on capacitor size. No instabilities or anomalous behavior were observed in the thruster or power system at any operating condition investigated, including near and at the array peak power point. Thruster startup using the anode propellant flow as the power 'switch' was shown to be simple and reliable with system transients mitigated by the proper selection of filter capacitance size. Shutdown via cutoff of propellant flow was also demonstrated. A simple electrical circuit model was developed and is shown to have good agreement with the experimental data.

  20. Sturgeon conservation genomics: SNP discovery and validation using RAD sequencing.

    PubMed

    Ogden, R; Gharbi, K; Mugue, N; Martinsohn, J; Senn, H; Davey, J W; Pourkazemi, M; McEwing, R; Eland, C; Vidotto, M; Sergeev, A; Congiu, L

    2013-06-01

    Caviar-producing sturgeons belonging to the genus Acipenser are considered to be one of the most endangered species groups in the world. Continued overfishing in spite of increasing legislation, zero catch quotas and extensive aquaculture production have led to the collapse of wild stocks across Europe and Asia. The evolutionary relationships among Adriatic, Russian, Persian and Siberian sturgeons are complex because of past introgression events and remain poorly understood. Conservation management, traceability and enforcement suffer a lack of appropriate DNA markers for the genetic identification of sturgeon at the species, population and individual level. This study employed RAD sequencing to discover and characterize single nucleotide polymorphism (SNP) DNA markers for use in sturgeon conservation in these four tetraploid species over three biological levels, using a single sequencing lane. Four population meta-samples and eight individual samples from one family were barcoded separately before sequencing. Analysis of 14.4 Gb of paired-end RAD data focused on the identification of SNPs in the paired-end contig, with subsequent in silico and empirical validation of candidate markers. Thousands of putatively informative markers were identified including, for the first time, SNPs that show population-wide differentiation between Russian and Persian sturgeons, representing an important advance in our ability to manage these cryptic species. The results highlight the challenges of genotyping-by-sequencing in polyploid taxa, while establishing the potential genetic resources for developing a new range of caviar traceability and enforcement tools. PMID:23473098

  1. Porcine colonization of the Americas: a 60k SNP story

    PubMed Central

    Burgos-Paz, W; Souza, C A; Megens, H J; Ramayo-Caldas, Y; Melo, M; Lemús-Flores, C; Caal, E; Soto, H W; Martínez, R; Álvarez, L A; Aguirre, L; Iñiguez, V; Revidatti, M A; Martínez-López, O R; Llambi, S; Esteve-Codina, A; Rodríguez, M C; Crooijmans, R P M A; Paiva, S R; Schook, L B; Groenen, M A M; Pérez-Enciso, M

    2013-01-01

    The pig, Sus scrofa, is a foreign species to the American continent. Although pigs originally introduced in the Americas should be related to those from the Iberian Peninsula and Canary islands, the phylogeny of current creole pigs that now populate the continent is likely to be very complex. Because of the extreme climates that America harbors, these populations also provide a unique example of a fast evolutionary phenomenon of adaptation. Here, we provide a genome wide study of these issues by genotyping, with a 60k SNP chip, 206 village pigs sampled across 14 countries and 183 pigs from outgroup breeds that are potential founders of the American populations, including wild boar, Iberian, international and Chinese breeds. Results show that American village pigs are primarily of European ancestry, although the observed genetic landscape is that of a complex conglomerate. There was no correlation between genetic and geographical distances, neither continent wide nor when analyzing specific areas. Most populations showed a clear admixed structure where the Iberian pig was not necessarily the main component, illustrating how international breeds, but also Chinese pigs, have contributed to extant genetic composition of American village pigs. We also observe that many genes related to the cardiovascular system show an increased differentiation between altiplano and genetically related pigs living near sea level. PMID:23250008

  2. Porcine colonization of the Americas: a 60k SNP story.

    PubMed

    Burgos-Paz, W; Souza, C A; Megens, H J; Ramayo-Caldas, Y; Melo, M; Lemús-Flores, C; Caal, E; Soto, H W; Martínez, R; Alvarez, L A; Aguirre, L; Iñiguez, V; Revidatti, M A; Martínez-López, O R; Llambi, S; Esteve-Codina, A; Rodríguez, M C; Crooijmans, R P M A; Paiva, S R; Schook, L B; Groenen, M A M; Pérez-Enciso, M

    2013-04-01

    The pig, Sus scrofa, is a foreign species to the American continent. Although pigs originally introduced in the Americas should be related to those from the Iberian Peninsula and Canary islands, the phylogeny of current creole pigs that now populate the continent is likely to be very complex. Because of the extreme climates that America harbors, these populations also provide a unique example of a fast evolutionary phenomenon of adaptation. Here, we provide a genome wide study of these issues by genotyping, with a 60k SNP chip, 206 village pigs sampled across 14 countries and 183 pigs from outgroup breeds that are potential founders of the American populations, including wild boar, Iberian, international and Chinese breeds. Results show that American village pigs are primarily of European ancestry, although the observed genetic landscape is that of a complex conglomerate. There was no correlation between genetic and geographical distances, neither continent wide nor when analyzing specific areas. Most populations showed a clear admixed structure where the Iberian pig was not necessarily the main component, illustrating how international breeds, but also Chinese pigs, have contributed to extant genetic composition of American village pigs. We also observe that many genes related to the cardiovascular system show an increased differentiation between altiplano and genetically related pigs living near sea level.

  3. Sturgeon conservation genomics: SNP discovery and validation using RAD sequencing.

    PubMed

    Ogden, R; Gharbi, K; Mugue, N; Martinsohn, J; Senn, H; Davey, J W; Pourkazemi, M; McEwing, R; Eland, C; Vidotto, M; Sergeev, A; Congiu, L

    2013-06-01

    Caviar-producing sturgeons belonging to the genus Acipenser are considered to be one of the most endangered species groups in the world. Continued overfishing in spite of increasing legislation, zero catch quotas and extensive aquaculture production have led to the collapse of wild stocks across Europe and Asia. The evolutionary relationships among Adriatic, Russian, Persian and Siberian sturgeons are complex because of past introgression events and remain poorly understood. Conservation management, traceability and enforcement suffer a lack of appropriate DNA markers for the genetic identification of sturgeon at the species, population and individual level. This study employed RAD sequencing to discover and characterize single nucleotide polymorphism (SNP) DNA markers for use in sturgeon conservation in these four tetraploid species over three biological levels, using a single sequencing lane. Four population meta-samples and eight individual samples from one family were barcoded separately before sequencing. Analysis of 14.4 Gb of paired-end RAD data focused on the identification of SNPs in the paired-end contig, with subsequent in silico and empirical validation of candidate markers. Thousands of putatively informative markers were identified including, for the first time, SNPs that show population-wide differentiation between Russian and Persian sturgeons, representing an important advance in our ability to manage these cryptic species. The results highlight the challenges of genotyping-by-sequencing in polyploid taxa, while establishing the potential genetic resources for developing a new range of caviar traceability and enforcement tools.

  4. Cluster-localized sparse logistic regression for SNP data.

    PubMed

    Binder, Harald; Müller, Tina; Schwender, Holger; Golka, Klaus; Steffens, Michael; Hengstler, Jan G; Ickstadt, Katja; Schumacher, Martin

    2012-08-14

    The task of analyzing high-dimensional single nucleotide polymorphism (SNP) data in a case-control design using multivariable techniques has only recently been tackled. While many available approaches investigate only main effects in a high-dimensional setting, we propose a more flexible technique, cluster-localized regression (CLR), based on localized logistic regression models, that allows different SNPs to have an effect for different groups of individuals. Separate multivariable regression models are fitted for the different groups of individuals by incorporating weights into componentwise boosting, which provides simultaneous variable selection, hence sparse fits. For model fitting, these groups of individuals are identified using a clustering approach, where each group may be defined via different SNPs. This allows for representing complex interaction patterns, such as compositional epistasis, that might not be detected by a single main effects model. In a simulation study, the CLR approach results in improved prediction performance, compared to the main effects approach, and identification of important SNPs in several scenarios. Improved prediction performance is also obtained for an application example considering urinary bladder cancer. Some of the identified SNPs are predictive for all individuals, while others are only relevant for a specific group. Together with the sets of SNPs that define the groups, potential interaction patterns are uncovered.

  5. Interim report on updated microarray probes for the LLNL Burkholderia pseudomallei SNP array

    SciTech Connect

    Gardner, S; Jaing, C

    2012-03-27

    The overall goal of this project is to forensically characterize 100 unknown Burkholderia isolates in the US-Australia collaboration. We will identify genome-wide single nucleotide polymorphisms (SNPs) from B. pseudomallei and near neighbor species including B. mallei, B. thailandensis and B. oklahomensis. We will design microarray probes to detect these SNP markers and analyze 100 Burkholderia genomic DNAs extracted from environmental, clinical and near neighbor isolates from Australian collaborators on the Burkholderia SNP microarray. We will analyze the microarray genotyping results to characterize the genetic diversity of these new isolates and triage the samples for whole genome sequencing. In this interim report, we described the SNP analysis and the microarray probe design for the Burkholderia SNP microarray.

  6. Combined array CGH plus SNP genome analyses in a single assay for optimized clinical testing.

    PubMed

    Wiszniewska, Joanna; Bi, Weimin; Shaw, Chad; Stankiewicz, Pawel; Kang, Sung-Hae L; Pursley, Amber N; Lalani, Seema; Hixson, Patricia; Gambin, Tomasz; Tsai, Chun-hui; Bock, Hans-Georg; Descartes, Maria; Probst, Frank J; Scaglia, Fernando; Beaudet, Arthur L; Lupski, James R; Eng, Christine; Cheung, Sau Wai; Bacino, Carlos; Patel, Ankita

    2014-01-01

    In clinical diagnostics, both array comparative genomic hybridization (array CGH) and single nucleotide polymorphism (SNP) genotyping have proven to be powerful genomic technologies utilized for the evaluation of developmental delay, multiple congenital anomalies, and neuropsychiatric disorders. Differences in the ability to resolve genomic changes between these arrays may constitute an implementation challenge for clinicians: which platform (SNP vs array CGH) might best detect the underlying genetic cause for the disease in the patient? While only SNP arrays enable the detection of copy number neutral regions of absence of heterozygosity (AOH), they have limited ability to detect single-exon copy number variants (CNVs) due to the distribution of SNPs across the genome. To provide comprehensive clinical testing for both CNVs and copy-neutral AOH, we enhanced our custom-designed high-resolution oligonucleotide array that has exon-targeted coverage of 1860 genes with 60,000 SNP probes, referred to as Chromosomal Microarray Analysis - Comprehensive (CMA-COMP). Of the 3240 cases evaluated by this array, clinically significant CNVs were detected in 445 cases including 21 cases with exonic events. In addition, 162 cases (5.0%) showed at least one AOH region >10 Mb. We demonstrate that even though this array has a lower density of SNP probes than other commercially available SNP arrays, it reliably detected AOH events >10 Mb as well as exonic CNVs beyond the detection limitations of SNP genotyping. Thus, combining SNP probes and exon-targeted array CGH into one platform provides clinically useful genetic screening in an efficient manner.

  7. Combined array CGH plus SNP genome analyses in a single assay for optimized clinical testing

    PubMed Central

    Wiszniewska, Joanna; Bi, Weimin; Shaw, Chad; Stankiewicz, Pawel; Kang, Sung-Hae L; Pursley, Amber N; Lalani, Seema; Hixson, Patricia; Gambin, Tomasz; Tsai, Chun-hui; Bock, Hans-Georg; Descartes, Maria; Probst, Frank J; Scaglia, Fernando; Beaudet, Arthur L; Lupski, James R; Eng, Christine; Wai Cheung, Sau; Bacino, Carlos; Patel, Ankita

    2014-01-01

    In clinical diagnostics, both array comparative genomic hybridization (array CGH) and single nucleotide polymorphism (SNP) genotyping have proven to be powerful genomic technologies utilized for the evaluation of developmental delay, multiple congenital anomalies, and neuropsychiatric disorders. Differences in the ability to resolve genomic changes between these arrays may constitute an implementation challenge for clinicians: which platform (SNP vs array CGH) might best detect the underlying genetic cause for the disease in the patient? While only SNP arrays enable the detection of copy number neutral regions of absence of heterozygosity (AOH), they have limited ability to detect single-exon copy number variants (CNVs) due to the distribution of SNPs across the genome. To provide comprehensive clinical testing for both CNVs and copy-neutral AOH, we enhanced our custom-designed high-resolution oligonucleotide array that has exon-targeted coverage of 1860 genes with 60 000 SNP probes, referred to as Chromosomal Microarray Analysis – Comprehensive (CMA-COMP). Of the 3240 cases evaluated by this array, clinically significant CNVs were detected in 445 cases including 21 cases with exonic events. In addition, 162 cases (5.0%) showed at least one AOH region >10 Mb. We demonstrate that even though this array has a lower density of SNP probes than other commercially available SNP arrays, it reliably detected AOH events >10 Mb as well as exonic CNVs beyond the detection limitations of SNP genotyping. Thus, combining SNP probes and exon-targeted array CGH into one platform provides clinically useful genetic screening in an efficient manner. PMID:23695279

  8. Automated SNP detection in expressed sequence tags: statistical considerations and application to maritime pine sequences.

    PubMed

    Dantec, Loïck Le; Chagné, David; Pot, David; Cantin, Olivier; Garnier-Géré, Pauline; Bedon, Frank; Frigerio, Jean-Marc; Chaumeil, Philippe; Léger, Patrick; Garcia, Virginie; Laigret, Frédéric; De Daruvar, Antoine; Plomion, Christophe

    2004-02-01

    We developed an automated pipeline for the detection of single nucleotide polymorphisms (SNPs) in expressed sequence tag (EST) data sets, by combining three DNA sequence analysis programs: Phred, Phrap and PolyBayes. This application requires access to the individual electrophoregram traces. First, a reference set of 65 SNPs was obtained from the sequencing of 30 gametes in 13 maritime pine (Pinus pinaster Ait.) gene fragments (6671 bp), resulting in a frequency of 1 SNP every 102.6 bp. Second, parameters of the three programs were optimized in order to retrieve as many true SNPs, while keeping the rate of false positive as low as possible. Overall, the efficiency of detection of true SNPs was 83.1%. However, this rate varied largely as a function of the rare SNP allele frequency: down to 41% for rare SNP alleles (frequency < 10%), up to 98% for allele frequencies above 10%. Third, the detection method was applied to the 18498 assembled maritime pine (Pinus pinaster Ait.) ESTs, allowing to identify a total of 1400 candidate SNPs, in contigs containing between 4 and 20 sequence reads. These genetic resources, described for the first time in a forest tree species, were made available at http://www.pierroton.inra/genetics/Pinesnps. We also derived an analytical expression for the SNP detection probability as a function of the SNP allele frequency, the number of haploid genomes used to generate the EST sequence database, and the sample size of the contigs considered for SNP detection. The frequency of the SNP allele was shown to be the main factor influencing the probability of SNP detection.

  9. THE OPTICAL SPECTRA OF SPITZER 24 mum GALAXIES IN THE COSMIC EVOLUTION SURVEY FIELD. II. FAINT INFRARED SOURCES IN THE zCOSMOS-BRIGHT 10k CATALOG

    SciTech Connect

    Caputi, K. I.; Lilly, S. J.; Maier, C.; Carollo, C. M.; Aussel, H.; Floc'h, E. Le; Frayer, D.; Contini, T.; Kneib, J.-P.; Le Fevre, O.; Mainieri, V.; Renzini, A.; Scodeggio, M.; Scoville, N.; Zamorani, G.; Bardelli, S.; Bolzonella, M.; Coppa, G.; Bongiorno, A.

    2009-12-20

    We have used the zCOSMOS-bright 10k sample to identify 3244 Spitzer/MIPS 24 mum-selected galaxies with 0.06 mJy < S{sub 24{sub m}}u{sub m} approx< 0.50 mJy and I{sub AB} < 22.5, over 1.5 deg{sup 2} of the COSMOS field, and studied different spectral properties, depending on redshift. At 0.2 < z < 0.3, we found that different reddening laws of common use in the literature explain the dust extinction properties of approx80% of our infrared (IR) sources, within the error bars. For up to 16% of objects, instead, the Halpha lambda6563/Hbeta lambda4861 ratios are too high for their IR/UV attenuations, which is probably a consequence of inhomogeneous dust distributions. In only a few of our galaxies at 0.2 < z < 0.3, the IR emission could be mainly produced by dust heated by old rather than young stars. Besides, the line ratios of approx22% of our galaxies suggest that they might be star-formation/nuclear-activity composite systems. At 0.5 < z < 0.7, we estimated galaxy metallicities for 301 galaxies: at least 12% of them are securely below the upper-branch mass-metallicity trend, which is consistent with the local relation. Finally, we performed a combined analysis of the H{sub d}elta equivalent width versus D{sub n} (4000) diagram for 1722 faint and bright 24 mum galaxies at 0.6 < z < 1.0, spanning two decades in mid-IR luminosity. We found that, while secondary bursts of star formation are necessary to explain the position of the most luminous IR galaxies in that diagram, quiescent, exponentially declining star formation histories can well reproduce the spectral properties of approx40% of the less luminous sources. Our results suggest a transition in the possible modes of star formation at total IR luminosities L{sub TIR} approx (3 +- 2) x 10{sup 11} L{sub sun}.

  10. Electrochemical Li Topotactic Reaction in Layered SnP3 for Superior Li-Ion Batteries

    PubMed Central

    Park, Jae-Wan; Park, Cheol-Min

    2016-01-01

    The development of new anode materials having high electrochemical performances and interesting reaction mechanisms is highly required to satisfy the need for long-lasting mobile electronic devices and electric vehicles. Here, we report a layer crystalline structured SnP3 and its unique electrochemical behaviors with Li. The SnP3 was simply synthesized through modification of Sn crystallography by combination with P and its potential as an anode material for LIBs was investigated. During Li insertion reaction, the SnP3 anode showed an interesting two-step electrochemical reaction mechanism comprised of a topotactic transition (0.7–2.0 V) and a conversion (0.0–2.0 V) reaction. When the SnP3-based composite electrode was tested within the topotactic reaction region (0.7–2.0 V) between SnP3 and LixSnP3 (x ≤ 4), it showed excellent electrochemical properties, such as a high volumetric capacity (1st discharge/charge capacity was 840/663 mA h cm−3) with a high initial coulombic efficiency, stable cycle behavior (636 mA h cm−3 over 100 cycles), and fast rate capability (550 mA h cm−3 at 3C). This layered SnP3 anode will be applicable to a new anode material for rechargeable LIBs. PMID:27775090

  11. QTL scanning for rice yield using a whole genome SNP array.

    PubMed

    Tan, Cong; Han, Zhongmin; Yu, Huihui; Zhan, Wei; Xie, Weibo; Chen, Xun; Zhao, Hu; Zhou, Fasong; Xing, Yongzhong

    2013-12-20

    High-throughput SNP genotyping is widely used for plant genetic studies. Recently, a RICE6K SNP array has been developed based on the Illumina Bead Array platform and Infinium SNP assay technology for genome-wide evaluation of allelic variations and breeding applications. In this study, the RICE6K SNP array was used to genotype a recombinant inbred line (RIL) population derived from the cross between the indica variety, Zhenshan 97, and the japonica variety, Xizang 2. A total of 3324 SNP markers of high quality were identified and were grouped into 1495 recombination bins in the RIL population. A high-density linkage map, consisting of the 1495 bins, was developed, covering 1591.2 cM and with average length of 1.1 cM per bin. Segregation distortions were observed in 24 regions of the 11 chromosomes in the RILs. One half of the distorted regions contained fertility genes that had been previously reported. A total of 23 QTLs were identified for yield. Seven QTLs were firstly detected in this study. The positive alleles from about half of the identified QTLs came from Zhenshan 97 and they had lower phenotypic values than Xizang 2. This indicated that favorable alleles for breeding were dispersed in both parents and pyramiding favorable alleles could develop elite lines. The size of the mapping population for QTL analysis using high throughput SNP genotyping platform is also discussed.

  12. SNP and mutation data on the web - hidden treasures for uncovering.

    PubMed

    Barnes, Michael R

    2002-01-01

    SNP data has grown exponentially over the last two years, SNP database evolution has matched this growth, as initial development of several independent SNP databases has given way to one central SNP database, dbSNP. Other SNP databases have instead evolved to complement this central database by providing gene specific focus and an increased level of curation and analysis on subsets of data, derived from the central data set. By contrast, human mutation data, which has been collected over many years, is still stored in disparate sources, although moves are afoot to move to a similar central database. These developments are timely, human mutation and polymorphism data both hold complementary keys to a better understanding of how genes function and malfunction in disease. The impending availability of a complete human genome presents us with an ideal framework to integrate both these forms of data, as our understanding of the mechanisms of disease increase, the full genomic context of variation may become increasingly significant.

  13. Species Delimitation using Genome-Wide SNP Data

    PubMed Central

    Leaché, Adam D.; Fujita, Matthew K.; Minin, Vladimir N.; Bouckaert, Remco R.

    2014-01-01

    The multispecies coalescent has provided important progress for evolutionary inferences, including increasing the statistical rigor and objectivity of comparisons among competing species delimitation models. However, Bayesian species delimitation methods typically require brute force integration over gene trees via Markov chain Monte Carlo (MCMC), which introduces a large computation burden and precludes their application to genomic-scale data. Here we combine a recently introduced dynamic programming algorithm for estimating species trees that bypasses MCMC integration over gene trees with sophisticated methods for estimating marginal likelihoods, needed for Bayesian model selection, to provide a rigorous and computationally tractable technique for genome-wide species delimitation. We provide a critical yet simple correction that brings the likelihoods of different species trees, and more importantly their corresponding marginal likelihoods, to the same common denominator, which enables direct and accurate comparisons of competing species delimitation models using Bayes factors. We test this approach, which we call Bayes factor delimitation (*with genomic data; BFD*), using common species delimitation scenarios with computer simulations. Varying the numbers of loci and the number of samples suggest that the approach can distinguish the true model even with few loci and limited samples per species. Misspecification of the prior for population size θ has little impact on support for the true model. We apply the approach to West African forest geckos (Hemidactylus fasciatus complex) using genome-wide SNP data. This new Bayesian method for species delimitation builds on a growing trend for objective species delimitation methods with explicit model assumptions that are easily tested. [Bayes factor; model testing; phylogeography; RADseq; simulation; speciation.] PMID:24627183

  14. Comparison of genetic distance measures using human SNP genotype data.

    PubMed

    Libiger, Ondrej; Nievergelt, Caroline M; Schork, Nicholas J

    2009-08-01

    Quantification of the genetic distance between populations is instrumental in many genetic research initiatives, and a large number of formulas for this purpose have been proposed. However, selection of an appropriate measure for assessing genetic distance between real-world human populations that diverged as a result of mechanisms that are not fully known can be a challenging task. We compared results from nine widely used genetic distance measures to high-density whole-genome SNP genotype data obtained on individuals from 51 world populations. Using population trees and generalized analysis of molecular variance, we found that contradictory inferences could be drawn from analyses that used different distance measures. We determined the grouping of the distance measures in terms of similarity and consistency of their values using concordance, consistency, and Procrustes analyses. Overall, the Cavalli-Sforza and Edwards distance measure differed the most from the other measures. Wright's F(ST) for diploid data, the Latter and Reynolds distances, and Nei's minimum distance measures each yielded values that were most consistent with the other eight distance measures in terms of ordering populations based on genetic distance. The Cavalli-Sforza and Edwards distance and Nei's geometric distance were least consistent. Simulation studies showed that the Cavalli-Sforza and Edwards distance is relatively more sensitive in distinguishing genetically similar populations and that the Reynolds genetic distance provides the highest sensitivity for highly divergent populations. Finally, our study suggests that using the Cavalli-Sforza and Edwards distance may provide less power for studies concerning human migration history.

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

    PubMed

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

    2005-12-01

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

  16. Identification of Laying-Related SNP Markers in Geese Using RAD Sequencing

    PubMed Central

    Yu, ShiGang; Chu, WeiWei; Zhang, LiFan; Han, HouMing; Zhao, RongXue; Wu, Wei; Zhu, JiangNing; Dodson, Michael V.; Wei, Wei; Liu, HongLin; Chen, Jie

    2015-01-01

    Laying performance is an important economical trait of goose production. As laying performance is of low heritability, it is of significance to develop a marker-assisted selection (MAS) strategy for this trait. Definition of sequence variation related to the target trait is a prerequisite of quantitating MAS, but little is presently known about the goose genome, which greatly hinders the identification of genetic markers for the laying traits of geese. Recently developed restriction site-associated DNA (RAD) sequencing is a possible approach for discerning large-scale single nucleotide polymorphism (SNP) and reducing the complexity of a genome without having reference genomic information available. In the present study, we developed a pooled RAD sequencing strategy for detecting geese laying-related SNP. Two DNA pools were constructed, each consisting of equal amounts of genomic DNA from 10 individuals with either high estimated breeding value (HEBV) or low estimated breeding value (LEBV). A total of 139,013 SNP were obtained from 42,291,356 sequences, of which 18,771,943 were for LEBV and 23,519,413 were for HEBV cohorts. Fifty-five SNP which had different allelic frequencies in the two DNA pools were further validated by individual-based AS-PCR genotyping in the LEBV and HEBV cohorts. Ten out of 55 SNP exhibited distinct allele distributions in these two cohorts. These 10 SNP were further genotyped in a goose population of 492 geese to verify the association with egg numbers. The result showed that 8 of 10 SNP were associated with egg numbers. Additionally, liner regression analysis revealed that SNP Record-111407, 106975 and 112359 were involved in a multiplegene network affecting laying performance. We used IPCR to extend the unknown regions flanking the candidate RAD tags. The obtained sequences were subjected to BLAST to retrieve the orthologous genes in either ducks or chickens. Five novel genes were cloned for geese which harbored the candidate laying

  17. Optimal Design of Low-Density SNP Arrays for Genomic Prediction: Algorithm and Applications.

    PubMed

    Wu, Xiao-Lin; Xu, Jiaqi; Feng, Guofei; Wiggans, George R; Taylor, Jeremy F; He, Jun; Qian, Changsong; Qiu, Jiansheng; Simpson, Barry; Walker, Jeremy; Bauck, Stewart

    2016-01-01

    Low-density (LD) single nucleotide polymorphism (SNP) arrays provide a cost-effective solution for genomic prediction and selection, but algorithms and computational tools are needed for the optimal design of LD SNP chips. A multiple-objective, local optimization (MOLO) algorithm was developed for design of optimal LD SNP chips that can be imputed accurately to medium-density (MD) or high-density (HD) SNP genotypes for genomic prediction. The objective function facilitates maximization of non-gap map length and system information for the SNP chip, and the latter is computed either as locus-averaged (LASE) or haplotype-averaged Shannon entropy (HASE) and adjusted for uniformity of the SNP distribution. HASE performed better than LASE with ≤1,000 SNPs, but required considerably more computing time. Nevertheless, the differences diminished when >5,000 SNPs were selected. Optimization was accomplished conditionally on the presence of SNPs that were obligated to each chromosome. The frame location of SNPs on a chip can be either uniform (evenly spaced) or non-uniform. For the latter design, a tunable empirical Beta distribution was used to guide location distribution of frame SNPs such that both ends of each chromosome were enriched with SNPs. The SNP distribution on each chromosome was finalized through the objective function that was locally and empirically maximized. This MOLO algorithm was capable of selecting a set of approximately evenly-spaced and highly-informative SNPs, which in turn led to increased imputation accuracy compared with selection solely of evenly-spaced SNPs. Imputation accuracy increased with LD chip size, and imputation error rate was extremely low for chips with ≥3,000 SNPs. Assuming that genotyping or imputation error occurs at random, imputation error rate can be viewed as the upper limit for genomic prediction error. Our results show that about 25% of imputation error rate was propagated to genomic prediction in an Angus population. The

  18. Optimal Design of Low-Density SNP Arrays for Genomic Prediction: Algorithm and Applications

    PubMed Central

    Wu, Xiao-Lin; Xu, Jiaqi; Feng, Guofei; Wiggans, George R.; Taylor, Jeremy F.; He, Jun; Qian, Changsong; Qiu, Jiansheng; Simpson, Barry; Walker, Jeremy; Bauck, Stewart

    2016-01-01

    Low-density (LD) single nucleotide polymorphism (SNP) arrays provide a cost-effective solution for genomic prediction and selection, but algorithms and computational tools are needed for the optimal design of LD SNP chips. A multiple-objective, local optimization (MOLO) algorithm was developed for design of optimal LD SNP chips that can be imputed accurately to medium-density (MD) or high-density (HD) SNP genotypes for genomic prediction. The objective function facilitates maximization of non-gap map length and system information for the SNP chip, and the latter is computed either as locus-averaged (LASE) or haplotype-averaged Shannon entropy (HASE) and adjusted for uniformity of the SNP distribution. HASE performed better than LASE with ≤1,000 SNPs, but required considerably more computing time. Nevertheless, the differences diminished when >5,000 SNPs were selected. Optimization was accomplished conditionally on the presence of SNPs that were obligated to each chromosome. The frame location of SNPs on a chip can be either uniform (evenly spaced) or non-uniform. For the latter design, a tunable empirical Beta distribution was used to guide location distribution of frame SNPs such that both ends of each chromosome were enriched with SNPs. The SNP distribution on each chromosome was finalized through the objective function that was locally and empirically maximized. This MOLO algorithm was capable of selecting a set of approximately evenly-spaced and highly-informative SNPs, which in turn led to increased imputation accuracy compared with selection solely of evenly-spaced SNPs. Imputation accuracy increased with LD chip size, and imputation error rate was extremely low for chips with ≥3,000 SNPs. Assuming that genotyping or imputation error occurs at random, imputation error rate can be viewed as the upper limit for genomic prediction error. Our results show that about 25% of imputation error rate was propagated to genomic prediction in an Angus population. The

  19. Identification of Laying-Related SNP Markers in Geese Using RAD Sequencing.

    PubMed

    Yu, ShiGang; Chu, WeiWei; Zhang, LiFan; Han, HouMing; Zhao, RongXue; Wu, Wei; Zhu, JiangNing; Dodson, Michael V; Wei, Wei; Liu, HongLin; Chen, Jie

    2015-01-01

    Laying performance is an important economical trait of goose production. As laying performance is of low heritability, it is of significance to develop a marker-assisted selection (MAS) strategy for this trait. Definition of sequence variation related to the target trait is a prerequisite of quantitating MAS, but little is presently known about the goose genome, which greatly hinders the identification of genetic markers for the laying traits of geese. Recently developed restriction site-associated DNA (RAD) sequencing is a possible approach for discerning large-scale single nucleotide polymorphism (SNP) and reducing the complexity of a genome without having reference genomic information available. In the present study, we developed a pooled RAD sequencing strategy for detecting geese laying-related SNP. Two DNA pools were constructed, each consisting of equal amounts of genomic DNA from 10 individuals with either high estimated breeding value (HEBV) or low estimated breeding value (LEBV). A total of 139,013 SNP were obtained from 42,291,356 sequences, of which 18,771,943 were for LEBV and 23,519,413 were for HEBV cohorts. Fifty-five SNP which had different allelic frequencies in the two DNA pools were further validated by individual-based AS-PCR genotyping in the LEBV and HEBV cohorts. Ten out of 55 SNP exhibited distinct allele distributions in these two cohorts. These 10 SNP were further genotyped in a goose population of 492 geese to verify the association with egg numbers. The result showed that 8 of 10 SNP were associated with egg numbers. Additionally, liner regression analysis revealed that SNP Record-111407, 106975 and 112359 were involved in a multiplegene network affecting laying performance. We used IPCR to extend the unknown regions flanking the candidate RAD tags. The obtained sequences were subjected to BLAST to retrieve the orthologous genes in either ducks or chickens. Five novel genes were cloned for geese which harbored the candidate laying

  20. Identification of Laying-Related SNP Markers in Geese Using RAD Sequencing.

    PubMed

    Yu, ShiGang; Chu, WeiWei; Zhang, LiFan; Han, HouMing; Zhao, RongXue; Wu, Wei; Zhu, JiangNing; Dodson, Michael V; Wei, Wei; Liu, HongLin; Chen, Jie

    2015-01-01

    Laying performance is an important economical trait of goose production. As laying performance is of low heritability, it is of significance to develop a marker-assisted selection (MAS) strategy for this trait. Definition of sequence variation related to the target trait is a prerequisite of quantitating MAS, but little is presently known about the goose genome, which greatly hinders the identification of genetic markers for the laying traits of geese. Recently developed restriction site-associated DNA (RAD) sequencing is a possible approach for discerning large-scale single nucleotide polymorphism (SNP) and reducing the complexity of a genome without having reference genomic information available. In the present study, we developed a pooled RAD sequencing strategy for detecting geese laying-related SNP. Two DNA pools were constructed, each consisting of equal amounts of genomic DNA from 10 individuals with either high estimated breeding value (HEBV) or low estimated breeding value (LEBV). A total of 139,013 SNP were obtained from 42,291,356 sequences, of which 18,771,943 were for LEBV and 23,519,413 were for HEBV cohorts. Fifty-five SNP which had different allelic frequencies in the two DNA pools were further validated by individual-based AS-PCR genotyping in the LEBV and HEBV cohorts. Ten out of 55 SNP exhibited distinct allele distributions in these two cohorts. These 10 SNP were further genotyped in a goose population of 492 geese to verify the association with egg numbers. The result showed that 8 of 10 SNP were associated with egg numbers. Additionally, liner regression analysis revealed that SNP Record-111407, 106975 and 112359 were involved in a multiplegene network affecting laying performance. We used IPCR to extend the unknown regions flanking the candidate RAD tags. The obtained sequences were subjected to BLAST to retrieve the orthologous genes in either ducks or chickens. Five novel genes were cloned for geese which harbored the candidate laying

  1. HapRice, an SNP haplotype database and a web tool for rice.

    PubMed

    Yonemaru, Jun-ichi; Ebana, Kaworu; Yano, Masahiro

    2014-01-01

    Genome-wide single nucleotide polymorphism (SNP) analysis is a promising tool to examine the genetic diversity of rice populations and genetic traits of scientific and economic importance. Next-generation sequencing technology has accelerated the re-sequencing of diverse rice varieties and the discovery of genome-wide SNPs. Notably, validation of these SNPs by a high-throughput genotyping system, such as an SNP array, could provide a manageable and highly accurate SNP set. To enhance the potential utility of genome-wide SNPs for geneticists and breeders, analysis tools need to be developed. Here, we constructed an SNP haplotype database, which allows visualization of the allele frequency of all SNPs in the genome browser. We calculated the allele frequencies of 3,334 SNPs in 76 accessions from the world rice collection and 3,252 SNPs in 177 Japanese rice accessions; all these SNPs have been validated in our previous studies. The SNP haplotypes were defined by the allele frequency in each cultivar group (aus, indica, tropical japonica and temperate japonica) for the world rice accessions, and in non-irrigated and three irrigated groups (three variety registration periods) for Japanese rice accessions. We also developed web tools for finding polymorphic SNPs between any two rice accessions and for the primer design to develop cleaved amplified polymorphic sequence markers at any SNP. The 'HapRice' database and the web tools can be accessed at http://qtaro.abr.affrc.go.jp/index.html. In addition, we established a core SNP set consisting of 768 SNPs uniformly distributed in the rice genome; this set is of a practically appropriate size for use in rice genetic analysis.

  2. fcGENE: A Versatile Tool for Processing and Transforming SNP Datasets

    PubMed Central

    Roshyara, Nab Raj; Scholz, Markus

    2014-01-01

    Background Modern analysis of high-dimensional SNP data requires a number of biometrical and statistical methods such as pre-processing, analysis of population structure, association analysis and genotype imputation. Software used for these purposes often rely on specific and incompatible input and output data formats. Therefore extensive data management including multiple format conversions is necessary during analyses. Methods In order to support fast and efficient management and bio-statistical quality control of high-dimensional SNP data, we developed the publically available software fcGENE using C++ object-oriented programming language. This software simplifies and automates the use of different existing analysis packages, especially during the workflow of genotype imputations and corresponding analyses. Results fcGENE transforms SNP data and imputation results into different formats required for a large variety of analysis packages such as PLINK, SNPTEST, HAPLOVIEW, EIGENSOFT, GenABEL and tools used for genotype imputation such as MaCH, IMPUTE, BEAGLE and others. Data Management tasks like merging, splitting, extracting SNP and pedigree information can be performed. fcGENE also supports a number of bio-statistical quality control processes and quality based filtering processes at SNP- and sample-wise level. The tool also generates templates of commands required to run specific software packages, especially those required for genotype imputation. We demonstrate the functionality of fcGENE by example workflows of SNP data analyses and provide a comprehensive manual of commands, options and applications. Conclusions We have developed a user-friendly open-source software fcGENE, which comprehensively supports SNP data management, quality control and analysis workflows. Download statistics and corresponding feedbacks indicate that software is highly recognised and extensively applied by the scientific community. PMID:25050709

  3. Does replication groups scoring reduce false positive rate in SNP interaction discovery?

    PubMed Central

    2010-01-01

    Background Computational methods that infer single nucleotide polymorphism (SNP) interactions from phenotype data may uncover new biological mechanisms in non-Mendelian diseases. However, practical aspects of such analysis face many problems. Present experimental studies typically use SNP arrays with hundreds of thousands of SNPs but record only hundreds of samples. Candidate SNP pairs inferred by interaction analysis may include a high proportion of false positives. Recently, Gayan et al. (2008) proposed to reduce the number of false positives by combining results of interaction analysis performed on subsets of data (replication groups), rather than analyzing the entire data set directly. If performing as hypothesized, replication groups scoring could improve interaction analysis and also any type of feature ranking and selection procedure in systems biology. Because Gayan et al. do not compare their approach to the standard interaction analysis techniques, we here investigate if replication groups indeed reduce the number of reported false positive interactions. Results A set of simulated and false interaction-imputed experimental SNP data sets were used to compare the inference of SNP-SNP interactions by means of replication groups to the standard approach where the entire data set was directly used to score all candidate SNP pairs. In all our experiments, the inference of interactions from the entire data set (e.g. without using the replication groups) reported fewer false positives. Conclusions With respect to the direct scoring approach the utility of replication groups does not reduce false positive rates, and may, depending on the data set, often perform worse. PMID:20092660

  4. High-throughput SNP genotyping in Cucurbita pepo for map construction and quantitative trait loci mapping

    PubMed Central

    2012-01-01

    Background Cucurbita pepo is a member of the Cucurbitaceae family, the second- most important horticultural family in terms of economic importance after Solanaceae. The "summer squash" types, including Zucchini and Scallop, rank among the highest-valued vegetables worldwide. There are few genomic tools available for this species. The first Cucurbita transcriptome, along with a large collection of Single Nucleotide Polymorphisms (SNP), was recently generated using massive sequencing. A set of 384 SNP was selected to generate an Illumina GoldenGate assay in order to construct the first SNP-based genetic map of Cucurbita and map quantitative trait loci (QTL). Results We herein present the construction of the first SNP-based genetic map of Cucurbita pepo using a population derived from the cross of two varieties with contrasting phenotypes, representing the main cultivar groups of the species' two subspecies: Zucchini (subsp. pepo) × Scallop (subsp. ovifera). The mapping population was genotyped with 384 SNP, a set of selected EST-SNP identified in silico after massive sequencing of the transcriptomes of both parents, using the Illumina GoldenGate platform. The global success rate of the assay was higher than 85%. In total, 304 SNP were mapped, along with 11 SSR from a previous map, giving a map density of 5.56 cM/marker. This map was used to infer syntenic relationships between C. pepo and cucumber and to successfully map QTL that control plant, flowering and fruit traits that are of benefit to squash breeding. The QTL effects were validated in backcross populations. Conclusion Our results show that massive sequencing in different genotypes is an excellent tool for SNP discovery, and that the Illumina GoldenGate platform can be successfully applied to constructing genetic maps and performing QTL analysis in Cucurbita. This is the first SNP-based genetic map in the Cucurbita genus and is an invaluable new tool for biological research, especially considering that most

  5. CsSNP: A Web-Based Tool for the Detecting of Comparative Segments SNPs.

    PubMed

    Wang, Yi; Wang, Shuangshuang; Zhou, Dongjie; Yang, Shuai; Xu, Yongchao; Yang, Chao; Yang, Long

    2016-07-01

    SNP (single nucleotide polymorphism) is a popular tool for the study of genetic diversity, evolution, and other areas. Therefore, it is necessary to develop a convenient, utility, robust, rapid, and open source detecting-SNP tool for all researchers. Since the detection of SNPs needs special software and series steps including alignment, detection, analysis and present, the study of SNPs is limited for nonprofessional users. CsSNP (Comparative segments SNP, http://biodb.sdau.edu.cn/cssnp/ ) is a freely available web tool based on the Blat, Blast, and Perl programs to detect comparative segments SNPs and to show the detail information of SNPs. The results are filtered and presented in the statistics figure and a Gbrowse map. This platform contains the reference genomic sequences and coding sequences of 60 plant species, and also provides new opportunities for the users to detect SNPs easily. CsSNP is provided a convenient tool for nonprofessional users to find comparative segments SNPs in their own sequences, and give the users the information and the analysis of SNPs, and display these data in a dynamic map. It provides a new method to detect SNPs and may accelerate related studies. PMID:27347883

  6. Supervised learning-based tagSNP selection for genome-wide disease classifications

    PubMed Central

    Liu, Qingzhong; Yang, Jack; Chen, Zhongxue; Yang, Mary Qu; Sung, Andrew H; Huang, Xudong

    2008-01-01

    Background Comprehensive evaluation of common genetic variations through association of single nucleotide polymorphisms (SNPs) with complex human diseases on the genome-wide scale is an active area in human genome research. One of the fundamental questions in a SNP-disease association study is to find an optimal subset of SNPs with predicting power for disease status. To find that subset while reducing study burden in terms of time and costs, one can potentially reconcile information redundancy from associations between SNP markers. Results We have developed a feature selection method named Supervised Recursive Feature Addition (SRFA). This method combines supervised learning and statistical measures for the chosen candidate features/SNPs to reconcile the redundancy information and, in doing so, improve the classification performance in association studies. Additionally, we have proposed a Support Vector based Recursive Feature Addition (SVRFA) scheme in SNP-disease association analysis. Conclusions We have proposed using SRFA with different statistical learning classifiers and SVRFA for both SNP selection and disease classification and then applying them to two complex disease data sets. In general, our approaches outperform the well-known feature selection method of Support Vector Machine Recursive Feature Elimination and logic regression-based SNP selection for disease classification in genetic association studies. Our study further indicates that both genetic and environmental variables should be taken into account when doing disease predictions and classifications for the most complex human diseases that have gene-environment interactions. PMID:18366619

  7. Highly specific SNP detection using 2D graphene electronics and DNA strand displacement

    PubMed Central

    Hwang, Michael T.; Landon, Preston B.; Lee, Joon; Choi, Duyoung; Mo, Alexander H.; Glinsky, Gennadi; Lal, Ratnesh

    2016-01-01

    Single-nucleotide polymorphisms (SNPs) in a gene sequence are markers for a variety of human diseases. Detection of SNPs with high specificity and sensitivity is essential for effective practical implementation of personalized medicine. Current DNA sequencing, including SNP detection, primarily uses enzyme-based methods or fluorophore-labeled assays that are time-consuming, need laboratory-scale settings, and are expensive. Previously reported electrical charge-based SNP detectors have insufficient specificity and accuracy, limiting their effectiveness. Here, we demonstrate the use of a DNA strand displacement-based probe on a graphene field effect transistor (FET) for high-specificity, single-nucleotide mismatch detection. The single mismatch was detected by measuring strand displacement-induced resistance (and hence current) change and Dirac point shift in a graphene FET. SNP detection in large double-helix DNA strands (e.g., 47 nt) minimize false-positive results. Our electrical sensor-based SNP detection technology, without labeling and without apparent cross-hybridization artifacts, would allow fast, sensitive, and portable SNP detection with single-nucleotide resolution. The technology will have a wide range of applications in digital and implantable biosensors and high-throughput DNA genotyping, with transformative implications for personalized medicine. PMID:27298347

  8. Development of an automated SNP analysis method using a paramagnetic beads handling robot.

    PubMed

    Hagiwara, Hiroko; Sawakami-Kobayashi, Kazumi; Yamamoto, Midori; Iwasaki, Shoji; Sugiura, Mika; Abe, Hatsumi; Kunihiro-Ohashi, Sumiko; Takase, Kumiko; Yamane, Noriko; Kato, Kaoru; Son, Renkon; Nakamura, Michihiro; Segawa, Osamu; Yoshida, Mamiko; Yohda, Masafumi; Tajima, Hideji; Kobori, Masato; Takahama, Yousuke; Itakura, Mitsuo; Machida, Masayuki

    2007-10-01

    Biological and medical importance of the single nucleotide polymorphism (SNP) has led to development of a wide variety of methods for SNP typing. Aiming for establishing highly reliable and fully automated SNP typing, we have developed the adapter ligation method in combination with the paramagnetic beads handling technology, Magtration(R). The method utilizes sequence specific ligation between the fluorescently labeled adapter and the sample DNAs at the cohesive end produced by a type IIS restriction enzyme. Evaluation of the method using human genomic DNA showed clear discrimination of the three genotypes without ambiguity using the same reaction condition for any SNPs examined. The operations following PCR amplification were automatically performed by the Magtration(R)-based robot that we have previously developed. Multiplex typing of two SNPs in a single reaction by using four fluorescent dyes was successfully preformed at the almost same sensitivity and reliability as the single typing. These results demonstrate that the automated paramagnetic beads handling technology, Magtration(R), is highly adaptable to the automated SNP analysis and that our method best fits to an automated in-house SNP typing for laboratory and medical uses.

  9. Highly specific SNP detection using 2D graphene electronics and DNA strand displacement.

    PubMed

    Hwang, Michael T; Landon, Preston B; Lee, Joon; Choi, Duyoung; Mo, Alexander H; Glinsky, Gennadi; Lal, Ratnesh

    2016-06-28

    Single-nucleotide polymorphisms (SNPs) in a gene sequence are markers for a variety of human diseases. Detection of SNPs with high specificity and sensitivity is essential for effective practical implementation of personalized medicine. Current DNA sequencing, including SNP detection, primarily uses enzyme-based methods or fluorophore-labeled assays that are time-consuming, need laboratory-scale settings, and are expensive. Previously reported electrical charge-based SNP detectors have insufficient specificity and accuracy, limiting their effectiveness. Here, we demonstrate the use of a DNA strand displacement-based probe on a graphene field effect transistor (FET) for high-specificity, single-nucleotide mismatch detection. The single mismatch was detected by measuring strand displacement-induced resistance (and hence current) change and Dirac point shift in a graphene FET. SNP detection in large double-helix DNA strands (e.g., 47 nt) minimize false-positive results. Our electrical sensor-based SNP detection technology, without labeling and without apparent cross-hybridization artifacts, would allow fast, sensitive, and portable SNP detection with single-nucleotide resolution. The technology will have a wide range of applications in digital and implantable biosensors and high-throughput DNA genotyping, with transformative implications for personalized medicine.

  10. Mining and Analysis of SNP in Response to Salinity Stress in Upland Cotton (Gossypium hirsutum L.)

    PubMed Central

    Wang, Xiaoge; Lu, Xuke; Wang, Junjuan; Wang, Delong; Yin, Zujun; Fan, Weili; Wang, Shuai; Ye, Wuwei

    2016-01-01

    Salinity stress is a major abiotic factor that affects crop output, and as a pioneer crop in saline and alkaline land, salt tolerance study of cotton is particularly important. In our experiment, four salt-tolerance varieties with different salt tolerance indexes including CRI35 (65.04%), Kanghuanwei164 (56.19%), Zhong9807 (55.20%) and CRI44 (50.50%), as well as four salt-sensitive cotton varieties including Hengmian3 (48.21%), GK50 (40.20%), Xinyan96-48 (34.90%), ZhongS9612 (24.80%) were used as the materials. These materials were divided into salt-tolerant group (ST) and salt-sensitive group (SS). Illumina Cotton SNP 70K Chip was used to detect SNP in different cotton varieties. SNPv (SNP variation of the same seedling pre- and after- salt stress) in different varieties were screened; polymorphic SNP and SNPr (SNP related to salt tolerance) were obtained. Annotation and analysis of these SNPs showed that (1) the induction efficiency of salinity stress on SNPv of cotton materials with different salt tolerance index was different, in which the induction efficiency on salt-sensitive materials was significantly higher than that on salt-tolerant materials. The induction of salt stress on SNPv was obviously biased. (2) SNPv induced by salt stress may be related to the methylation changes under salt stress. (3) SNPr may influence salt tolerance of plants by affecting the expression of salt-tolerance related genes. PMID:27355327

  11. Highly specific SNP detection using 2D graphene electronics and DNA strand displacement.

    PubMed

    Hwang, Michael T; Landon, Preston B; Lee, Joon; Choi, Duyoung; Mo, Alexander H; Glinsky, Gennadi; Lal, Ratnesh

    2016-06-28

    Single-nucleotide polymorphisms (SNPs) in a gene sequence are markers for a variety of human diseases. Detection of SNPs with high specificity and sensitivity is essential for effective practical implementation of personalized medicine. Current DNA sequencing, including SNP detection, primarily uses enzyme-based methods or fluorophore-labeled assays that are time-consuming, need laboratory-scale settings, and are expensive. Previously reported electrical charge-based SNP detectors have insufficient specificity and accuracy, limiting their effectiveness. Here, we demonstrate the use of a DNA strand displacement-based probe on a graphene field effect transistor (FET) for high-specificity, single-nucleotide mismatch detection. The single mismatch was detected by measuring strand displacement-induced resistance (and hence current) change and Dirac point shift in a graphene FET. SNP detection in large double-helix DNA strands (e.g., 47 nt) minimize false-positive results. Our electrical sensor-based SNP detection technology, without labeling and without apparent cross-hybridization artifacts, would allow fast, sensitive, and portable SNP detection with single-nucleotide resolution. The technology will have a wide range of applications in digital and implantable biosensors and high-throughput DNA genotyping, with transformative implications for personalized medicine. PMID:27298347

  12. Genome-Wide SNP Calling Using Next Generation Sequencing Data in Tomato

    PubMed Central

    Kim, Ji-Eun; Oh, Sang-Keun; Lee, Jeong-Hee; Lee, Bo-Mi; Jo, Sung-Hwan

    2014-01-01

    The tomato (Solanum lycopersicum L.) is a model plant for genome research in Solanaceae, as well as for studying crop breeding. Genome-wide single nucleotide polymorphisms (SNPs) are a valuable resource in genetic research and breeding. However, to do discovery of genome-wide SNPs, most methods require expensive high-depth sequencing. Here, we describe a method for SNP calling using a modified version of SAMtools that improved its sensitivity. We analyzed 90 Gb of raw sequence data from next-generation sequencing of two resequencing and seven transcriptome data sets from several tomato accessions. Our study identified 4,812,432 non-redundant SNPs. Moreover, the workflow of SNP calling was improved by aligning the reference genome with its own raw data. Using this approach, 131,785 SNPs were discovered from transcriptome data of seven accessions. In addition, 4,680,647 SNPs were identified from the genome of S. pimpinellifolium, which are 60 times more than 71,637 of the PI212816 transcriptome. SNP distribution was compared between the whole genome and transcriptome of S. pimpinellifolium. Moreover, we surveyed the location of SNPs within genic and intergenic regions. Our results indicated that the sufficient genome-wide SNP markers and very sensitive SNP calling method allow for application of marker assisted breeding and genome-wide association studies. PMID:24552708

  13. CsSNP: A Web-Based Tool for the Detecting of Comparative Segments SNPs.

    PubMed

    Wang, Yi; Wang, Shuangshuang; Zhou, Dongjie; Yang, Shuai; Xu, Yongchao; Yang, Chao; Yang, Long

    2016-07-01

    SNP (single nucleotide polymorphism) is a popular tool for the study of genetic diversity, evolution, and other areas. Therefore, it is necessary to develop a convenient, utility, robust, rapid, and open source detecting-SNP tool for all researchers. Since the detection of SNPs needs special software and series steps including alignment, detection, analysis and present, the study of SNPs is limited for nonprofessional users. CsSNP (Comparative segments SNP, http://biodb.sdau.edu.cn/cssnp/ ) is a freely available web tool based on the Blat, Blast, and Perl programs to detect comparative segments SNPs and to show the detail information of SNPs. The results are filtered and presented in the statistics figure and a Gbrowse map. This platform contains the reference genomic sequences and coding sequences of 60 plant species, and also provides new opportunities for the users to detect SNPs easily. CsSNP is provided a convenient tool for nonprofessional users to find comparative segments SNPs in their own sequences, and give the users the information and the analysis of SNPs, and display these data in a dynamic map. It provides a new method to detect SNPs and may accelerate related studies.

  14. Transcriptome sequencing for SNP discovery across Cucumis melo

    PubMed Central

    2012-01-01

    from India and Africa as compared to commercial cultivars, cultigens and landraces from Eastern Europe, Western Asia and the Mediterranean basin is consistent with the evolutionary history proposed for the species. Group-specific SNVs that will be useful in introgression programs were also detected. In a sample of 143 selected putative SNPs, we verified 93% of the polymorphisms in a panel of 78 genotypes. Conclusions This study provides the first comprehensive resequencing data for wild, exotic, and cultivated (landraces and commercial) melon transcriptomes, yielding the largest melon SNP collection available to date and representing a notable sample of the species diversity. This data provides a valuable resource for creating a catalog of allelic variants of melon genes and it will aid in future in-depth studies of population genetics, marker-assisted breeding, and gene identification aimed at developing improved varieties. PMID:22726804

  15. A SNP-Based Molecular Barcode for Characterization of Common Wheat

    PubMed Central

    Gao, LiFeng; Jia, JiZeng; Kong, XiuYing

    2016-01-01

    Wheat is grown as a staple crop worldwide. It is important to develop an effective genotyping tool for this cereal grain both to identify germplasm diversity and to protect the rights of breeders. Single-nucleotide polymorphism (SNP) genotyping provides a means for developing a practical, rapid, inexpensive and high-throughput assay. Here, we investigated SNPs as robust markers of genetic variation for typing wheat cultivars. We identified SNPs from an array of 9000 across a collection of 429 well-known wheat cultivars grown in China, of which 43 SNP markers with high minor allele frequency and variations discriminated the selected wheat varieties and their wild ancestors. This SNP-based barcode will allow for the rapid and precise identification of wheat germplasm resources and newly released varieties and will further assist in the wheat breeding program. PMID:26985664

  16. The NHGRI GWAS Catalog, a curated resource of SNP-trait associations.

    PubMed

    Welter, Danielle; MacArthur, Jacqueline; Morales, Joannella; Burdett, Tony; Hall, Peggy; Junkins, Heather; Klemm, Alan; Flicek, Paul; Manolio, Teri; Hindorff, Lucia; Parkinson, Helen

    2014-01-01

    The National Human Genome Research Institute (NHGRI) Catalog of Published Genome-Wide Association Studies (GWAS) Catalog provides a publicly available manually curated collection of published GWAS assaying at least 100,000 single-nucleotide polymorphisms (SNPs) and all SNP-trait associations with P <1 × 10(-5). The Catalog includes 1751 curated publications of 11 912 SNPs. In addition to the SNP-trait association data, the Catalog also publishes a quarterly diagram of all SNP-trait associations mapped to the SNPs' chromosomal locations. The Catalog can be accessed via a tabular web interface, via a dynamic visualization on the human karyotype, as a downloadable tab-delimited file and as an OWL knowledge base. This article presents a number of recent improvements to the Catalog, including novel ways for users to interact with the Catalog and changes to the curation infrastructure.

  17. Developing single nucleotide polymorphism (SNP) markers from transcriptome sequences for identification of longan (Dimocarpus longan) germplasm

    PubMed Central

    Wang, Boyi; Tan, Hua-Wei; Fang, Wanping; Meinhardt, Lyndel W; Mischke, Sue; Matsumoto, Tracie; Zhang, Dapeng

    2015-01-01

    Longan (Dimocarpus longan Lour.) is an important tropical fruit tree crop. Accurate varietal identification is essential for germplasm management and breeding. Using longan transcriptome sequences from public databases, we developed single nucleotide polymorphism (SNP) markers; validated 60 SNPs in 50 longan germplasm accessions, including cultivated varieties and wild germplasm; and designated 25 SNP markers that unambiguously identified all tested longan varieties with high statistical rigor (P<0.0001). Multiple trees from the same clone were verified and off-type trees were identified. Diversity analysis revealed genetic relationships among analyzed accessions. Cultivated varieties differed significantly from wild populations (Fst=0.300; P<0.001), demonstrating untapped genetic diversity for germplasm conservation and utilization. Within cultivated varieties, apparent differences between varieties from China and those from Thailand and Hawaii indicated geographic patterns of genetic differentiation. These SNP markers provide a powerful tool to manage longan genetic resources and breeding, with accurate and efficient genotype identification. PMID:26504559

  18. Cross-Species Application of SNP Chips is Not Suitable for Identifying Runs of Homozygosity.

    PubMed

    Shafer, Aaron B A; Miller, Joshua M; Kardos, Marty

    2016-03-01

    Cross-species application of single-nucleotide polymorphism (SNP) chips is a valid, relatively cost-effective alternative to the high-throughput sequencing methods generally required to obtain a genome-wide sampling of polymorphisms. Kharzinova et al. (2015) examined the applicability of SNP chips developed in domestic bovids (cattle and sheep) to a semi-wild cervid (reindeer). The ancestors of bovids and cervids diverged between 20 and 30 million years ago (Hassanin and Douzery 2003; Bibi et al. 2013). Empirical work has shown that for a SNP chip developed in a bovid and applied to a cervid species, approximately 50% genotype success with 1% of the loci being polymorphic is expected (Miller et al. 2012). The genotyping of Kharzinova et al. (2015) follows this pattern; however, these data are not appropriate for identifying runs of homozygosity (ROH) and can be problematic for estimating linkage disequilibrium (LD) and we caution readers in this regard.

  19. Cross-Species Application of SNP Chips is Not Suitable for Identifying Runs of Homozygosity.

    PubMed

    Shafer, Aaron B A; Miller, Joshua M; Kardos, Marty

    2016-03-01

    Cross-species application of single-nucleotide polymorphism (SNP) chips is a valid, relatively cost-effective alternative to the high-throughput sequencing methods generally required to obtain a genome-wide sampling of polymorphisms. Kharzinova et al. (2015) examined the applicability of SNP chips developed in domestic bovids (cattle and sheep) to a semi-wild cervid (reindeer). The ancestors of bovids and cervids diverged between 20 and 30 million years ago (Hassanin and Douzery 2003; Bibi et al. 2013). Empirical work has shown that for a SNP chip developed in a bovid and applied to a cervid species, approximately 50% genotype success with 1% of the loci being polymorphic is expected (Miller et al. 2012). The genotyping of Kharzinova et al. (2015) follows this pattern; however, these data are not appropriate for identifying runs of homozygosity (ROH) and can be problematic for estimating linkage disequilibrium (LD) and we caution readers in this regard. PMID:26774056

  20. k-merSNP discovery: Software for alignment-and reference-free scalable SNP discovery, phylogenetics, and annotation for hundreds of microbial genomes

    SciTech Connect

    2014-11-18

    With the flood of whole genome finished and draft microbial sequences, we need faster, more scalable bioinformatics tools for sequence comparison. An algorithm is described to find single nucleotide polymorphisms (SNPs) in whole genome data. It scales to hundreds of bacterial or viral genomes, and can be used for finished and/or draft genomes available as unassembled contigs or raw, unassembled reads. The method is fast to compute, finding SNPs and building a SNP phylogeny in minutes to hours, depending on the size and diversity of the input sequences. The SNP-based trees that result are consistent with known taxonomy and trees determined in other studies. The approach we describe can handle many gigabases of sequence in a single run. The algorithm is based on k-mer analysis.

  1. k-merSNP discovery: Software for alignment-and reference-free scalable SNP discovery, phylogenetics, and annotation for hundreds of microbial genomes

    2014-11-18

    With the flood of whole genome finished and draft microbial sequences, we need faster, more scalable bioinformatics tools for sequence comparison. An algorithm is described to find single nucleotide polymorphisms (SNPs) in whole genome data. It scales to hundreds of bacterial or viral genomes, and can be used for finished and/or draft genomes available as unassembled contigs or raw, unassembled reads. The method is fast to compute, finding SNPs and building a SNP phylogeny inmore » minutes to hours, depending on the size and diversity of the input sequences. The SNP-based trees that result are consistent with known taxonomy and trees determined in other studies. The approach we describe can handle many gigabases of sequence in a single run. The algorithm is based on k-mer analysis.« less

  2. An integrated SNP mining and utilization (ISMU) pipeline for next generation sequencing data.

    PubMed

    Azam, Sarwar; Rathore, Abhishek; Shah, Trushar M; Telluri, Mohan; Amindala, BhanuPrakash; Ruperao, Pradeep; Katta, Mohan A V S K; Varshney, Rajeev K

    2014-01-01

    Open source single nucleotide polymorphism (SNP) discovery pipelines for next generation sequencing data commonly requires working knowledge of command line interface, massive computational resources and expertise which is a daunting task for biologists. Further, the SNP information generated may not be readily used for downstream processes such as genotyping. Hence, a comprehensive pipeline has been developed by integrating several open source next generation sequencing (NGS) tools along with a graphical user interface called Integrated SNP Mining and Utilization (ISMU) for SNP discovery and their utilization by developing genotyping assays. The pipeline features functionalities such as pre-processing of raw data, integration of open source alignment tools (Bowtie2, BWA, Maq, NovoAlign and SOAP2), SNP prediction (SAMtools/SOAPsnp/CNS2snp and CbCC) methods and interfaces for developing genotyping assays. The pipeline outputs a list of high quality SNPs between all pairwise combinations of genotypes analyzed, in addition to the reference genome/sequence. Visualization tools (Tablet and Flapjack) integrated into the pipeline enable inspection of the alignment and errors, if any. The pipeline also provides a confidence score or polymorphism information content value with flanking sequences for identified SNPs in standard format required for developing marker genotyping (KASP and Golden Gate) assays. The pipeline enables users to process a range of NGS datasets such as whole genome re-sequencing, restriction site associated DNA sequencing and transcriptome sequencing data at a fast speed. The pipeline is very useful for plant genetics and breeding community with no computational expertise in order to discover SNPs and utilize in genomics, genetics and breeding studies. The pipeline has been parallelized to process huge datasets of next generation sequencing. It has been developed in Java language and is available at http://hpc.icrisat.cgiar.org/ISMU as a standalone

  3. SNP markers-based map construction and genome-wide linkage analysis in Brassica napus.

    PubMed

    Raman, Harsh; Dalton-Morgan, Jessica; Diffey, Simon; Raman, Rosy; Alamery, Salman; Edwards, David; Batley, Jacqueline

    2014-09-01

    An Illumina Infinium array comprising 5306 single nucleotide polymorphism (SNP) markers was used to genotype 175 individuals of a doubled haploid population derived from a cross between Skipton and Ag-Spectrum, two Australian cultivars of rapeseed (Brassica napus L.). A genetic linkage map based on 613 SNP and 228 non-SNP (DArT, SSR, SRAP and candidate gene markers) covering 2514.8 cM was constructed and further utilized to identify loci associated with flowering time and resistance to blackleg, a disease caused by the fungus Leptosphaeria maculans. Comparison between genetic map positions of SNP markers and the sequenced Brassica rapa (A) and Brassica oleracea (C) genome scaffolds showed several genomic rearrangements in the B. napus genome. A major locus controlling resistance to L. maculans was identified at both seedling and adult plant stages on chromosome A07. QTL analyses revealed that up to 40.2% of genetic variation for flowering time was accounted for by loci having quantitative effects. Comparative mapping showed Arabidopsis and Brassica flowering genes such as Phytochrome A/D, Flowering Locus C and agamous-Like MADS box gene AGL1 map within marker intervals associated with flowering time in a DH population from Skipton/Ag-Spectrum. Genomic regions associated with flowering time and resistance to L. maculans had several SNP markers mapped within 10 cM. Our results suggest that SNP markers will be suitable for various applications such as trait introgression, comparative mapping and high-resolution mapping of loci in B. napus.

  4. Vitis Phylogenomics: Hybridization Intensities from a SNP Array Outperform Genotype Calls

    PubMed Central

    Miller, Allison J.; Matasci, Naim; Schwaninger, Heidi; Aradhya, Mallikarjuna K.; Prins, Bernard; Zhong, Gan-Yuan; Simon, Charles; Buckler, Edward S.; Myles, Sean

    2013-01-01

    Understanding relationships among species is a fundamental goal of evolutionary biology. Single nucleotide polymorphisms (SNPs) identified through next generation sequencing and related technologies enable phylogeny reconstruction by providing unprecedented numbers of characters for analysis. One approach to SNP-based phylogeny reconstruction is to identify SNPs in a subset of individuals, and then to compile SNPs on an array that can be used to genotype additional samples at hundreds or thousands of sites simultaneously. Although powerful and efficient, this method is subject to ascertainment bias because applying variation discovered in a representative subset to a larger sample favors identification of SNPs with high minor allele frequencies and introduces bias against rare alleles. Here, we demonstrate that the use of hybridization intensity data, rather than genotype calls, reduces the effects of ascertainment bias. Whereas traditional SNP calls assess known variants based on diversity housed in the discovery panel, hybridization intensity data survey variation in the broader sample pool, regardless of whether those variants are present in the initial SNP discovery process. We apply SNP genotype and hybridization intensity data derived from the Vitis9kSNP array developed for grape to show the effects of ascertainment bias and to reconstruct evolutionary relationships among Vitis species. We demonstrate that phylogenies constructed using hybridization intensities suffer less from the distorting effects of ascertainment bias, and are thus more accurate than phylogenies based on genotype calls. Moreover, we reconstruct the phylogeny of the genus Vitis using hybridization data, show that North American subgenus Vitis species are monophyletic, and resolve several previously poorly known relationships among North American species. This study builds on earlier work that applied the Vitis9kSNP array to evolutionary questions within Vitis vinifera and has general

  5. Pathways of distinction analysis: a new technique for multi-SNP analysis of GWAS data.

    PubMed

    Braun, Rosemary; Buetow, Kenneth

    2011-06-01

    Genome-wide association studies (GWAS) have become increasingly common due to advances in technology and have permitted the identification of differences in single nucleotide polymorphism (SNP) alleles that are associated with diseases. However, while typical GWAS analysis techniques treat markers individually, complex diseases (cancers, diabetes, and Alzheimers, amongst others) are unlikely to have a single causative gene. Thus, there is a pressing need for multi-SNP analysis methods that can reveal system-level differences in cases and controls. Here, we present a novel multi-SNP GWAS analysis method called Pathways of Distinction Analysis (PoDA). The method uses GWAS data and known pathway-gene and gene-SNP associations to identify pathways that permit, ideally, the distinction of cases from controls. The technique is based upon the hypothesis that, if a pathway is related to disease risk, cases will appear more similar to other cases than to controls (or vice versa) for the SNPs associated with that pathway. By systematically applying the method to all pathways of potential interest, we can identify those for which the hypothesis holds true, i.e., pathways containing SNPs for which the samples exhibit greater within-class similarity than across classes. Importantly, PoDA improves on existing single-SNP and SNP-set enrichment analyses, in that it does not require the SNPs in a pathway to exhibit independent main effects. This permits PoDA to reveal pathways in which epistatic interactions drive risk. In this paper, we detail the PoDA method and apply it to two GWAS: one of breast cancer and the other of liver cancer. The results obtained strongly suggest that there exist pathway-wide genomic differences that contribute to disease susceptibility. PoDA thus provides an analytical tool that is complementary to existing techniques and has the power to enrich our understanding of disease genomics at the systems-level.

  6. Mycobacterium leprae in Colombia described by SNP7614 in gyrA, two minisatellites and geography

    PubMed Central

    Cardona-Castro, Nora; Beltrán-Alzate, Juan Camilo; Romero-Montoya, Irma Marcela; Li, Wei; Brennan, Patrick J; Vissa, Varalakshmi

    2013-01-01

    New cases of leprosy are still being detected in Colombia after the country declared achievement of the WHO defined ‘elimination’ status. To study the ecology of leprosy in endemic regions, a combination of geographic and molecular tools were applied for a group of 201 multibacillary patients including six multi-case families from eleven departments. The location (latitude and longitude) of patient residences were mapped. Slit skin smears and/or skin biopsies were collected and DNA was extracted. Standard agarose gel electrophoresis following a multiplex PCR-was developed for rapid and inexpensive strain typing of M. leprae based on copy numbers of two VNTR minisatellite loci 27-5 and 12-5. A SNP (C/T) in gyrA (SNP7614) was mapped by introducing a novel PCR-RFLP into an ongoing drug resistance surveillance effort. Multiple genotypes were detected combining the three molecular markers. The two frequent genotypes in Colombia were SNP7614(C)/27-5(5)/12-5(4) [C54] predominantly distributed in the Atlantic departments and SNP7614 (T)/27-5(4)/12-5(5) [T45] associated with the Andean departments. A novel genotype SNP7614 (C)/27-5(6)/12-5(4) [C64] was detected in cities along the Magdalena river which separates the Andean from Atlantic departments; a subset was further characterized showing association with a rare allele of minisatellite 23-3 and the SNP type 1 of M. leprae. The genotypes within intra-family cases were conserved. Overall, this is the first large scale study that utilized simple and rapid assay formats for identification of major strain types and their distribution in Colombia. It provides the framework for further strain type discrimination and geographic information systems as tools for tracing transmission of leprosy. PMID:23291420

  7. Mycobacterium leprae in Colombia described by SNP7614 in gyrA, two minisatellites and geography.

    PubMed

    Cardona-Castro, Nora; Beltrán-Alzate, Juan Camilo; Romero-Montoya, Irma Marcela; Li, Wei; Brennan, Patrick J; Vissa, Varalakshmi

    2013-03-01

    New cases of leprosy are still being detected in Colombia after the country declared achievement of the WHO defined 'elimination' status. To study the ecology of leprosy in endemic regions, a combination of geographic and molecular tools were applied for a group of 201 multibacillary patients including six multi-case families from eleven departments. The location (latitude and longitude) of patient residences were mapped. Slit skin smears and/or skin biopsies were collected and DNA was extracted. Standard agarose gel electrophoresis following a multiplex PCR-was developed for rapid and inexpensive strain typing of Mycobacterium leprae based on copy numbers of two VNTR minisatellite loci 27-5 and 12-5. A SNP (C/T) in gyrA (SNP7614) was mapped by introducing a novel PCR-RFLP into an ongoing drug resistance surveillance effort. Multiple genotypes were detected combining the three molecular markers. The two frequent genotypes in Colombia were SNP7614(C)/27-5(5)/12-5(4) [C54] predominantly distributed in the Atlantic departments and SNP7614 (T)/27-5(4)/12-5(5) [T45] associated with the Andean departments. A novel genotype SNP7614 (C)/27-5(6)/12-5(4) [C64] was detected in cities along the Magdalena river which separates the Andean from Atlantic departments; a subset was further characterized showing association with a rare allele of minisatellite 23-3 and the SNP type 1 of M. leprae. The genotypes within intra-family cases were conserved. Overall, this is the first large scale study that utilized simple and rapid assay formats for identification of major strain types and their distribution in Colombia. It provides the framework for further strain type discrimination and geographic information systems as tools for tracing transmission of leprosy. PMID:23291420

  8. ComB: SNP calling and mapping analysis for color and nucleotide space platforms.

    PubMed

    Souaiaia, Tade; Frazier, Zach; Chen, Ting

    2011-06-01

    The determination of single nucleotide polymorphisms (SNPs) has become faster and more cost effective since the advent of short read data from next generation sequencing platforms such as Roche's 454 Sequencer, Illumina's Solexa platform, and Applied Biosystems SOLiD sequencer. The SOLiD sequencing platform, which is capable of producing more than 6 GB of sequence data in a single run, uses a unique encoding scheme where color reads represent transitions between adjacent nucleotides. The determination of SNPs from color reads usually involves the translation of color alignments to likely nucleotide strings to facilitate the use of tools designed for nucleotide reads. This technique results in the loss of significant information in the color read, producing many incorrect SNP calls, especially if regions exist with dense or adjacent polymorphism. Additionally, color reads align ambiguously and incorrectly more often than nucleotide reads making integrated SNP calling a difficult challenge. We have developed ComB, a SNP calling tool which operates directly in color space, using a Bayesian model to incorporate unique and ambiguous reads to iteratively determine SNP identity. ComB is capable of accurately calling short consecutive nucleotide polymorphisms and densely clustered SNPs; both of which other SNP calling tools fail to identify. ComB, which is capable of using billions of short reads to accurately and efficiently perform whole human genome SNP calling in parallel, is also capable of using sequence data or even integrating sequence and color space data sets. We use real and simulated data to demonstrate that ComB's iterative strategy and recalibration of quality scores allow it to discover more true SNPs while calling fewer false positives than tools which use only color alignments as well as tools which translate color reads to nucleotide strings.

  9. Linkage Analysis and QTL Mapping Using SNP Dosage Data in a Tetraploid Potato Mapping Population

    PubMed Central

    Hackett, Christine A.; McLean, Karen; Bryan, Glenn J.

    2013-01-01

    New sequencing and genotyping technologies have enabled researchers to generate high density SNP genotype data for mapping populations. In polyploid species, SNP data usually contain a new type of information, the allele dosage, which is not used by current methodologies for linkage analysis and QTL mapping. Here we extend existing methodology to use dosage data on SNPs in an autotetraploid mapping population. The SNP dosages are inferred from allele intensity ratios using normal mixture models. The steps of the linkage analysis (testing for distorted segregation, clustering SNPs, calculation of recombination fractions and LOD scores, ordering of SNPs and inference of parental phase) are extended to use the dosage information. For QTL analysis, the probability of each possible offspring genotype is inferred at a grid of locations along the chromosome from the ordered parental genotypes and phases and the offspring dosages. A normal mixture model is then used to relate trait values to the offspring genotypes and to identify the most likely locations for QTLs. These methods are applied to analyse a tetraploid potato mapping population of parents and 190 offspring, genotyped using an Infinium 8300 Potato SNP Array. Linkage maps for each of the 12 chromosomes are constructed. The allele intensity ratios are mapped as quantitative traits to check that their position and phase agrees with that of the corresponding SNP. This analysis confirms most SNP positions, and eliminates some problem SNPs to give high-density maps for each chromosome, with between 74 and 152 SNPs mapped and between 100 and 300 further SNPs allocated to approximate bins. Low numbers of double reduction products were detected. Overall 3839 of the 5378 polymorphic SNPs can be assigned putative genetic locations. This methodology can be applied to construct high-density linkage maps in any autotetraploid species, and could also be extended to higher autopolyploids. PMID:23704960

  10. RAD tag sequencing as a source of SNP markers in Cynara cardunculus L

    PubMed Central

    2012-01-01

    Background The globe artichoke (Cynara cardunculus L. var. scolymus) genome is relatively poorly explored, especially compared to those of the other major Asteraceae crops sunflower and lettuce. No SNP markers are in the public domain. We have combined the recently developed restriction-site associated DNA (RAD) approach with the Illumina DNA sequencing platform to effect the rapid and mass discovery of SNP markers for C. cardunculus. Results RAD tags were sequenced from the genomic DNA of three C. cardunculus mapping population parents, generating 9.7 million reads, corresponding to ~1 Gbp of sequence. An assembly based on paired ends produced ~6.0 Mbp of genomic sequence, separated into ~19,000 contigs (mean length 312 bp), of which ~21% were fragments of putative coding sequence. The shared sequences allowed for the discovery of ~34,000 SNPs and nearly 800 indels, equivalent to a SNP frequency of 5.6 per 1,000 nt, and an indel frequency of 0.2 per 1,000 nt. A sample of heterozygous SNP loci was mapped by CAPS assays and this exercise provided validation of our mining criteria. The repetitive fraction of the genome had a high representation of retrotransposon sequence, followed by simple repeats, AT-low complexity regions and mobile DNA elements. The genomic k-mers distribution and CpG rate of C. cardunculus, compared with data derived from three whole genome-sequenced dicots species, provided a further evidence of the random representation of the C. cardunculus genome generated by RAD sampling. Conclusion The RAD tag sequencing approach is a cost-effective and rapid method to develop SNP markers in a highly heterozygous species. Our approach permitted to generate a large and robust SNP datasets by the adoption of optimized filtering criteria. PMID:22214349

  11. A technical platform for PCR-based SNP screening in cereals and other crops.

    PubMed

    Wang, Zining

    2014-01-01

    With the rapid development of sequencing technologies and sequenced genomes, single-nucleotide polymorphisms (SNPs) have become a common genomic tool in the study of biological diversity, genome variation, gene mapping, cloning, and marker-assisted selection. In this chapter, PCR-based SNP screening is discussed in detail. This includes preparation of solutions and buffers, designing of tetra-primers, PCR for DNA amplification, gel electrophoresis, and SNP screening. By grasping the techniques and experience from the wet laboratories, researchers can quickly use this genomic tool to tackle problems in their research.

  12. Evaluation of the Ion Torrent™ HID SNP 169-plex: A SNP typing assay developed for human identification by second generation sequencing.

    PubMed

    Børsting, Claus; Fordyce, Sarah L; Olofsson, Jill; Mogensen, Helle Smidt; Morling, Niels

    2014-09-01

    The Ion Torrent™ HID SNP assay amplified 136 autosomal SNPs and 33 Y-chromosome markers in one PCR and the markers were subsequently typed using the Ion PGM™ second generation sequencing platform. A total of 51 of the autosomal SNPs were selected from the SNPforID panel that is routinely used in our ISO 17025 accredited laboratory. Concordance between the Ion Torrent™ HID SNP assay and the SNPforID assay was tested by typing 44 Iraqis twice with the Ion Torrent™ HID SNP assay. The same samples were previously typed with the SNPforID assay and the Y-chromosome haplogroups of the individuals were previously identified by typing 45 Y-chromosome SNPs. Full concordance between the assays were obtained except for the SNP genotypes of two SNPs. These SNPs were among the eight SNPs (rs2399332, rs1029047, rs10776839, rs4530059, rs8037429, rs430046, rs1031825 and rs1523537) with inconsistent allele balance among samples. These SNPs should be excluded from the panel. The optimal amount of DNA in the PCR seemed to be ≥0.5ng. Allele drop-outs were rare and only seen in experiments with <0.5ng input DNA and with a coverage of <50reads. No allele drop-in was observed. The great majority of the heterozygote allele balances were between 0.6 and 1.6, which is comparable to the heterozygote balances of STRs typed with PCR-CE. The number of reads with base calls that differed from the genotype call was typically less than five. This allowed detection of 1:100 mixtures with a high degree of certainty in experiments with a high total depth of coverage. In conclusion, the Ion PGM™ is a very promising platform for forensic genetics. However, the secondary sequence analysis software made wrong genotype calls from correctly sequenced alleles. These types of errors must be corrected before the platform can be used in case work. Furthermore, the sequence analysis software should be further developed and include quality settings for each SNP based on validation studies. PMID

  13. MDM2 promoter SNP55 (rs2870820) affects risk of colon cancer but not breast-, lung-, or prostate cancer.

    PubMed

    Helwa, Reham; Gansmo, Liv B; Romundstad, Pål; Hveem, Kristian; Vatten, Lars; Ryan, Bríd M; Harris, Curtis C; Lønning, Per E; Knappskog, Stian

    2016-01-01

    Two functional SNPs (SNP285G > C; rs117039649 and SNP309T > G; rs2279744) have previously been reported to modulate Sp1 transcription factor binding to the promoter of the proto-oncogene MDM2, and to influence cancer risk. Recently, a third SNP (SNP55C > T; rs2870820) was also reported to affect Sp1 binding and MDM2 transcription. In this large population based case-control study, we genotyped MDM2 SNP55 in 10,779 Caucasian individuals, previously genotyped for SNP309 and SNP285, including cases of colon (n = 1,524), lung (n = 1,323), breast (n = 1,709) and prostate cancer (n = 2,488) and 3,735 non-cancer controls, as well as 299 healthy African-Americans. Applying the dominant model, we found an elevated risk of colon cancer among individuals harbouring SNP55TT/CT genotypes compared to the SNP55CC genotype (OR = 1.15; 95% CI = 1.01-1.30). The risk was found to be highest for left-sided colon cancer (OR = 1.21; 95% CI = 1.00-1.45) and among females (OR = 1.32; 95% CI = 1.01-1.74). Assessing combined genotypes, we found the highest risk of colon cancer among individuals harbouring the SNP55TT or CT together with the SNP309TG genotype (OR = 1.21; 95% CI = 1.00-1.46). Supporting the conclusions from the risk estimates, we found colon cancer cases carrying the SNP55TT/CT genotypes to be diagnosed at younger age as compared to SNP55CC (p = 0.053), in particular among patients carrying the SNP309TG/TT genotypes (p = 0.009). PMID:27624283

  14. MDM2 promoter SNP55 (rs2870820) affects risk of colon cancer but not breast-, lung-, or prostate cancer

    PubMed Central

    Helwa, Reham; Gansmo, Liv B.; Romundstad, Pål; Hveem, Kristian; Vatten, Lars; Ryan, Bríd M.; Harris, Curtis C.; Lønning, Per E.; Knappskog, Stian

    2016-01-01

    Two functional SNPs (SNP285G > C; rs117039649 and SNP309T > G; rs2279744) have previously been reported to modulate Sp1 transcription factor binding to the promoter of the proto-oncogene MDM2, and to influence cancer risk. Recently, a third SNP (SNP55C > T; rs2870820) was also reported to affect Sp1 binding and MDM2 transcription. In this large population based case-control study, we genotyped MDM2 SNP55 in 10,779 Caucasian individuals, previously genotyped for SNP309 and SNP285, including cases of colon (n = 1,524), lung (n = 1,323), breast (n = 1,709) and prostate cancer (n = 2,488) and 3,735 non-cancer controls, as well as 299 healthy African-Americans. Applying the dominant model, we found an elevated risk of colon cancer among individuals harbouring SNP55TT/CT genotypes compared to the SNP55CC genotype (OR = 1.15; 95% CI = 1.01–1.30). The risk was found to be highest for left-sided colon cancer (OR = 1.21; 95% CI = 1.00–1.45) and among females (OR = 1.32; 95% CI = 1.01–1.74). Assessing combined genotypes, we found the highest risk of colon cancer among individuals harbouring the SNP55TT or CT together with the SNP309TG genotype (OR = 1.21; 95% CI = 1.00–1.46). Supporting the conclusions from the risk estimates, we found colon cancer cases carrying the SNP55TT/CT genotypes to be diagnosed at younger age as compared to SNP55CC (p = 0.053), in particular among patients carrying the SNP309TG/TT genotypes (p = 0.009). PMID:27624283

  15. Priming of seeds with nitric oxide donor sodium nitroprusside (SNP) alleviates the inhibition on wheat seed germination by salt stress.

    PubMed

    Duan, Pei; Ding, Feng; Wang, Fang; Wang, Bao-Shan

    2007-06-01

    The effect of SNP, an NO donor, on seed germination of wheat (Triticum aestivum L. cv. 'DK961') under salt stress was studied. The results showed that priming of seeds with 0.06 mmol/L SNP for 24 h markedly alleviated the decrease of the germination percentage, germination index, vigor index and imbibition rate of wheat seeds under salt stress. SNP significantly alleviated the decrease of the beta-amylase activity but almost did not affect the alpha-amylase activity of wheat seeds under salt stress. SNP slightly increased the alpha-amylase isoenzymes (especially isoenzyme 3) and significantly increased the beta-amylase isoenzymes (especially isoenzyme d, e, f and g). SNP pretreatment decreased Na(+) content, but increased the K(+) content, resulting in a mark increase of K(+)/Na(+) ratio of wheat seedlings under salt stress. These results suggested that NO is involved in promoting wheat seed germination under salt stress by increasing the beta-amylase activity.

  16. An improved consensus linkage map of barley based on flow-sorted chromosomes and SNP markers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recent advances in high-throughput genotyping have made it easier to combine information from different mapping populations into consensus genetic maps, which provide increased marker density and genome coverage compared to individual maps. Previously, a SNP-based genotyping platform was developed a...

  17. Identification of a SNP marker associated with WB242 nematode resistance in sugar beet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The beet-cyst nematode (Heterodera schachtii Schmidt) is one of the major diseases of sugar beet. The identification of molecular markers associated to the nematode resistance would be helpful for developing resistant varieties. The aim of this study was the identification of SNP (Single Nucleotide ...

  18. Use of microsatellite and SNP markers to characterize biotypes in Hessian fly

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Exploration of the biotype structure of Hessian fly, Mayetiola destructor (Say), would improve our knowledge regarding variation in virulence phenotypes and difference in genetic background. The objective of this study was to develop and test a panel of 18 microsatellite and 22 SNP markers to reveal...

  19. Association of Agronomic Traits with SNP Markers in Durum Wheat (Triticum turgidum L. durum (Desf.))

    PubMed Central

    Hu, Xin; Ren, Jing; Ren, Xifeng; Huang, Sisi; Sabiel, Salih A. I.; Luo, Mingcheng; Nevo, Eviatar; Fu, Chunjie; Peng, Junhua; Sun, Dongfa

    2015-01-01

    Association mapping is a powerful approach to detect associations between traits of interest and genetic markers based on linkage disequilibrium (LD) in molecular plant breeding. In this study, 150 accessions of worldwide originated durum wheat germplasm (Triticum turgidum spp. durum) were genotyped using 1,366 SNP markers. The extent of LD on each chromosome was evaluated. Association of single nucleotide polymorphisms (SNP) markers with ten agronomic traits measured in four consecutive years was analyzed under a mix linear model (MLM). Two hundred and one significant association pairs were detected in the four years. Several markers were associated with one trait, and also some markers were associated with multiple traits. Some of the associated markers were in agreement with previous quantitative trait loci (QTL) analyses. The function and homology analyses of the corresponding ESTs of some SNP markers could explain many of the associations for plant height, length of main spike, number of spikelets on main spike, grain number per plant, and 1000-grain weight, etc. The SNP associations for the observed traits are generally clustered in specific chromosome regions of the wheat genome, mainly in 2A, 5A, 6A, 7A, 1B, and 6B chromosomes. This study demonstrates that association mapping can complement and enhance previous QTL analyses and provide additional information for marker-assisted selection. PMID:26110423

  20. MAFsnp: A Multi-Sample Accurate and Flexible SNP Caller Using Next-Generation Sequencing Data.

    PubMed

    Hu, Jiyuan; Li, Tengfei; Xiu, Zidi; Zhang, Hong

    2015-01-01

    Most existing statistical methods developed for calling single nucleotide polymorphisms (SNPs) using next-generation sequencing (NGS) data are based on Bayesian frameworks, and there does not exist any SNP caller that produces p-values for calling SNPs in a frequentist framework. To fill in this gap, we develop a new method MAFsnp, a Multiple-sample based Accurate and Flexible algorithm for calling SNPs with NGS data. MAFsnp is based on an estimated likelihood ratio test (eLRT) statistic. In practical situation, the involved parameter is very close to the boundary of the parametric space, so the standard large sample property is not suitable to evaluate the finite-sample distribution of the eLRT statistic. Observing that the distribution of the test statistic is a mixture of zero and a continuous part, we propose to model the test statistic with a novel two-parameter mixture distribution. Once the parameters in the mixture distribution are estimated, p-values can be easily calculated for detecting SNPs, and the multiple-testing corrected p-values can be used to control false discovery rate (FDR) at any pre-specified level. With simulated data, MAFsnp is shown to have much better control of FDR than the existing SNP callers. Through the application to two real datasets, MAFsnp is also shown to outperform the existing SNP callers in terms of calling accuracy. An R package "MAFsnp" implementing the new SNP caller is freely available at http://homepage.fudan.edu.cn/zhangh/softwares/.

  1. Association mapping of resistance to leaf rust in emmer wheat using high throughput SNP markers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Emmer wheat (Triticum turgidum L. subsp. dicoccum) is known to be a useful source of genes for many desirable characters for improvement of modern cultivated wheat. Recently, a panel of 181 emmer wheat accessions has been genotyped with wheat 9K SNP (single nucleotide polymorphism) markers and exte...

  2. Longevity and plasticity of CFTR provide an argument for noncanonical SNP organization in hominid DNA.

    PubMed

    Hill, Aubrey E; Plyler, Zackery E; Tiwari, Hemant; Patki, Amit; Tully, Joel P; McAtee, Christopher W; Moseley, Leah A; Sorscher, Eric J

    2014-01-01

    Like many other ancient genes, the cystic fibrosis transmembrane conductance regulator (CFTR) has survived for hundreds of millions of years. In this report, we consider whether such prodigious longevity of an individual gene--as opposed to an entire genome or species--should be considered surprising in the face of eons of relentless DNA replication errors, mutagenesis, and other causes of sequence polymorphism. The conventions that modern human SNP patterns result either from purifying selection or random (neutral) drift were not well supported, since extant models account rather poorly for the known plasticity and function (or the established SNP distributions) found in a multitude of genes such as CFTR. Instead, our analysis can be taken as a polemic indicating that SNPs in CFTR and many other mammalian genes may have been generated--and continue to accrue--in a fundamentally more organized manner than would otherwise have been expected. The resulting viewpoint contradicts earlier claims of 'directional' or 'intelligent design-type' SNP formation, and has important implications regarding the pace of DNA adaptation, the genesis of conserved non-coding DNA, and the extent to which eukaryotic SNP formation should be viewed as adaptive. PMID:25350658

  3. A novel approach to analyzing fMRI and SNP data via parallel independent component analysis

    NASA Astrophysics Data System (ADS)

    Liu, Jingyu; Pearlson, Godfrey; Calhoun, Vince; Windemuth, Andreas

    2007-03-01

    There is current interest in understanding genetic influences on brain function in both the healthy and the disordered brain. Parallel independent component analysis, a new method for analyzing multimodal data, is proposed in this paper and applied to functional magnetic resonance imaging (fMRI) and a single nucleotide polymorphism (SNP) array. The method aims to identify the independent components of each modality and the relationship between the two modalities. We analyzed 92 participants, including 29 schizophrenia (SZ) patients, 13 unaffected SZ relatives, and 50 healthy controls. We found a correlation of 0.79 between one fMRI component and one SNP component. The fMRI component consists of activations in cingulate gyrus, multiple frontal gyri, and superior temporal gyrus. The related SNP component is contributed to significantly by 9 SNPs located in sets of genes, including those coding for apolipoprotein A-I, and C-III, malate dehydrogenase 1 and the gamma-aminobutyric acid alpha-2 receptor. A significant difference in the presences of this SNP component is found between the SZ group (SZ patients and their relatives) and the control group. In summary, we constructed a framework to identify the interactions between brain functional and genetic information; our findings provide new insight into understanding genetic influences on brain function in a common mental disorder.

  4. SNP-microarrays can accurately identify the presence of an individual in complex forensic DNA mixtures.

    PubMed

    Voskoboinik, Lev; Ayers, Sheri B; LeFebvre, Aaron K; Darvasi, Ariel

    2015-05-01

    Common forensic and mass disaster scenarios present DNA evidence that comprises a mixture of several contributors. Identifying the presence of an individual in such mixtures has proven difficult. In the current study, we evaluate the practical usefulness of currently available "off-the-shelf" SNP microarrays for such purposes. We found that a set of 3000 SNPs specifically selected for this purpose can accurately identify the presence of an individual in complex DNA mixtures of various compositions. For example, individuals contributing as little as 5% to a complex DNA mixture can be robustly identified even if the starting DNA amount was as little as 5.0ng and had undergone whole-genome amplification (WGA) prior to SNP analysis. The work presented in this study represents proof-of-principle that our previously proposed approach, can work with real "forensic-type" samples. Furthermore, in the absence of a low-density focused forensic SNP microarray, the use of standard, currently available high-density SNP microarrays can be similarly used and even increase statistical power due to the larger amount of available information.

  5. De Novo sequencing of sunflower genome for SNP discovery using RAD (Restriction site Associated DNA) approach

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Application of Single Nucleotide Polymorphism (SNP) marker technology as a tool in sunflower breeding programs offers enormous potential to improve sunflower genetics, and facilitate faster release of sunflower hybrids to the market place. Through a National Sunflower Association (NSA) funded initia...

  6. Utilization of a whole genome SNP panel for efficient genetic mapping in the mouse

    PubMed Central

    Moran, Jennifer L.; Bolton, Andrew D.; Tran, Pamela V.; Brown, Alison; Dwyer, Noelle D.; Manning, Danielle K.; Bjork, Bryan C.; Li, Cheng; Montgomery, Kate; Siepka, Sandra M.; Vitaterna, Martha Hotz; Takahashi, Joseph S.; Wiltshire, Tim; Kwiatkowski, David J.; Kucherlapati, Raju; Beier, David R.

    2006-01-01

    Phenotype-driven genetics can be used to create mouse models of human disease and birth defects. However, the utility of these mutant models is limited without identification of the causal gene. To facilitate genetic mapping, we developed a fixed single nucleotide polymorphism (SNP) panel of 394 SNPs as an alternative to analyses using simple sequence length polymorphism (SSLP) marker mapping. With the SNP panel, chromosomal locations for 22 monogenic mutants were identified. The average number of affected progeny genotyped for mapped monogenic mutations is nine. Map locations for several mutants have been obtained with as few as four affected progeny. The average size of genetic intervals obtained for these mutants is 43 Mb, with a range of 17–83 Mb. Thus, our SNP panel allows for identification of moderate resolution map position with small numbers of mice in a high-throughput manner. Importantly, the panel is suitable for mapping crosses from many inbred and wild-derived inbred strain combinations. The chromosomal localizations obtained with the SNP panel allow one to quickly distinguish between potentially novel loci or remutations in known genes, and facilitates fine mapping and positional cloning. By using this approach, we identified DNA sequence changes in two ethylnitrosourea-induced mutants. PMID:16461637

  7. Fine mapping of copy number variations on two cattle genome assemblies using high density SNP array

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Btau_4.0 and UMD3.1 are two distinct cattle reference genome assemblies. In our previous study using the low density BovineSNP50 array, we reported a copy number variation (CNV) analysis on Btau_4.0 with 521 animals of 21 cattle breeds, yielding 682 CNV regions with a total length of 139.8 megabases...

  8. Making a chocolate chip: development and evaluation of a 6K SNP array for Theobroma cacao.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Theobroma cacao, the key ingredient in chocolate production, is one of the world's most important tree fruit crops, with ~4,000,000 metric tons produced across 50 countries. To move towards gene discovery and marker-assisted breeding in cacao, a single-nucleotide polymorphism (SNP) identification pr...

  9. Optimal design of low-density SNP arrays for genomic prediction: algorithm and applications

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Low-density (LD) single nucleotide polymorphism (SNP) arrays provide a cost-effective solution for genomic prediction and selection, but algorithms and computational tools are needed for their optimal design. A multiple-objective, local optimization (MOLO) algorithm was developed for design of optim...

  10. Longevity and Plasticity of CFTR Provide an Argument for Noncanonical SNP Organization in Hominid DNA

    PubMed Central

    Hill, Aubrey E.; Plyler, Zackery E.; Tiwari, Hemant; Patki, Amit; Tully, Joel P.; McAtee, Christopher W.; Moseley, Leah A.; Sorscher, Eric J.

    2014-01-01

    Like many other ancient genes, the cystic fibrosis transmembrane conductance regulator (CFTR) has survived for hundreds of millions of years. In this report, we consider whether such prodigious longevity of an individual gene – as opposed to an entire genome or species – should be considered surprising in the face of eons of relentless DNA replication errors, mutagenesis, and other causes of sequence polymorphism. The conventions that modern human SNP patterns result either from purifying selection or random (neutral) drift were not well supported, since extant models account rather poorly for the known plasticity and function (or the established SNP distributions) found in a multitude of genes such as CFTR. Instead, our analysis can be taken as a polemic indicating that SNPs in CFTR and many other mammalian genes may have been generated—and continue to accrue—in a fundamentally more organized manner than would otherwise have been expected. The resulting viewpoint contradicts earlier claims of ‘directional’ or ‘intelligent design-type’ SNP formation, and has important implications regarding the pace of DNA adaptation, the genesis of conserved non-coding DNA, and the extent to which eukaryotic SNP formation should be viewed as adaptive. PMID:25350658

  11. SNP discovery in complex allotetraploid genomes (Gossypium spp., Malvaceae) using genotyping by sequencing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dramatic decreases in the cost of DNA sequencing have enabled the development of very large numbers of markers based on single nucleotide polymorphism (SNP) for phylogenetic studies, population genetics, linkage mapping, marker-assisted breeding and other applications. Using Illumina next-generatio...

  12. Measuring diversity in Gossypium hirsutum using the CottonSNP63K Array

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A CottonSNP63K array and accompanying cluster file has been developed and includes 45,104 intra-specific SNPs and 17,954 inter-specific SNPs for automated genotyping of cotton (Gossypium spp.) samples. Development of the cluster file included genotyping of 1,156 samples, a subset of which were iden...

  13. Changes in variance explained by top SNP windows over generations for three traits in broiler chicken.

    PubMed

    Fragomeni, Breno de Oliveira; Misztal, Ignacy; Lourenco, Daniela Lino; Aguilar, Ignacio; Okimoto, Ronald; Muir, William M

    2014-01-01

    The purpose of this study was to determine if the set of genomic regions inferred as accounting for the majority of genetic variation in quantitative traits remain stable over multiple generations of selection. The data set contained phenotypes for five generations of broiler chicken for body weight, breast meat, and leg score. The population consisted of 294,632 animals over five generations and also included genotypes of 41,036 single nucleotide polymorphism (SNP) for 4,866 animals, after quality control. The SNP effects were calculated by a GWAS type analysis using single step genomic BLUP approach for generations 1-3, 2-4, 3-5, and 1-5. Variances were calculated for windows of 20 SNP. The top ten windows for each trait that explained the largest fraction of the genetic variance across generations were examined. Across generations, the top 10 windows explained more than 0.5% but less than 1% of the total variance. Also, the pattern of the windows was not consistent across generations. The windows that explained the greatest variance changed greatly among the combinations of generations, with a few exceptions. In many cases, a window identified as top for one combination, explained less than 0.1% for the other combinations. We conclude that identification of top SNP windows for a population may have little predictive power for genetic selection in the following generations for the traits here evaluated.

  14. Changes in variance explained by top SNP windows over generations for three traits in broiler chicken

    PubMed Central

    Fragomeni, Breno de Oliveira; Misztal, Ignacy; Lourenco, Daniela Lino; Aguilar, Ignacio; Okimoto, Ronald; Muir, William M.

    2014-01-01

    The purpose of this study was to determine if the set of genomic regions inferred as accounting for the majority of genetic variation in quantitative traits remain stable over multiple generations of selection. The data set contained phenotypes for five generations of broiler chicken for body weight, breast meat, and leg score. The population consisted of 294,632 animals over five generations and also included genotypes of 41,036 single nucleotide polymorphism (SNP) for 4,866 animals, after quality control. The SNP effects were calculated by a GWAS type analysis using single step genomic BLUP approach for generations 1–3, 2–4, 3–5, and 1–5. Variances were calculated for windows of 20 SNP. The top ten windows for each trait that explained the largest fraction of the genetic variance across generations were examined. Across generations, the top 10 windows explained more than 0.5% but less than 1% of the total variance. Also, the pattern of the windows was not consistent across generations. The windows that explained the greatest variance changed greatly among the combinations of generations, with a few exceptions. In many cases, a window identified as top for one combination, explained less than 0.1% for the other combinations. We conclude that identification of top SNP windows for a population may have little predictive power for genetic selection in the following generations for the traits here evaluated. PMID:25324857

  15. The use of SNP data for the monitoring of genetic diversity in cattle breeds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    LD between SNPs contains information about effective population size. In this study, we investigate the use of genome-wide SNP data for marker based estimation of effective population size for two taurine cattle breeds of Africa and two local cattle breeds of Switzerland. Estimated recombination rat...

  16. SNP-based high density genetic map and mapping of btwd1 dwarfing gene in barley

    PubMed Central

    Ren, Xifeng; Wang, Jibin; Liu, Lipan; Sun, Genlou; Li, Chengdao; Luo, Hong; Sun, Dongfa

    2016-01-01

    A high-density linkage map is a valuable tool for functional genomics and breeding. A newly developed sequence-based marker technology, restriction site associated DNA (RAD) sequencing, has been proven to be powerful for the rapid discovery and genotyping of genome-wide single nucleotide polymorphism (SNP) markers and for the high-density genetic map construction. The objective of this research was to construct a high-density genetic map of barley using RAD sequencing. 1894 high-quality SNP markers were developed and mapped onto all seven chromosomes together with 68 SSR markers. These 1962 markers constituted a total genetic length of 1375.8 cM and an average of 0.7 cM between adjacent loci. The number of markers within each linkage group ranged from 209 to 396. The new recessive dwarfing gene btwd1 in Huaai 11 was mapped onto the high density linkage maps. The result showed that the btwd1 is positioned between SNP marks 7HL_6335336 and 7_249275418 with a genetic distance of 0.9 cM and 0.7 cM on chromosome 7H, respectively. The SNP-based high-density genetic map developed and the dwarfing gene btwd1 mapped in this study provide critical information for position cloning of the btwd1 gene and molecular breeding of barley. PMID:27530597

  17. SNP-based high density genetic map and mapping of btwd1 dwarfing gene in barley.

    PubMed

    Ren, Xifeng; Wang, Jibin; Liu, Lipan; Sun, Genlou; Li, Chengdao; Luo, Hong; Sun, Dongfa

    2016-01-01

    A high-density linkage map is a valuable tool for functional genomics and breeding. A newly developed sequence-based marker technology, restriction site associated DNA (RAD) sequencing, has been proven to be powerful for the rapid discovery and genotyping of genome-wide single nucleotide polymorphism (SNP) markers and for the high-density genetic map construction. The objective of this research was to construct a high-density genetic map of barley using RAD sequencing. 1894 high-quality SNP markers were developed and mapped onto all seven chromosomes together with 68 SSR markers. These 1962 markers constituted a total genetic length of 1375.8 cM and an average of 0.7 cM between adjacent loci. The number of markers within each linkage group ranged from 209 to 396. The new recessive dwarfing gene btwd1 in Huaai 11 was mapped onto the high density linkage maps. The result showed that the btwd1 is positioned between SNP marks 7HL_6335336 and 7_249275418 with a genetic distance of 0.9 cM and 0.7 cM on chromosome 7H, respectively. The SNP-based high-density genetic map developed and the dwarfing gene btwd1 mapped in this study provide critical information for position cloning of the btwd1 gene and molecular breeding of barley.

  18. A web-based genome browser for 'SNP-aware' assay design

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Human and animal genomes contain an abundance of single nucleotide polymorphisms (SNPs) that are useful for genetic testing. However, the relatively large number of SNPs present in diverse populations can pose serious problems when designing assays. It is important to “mask” some SNP positions so ...

  19. The impact of SNP fingerprinting and parentage analysis on the effectiveness of variety recommendations in cacao

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Evidence for the impact of mislabeling and/or pollen contamination on consistency of field performance has been lacking to reinforce the need for strict adherence to quality control protocols in cacao seed garden and germplasm plot management. The present study used SNP fingerprinting at 64 loci to ...

  20. SNP-based high density genetic map and mapping of btwd1 dwarfing gene in barley.

    PubMed

    Ren, Xifeng; Wang, Jibin; Liu, Lipan; Sun, Genlou; Li, Chengdao; Luo, Hong; Sun, Dongfa

    2016-01-01

    A high-density linkage map is a valuable tool for functional genomics and breeding. A newly developed sequence-based marker technology, restriction site associated DNA (RAD) sequencing, has been proven to be powerful for the rapid discovery and genotyping of genome-wide single nucleotide polymorphism (SNP) markers and for the high-density genetic map construction. The objective of this research was to construct a high-density genetic map of barley using RAD sequencing. 1894 high-quality SNP markers were developed and mapped onto all seven chromosomes together with 68 SSR markers. These 1962 markers constituted a total genetic length of 1375.8 cM and an average of 0.7 cM between adjacent loci. The number of markers within each linkage group ranged from 209 to 396. The new recessive dwarfing gene btwd1 in Huaai 11 was mapped onto the high density linkage maps. The result showed that the btwd1 is positioned between SNP marks 7HL_6335336 and 7_249275418 with a genetic distance of 0.9 cM and 0.7 cM on chromosome 7H, respectively. The SNP-based high-density genetic map developed and the dwarfing gene btwd1 mapped in this study provide critical information for position cloning of the btwd1 gene and molecular breeding of barley. PMID:27530597

  1. Verification of genetic identity of introduced cacao germplasm in Ghana using single nucleotide polymorphism (SNP) markers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Accurate identification of individual genotypes is important for cacao (Theobroma cacao L.) breeding, germplasm conservation and seed propagation. The development of single nucleotide polymorphism (SNP) markers in cacao offers an effective way to use a high-throughput genotyping system for cacao gen...

  2. Applying SNP marker technology in the cacao breeding program at the Cocoa Research Institute of Ghana

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this investigation 45 parental cacao plants and five progeny derived from the parental stock studied were genotyped using six SNP markers to determine off-types or mislabeled clones and to authenticate crosses made in the Cocoa Research Institute of Ghana (CRIG) breeding program. Investigation wa...

  3. Estimating the effect of SNP genotype on quantitative traits from pooled DNA samples

    PubMed Central

    2012-01-01

    Background Studies to detect associations between DNA markers and traits of interest in humans and livestock benefit from increasing the number of individuals genotyped. Performing association studies on pooled DNA samples can provide greater power for a given cost. For quantitative traits, the effect of an SNP is measured in the units of the trait and here we propose and demonstrate a method to estimate SNP effects on quantitative traits from pooled DNA data. Methods To obtain estimates of SNP effects from pooled DNA samples, we used logistic regression of estimated allele frequencies in pools on phenotype. The method was tested on a simulated dataset, and a beef cattle dataset using a model that included principal components from a genomic correlation matrix derived from the allele frequencies estimated from the pooled samples. The performance of the obtained estimates was evaluated by comparison with estimates obtained using regression of phenotype on genotype from individual samples of DNA. Results For the simulated data, the estimates of SNP effects from pooled DNA are similar but asymptotically different to those from individual DNA data. Error in estimating allele frequencies had a large effect on the accuracy of estimated SNP effects. For the beef cattle dataset, the principal components of the genomic correlation matrix from pooled DNA were consistent with known breed groups, and could be used to account for population stratification. Correctly modeling the contemporary group structure was essential to achieve estimates similar to those from individual DNA data, and pooling DNA from individuals within groups was superior to pooling DNA across groups. For a fixed number of assays, pooled DNA samples produced results that were more correlated with results from individual genotyping data than were results from one random individual assayed from each pool. Conclusions Use of logistic regression of allele frequency on phenotype makes it possible to estimate SNP

  4. Development and Characterization of a High Density SNP Genotyping Assay for Cattle

    PubMed Central

    Matukumalli, Lakshmi K.; Lawley, Cynthia T.; Schnabel, Robert D.; Taylor, Jeremy F.; Allan, Mark F.; Heaton, Michael P.; O'Connell, Jeff; Moore, Stephen S.; Smith, Timothy P. L.; Sonstegard, Tad S.; Van Tassell, Curtis P.

    2009-01-01

    The success of genome-wide association (GWA) studies for the detection of sequence variation affecting complex traits in human has spurred interest in the use of large-scale high-density single nucleotide polymorphism (SNP) genotyping for the identification of quantitative trait loci (QTL) and for marker-assisted selection in model and agricultural species. A cost-effective and efficient approach for the development of a custom genotyping assay interrogating 54,001 SNP loci to support GWA applications in cattle is described. A novel algorithm for achieving a compressed inter-marker interval distribution proved remarkably successful, with median interval of 37 kb and maximum predicted gap of <350 kb. The assay was tested on a panel of 576 animals from 21 cattle breeds and six outgroup species and revealed that from 39,765 to 46,492 SNP are polymorphic within individual breeds (average minor allele frequency (MAF) ranging from 0.24 to 0.27). The assay also identified 79 putative copy number variants in cattle. Utility for GWA was demonstrated by localizing known variation for coat color and the presence/absence of horns to their correct genomic locations. The combination of SNP selection and the novel spacing algorithm allows an efficient approach for the development of high-density genotyping platforms in species having full or even moderate quality draft sequence. Aspects of the approach can be exploited in species which lack an available genome sequence. The BovineSNP50 assay described here is commercially available from Illumina and provides a robust platform for mapping disease genes and QTL in cattle. PMID:19390634

  5. SNP discovery in candidate adaptive genes using exon capture in a free-ranging alpine ungulate.

    PubMed

    Roffler, Gretchen H; Amish, Stephen J; Smith, Seth; Cosart, Ted; Kardos, Marty; Schwartz, Michael K; Luikart, Gordon

    2016-09-01

    Identification of genes underlying genomic signatures of natural selection is key to understanding adaptation to local conditions. We used targeted resequencing to identify SNP markers in 5321 candidate adaptive genes associated with known immunological, metabolic and growth functions in ovids and other ungulates. We selectively targeted 8161 exons in protein-coding and nearby 5' and 3' untranslated regions of chosen candidate genes. Targeted sequences were taken from bighorn sheep (Ovis canadensis) exon capture data and directly from the domestic sheep genome (Ovis aries v. 3; oviAri3). The bighorn sheep sequences used in the Dall's sheep (Ovis dalli dalli) exon capture aligned to 2350 genes on the oviAri3 genome with an average of 2 exons each. We developed a microfluidic qPCR-based SNP chip to genotype 476 Dall's sheep from locations across their range and test for patterns of selection. Using multiple corroborating approaches (lositan and bayescan), we detected 28 SNP loci potentially under selection. We additionally identified candidate loci significantly associated with latitude, longitude, precipitation and temperature, suggesting local environmental adaptation. The three methods demonstrated consistent support for natural selection on nine genes with immune and disease-regulating functions (e.g. Ovar-DRA, APC, BATF2, MAGEB18), cell regulation signalling pathways (e.g. KRIT1, PI3K, ORRC3), and respiratory health (CYSLTR1). Characterizing adaptive allele distributions from novel genetic techniques will facilitate investigation of the influence of environmental variation on local adaptation of a northern alpine ungulate throughout its range. This research demonstrated the utility of exon capture for gene-targeted SNP discovery and subsequent SNP chip genotyping using low-quality samples in a nonmodel species. PMID:27327375

  6. Development and Validation of a High-Density SNP Genotyping Array for African Oil Palm.

    PubMed

    Kwong, Qi Bin; Teh, Chee Keng; Ong, Ai Ling; Heng, Huey Ying; Lee, Heng Leng; Mohamed, Mohaimi; Low, Joel Zi-Bin; Apparow, Sukganah; Chew, Fook Tim; Mayes, Sean; Kulaveerasingam, Harikrishna; Tammi, Martti; Appleton, David Ross

    2016-08-01

    High-density single nucleotide polymorphism (SNP) genotyping arrays are powerful tools that can measure the level of genetic polymorphism within a population. To develop a whole-genome SNP array for oil palms, SNP discovery was performed using deep resequencing of eight libraries derived from 132 Elaeis guineensis and Elaeis oleifera palms belonging to 59 origins, resulting in the discovery of >3 million putative SNPs. After SNP filtering, the Illumina OP200K custom array was built with 170 860 successful probes. Phenetic clustering analysis revealed that the array could distinguish between palms of different origins in a way consistent with pedigree records. Genome-wide linkage disequilibrium declined more slowly for the commercial populations (ranging from 120 kb at r(2) = 0.43 to 146 kb at r(2) = 0.50) when compared with the semi-wild populations (19.5 kb at r(2) = 0.22). Genetic fixation mapping comparing the semi-wild and commercial population identified 321 selective sweeps. A genome-wide association study (GWAS) detected a significant peak on chromosome 2 associated with the polygenic component of the shell thickness trait (based on the trait shell-to-fruit; S/F %) in tenera palms. Testing of a genomic selection model on the same trait resulted in good prediction accuracy (r = 0.65) with 42% of the S/F % variation explained. The first high-density SNP genotyping array for oil palm has been developed and shown to be robust for use in genetic studies and with potential for developing early trait prediction to shorten the oil palm breeding cycle.

  7. SNP discovery in the transcriptome of white Pacific shrimp Litopenaeus vannamei by next generation sequencing.

    PubMed

    Yu, Yang; Wei, Jiankai; Zhang, Xiaojun; Liu, Jingwen; Liu, Chengzhang; Li, Fuhua; Xiang, Jianhai

    2014-01-01

    The application of next generation sequencing technology has greatly facilitated high throughput single nucleotide polymorphism (SNP) discovery and genotyping in genetic research. In the present study, SNPs were discovered based on two transcriptomes of Litopenaeus vannamei (L. vannamei) generated from Illumina sequencing platform HiSeq 2000. One transcriptome of L. vannamei was obtained through sequencing on the RNA from larvae at mysis stage and its reference sequence was de novo assembled. The data from another transcriptome were downloaded from NCBI and the reads of the two transcriptomes were mapped separately to the assembled reference by BWA. SNP calling was performed using SAMtools. A total of 58,717 and 36,277 SNPs with high quality were predicted from the two transcriptomes, respectively. SNP calling was also performed using the reads of two transcriptomes together, and a total of 96,040 SNPs with high quality were predicted. Among these 96,040 SNPs, 5,242 and 29,129 were predicted as non-synonymous and synonymous SNPs respectively. Characterization analysis of the predicted SNPs in L. vannamei showed that the estimated SNP frequency was 0.21% (one SNP per 476 bp) and the estimated ratio for transition to transversion was 2.0. Fifty SNPs were randomly selected for validation by Sanger sequencing after PCR amplification and 76% of SNPs were confirmed, which indicated that the SNPs predicted in this study were reliable. These SNPs will be very useful for genetic study in L. vannamei, especially for the high density linkage map construction and genome-wide association studies.

  8. Estrogen, SNP-Dependent Chemokine Expression and Selective Estrogen Receptor Modulator Regulation.

    PubMed

    Ho, Ming-Fen; Bongartz, Tim; Liu, Mohan; Kalari, Krishna R; Goss, Paul E; Shepherd, Lois E; Goetz, Matthew P; Kubo, Michiaki; Ingle, James N; Wang, Liewei; Weinshilboum, Richard M

    2016-03-01

    We previously reported, on the basis of a genome-wide association study for aromatase inhibitor-induced musculoskeletal symptoms, that single-nucleotide polymorphisms (SNPs) near the T-cell leukemia/lymphoma 1A (TCL1A) gene were associated with aromatase inhibitor-induced musculoskeletal pain and with estradiol (E2)-induced TCL1A expression. Furthermore, variation in TCL1A expression influenced the downstream expression of proinflammatory cytokines and cytokine receptors. Specifically, the top hit genome-wide association study SNP, rs11849538, created a functional estrogen response element (ERE) that displayed estrogen receptor (ER) binding and increased E2 induction of TCL1A expression only for the variant SNP genotype. In the present study, we pursued mechanisms underlying the E2-SNP-dependent regulation of TCL1A expression and, in parallel, our subsequent observations that SNPs at a distance from EREs can regulate ERα binding and that ER antagonists can reverse phenotypes associated with those SNPs. Specifically, we performed a series of functional genomic studies using a large panel of lymphoblastoid cell lines with dense genomic data that demonstrated that TCL1A SNPs at a distance from EREs can modulate ERα binding and expression of TCL1A as well as the expression of downstream immune mediators. Furthermore, 4-hydroxytamoxifen or fulvestrant could reverse these SNP-genotype effects. Similar results were found for SNPs in the IL17A cytokine and CCR6 chemokine receptor genes. These observations greatly expand our previous results and support the existence of a novel molecular mechanism that contributes to the complex interplay between estrogens and immune systems. They also raise the possibility of the pharmacological manipulation of the expression of proinflammatory cytokines and chemokines in a SNP genotype-dependent fashion. PMID:26866883

  9. SNP discovery in candidate adaptive genes using exon capture in a free-ranging alpine ungulate.

    PubMed

    Roffler, Gretchen H; Amish, Stephen J; Smith, Seth; Cosart, Ted; Kardos, Marty; Schwartz, Michael K; Luikart, Gordon

    2016-09-01

    Identification of genes underlying genomic signatures of natural selection is key to understanding adaptation to local conditions. We used targeted resequencing to identify SNP markers in 5321 candidate adaptive genes associated with known immunological, metabolic and growth functions in ovids and other ungulates. We selectively targeted 8161 exons in protein-coding and nearby 5' and 3' untranslated regions of chosen candidate genes. Targeted sequences were taken from bighorn sheep (Ovis canadensis) exon capture data and directly from the domestic sheep genome (Ovis aries v. 3; oviAri3). The bighorn sheep sequences used in the Dall's sheep (Ovis dalli dalli) exon capture aligned to 2350 genes on the oviAri3 genome with an average of 2 exons each. We developed a microfluidic qPCR-based SNP chip to genotype 476 Dall's sheep from locations across their range and test for patterns of selection. Using multiple corroborating approaches (lositan and bayescan), we detected 28 SNP loci potentially under selection. We additionally identified candidate loci significantly associated with latitude, longitude, precipitation and temperature, suggesting local environmental adaptation. The three methods demonstrated consistent support for natural selection on nine genes with immune and disease-regulating functions (e.g. Ovar-DRA, APC, BATF2, MAGEB18), cell regulation signalling pathways (e.g. KRIT1, PI3K, ORRC3), and respiratory health (CYSLTR1). Characterizing adaptive allele distributions from novel genetic techniques will facilitate investigation of the influence of environmental variation on local adaptation of a northern alpine ungulate throughout its range. This research demonstrated the utility of exon capture for gene-targeted SNP discovery and subsequent SNP chip genotyping using low-quality samples in a nonmodel species.

  10. Development and Validation of a High-Density SNP Genotyping Array for African Oil Palm.

    PubMed

    Kwong, Qi Bin; Teh, Chee Keng; Ong, Ai Ling; Heng, Huey Ying; Lee, Heng Leng; Mohamed, Mohaimi; Low, Joel Zi-Bin; Apparow, Sukganah; Chew, Fook Tim; Mayes, Sean; Kulaveerasingam, Harikrishna; Tammi, Martti; Appleton, David Ross

    2016-08-01

    High-density single nucleotide polymorphism (SNP) genotyping arrays are powerful tools that can measure the level of genetic polymorphism within a population. To develop a whole-genome SNP array for oil palms, SNP discovery was performed using deep resequencing of eight libraries derived from 132 Elaeis guineensis and Elaeis oleifera palms belonging to 59 origins, resulting in the discovery of >3 million putative SNPs. After SNP filtering, the Illumina OP200K custom array was built with 170 860 successful probes. Phenetic clustering analysis revealed that the array could distinguish between palms of different origins in a way consistent with pedigree records. Genome-wide linkage disequilibrium declined more slowly for the commercial populations (ranging from 120 kb at r(2) = 0.43 to 146 kb at r(2) = 0.50) when compared with the semi-wild populations (19.5 kb at r(2) = 0.22). Genetic fixation mapping comparing the semi-wild and commercial population identified 321 selective sweeps. A genome-wide association study (GWAS) detected a significant peak on chromosome 2 associated with the polygenic component of the shell thickness trait (based on the trait shell-to-fruit; S/F %) in tenera palms. Testing of a genomic selection model on the same trait resulted in good prediction accuracy (r = 0.65) with 42% of the S/F % variation explained. The first high-density SNP genotyping array for oil palm has been developed and shown to be robust for use in genetic studies and with potential for developing early trait prediction to shorten the oil palm breeding cycle. PMID:27112659

  11. The easy road to genome-wide medium density SNP screening in a non-model species: development and application of a 10 K SNP-chip for the house sparrow (Passer domesticus).

    PubMed

    Hagen, Ingerid J; Billing, Anna M; Rønning, Bernt; Pedersen, Sindre A; Pärn, Henrik; Slate, Jon; Jensen, Henrik

    2013-05-01

    With the advent of next generation sequencing, new avenues have opened to study genomics in wild populations of non-model species. Here, we describe a successful approach to a genome-wide medium density Single Nucleotide Polymorphism (SNP) panel in a non-model species, the house sparrow (Passer domesticus), through the development of a 10 K Illumina iSelect HD BeadChip. Genomic DNA and cDNA derived from six individuals were sequenced on a 454 GS FLX system and generated a total of 1.2 million sequences, in which SNPs were detected. As no reference genome exists for the house sparrow, we used the zebra finch (Taeniopygia guttata) reference genome to determine the most likely position of each SNP. The 10 000 SNPs on the SNP-chip were selected to be distributed evenly across 31 chromosomes, giving on average one SNP per 100 000 bp. The SNP-chip was screened across 1968 individual house sparrows from four island populations. Of the original 10 000 SNPs, 7413 were found to be variable, and 99% of these SNPs were successfully called in at least 93% of all individuals. We used the SNP-chip to demonstrate the ability of such genome-wide marker data to detect population sub-division, and compared these results to similar analyses using microsatellites. The SNP-chip will be used to map Quantitative Trait Loci (QTL) for fitness-related phenotypic traits in natural populations.

  12. Identification of differently expressed genes with specific SNP Loci for breast cancer by the integration of SNP and gene expression profiling analyses.

    PubMed

    Yuan, Pengfei; Liu, Dechun; Deng, Miao; Liu, Jiangbo; Wang, Jianguang; Zhang, Like; Liu, Qipeng; Zhang, Ting; Chen, Yanbin; Jin, Gaoyuan

    2015-04-01

    This study aims to explore the relationship between gene polymorphism and breast cancer, and to screen DEGs (differentially expressed genes) with SNPs (single nucleotide polymorphisms) related to breast cancer. The SNPs of 17 patients and the preprocessed SNP profiling GSE 32258 (38 cases of normal breast cells) were combined to identify their correlation with breast cancer using chi-square test. The gene expression profiling batch8_9 (38 cases of patients and 8 cases of normal tissue) was preprocessed with limma package, and the DEGs were filtered out. Then fisher's method was applied to integrate DEGs and SNPs associated with breast cancer. With NetBox software, TRED (Transcriptional Regulatory Element Database) and UCSC (University of California Santa Cruz) database, genes-associated network and transcriptional regulatory network were constructed using cytoscape software. Further, GO (Gene Ontology) and KEGG analyses were performed for genes in the networks by using siggenes. In total, 332 DEGs were identified. There were 160 breast cancer-related SNPs related to 106 genes of gene expression profiling (19 were significant DEGs). Finally, 11co-correlated DEGs were selected. In genes-associated network, 9 significant DEGs were correlated to 23 LINKER genes while, in transcriptional regulatory network, E2F1 had regulatory relationships with 7 DEGs including MTUS1, CD44, CCNB1 and CCND2. KRAS with SNP locus of rs1137282 was involved in 35 KEGG pathways. The genes of MTUS1, CD44, CCNB1, CCND2 and KRAS with specific SNP loci may be used as biomarkers for diagnosis of breast cancer. Besides, E2F1 was recognized as the transcription factor of 7 DEGs including MTUS1, CD44, CCNB1 and CCND2.

  13. Evaluation of probabilistic and logical inference for a SNP annotation system.

    PubMed

    Shen, Terry H; Tarczy-Hornoch, Peter; Detwiler, Landon T; Cadag, Eithon; Carlson, Christopher S

    2010-06-01

    Genome wide association studies (GWAS) are an important approach to understanding the genetic mechanisms behind human diseases. Single nucleotide polymorphisms (SNPs) are the predominant markers used in genome wide association studies, and the ability to predict which SNPs are likely to be functional is important for both a priori and a posteriori analyses of GWA studies. This article describes the design, implementation and evaluation of a family of systems for the purpose of identifying SNPs that may cause a change in phenotypic outcomes. The methods described in this article characterize the feasibility of combinations of logical and probabilistic inference with federated data integration for both point and regional SNP annotation and analysis. Evaluations of the methods demonstrate the overall strong predictive value of logical, and logical with probabilistic, inference applied to the domain of SNP annotation.

  14. Nanoparticle-based detection and quantification of DNA with single nucleotide polymorphism (SNP) discrimination selectivity

    PubMed Central

    Qin, Wei Jie; Yung, Lin Yue Lanry

    2007-01-01

    Sequence-specific DNA detection is important in various biomedical applications such as gene expression profiling, disease diagnosis and treatment, drug discovery and forensic analysis. Here we report a gold nanoparticle-based method that allows DNA detection and quantification and is capable of single nucleotide polymorphism (SNP) discrimination. The precise quantification of single-stranded DNA is due to the formation of defined nanoparticle-DNA conjugate groupings in the presence of target/linker DNA. Conjugate groupings were characterized and quantified by gel electrophoresis. A linear correlation between the amount of target DNA and conjugate groupings was found. For SNP detection, single base mismatch discrimination was achieved for both the end- and center-base mismatch. The method described here may be useful for the development of a simple and quantitative DNA detection assay. PMID:17720714

  15. Cultivar origin and admixture detection in Turkish olive oils by SNP-based CAPS assays.

    PubMed

    Uncu, Ali Tevfik; Frary, Anne; Doganlar, Sami

    2015-03-01

    The aim of this study was to establish a DNA-based identification key to ascertain the cultivar origin of Turkish monovarietal olive oils. To reach this aim, we sequenced short fragments from five olive genes for SNP (single nucleotide polymorphism) identification and developed CAPS (cleaved amplified polymorphic DNA) assays for SNPs that alter restriction enzyme recognition motifs. When applied on the oils of 17 olive cultivars, a maximum of five CAPS assays were necessary to discriminate the varietal origin of the samples. We also tested the efficiency and limit of our approach for detecting olive oil admixtures. As a result of the analysis, we were able to detect admixing down to a limit of 20%. The SNP-based CAPS assays developed in this work can be used for testing and verification of the authenticity of Turkish monovarietal olive oils, for olive tree certification, and in germplasm characterization and preservation studies.

  16. Functional analysis of deep intronic SNP rs13438494 in intron 24 of PCLO gene.

    PubMed

    Seo, Seunghee; Takayama, Kanako; Uno, Kyosuke; Ohi, Kazutaka; Hashimoto, Ryota; Nishizawa, Daisuke; Ikeda, Kazutaka; Ozaki, Norio; Nabeshima, Toshitaka; Miyamoto, Yoshiaki; Nitta, Atsumi

    2013-01-01

    The single nucleotide polymorphism (SNP) rs13438494 in intron 24 of PCLO was significantly associated with bipolar disorder in a meta-analysis of genome-wide association studies. In this study, we performed functional minigene analysis and bioinformatics prediction of splicing regulatory sequences to characterize the deep intronic SNP rs13438494. We constructed minigenes with A and C alleles containing exon 24, intron 24, and exon 25 of PCLO to assess the genetic effect of rs13438494 on splicing. We found that the C allele of rs13438494 reduces the splicing efficiency of the PCLO minigene. In addition, prediction analysis of enhancer/silencer motifs using the Human Splice Finder web tool indicated that rs13438494 induces the abrogation or creation of such binding sites. Our results indicate that rs13438494 alters splicing efficiency by creating or disrupting a splicing motif, which functions by binding of splicing regulatory proteins, and may ultimately result in bipolar disorder in affected people.

  17. SNP analysis using a molecular beacon-based operating cooperatively (OC) sensor.

    PubMed

    Cornett, Evan M; Kolpashchikov, Dmitry M

    2013-01-01

    Analysis of single-nucleotide polymorphisms (SNPs) is important for diagnosis of infectious and genetic diseases, for environment and population studies, as well as in forensic applications. Herein is a detailed description to design an "operating cooperatively" (OC) sensor for highly specific SNP analysis. OC sensors use two unmodified DNA adaptor strands and a molecular beacon probe to detect a nucleic acid targets with exceptional specificity towards SNPs. Genotyping can be accomplished at room temperature in a homogenous assay. The approach is easily adaptable for any nucleic acid target, and has been successfully used for analysis of targets with complex secondary structures. Additionally, OC sensors are an easy-to-design and cost-effective method for SNP analysis and nucleic acid detection.

  18. Genome-wide SNP association-based localization of a dwarfism gene in Friesian dwarf horses.

    PubMed

    Orr, N; Back, W; Gu, J; Leegwater, P; Govindarajan, P; Conroy, J; Ducro, B; Van Arendonk, J A M; MacHugh, D E; Ennis, S; Hill, E W; Brama, P A J

    2010-12-01

    The recent completion of the horse genome and commercial availability of an equine SNP genotyping array has facilitated the mapping of disease genes. We report putative localization of the gene responsible for dwarfism, a trait in Friesian horses that is thought to have a recessive mode of inheritance, to a 2-MB region of chromosome 14 using just 10 affected animals and 10 controls. We successfully genotyped 34,429 SNPs that were tested for association with dwarfism using chi-square tests. The most significant SNP in our study, BIEC2-239376 (P(2df)=4.54 × 10(-5), P(rec)=7.74 × 10(-6)), is located close to a gene implicated in human dwarfism. Fine-mapping and resequencing analyses did not aid in further localization of the causative variant, and replication of our findings in independent sample sets will be necessary to confirm these results.

  19. Full-dimensional quantum calculations of the dissociation energy, zero-point, and 10 K properties of H7+/D7+ clusters using an ab initio potential energy surface

    NASA Astrophysics Data System (ADS)

    Barragán, Patricia; Pérez de Tudela, Ricardo; Qu, Chen; Prosmiti, Rita; Bowman, Joel M.

    2013-07-01

    Diffusion Monte Carlo (DMC) and path-integral Monte Carlo computations of the vibrational ground state and 10 K equilibrium state properties of the H_7^+/D_7^+ cations are presented, using an ab initio full-dimensional potential energy surface. The DMC zero-point energies of dissociated fragments H_5^+(D_5^+)+H2(D2) are also calculated and from these results and the electronic dissociation energy, dissociation energies, D0, of 752 ± 15 and 980 ± 14 cm-1 are reported for H_7^+ and D_7^+, respectively. Due to the known error in the electronic dissociation energy of the potential surface, these quantities are underestimated by roughly 65 cm-1. These values are rigorously determined for first time, and compared with previous theoretical estimates from electronic structure calculations using standard harmonic analysis, and available experimental measurements. Probability density distributions are also computed for the ground vibrational and 10 K state of H_7^+ and D_7^+. These are qualitatively described as a central H_3^+/D_3^+ core surrounded by "solvent" H2/D2 molecules that nearly freely rotate.

  20. KEY COMPARISON: Final report on bilateral comparison of 10 kΩ standards (ongoing BIPM key comparison BIPM.EM-K13.b) between the NIMT-Thailand and the BIPM

    NASA Astrophysics Data System (ADS)

    Goebel, R.; Kurupakorn, C.; Fletcher, N.; Stock, M.

    2010-01-01

    This report describes the results obtained from a NIMT (Thailand)-BIPM bilateral comparison of 10 kΩ resistance standards in 2009. The comparison was carried out in the framework of the BIPM ongoing key comparison BIPM.EM-K13.b. Two BIPM 10 kΩ travelling standards of SR104 type were calibrated first at the BIPM, then at the NMIT and again at the BIPM after their return. The stability of the transfer standards was such that the uncertainty associated with the transfer was smaller than the uncertainty arising from the calibrations. The mean difference between the NIMT and the BIPM calibrations was found to be significantly larger than the expanded uncertainty (k = 2) of the comparison. However, this exercise allowed previously undetected sources of errors to be detected in the NIMT facility. A new bilateral comparison can be organized as soon as these problems are fixed. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCEM, according to the provisions of the CIPM Mutual Recognition Arrangement (MRA).

  1. Haplotype inference from unphased SNP data in heterozygous polyploids based on SAT

    PubMed Central

    Neigenfind, Jost; Gyetvai, Gabor; Basekow, Rico; Diehl, Svenja; Achenbach, Ute; Gebhardt, Christiane; Selbig, Joachim; Kersten, Birgit

    2008-01-01

    Background Haplotype inference based on unphased SNP markers is an important task in population genetics. Although there are different approaches to the inference of haplotypes in diploid species, the existing software is not suitable for inferring haplotypes from unphased SNP data in polyploid species, such as the cultivated potato (Solanum tuberosum). Potato species are tetraploid and highly heterozygous. Results Here we present the software SATlotyper which is able to handle polyploid and polyallelic data. SATlo-typer uses the Boolean satisfiability problem to formulate Haplotype Inference by Pure Parsimony. The software excludes existing haplotype inferences, thus allowing for calculation of alternative inferences. As it is not known which of the multiple haplotype inferences are best supported by the given unphased data set, we use a bootstrapping procedure that allows for scoring of alternative inferences. Finally, by means of the bootstrapping scores, it is possible to optimise the phased genotypes belonging to a given haplotype inference. The program is evaluated with simulated and experimental SNP data generated for heterozygous tetraploid populations of potato. We show that, instead of taking the first haplotype inference reported by the program, we can significantly improve the quality of the final result by applying additional methods that include scoring of the alternative haplotype inferences and genotype optimisation. For a sub-population of nineteen individuals, the predicted results computed by SATlotyper were directly compared with results obtained by experimental haplotype inference via sequencing of cloned amplicons. Prediction and experiment gave similar results regarding the inferred haplotypes and phased genotypes. Conclusion Our results suggest that Haplotype Inference by Pure Parsimony can be solved efficiently by the SAT approach, even for data sets of unphased SNP from heterozygous polyploids. SATlotyper is freeware and is distributed as

  2. MAFsnp: A Multi-Sample Accurate and Flexible SNP Caller Using Next-Generation Sequencing Data.

    PubMed

    Hu, Jiyuan; Li, Tengfei; Xiu, Zidi; Zhang, Hong

    2015-01-01

    Most existing statistical methods developed for calling single nucleotide polymorphisms (SNPs) using next-generation sequencing (NGS) data are based on Bayesian frameworks, and there does not exist any SNP caller that produces p-values for calling SNPs in a frequentist framework. To fill in this gap, we develop a new method MAFsnp, a Multiple-sample based Accurate and Flexible algorithm for calling SNPs with NGS data. MAFsnp is based on an estimated likelihood ratio test (eLRT) statistic. In practical situation, the involved parameter is very close to the boundary of the parametric space, so the standard large sample property is not suitable to evaluate the finite-sample distribution of the eLRT statistic. Observing that the distribution of the test statistic is a mixture of zero and a continuous part, we propose to model the test statistic with a novel two-parameter mixture distribution. Once the parameters in the mixture distribution are estimated, p-values can be easily calculated for detecting SNPs, and the multiple-testing corrected p-values can be used to control false discovery rate (FDR) at any pre-specified level. With simulated data, MAFsnp is shown to have much better control of FDR than the existing SNP callers. Through the application to two real datasets, MAFsnp is also shown to outperform the existing SNP callers in terms of calling accuracy. An R package "MAFsnp" implementing the new SNP caller is freely available at http://homepage.fudan.edu.cn/zhangh/softwares/. PMID:26309201

  3. SNP discovery using Next Generation Transcriptomic Sequencing in Atlantic herring (Clupea harengus).

    PubMed

    Helyar, Sarah J; Limborg, Morten T; Bekkevold, Dorte; Babbucci, Massimiliano; van Houdt, Jeroen; Maes, Gregory E; Bargelloni, Luca; Nielsen, Rasmus O; Taylor, Martin I; Ogden, Rob; Cariani, Alessia; Carvalho, Gary R; Panitz, Frank

    2012-01-01

    The introduction of Next Generation Sequencing (NGS) has revolutionised population genetics, providing studies of non-model species with unprecedented genomic coverage, allowing evolutionary biologists to address questions previously far beyond the reach of available resources. Furthermore, the simple mutation model of Single Nucleotide Polymorphisms (SNPs) permits cost-effective high-throughput genotyping in thousands of individuals simultaneously. Genomic resources are scarce for the Atlantic herring (Clupea harengus), a small pelagic species that sustains high revenue fisheries. This paper details the development of 578 SNPs using a combined NGS and high-throughput genotyping approach. Eight individuals covering the species distribution in the eastern Atlantic were bar-coded and multiplexed into a single cDNA library and sequenced using the 454 GS FLX platform. SNP discovery was performed by de novo sequence clustering and contig assembly, followed by the mapping of reads against consensus contig sequences. Selection of candidate SNPs for genotyping was conducted using an in silico approach. SNP validation and genotyping were performed simultaneously using an Illumina 1,536 GoldenGate assay. Although the conversion rate of candidate SNPs in the genotyping assay cannot be predicted in advance, this approach has the potential to maximise cost and time efficiencies by avoiding expensive and time-consuming laboratory stages of SNP validation. Additionally, the in silico approach leads to lower ascertainment bias in the resulting SNP panel as marker selection is based only on the ability to design primers and the predicted presence of intron-exon boundaries. Consequently SNPs with a wider spectrum of minor allele frequencies (MAFs) will be genotyped in the final panel. The genomic resources presented here represent a valuable multi-purpose resource for developing informative marker panels for population discrimination, microarray development and for population

  4. SNP Discovery Using Next Generation Transcriptomic Sequencing in Atlantic Herring (Clupea harengus)

    PubMed Central

    Bekkevold, Dorte; Babbucci, Massimiliano; van Houdt, Jeroen; Maes, Gregory E.; Bargelloni, Luca; Nielsen, Rasmus O.; Taylor, Martin I.; Ogden, Rob; Cariani, Alessia; Carvalho, Gary R.; Consortium, FishPopTrace; Panitz, Frank

    2012-01-01

    The introduction of Next Generation Sequencing (NGS) has revolutionised population genetics, providing studies of non-model species with unprecedented genomic coverage, allowing evolutionary biologists to address questions previously far beyond the reach of available resources. Furthermore, the simple mutation model of Single Nucleotide Polymorphisms (SNPs) permits cost-effective high-throughput genotyping in thousands of individuals simultaneously. Genomic resources are scarce for the Atlantic herring (Clupea harengus), a small pelagic species that sustains high revenue fisheries. This paper details the development of 578 SNPs using a combined NGS and high-throughput genotyping approach. Eight individuals covering the species distribution in the eastern Atlantic were bar-coded and multiplexed into a single cDNA library and sequenced using the 454 GS FLX platform. SNP discovery was performed by de novo sequence clustering and contig assembly, followed by the mapping of reads against consensus contig sequences. Selection of candidate SNPs for genotyping was conducted using an in silico approach. SNP validation and genotyping were performed simultaneously using an Illumina 1,536 GoldenGate assay. Although the conversion rate of candidate SNPs in the genotyping assay cannot be predicted in advance, this approach has the potential to maximise cost and time efficiencies by avoiding expensive and time-consuming laboratory stages of SNP validation. Additionally, the in silico approach leads to lower ascertainment bias in the resulting SNP panel as marker selection is based only on the ability to design primers and the predicted presence of intron-exon boundaries. Consequently SNPs with a wider spectrum of minor allele frequencies (MAFs) will be genotyped in the final panel. The genomic resources presented here represent a valuable multi-purpose resource for developing informative marker panels for population discrimination, microarray development and for population

  5. Haplotype Block Partitioning and Tag SNP Selection Using Genotype Data and Their Applications to Association Studies

    PubMed Central

    Zhang, Kui; Qin, Zhaohui S.; Liu, Jun S.; Chen, Ting; Waterman, Michael S.; Sun, Fengzhu

    2004-01-01

    Recent studies have revealed that linkage disequilibrium (LD) patterns vary across the human genome with some regions of high LD interspersed by regions of low LD. A small fraction of SNPs (tag SNPs) is sufficient to capture most of the haplotype structure of the human genome. In this paper, we develop a method to partition haplotypes into blocks and to identify tag SNPs based on genotype data by combining a dynamic programming algorithm for haplotype block partitioning and tag SNP selection based on haplotype data with a variation of the expectation maximization (EM) algorithm for haplotype inference. We assess the effects of using either haplotype or genotype data in haplotype block identification and tag SNP selection as a function of several factors, including sample size, density or number of SNPs studied, allele frequencies, fraction of missing data, and genotyping error rate, using extensive simulations. We find that a modest number of haplotype or genotype samples will result in consistent block partitions and tag SNP selection. The power of association studies based on tag SNPs using genotype data is similar to that using haplotype data. PMID:15078859

  6. Rapid Detection of Rare Deleterious Variants by Next Generation Sequencing with Optional Microarray SNP Genotype Data

    PubMed Central

    Watson, Christopher M.; Crinnion, Laura A.; Gurgel‐Gianetti, Juliana; Harrison, Sally M.; Daly, Catherine; Antanavicuite, Agne; Lascelles, Carolina; Markham, Alexander F.; Pena, Sergio D. J.; Bonthron, David T.

    2015-01-01

    ABSTRACT Autozygosity mapping is a powerful technique for the identification of rare, autosomal recessive, disease‐causing genes. The ease with which this category of disease gene can be identified has greatly increased through the availability of genome‐wide SNP genotyping microarrays and subsequently of exome sequencing. Although these methods have simplified the generation of experimental data, its analysis, particularly when disparate data types must be integrated, remains time consuming. Moreover, the huge volume of sequence variant data generated from next generation sequencing experiments opens up the possibility of using these data instead of microarray genotype data to identify disease loci. To allow these two types of data to be used in an integrated fashion, we have developed AgileVCFMapper, a program that performs both the mapping of disease loci by SNP genotyping and the analysis of potentially deleterious variants using exome sequence variant data, in a single step. This method does not require microarray SNP genotype data, although analysis with a combination of microarray and exome genotype data enables more precise delineation of disease loci, due to superior marker density and distribution. PMID:26037133

  7. SNP typing reveals similarity in Mycobacterium tuberculosis genetic diversity between Portugal and Northeast Brazil.

    PubMed

    Lopes, Joao S; Marques, Isabel; Soares, Patricia; Nebenzahl-Guimaraes, Hanna; Costa, Joao; Miranda, Anabela; Duarte, Raquel; Alves, Adriana; Macedo, Rita; Duarte, Tonya A; Barbosa, Theolis; Oliveira, Martha; Nery, Joilda S; Boechat, Neio; Pereira, Susan M; Barreto, Mauricio L; Pereira-Leal, Jose; Gomes, Maria Gabriela Miranda; Penha-Goncalves, Carlos

    2013-08-01

    Human tuberculosis is an infectious disease caused by bacteria from the Mycobacterium tuberculosis complex (MTBC). Although spoligotyping and MIRU-VNTR are standard methodologies in MTBC genetic epidemiology, recent studies suggest that Single Nucleotide Polymorphisms (SNP) are advantageous in phylogenetics and strain group/lineages identification. In this work we use a set of 79 SNPs to characterize 1987 MTBC isolates from Portugal and 141 from Northeast Brazil. All Brazilian samples were further characterized using spolygotyping. Phylogenetic analysis against a reference set revealed that about 95% of the isolates in both populations are singly attributed to bacterial lineage 4. Within this lineage, the most frequent strain groups in both Portugal and Brazil are LAM, followed by Haarlem and X. Contrary to these groups, strain group T showed a very different prevalence between Portugal (10%) and Brazil (1.5%). Spoligotype identification shows about 10% of mis-matches compared to the use of SNPs and a little more than 1% of strains unidentifiability. The mis-matches are observed in the most represented groups of our sample set (i.e., LAM and Haarlem) in almost the same proportion. Besides being more accurate in identifying strain groups/lineages, SNP-typing can also provide phylogenetic relationships between strain groups/lineages and, thus, indicate cases showing phylogenetic incongruence. Overall, the use of SNP-typing revealed striking similarities between MTBC populations from Portugal and Brazil.

  8. SNP genotyping in melons: genetic variation, population structure, and linkage disequilibrium.

    PubMed

    Esteras, Cristina; Formisano, Gelsomina; Roig, Cristina; Díaz, Aurora; Blanca, José; Garcia-Mas, Jordi; Gómez-Guillamón, María Luisa; López-Sesé, Ana Isabel; Lázaro, Almudena; Monforte, Antonio J; Picó, Belén

    2013-05-01

    Novel sequencing technologies were recently used to generate sequences from multiple melon (Cucumis melo L.) genotypes, enabling the in silico identification of large single nucleotide polymorphism (SNP) collections. In order to optimize the use of these markers, SNP validation and large-scale genotyping are necessary. In this paper, we present the first validated design for a genotyping array with 768 SNPs that are evenly distributed throughout the melon genome. This customized Illumina GoldenGate assay was used to genotype a collection of 74 accessions, representing most of the botanical groups of the species. Of the assayed loci, 91 % were successfully genotyped. The array provided a large number of polymorphic SNPs within and across accessions. This set of SNPs detected high levels of variation in accessions from this crop's center of origin as well as from several other areas of melon diversification. Allele distribution throughout the genome revealed regions that distinguished between the two main groups of cultivated accessions (inodorus and cantalupensis). Population structure analysis showed a subdivision into five subpopulations, reflecting the history of the crop. A considerably low level of LD was detected, which decayed rapidly within a few kilobases. Our results show that the GoldenGate assay can be used successfully for high-throughput SNP genotyping in melon. Since many of the genotyped accessions are currently being used as the parents of breeding populations in various programs, this set of mapped markers could be used for future mapping and breeding efforts.

  9. SNP Marker Discovery in Pima Cotton (Gossypium barbadense L.) Leaf Transcriptomes

    PubMed Central

    Kottapalli, Pratibha; Ulloa, Mauricio; Kottapalli, Kameswara Rao; Payton, Paxton; Burke, John

    2016-01-01

    The objective of this study was to explore the known narrow genetic diversity and discover single-nucleotide polymorphic (SNP) markers for marker-assisted breeding within Pima cotton (Gossypium barbadense L.) leaf transcriptomes. cDNA from 25-day plants of three diverse cotton genotypes [Pima S6 (PS6), Pima S7 (PS7), and Pima 3-79 (P3-79)] was sequenced on Illumina sequencing platform. A total of 28.9 million reads (average read length of 138 bp) were generated by sequencing cDNA libraries of these three genotypes. The de novo assembly of reads generated transcriptome sets of 26,369 contigs for PS6, 25,870 contigs for PS7, and 24,796 contigs for P3-79. A Pima leaf reference transcriptome was generated consisting of 42,695 contigs. More than 10,000 single-nucleotide polymorphisms (SNPs) were identified between the genotypes, with 100% SNP frequency and a minimum of eight sequencing reads. The most prevalent SNP substitutions were C—T and A—G in these cotton genotypes. The putative SNPs identified can be utilized for characterizing genetic diversity, genotyping, and eventually in Pima cotton breeding through marker-assisted selection. PMID:27721653

  10. Making a chocolate chip: development and evaluation of a 6K SNP array for Theobroma cacao.

    PubMed

    Livingstone, Donald; Royaert, Stefan; Stack, Conrad; Mockaitis, Keithanne; May, Greg; Farmer, Andrew; Saski, Christopher; Schnell, Ray; Kuhn, David; Motamayor, Juan Carlos

    2015-08-01

    Theobroma cacao, the key ingredient in chocolate production, is one of the world's most important tree fruit crops, with ∼4,000,000 metric tons produced across 50 countries. To move towards gene discovery and marker-assisted breeding in cacao, a single-nucleotide polymorphism (SNP) identification project was undertaken using RNAseq data from 16 diverse cacao cultivars. RNA sequences were aligned to the assembled transcriptome of the cultivar Matina 1-6, and 330,000 SNPs within coding regions were identified. From these SNPs, a subset of 6,000 high-quality SNPs were selected for inclusion on an Illumina Infinium SNP array: the Cacao6kSNP array. Using Cacao6KSNP array data from over 1,000 cacao samples, we demonstrate that our custom array produces a saturated genetic map and can be used to distinguish among even closely related genotypes. Our study enhances and expands the genetic resources available to the cacao research community, and provides the genome-scale set of tools that are critical for advancing breeding with molecular markers in an agricultural species with high genetic diversity.

  11. High-throughput SNP-genotyping analysis of the relationships among Ponto-Caspian sturgeon species

    PubMed Central

    Rastorguev, Sergey M; Nedoluzhko, Artem V; Mazur, Alexander M; Gruzdeva, Natalia M; Volkov, Alexander A; Barmintseva, Anna E; Mugue, Nikolai S; Prokhortchouk, Egor B

    2013-01-01

    Abstract Legally certified sturgeon fisheries require population protection and conservation methods, including DNA tests to identify the source of valuable sturgeon roe. However, the available genetic data are insufficient to distinguish between different sturgeon populations, and are even unable to distinguish between some species. We performed high-throughput single-nucleotide polymorphism (SNP)-genotyping analysis on different populations of Russian (Acipenser gueldenstaedtii), Persian (A. persicus), and Siberian (A. baerii) sturgeon species from the Caspian Sea region (Volga and Ural Rivers), the Azov Sea, and two Siberian rivers. We found that Russian sturgeons from the Volga and Ural Rivers were essentially indistinguishable, but they differed from Russian sturgeons in the Azov Sea, and from Persian and Siberian sturgeons. We identified eight SNPs that were sufficient to distinguish these sturgeon populations with 80% confidence, and allowed the development of markers to distinguish sturgeon species. Finally, on the basis of our SNP data, we propose that the A. baerii-like mitochondrial DNA found in some Russian sturgeons from the Caspian Sea arose via an introgression event during the Pleistocene glaciation. In the present study, the high-throughput genotyping analysis of several sturgeon populations was performed. SNP markers for species identification were defined. The possible explanation of the baerii-like mitotype presence in some Russian sturgeons in the Caspian Sea was suggested. PMID:24567827

  12. A whole-genome SNP array (RICE6K) for genomic breeding in rice.

    PubMed

    Yu, Huihui; Xie, Weibo; Li, Jing; Zhou, Fasong; Zhang, Qifa

    2014-01-01

    The advances in genotyping technology provide an opportunity to use genomic tools in crop breeding. As compared to field selections performed in conventional breeding programmes, genomics-based genotype screen can potentially reduce number of breeding cycles and more precisely integrate target genes for particular traits into an ideal genetic background. We developed a whole-genome single nucleotide polymorphism (SNP) array, RICE6K, based on Infinium technology, using representative SNPs selected from more than four million SNPs identified from resequencing data of more than 500 rice landraces. RICE6K contains 5102 SNP and insertion-deletion (InDel) markers, about 4500 of which were of high quality in the tested rice lines producing highly repeatable results. Forty-five functional markers that are located inside 28 characterized genes of important traits can be detected using RICE6K. The SNP markers are evenly distributed on the 12 chromosomes of rice with the average density of 12 SNPs per 1 Mb and can provide information for polymorphisms between indica and japonica subspecies as well as varieties within indica and japonica groups. Application tests of RICE6K showed that the array is suitable for rice germplasm fingerprinting, genotyping bulked segregating pools, seed authenticity check and genetic background selection. These results suggest that RICE6K provides an efficient and reliable genotyping tool for rice genomic breeding.

  13. Pyrosequencing protocol using a universal biotinylated primer for mutation detection and SNP genotyping.

    PubMed

    Royo, Jose Luis; Hidalgo, Manuel; Ruiz, Agustin

    2007-01-01

    DNA sequencing has markedly changed the nature of biomedical research, identifying millions of polymorphisms along the human genome that now require further analysis to study the genetic basis of human diseases. Among the DNA-sequencing platforms available, Pyrosequencing has become a useful tool for medium-throughput single nucleotide polymorphism (SNP) genotyping, mutation detection, copy-number studies and DNA methylation analysis. Its 96-well genotyping format allows reliable results to be obtained at reasonable costs in a few minutes. However, a specific biotinylated primer is usually required for each SNP under study to allow the capture of single-stranded DNA template for the Pyrosequencing assay. Here, we present an alternative to the standard labeling of PCR products for analysis by Pyrosequencing that circumvents the requirement of specific biotinylated primers for each SNP of interest. This protocol uses a single biotinylated primer that is simultaneously incorporated into all M13-tagged PCR products during the amplification reaction. The protocol covers all steps from the PCR amplification and capture of single-stranded template, its preparation, and the Pyrosequencing assay itself. Once the correct primer stoichiometry has been determined, the assay takes around 2 h for PCR amplification, followed by 15-20 min (per plate) to obtain the genotypes.

  14. Making a chocolate chip: development and evaluation of a 6K SNP array for Theobroma cacao

    PubMed Central

    Livingstone, Donald; Royaert, Stefan; Stack, Conrad; Mockaitis, Keithanne; May, Greg; Farmer, Andrew; Saski, Christopher; Schnell, Ray; Kuhn, David; Motamayor, Juan Carlos

    2015-01-01

    Theobroma cacao, the key ingredient in chocolate production, is one of the world's most important tree fruit crops, with ∼4,000,000 metric tons produced across 50 countries. To move towards gene discovery and marker-assisted breeding in cacao, a single-nucleotide polymorphism (SNP) identification project was undertaken using RNAseq data from 16 diverse cacao cultivars. RNA sequences were aligned to the assembled transcriptome of the cultivar Matina 1-6, and 330,000 SNPs within coding regions were identified. From these SNPs, a subset of 6,000 high-quality SNPs were selected for inclusion on an Illumina Infinium SNP array: the Cacao6kSNP array. Using Cacao6KSNP array data from over 1,000 cacao samples, we demonstrate that our custom array produces a saturated genetic map and can be used to distinguish among even closely related genotypes. Our study enhances and expands the genetic resources available to the cacao research community, and provides the genome-scale set of tools that are critical for advancing breeding with molecular markers in an agricultural species with high genetic diversity. PMID:26070980

  15. PEAS V1.0: a package for elementary analysis of SNP data.

    PubMed

    Xu, Shuhua; Gupta, Sanchit; Jin, Li

    2010-11-01

    We have developed a software package named PEAS to facilitate analyses of large data sets of single nucleotide polymorphisms (SNPs) for population genetics and molecular phylogenetics studies. PEAS reads SNP data in various formats as input and is versatile in data formatting; using PEAS, it is easy to create input files for many popular packages, such as STRUCTURE, frappe, Arlequin, Haploview, LDhat, PLINK, EIGENSOFT, PHASE, fastPHASE, MEGA and PHYLIP. In addition, PEAS fills up several analysis gaps in currently available computer programs in population genetics and molecular phylogenetics. Notably, (i) It calculates genetic distance matrices with bootstrapping for both individuals and populations from genome-wide high-density SNP data, and the output can be streamlined to MEGA and PHYLIP programs for further processing; (ii) It calculates genetic distances from STRUCTURE output and generates MEGA file to reconstruct component trees; (iii) It provides tools to conduct haplotype sharing analysis for phylogenetic studies based on high-density SNP data. To our knowledge, these analyses are not available in any other computer program. PEAS for Windows is freely available for academic users from http://www.picb.ac.cn/~xushua/index.files/Download_PEAS.htm. PMID:21565121

  16. Identification and SNP association analysis of a novel gene in chicken.

    PubMed

    Mei, Xingxing; Kang, Xiangtao; Liu, Xiaojun; Jia, Lijuan; Li, Hong; Li, Zhuanjian; Jiang, Ruirui

    2016-02-01

    A novel gene that was predicted to encode a long noncoding RNA (lncRNA) transcript was identified in a previous study that aimed to detect candidate genes related to growth rate differences between Chinese local breed Gushi chickens and Anka broilers. To characterise the biological function of the lncRNA, we cloned and sequenced the complete open reading frame of the gene. We performed quantitative real-time polymerase chain reaction (qPCR) to analyse the expression patterns of the lncRNA in different tissues of chicken at different development stages. The qPCR data showed that the novel lncRNA gene was expressed extensively, with the highest abundance in spleen and lung and the lowest abundance in pectoralis and leg muscle. Additionally, we identified a single nucleotide polymorphism (SNP) at the 5'-end of the gene and studied the association between the SNP and chicken growth traits using data from an F2 resource population of Gushi chickens and Anka broilers. The association analysis showed that the SNP was significantly (P < 0.05) associated with leg muscle weight, chest breadth, sternal length and body weight in chickens at 1 day, 4 weeks and 6 weeks of age. We concluded that the novel lncRNA gene, which we designated pouBW1, may play an important role in regulating chicken growth.

  17. SNP Discovery and Development of a High-Density Genotyping Array for Sunflower

    PubMed Central

    Bachlava, Eleni; Taylor, Christopher A.; Tang, Shunxue; Bowers, John E.; Mandel, Jennifer R.; Burke, John M.; Knapp, Steven J.

    2012-01-01

    Recent advances in next-generation DNA sequencing technologies have made possible the development of high-throughput SNP genotyping platforms that allow for the simultaneous interrogation of thousands of single-nucleotide polymorphisms (SNPs). Such resources have the potential to facilitate the rapid development of high-density genetic maps, and to enable genome-wide association studies as well as molecular breeding approaches in a variety of taxa. Herein, we describe the development of a SNP genotyping resource for use in sunflower (Helianthus annuus L.). This work involved the development of a reference transcriptome assembly for sunflower, the discovery of thousands of high quality SNPs based on the generation and analysis of ca. 6 Gb of transcriptome re-sequencing data derived from multiple genotypes, the selection of 10,640 SNPs for inclusion in the genotyping array, and the use of the resulting array to screen a diverse panel of sunflower accessions as well as related wild species. The results of this work revealed a high frequency of polymorphic SNPs and relatively high level of cross-species transferability. Indeed, greater than 95% of successful SNP assays revealed polymorphism, and more than 90% of these assays could be successfully transferred to related wild species. Analysis of the polymorphism data revealed patterns of genetic differentiation that were largely congruent with the evolutionary history of sunflower, though the large number of markers allowed for finer resolution than has previously been possible. PMID:22238659

  18. PredictSNP: robust and accurate consensus classifier for prediction of disease-related mutations.

    PubMed

    Bendl, Jaroslav; Stourac, Jan; Salanda, Ondrej; Pavelka, Antonin; Wieben, Eric D; Zendulka, Jaroslav; Brezovsky, Jan; Damborsky, Jiri

    2014-01-01

    Single nucleotide variants represent a prevalent form of genetic variation. Mutations in the coding regions are frequently associated with the development of various genetic diseases. Computational tools for the prediction of the effects of mutations on protein function are very important for analysis of single nucleotide variants and their prioritization for experimental characterization. Many computational tools are already widely employed for this purpose. Unfortunately, their comparison and further improvement is hindered by large overlaps between the training datasets and benchmark datasets, which lead to biased and overly optimistic reported performances. In this study, we have constructed three independent datasets by removing all duplicities, inconsistencies and mutations previously used in the training of evaluated tools. The benchmark dataset containing over 43,000 mutations was employed for the unbiased evaluation of eight established prediction tools: MAPP, nsSNPAnalyzer, PANTHER, PhD-SNP, PolyPhen-1, PolyPhen-2, SIFT and SNAP. The six best performing tools were combined into a consensus classifier PredictSNP, resulting into significantly improved prediction performance, and at the same time returned results for all mutations, confirming that consensus prediction represents an accurate and robust alternative to the predictions delivered by individual tools. A user-friendly web interface enables easy access to all eight prediction tools, the consensus classifier PredictSNP and annotations from the Protein Mutant Database and the UniProt database. The web server and the datasets are freely available to the academic community at http://loschmidt.chemi.muni.cz/predictsnp.

  19. Evaluation of Y chromosomal SNP haplogrouping in the HID-Ion AmpliSeq™ Identity Panel.

    PubMed

    Ochiai, Eriko; Minaguchi, Kiyoshi; Nambiar, Phrabhakaran; Kakimoto, Yu; Satoh, Fumiko; Nakatome, Masato; Miyashita, Keiko; Osawa, Motoki

    2016-09-01

    The Y chromosomal haplogroup determined from single nucleotide polymorphism (SNP) combinations is a valuable genetic marker to study ancestral male lineage and ethical distribution. Next-generation sequencing has been developed for widely diverse genetics fields. For this study, we demonstrate 34 Y-SNP typing employing the Ion PGM™ system to perform haplogrouping. DNA libraries were constructed using the HID-Ion AmpliSeq™ Identity Panel. Emulsion PCR was performed, then DNA sequences were analyzed on the Ion 314 and 316 Chip Kit v2. Some difficulties became apparent during the analytic processes. No-call was reported at rs2032599 and M479 in six samples, in which the least coverage was observed at M479. A minor misreading occurred at rs2032631 and M479. A real time PCR experiment using other pairs of oligonucleotide primers showed that these events might result from the flanking sequence. Finally, Y haplogroup was determined completely for 81 unrelated males including Japanese (n=59) and Malay (n=22) subjects. The allelic divergence differed between the two populations. In comparison with the conventional Sanger method, next-generation sequencing provides a comprehensive SNP analysis with convenient procedures, but further system improvement is necessary. PMID:27591541

  20. Making a chocolate chip: development and evaluation of a 6K SNP array for Theobroma cacao.

    PubMed

    Livingstone, Donald; Royaert, Stefan; Stack, Conrad; Mockaitis, Keithanne; May, Greg; Farmer, Andrew; Saski, Christopher; Schnell, Ray; Kuhn, David; Motamayor, Juan Carlos

    2015-08-01

    Theobroma cacao, the key ingredient in chocolate production, is one of the world's most important tree fruit crops, with ∼4,000,000 metric tons produced across 50 countries. To move towards gene discovery and marker-assisted breeding in cacao, a single-nucleotide polymorphism (SNP) identification project was undertaken using RNAseq data from 16 diverse cacao cultivars. RNA sequences were aligned to the assembled transcriptome of the cultivar Matina 1-6, and 330,000 SNPs within coding regions were identified. From these SNPs, a subset of 6,000 high-quality SNPs were selected for inclusion on an Illumina Infinium SNP array: the Cacao6kSNP array. Using Cacao6KSNP array data from over 1,000 cacao samples, we demonstrate that our custom array produces a saturated genetic map and can be used to distinguish among even closely related genotypes. Our study enhances and expands the genetic resources available to the cacao research community, and provides the genome-scale set of tools that are critical for advancing breeding with molecular markers in an agricultural species with high genetic diversity. PMID:26070980

  1. How to Use SNP_TATA_Comparator to Find a Significant Change in Gene Expression Caused by the Regulatory SNP of This Gene's Promoter via a Change in Affinity of the TATA-Binding Protein for This Promoter

    PubMed Central

    Ponomarenko, Mikhail; Rasskazov, Dmitry; Arkova, Olga; Ponomarenko, Petr; Suslov, Valentin; Savinkova, Ludmila; Kolchanov, Nikolay

    2015-01-01

    The use of biomedical SNP markers of diseases can improve effectiveness of treatment. Genotyping of patients with subsequent searching for SNPs more frequent than in norm is the only commonly accepted method for identification of SNP markers within the framework of translational research. The bioinformatics applications aimed at millions of unannotated SNPs of the “1000 Genomes” can make this search for SNP markers more focused and less expensive. We used our Web service involving Fisher's Z-score for candidate SNP markers to find a significant change in a gene's expression. Here we analyzed the change caused by SNPs in the gene's promoter via a change in affinity of the TATA-binding protein for this promoter. We provide examples and discuss how to use this bioinformatics application in the course of practical analysis of unannotated SNPs from the “1000 Genomes” project. Using known biomedical SNP markers, we identified 17 novel candidate SNP markers nearby: rs549858786 (rheumatoid arthritis); rs72661131 (cardiovascular events in rheumatoid arthritis); rs562962093 (stroke); rs563558831 (cyclophosphamide bioactivation); rs55878706 (malaria resistance, leukopenia), rs572527200 (asthma, systemic sclerosis, and psoriasis), rs371045754 (hemophilia B), rs587745372 (cardiovascular events); rs372329931, rs200209906, rs367732974, and rs549591993 (all four: cancer); rs17231520 and rs569033466 (both: atherosclerosis); rs63750953, rs281864525, and rs34166473 (all three: malaria resistance, thalassemia). PMID:26516624

  2. Efficient SNP Discovery by Combining Microarray and Lab-on-a-Chip Data for Animal Breeding and Selection

    PubMed Central

    Huang, Chao-Wei; Lin, Yu-Tsung; Ding, Shih-Torng; Lo, Ling-Ling; Wang, Pei-Hwa; Lin, En-Chung; Liu, Fang-Wei; Lu, Yen-Wen

    2015-01-01

    The genetic markers associated with economic traits have been widely explored for animal breeding. Among these markers, single-nucleotide polymorphism (SNPs) are gradually becoming a prevalent and effective evaluation tool. Since SNPs only focus on the genetic sequences of interest, it thereby reduces the evaluation time and cost. Compared to traditional approaches, SNP genotyping techniques incorporate informative genetic background, improve the breeding prediction accuracy and acquiesce breeding quality on the farm. This article therefore reviews the typical procedures of animal breeding using SNPs and the current status of related techniques. The associated SNP information and genotyping techniques, including microarray and Lab-on-a-Chip based platforms, along with their potential are highlighted. Examples in pig and poultry with different SNP loci linked to high economic trait values are given. The recommendations for utilizing SNP genotyping in nimal breeding are summarized.

  3. Efficient SNP Discovery by Combining Microarray and Lab-on-a-Chip Data for Animal Breeding and Selection

    PubMed Central

    Huang, Chao-Wei; Lin, Yu-Tsung; Ding, Shih-Torng; Lo, Ling-Ling; Wang, Pei-Hwa; Lin, En-Chung; Liu, Fang-Wei; Lu, Yen-Wen

    2015-01-01

    The genetic markers associated with economic traits have been widely explored for animal breeding. Among these markers, single-nucleotide polymorphism (SNPs) are gradually becoming a prevalent and effective evaluation tool. Since SNPs only focus on the genetic sequences of interest, it thereby reduces the evaluation time and cost. Compared to traditional approaches, SNP genotyping techniques incorporate informative genetic background, improve the breeding prediction accuracy and acquiesce breeding quality on the farm. This article therefore reviews the typical procedures of animal breeding using SNPs and the current status of related techniques. The associated SNP information and genotyping techniques, including microarray and Lab-on-a-Chip based platforms, along with their potential are highlighted. Examples in pig and poultry with different SNP loci linked to high economic trait values are given. The recommendations for utilizing SNP genotyping in nimal breeding are summarized. PMID:27600241

  4. Developing Single Nucleotide Polymorphism (SNP) markers from transcriptome sequences for the identification of longan (Dimocarpus longan) germplasm

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Longan (Dimocarpus longan Lour.) is an important tropical fruit tree crop. Accurate varietal identification is essential for germplasm management and breeding. Using longan transcriptome sequences from public databases, we developed single nucleotide polymorphism (SNP) markers; validated 60 SNPs in...

  5. Use of the Illumina GoldenGate assay for single nucleotide polymorphism (SNP) genotyping in cereal crops.

    PubMed

    Chao, Shiaoman; Lawley, Cindy

    2015-01-01

    Highly parallel genotyping assays, such as the GoldenGate assay developed by Illumina, capable of interrogating up to 3,072 single nucleotide polymorphisms (SNPs) simultaneously, have greatly facilitated genome-wide studies, particularly for crops with large and complex genome structures. In this report, we provide detailed information and guidelines regarding genomic DNA preparation, SNP assay design, SNP assay protocols, and genotype calling using Illumina's GenomeStudio software. PMID:25373766

  6. Comparison of SSR and SNP Markers in Estimation of Genetic Diversity and Population Structure of Indian Rice Varieties

    PubMed Central

    Singh, Amit Kumar; Kumar, Sundeep; Srinivasan, Kalyani; Tyagi, R. K.; Singh, N. K.; Singh, Rakesh

    2013-01-01

    Simple sequence repeat (SSR) and Single Nucleotide Polymorphic (SNP), the two most robust markers for identifying rice varieties were compared for assessment of genetic diversity and population structure. Total 375 varieties of rice from various regions of India archived at the Indian National GeneBank, NBPGR, New Delhi, were analyzed using thirty six genetic markers, each of hypervariable SSR (HvSSR) and SNP which were distributed across 12 rice chromosomes. A total of 80 alleles were amplified with the SSR markers with an average of 2.22 alleles per locus whereas, 72 alleles were amplified with SNP markers. Polymorphic information content (PIC) values for HvSSR ranged from 0.04 to 0.5 with an average of 0.25. In the case of SNP markers, PIC values ranged from 0.03 to 0.37 with an average of 0.23. Genetic relatedness among the varieties was studied; utilizing an unrooted tree all the genotypes were grouped into three major clusters with both SSR and SNP markers. Analysis of molecular variance (AMOVA) indicated that maximum diversity was partitioned between and within individual level but not between populations. Principal coordinate analysis (PCoA) with SSR markers showed that genotypes were uniformly distributed across the two axes with 13.33% of cumulative variation whereas, in case of SNP markers varieties were grouped into three broad groups across two axes with 45.20% of cumulative variation. Population structure were tested using K values from 1 to 20, but there was no clear population structure, therefore Ln(PD) derived Δk was plotted against the K to determine the number of populations. In case of SSR maximum Δk was at K=5 whereas, in case of SNP maximum Δk was found at K=15, suggesting that resolution of population was higher with SNP markers, but SSR were more efficient for diversity analysis. PMID:24367635

  7. TheSNPpit—A High Performance Database System for Managing Large Scale SNP Data

    PubMed Central

    Groeneveld, Eildert; Lichtenberg, Helmut

    2016-01-01

    The fast development of high throughput genotyping has opened up new possibilities in genetics while at the same time producing considerable data handling issues. TheSNPpit is a database system for managing large amounts of multi panel SNP genotype data from any genotyping platform. With an increasing rate of genotyping in areas like animal and plant breeding as well as human genetics, already now hundreds of thousand of individuals need to be managed. While the common database design with one row per SNP can manage hundreds of samples this approach becomes progressively slower as the size of the data sets increase until it finally fails completely once tens or even hundreds of thousands of individuals need to be managed. TheSNPpit has implemented three ideas to also accomodate such large scale experiments: highly compressed vector storage in a relational database, set based data manipulation, and a very fast export written in C with Perl as the base for the framework and PostgreSQL as the database backend. Its novel subset system allows the creation of named subsets based on the filtering of SNP (based on major allele frequency, no-calls, and chromosomes) and manually applied sample and SNP lists at negligible storage costs, thus avoiding the issue of proliferating file copies. The named subsets are exported for down stream analysis. PLINK ped and map files are processed as in- and outputs. TheSNPpit allows management of different panel sizes in the same population of individuals when higher density panels replace previous lower density versions as it occurs in animal and plant breeding programs. A completely generalized procedure allows storage of phenotypes. TheSNPpit only occupies 2 bits for storing a single SNP implying a capacity of 4 mio SNPs per 1MB of disk storage. To investigate performance scaling, a database with more than 18.5 mio samples has been created with 3.4 trillion SNPs from 12 panels ranging from 1000 through 20 mio SNPs resulting in a

  8. Identification of SNP and SSR Markers in Finger Millet Using Next Generation Sequencing Technologies.

    PubMed

    Gimode, Davis; Odeny, Damaris A; de Villiers, Etienne P; Wanyonyi, Solomon; Dida, Mathews M; Mneney, Emmarold E; Muchugi, Alice; Machuka, Jesse; de Villiers, Santie M

    2016-01-01

    Finger millet is an important cereal crop in eastern Africa and southern India with excellent grain storage quality and unique ability to thrive in extreme environmental conditions. Since negligible attention has been paid to improving this crop to date, the current study used Next Generation Sequencing (NGS) technologies to develop both Simple Sequence Repeat (SSR) and Single Nucleotide Polymorphism (SNP) markers. Genomic DNA from cultivated finger millet genotypes KNE755 and KNE796 was sequenced using both Roche 454 and Illumina technologies. Non-organelle sequencing reads were assembled into 207 Mbp representing approximately 13% of the finger millet genome. We identified 10,327 SSRs and 23,285 non-homeologous SNPs and tested 101 of each for polymorphism across a diverse set of wild and cultivated finger millet germplasm. For the 49 polymorphic SSRs, the mean polymorphism information content (PIC) was 0.42, ranging from 0.16 to 0.77. We also validated 92 SNP markers, 80 of which were polymorphic with a mean PIC of 0.29 across 30 wild and 59 cultivated accessions. Seventy-six of the 80 SNPs were polymorphic across 30 wild germplasm with a mean PIC of 0.30 while only 22 of the SNP markers showed polymorphism among the 59 cultivated accessions with an average PIC value of 0.15. Genetic diversity analysis using the polymorphic SNP markers revealed two major clusters; one of wild and another of cultivated accessions. Detailed STRUCTURE analysis confirmed this grouping pattern and further revealed 2 sub-populations within wild E. coracana subsp. africana. Both STRUCTURE and genetic diversity analysis assisted with the correct identification of the new germplasm collections. These polymorphic SSR and SNP markers are a significant addition to the existing 82 published SSRs, especially with regard to the previously reported low polymorphism levels in finger millet. Our results also reveal an unexploited finger millet genetic resource that can be included in the regional

  9. Identification of SNP and SSR Markers in Finger Millet Using Next Generation Sequencing Technologies

    PubMed Central

    Gimode, Davis; Odeny, Damaris A.; de Villiers, Etienne P.; Wanyonyi, Solomon; Dida, Mathews M.; Mneney, Emmarold E.; Muchugi, Alice; Machuka, Jesse; de Villiers, Santie M.

    2016-01-01

    Finger millet is an important cereal crop in eastern Africa and southern India with excellent grain storage quality and unique ability to thrive in extreme environmental conditions. Since negligible attention has been paid to improving this crop to date, the current study used Next Generation Sequencing (NGS) technologies to develop both Simple Sequence Repeat (SSR) and Single Nucleotide Polymorphism (SNP) markers. Genomic DNA from cultivated finger millet genotypes KNE755 and KNE796 was sequenced using both Roche 454 and Illumina technologies. Non-organelle sequencing reads were assembled into 207 Mbp representing approximately 13% of the finger millet genome. We identified 10,327 SSRs and 23,285 non-homeologous SNPs and tested 101 of each for polymorphism across a diverse set of wild and cultivated finger millet germplasm. For the 49 polymorphic SSRs, the mean polymorphism information content (PIC) was 0.42, ranging from 0.16 to 0.77. We also validated 92 SNP markers, 80 of which were polymorphic with a mean PIC of 0.29 across 30 wild and 59 cultivated accessions. Seventy-six of the 80 SNPs were polymorphic across 30 wild germplasm with a mean PIC of 0.30 while only 22 of the SNP markers showed polymorphism among the 59 cultivated accessions with an average PIC value of 0.15. Genetic diversity analysis using the polymorphic SNP markers revealed two major clusters; one of wild and another of cultivated accessions. Detailed STRUCTURE analysis confirmed this grouping pattern and further revealed 2 sub-populations within wild E. coracana subsp. africana. Both STRUCTURE and genetic diversity analysis assisted with the correct identification of the new germplasm collections. These polymorphic SSR and SNP markers are a significant addition to the existing 82 published SSRs, especially with regard to the previously reported low polymorphism levels in finger millet. Our results also reveal an unexploited finger millet genetic resource that can be included in the regional

  10. Identification of SNP and SSR Markers in Finger Millet Using Next Generation Sequencing Technologies.

    PubMed

    Gimode, Davis; Odeny, Damaris A; de Villiers, Etienne P; Wanyonyi, Solomon; Dida, Mathews M; Mneney, Emmarold E; Muchugi, Alice; Machuka, Jesse; de Villiers, Santie M

    2016-01-01

    Finger millet is an important cereal crop in eastern Africa and southern India with excellent grain storage quality and unique ability to thrive in extreme environmental conditions. Since negligible attention has been paid to improving this crop to date, the current study used Next Generation Sequencing (NGS) technologies to develop both Simple Sequence Repeat (SSR) and Single Nucleotide Polymorphism (SNP) markers. Genomic DNA from cultivated finger millet genotypes KNE755 and KNE796 was sequenced using both Roche 454 and Illumina technologies. Non-organelle sequencing reads were assembled into 207 Mbp representing approximately 13% of the finger millet genome. We identified 10,327 SSRs and 23,285 non-homeologous SNPs and tested 101 of each for polymorphism across a diverse set of wild and cultivated finger millet germplasm. For the 49 polymorphic SSRs, the mean polymorphism information content (PIC) was 0.42, ranging from 0.16 to 0.77. We also validated 92 SNP markers, 80 of which were polymorphic with a mean PIC of 0.29 across 30 wild and 59 cultivated accessions. Seventy-six of the 80 SNPs were polymorphic across 30 wild germplasm with a mean PIC of 0.30 while only 22 of the SNP markers showed polymorphism among the 59 cultivated accessions with an average PIC value of 0.15. Genetic diversity analysis using the polymorphic SNP markers revealed two major clusters; one of wild and another of cultivated accessions. Detailed STRUCTURE analysis confirmed this grouping pattern and further revealed 2 sub-populations within wild E. coracana subsp. africana. Both STRUCTURE and genetic diversity analysis assisted with the correct identification of the new germplasm collections. These polymorphic SSR and SNP markers are a significant addition to the existing 82 published SSRs, especially with regard to the previously reported low polymorphism levels in finger millet. Our results also reveal an unexploited finger millet genetic resource that can be included in the regional

  11. SNP genotypes of olfactory receptor genes associated with olfactory ability in German Shepherd dogs.

    PubMed

    Yang, M; Geng, G-J; Zhang, W; Cui, L; Zhang, H-X; Zheng, J-L

    2016-04-01

    To find out the relationship between SNP genotypes of canine olfactory receptor genes and olfactory ability, 28 males and 20 females from German Shepherd dogs in police service were scored by odor detection tests and analyzed using the Beckman GenomeLab SNPstream. The representative 22 SNP loci from the exonic regions of 12 olfactory receptor genes were investigated, and three kinds of odor (human, ice drug and trinitrotoluene) were detected. The results showed that the SNP genotypes at the OR10H1-like:c.632C>T, OR10H1-like:c.770A>T, OR2K2-like:c.518G>A, OR4C11-like:c.511T>G and OR4C11-like:c.692G>A loci had a statistically significant effect on the scenting abilities (P < 0.001). The kind of odor influenced the performances of the dogs (P < 0.001). In addition, there were interactions between genotype and the kind of odor at the following loci: OR10H1-like:c.632C>T, OR10H1-like:c.770A>T, OR4C11-like:c.511T>G and OR4C11-like:c.692G>A (P < 0.001). The dogs with genotype CC at the OR10H1-like:c.632C>T, genotype AA at the OR10H1-like:c.770A>T, genotype TT at the OR4C11-like:c.511T>G and genotype GG at the OR4C11-like:c.692G>A loci did better at detecting the ice drug. We concluded that there was linkage between certain SNP genotypes and the olfactory ability of dogs and that SNP genotypes might be useful in determining dogs' scenting potential.

  12. Allele frequencies for 40 autosomal SNP loci typed for US population samples using electrospray ionization mass spectrometry

    PubMed Central

    Kiesler, Kevin M.; Vallone, Peter M.

    2013-01-01

    Aim To type a set of 194 US African American, Caucasian, and Hispanic samples (self-declared ancestry) for 40 autosomal single nucleotide polymorphism (SNP) markers intended for human identification purposes. Methods Genotyping was performed on an automated commercial electrospray ionization time-of-flight mass spectrometer, the PLEX-ID. The 40 SNP markers were amplified in eight unique 5plex PCRs, desalted, and resolved based on amplicon mass. For each of the three US sample groups statistical analyses were performed on the resulting genotypes. Results The assay was found to be robust and capable of genotyping the 40 SNP markers consuming approximately 4 nanograms of template per sample. The combined random match probabilities for the 40 SNP assay ranged from 10−16 to 10−21. Conclusion The multiplex PLEX-ID SNP-40 assay is the first fully automated genotyping method capable of typing a panel of 40 forensically relevant autosomal SNP markers on a mass spectrometry platform. The data produced provided the first allele frequencies estimates for these 40 SNPs in a National Institute of Standards and Technology US population sample set. No population bias was detected although one locus deviated from its expected level of heterozygosity. PMID:23771752

  13. Supplementing High-Density SNP Microarrays for Additional Coverage of Disease-Related Genes: Addiction as a Paradigm

    SciTech Connect

    SacconePhD, Scott F; Chesler, Elissa J; Bierut, Laura J; Kalivas, Peter J; Lerman, Caryn; Saccone, Nancy L; Uhl, George R; Li, Chuan-Yun; Philip, Vivek M; Edenberg, Howard; Sherry, Steven; Feolo, Michael; Moyzis, Robert K; Rutter, Joni L

    2009-01-01

    Commercial SNP microarrays now provide comprehensive and affordable coverage of the human genome. However, some diseases have biologically relevant genomic regions that may require additional coverage. Addiction, for example, is thought to be influenced by complex interactions among many relevant genes and pathways. We have assembled a list of 486 biologically relevant genes nominated by a panel of experts on addiction. We then added 424 genes that showed evidence of association with addiction phenotypes through mouse QTL mappings and gene co-expression analysis. We demonstrate that there are a substantial number of SNPs in these genes that are not well represented by commercial SNP platforms. We address this problem by introducing a publicly available SNP database for addiction. The database is annotated using numeric prioritization scores indicating the extent of biological relevance. The scores incorporate a number of factors such as SNP/gene functional properties (including synonymy and promoter regions), data from mouse systems genetics and measures of human/mouse evolutionary conservation. We then used HapMap genotyping data to determine if a SNP is tagged by a commercial microarray through linkage disequilibrium. This combination of biological prioritization scores and LD tagging annotation will enable addiction researchers to supplement commercial SNP microarrays to ensure comprehensive coverage of biologically relevant regions.

  14. Mapping autism risk loci using genetic linkage and chromosomal rearrangements

    PubMed Central

    Szatmari, Peter; Paterson, Andrew; Zwaigenbaum, Lonnie; Roberts, Wendy; Brian, Jessica; Liu, Xiao-Qing; Vincent, John; Skaug, Jennifer; Thompson, Ann; Senman, Lili; Feuk, Lars; Qian, Cheng; Bryson, Susan; Jones, Marshall; Marshall, Christian; Scherer, Stephen; Vieland, Veronica; Bartlett, Christopher; Mangin, La Vonne; Goedken, Rhinda; Segre, Alberto; Pericak-Vance, Margaret; Cuccaro, Michael; Gilbert, John; Wright, Harry; Abramson, Ruth; Betancur, Catalina; Bourgeron, Thomas; Gillberg, Christopher; Leboyer, Marion; Buxbaum, Joseph; Davis, Kenneth; Hollander, Eric; Silverman, Jeremy; Hallmayer, Joachim; Lotspeich, Linda; Sutcliffe, James; Haines, Jonathan; Folstein, Susan; Piven, Joseph; Wassink, Thomas; Sheffield, Val; Geschwind, Daniel; Bucan, Maja; Brown, Ted; Cantor, Rita; Constantino, John; Gilliam, Conrad; Herbert, Martha; Lajonchere, Clara; Ledbetter, David; Lese-Martin, Christa; Miller, Janet; Nelson, Stan; Samango-Sprouse, Carol; Spence, Sarah; State, Matthew; Tanzi, Rudolph; Coon, Hilary; Dawson, Geraldine; Devlin, Bernie; Estes, Annette; Flodman, Pamela; Klei, Lambertus; Mcmahon, William; Minshew, Nancy; Munson, Jeff; Korvatska, Elena; Rodier, Patricia; Schellenberg, Gerard; Smith, Moyra; Spence, Anne; Stodgell, Chris; Tepper, Ping Guo; Wijsman, Ellen; Yu, Chang-En; Rogé, Bernadette; Mantoulan, Carine; Wittemeyer, Kerstin; Poustka, Annemarie; Felder, Bärbel; Klauck, Sabine; Schuster, Claudia; Poustka, Fritz; Bölte, Sven; Feineis-Matthews, Sabine; Herbrecht, Evelyn; Schmötzer, Gabi; Tsiantis, John; Papanikolaou, Katerina; Maestrini, Elena; Bacchelli, Elena; Blasi, Francesca; Carone, Simona; Toma, Claudio; Van Engeland, Herman; De Jonge, Maretha; Kemner, Chantal; Koop, Frederieke; Langemeijer, Marjolein; Hijmans, Channa; Staal, Wouter; Baird, Gillian; Bolton, Patrick; Rutter, Michael; Weisblatt, Emma; Green, Jonathan; Aldred, Catherine; Wilkinson, Julie-Anne; Pickles, Andrew; Le Couteur, Ann; Berney, Tom; Mcconachie, Helen; Bailey, Anthony; Francis, Kostas; Honeyman, Gemma; Hutchinson, Aislinn; Parr, Jeremy; Wallace, Simon; Monaco, Anthony; Barnby, Gabrielle; Kobayashi, Kazuhiro; Lamb, Janine; Sousa, Ines; Sykes, Nuala; Cook, Edwin; Guter, Stephen; Leventhal, Bennett; Salt, Jeff; Lord, Catherine; Corsello, Christina; Hus, Vanessa; Weeks, Daniel; Volkmar, Fred; Tauber, Maïté; Fombonne, Eric; Shih, Andy; Meyer, Kacie

    2007-01-01

    Autism spectrum disorders (ASD) are common, heritable neurodevelopmental conditions. The genetic architecture of ASD is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASD by using Affymetrix 10K single nucleotide polymorphism (SNP) arrays and 1168 families with ≥ 2 affected individuals to perform the largest linkage scan to date, while also analyzing copy number variation (CNV) in these families. Linkage and CNV analyses implicate chromosome 11p12-p13 and neurexins, respectively, amongst other candidate loci. Neurexins team with previously-implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for ASD. PMID:17322880

  15. SNP-SNP Interaction between TLR4 and MyD88 in Susceptibility to Coronary Artery Disease in the Chinese Han Population.

    PubMed

    Sun, Dandan; Sun, Liping; Xu, Qian; Gong, Yuehua; Wang, Honghu; Yang, Jun; Yuan, Yuan

    2016-03-01

    The toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88)-dependent signaling pathway plays a role in the initiation and progression of coronary artery disease (CAD). We investigated SNP-SNP interactions between the TLR4 and MyD88 genes in CAD susceptibility and assessed whether the effects of such interactions were modified by confounding risk factors (hyperglycemia, hyperlipidemia and Helicobacter pylori (H. pylori) infection). Participants with CAD (n = 424) and controls (n = 424) without CAD were enrolled. Polymerase chain restriction-restriction fragment length polymorphism was performed on genomic DNA to detect polymorphisms in TLR4 (rs10116253, rs10983755, and rs11536889) and MyD88 (rs7744). H. pylori infections were evaluated by enzyme-linked immunosorbent assays, and the cardiovascular risk factors for each subject were evaluated clinically. The significant interaction between TLR4 rs11536889 and MyD88 rs7744 was associated with an increased CAD risk (p value for interaction = 0.024). In conditions of hyperglycemia, the interaction effect was strengthened between TLR4 rs11536889 and MyD88 rs7744 (p value for interaction = 0.004). In hyperlipidemic participants, the interaction strength was also enhanced for TLR4 rs11536889 and MyD88 rs7744 (p value for interaction = 0.006). Thus, the novel interaction between TLR4 rs11536889 and MyD88 rs7744 was related with an increased risk of CAD, that could be strengthened by the presence of hyperglycemia or hyperlipidemia. PMID:26959040

  16. SNP-SNP Interaction between TLR4 and MyD88 in Susceptibility to Coronary Artery Disease in the Chinese Han Population.

    PubMed

    Sun, Dandan; Sun, Liping; Xu, Qian; Gong, Yuehua; Wang, Honghu; Yang, Jun; Yuan, Yuan

    2016-03-04

    The toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88)-dependent signaling pathway plays a role in the initiation and progression of coronary artery disease (CAD). We investigated SNP-SNP interactions between the TLR4 and MyD88 genes in CAD susceptibility and assessed whether the effects of such interactions were modified by confounding risk factors (hyperglycemia, hyperlipidemia and Helicobacter pylori (H. pylori) infection). Participants with CAD (n = 424) and controls (n = 424) without CAD were enrolled. Polymerase chain restriction-restriction fragment length polymorphism was performed on genomic DNA to detect polymorphisms in TLR4 (rs10116253, rs10983755, and rs11536889) and MyD88 (rs7744). H. pylori infections were evaluated by enzyme-linked immunosorbent assays, and the cardiovascular risk factors for each subject were evaluated clinically. The significant interaction between TLR4 rs11536889 and MyD88 rs7744 was associated with an increased CAD risk (p value for interaction = 0.024). In conditions of hyperglycemia, the interaction effect was strengthened between TLR4 rs11536889 and MyD88 rs7744 (p value for interaction = 0.004). In hyperlipidemic participants, the interaction strength was also enhanced for TLR4 rs11536889 and MyD88 rs7744 (p value for interaction = 0.006). Thus, the novel interaction between TLR4 rs11536889 and MyD88 rs7744 was related with an increased risk of CAD, that could be strengthened by the presence of hyperglycemia or hyperlipidemia.

  17. Heterologous Expression of MeLEA3: A 10 kDa Late Embryogenesis Abundant Protein of Cassava, Confers Tolerance to Abiotic Stress in Escherichia coli with Recombinant Protein Showing In Vitro Chaperone Activity.

    PubMed

    Barros, Nicolle L F; da Silva, Diehgo T; Marques, Deyvid N; de Brito, Fabiano M; dos Reis, Savio P; de Souza, Claudia R B

    2015-01-01

    Late embryogenesis abundant (LEA) proteins are small molecular weight proteins involved in acquisition of tolerance to drought, salinity, high temperature, cold, and freezing stress in many plants. Previous studies revealed a cDNA sequence coding for a 10 kDa atypical LEA protein, named MeLEA3, predicted to be located into mitochondria with potential role in salt stress response of cassava (Manihot esculenta Crantz). Here we aimed to produce the recombinant MeLEA3 protein by heterologous expression in Escherichia coli and evaluate the tolerance of bacteria expressing this protein under abiotic stress. Our result revealed that the recombinant MeLEA3 protein conferred a protective function against heat and salt stress in bacterial cells. Also, the recombinant MeLEA3 protein showed in vitro chaperone activity by protection of NdeI restriction enzyme activity under heat stress. PMID:25990084

  18. A GWAS SNP for Schizophrenia Is Linked to the Internal MIR137 Promoter and Supports Differential Allele-Specific Expression

    PubMed Central

    Warburton, Alix; Breen, Gerome; Bubb, Vivien J.; Quinn, John P.

    2016-01-01

    Single nucleotide polymorphisms (SNPs) within the MIR137 gene locus have been shown to confer risk for schizophrenia through genome-wide association studies (GWAS). The expression levels of microRNA-137 (miR-137) and its validated gene targets have also been shown to be disrupted in several neuropsychiatric conditions, including schizophrenia. Regulation of miR-137 expression is thus imperative for normal neuronal functioning. We previously characterized an internal promoter domain within the MIR137 gene that contained a variable number tandem repeat (VNTR) polymorphism and could alter the in vitro levels of miR-137 in a stimulus-induced and allele-specific manner. We now demonstrate that haplotype tagging-SNP analysis linked the rs1625579 GWAS SNP for schizophrenia to this internal MIR137 promoter through a proxy SNP rs2660304 located at this domain. We postulated that the rs2660304 promoter SNP may act as predisposing factor for schizophrenia through altering the levels of miR-137 expression in a genotype-dependent manner. Reporter gene analysis of the internal MIR137 promoter containing the common VNTR variant demonstrated genotype-dependent differences in promoter activity with respect to rs2660304. In line with previous reports, the major allele of the rs2660304 proxy SNP, which has previously been linked with schizophrenia risk through genetic association, resulted in downregulation of reporter gene expression in a tissue culture model. The genetic influence of the rs2660304 proxy SNP on the transcriptional activity of the internal MIR137 promoter, and thus the levels of miR-137 expression, therefore offers a distinct regulatory mechanism to explain the functional significance of the rs1625579 GWAS SNP for schizophrenia risk. PMID:26429811

  19. Deriving Gene Networks from SNP Associated with Triacylglycerol and Phospholipid Fatty Acid Fractions from Ribeyes of Angus Cattle

    PubMed Central

    Buchanan, Justin W.; Reecy, James M.; Garrick, Dorian J.; Duan, Qing; Beitz, Don C.; Koltes, James E.; Saatchi, Mahdi; Koesterke, Lars; Mateescu, Raluca G.

    2016-01-01

    The fatty acid profile of beef is a complex trait that can benefit from gene-interaction network analysis to understand relationships among loci that contribute to phenotypic variation. Phenotypic measures of fatty acid profile from triacylglycerol and phospholipid fractions of longissimus muscle, pedigree information, and Illumina 54 k bovine SNP genotypes were utilized to derive an annotated gene network associated with fatty acid composition in 1,833 Angus beef cattle. The Bayes-B statistical model was utilized to perform a genome wide association study to estimate associations between 54 k SNP genotypes and 39 individual fatty acid phenotypes within each fraction. Posterior means of the effects were estimated for each of the 54 k SNP and for the collective effects of all the SNP in every 1-Mb genomic window in terms of the proportion of genetic variance explained by the window. Windows that explained the largest proportions of genetic variance for individual lipids were found in the triacylglycerol fraction. There was almost no overlap in the genomic regions explaining variance between the triacylglycerol and phospholipid fractions. Partial correlations were used to identify correlated regions of the genome for the set of largest 1 Mb windows that explained up to 35% genetic variation in either fatty acid fraction. SNP were allocated to windows based on the bovine UMD3.1 assembly. Gene network clusters were generated utilizing a partial correlation and information theory algorithm. Results were used in conjunction with network scoring and visualization software to analyze correlated SNP across 39 fatty acid phenotypes to identify SNP of significance. Significant pathways implicated in fatty acid metabolism through GO term enrichment analysis included homeostasis of number of cells, homeostatic process, coenzyme/cofactor activity, and immunoglobulin. These results suggest different metabolic pathways regulate the development of different types of lipids found in

  20. Association of MDM2 SNP309 and TP53 Arg72Pro polymorphisms with risk of endometrial cancer

    PubMed Central

    YONEDA, TOMOKO; KUBOYAMA, AYUMI; KATO, KIYOKO; OHGAMI, TATSUHIRO; OKAMOTO, KANAKO; SAITO, TOSHIAKI; WAKE, NORIO

    2013-01-01

    The incidence of endometrial cancer, a common gynecological malignancy, is increasing in Japan. We have previously shown that the ER/MDM2/p53/p21 pathway plays an important role in endometrial carcinogenesis. In the present study, we investigated the effects of germline single nucleotide polymorphisms in murine double minute 2 (MDM2) SNP309, TP53 Arg72Pro, ESR1 PvuII and XbaI, and p21 codon 31 on endometrial cancer risk. We evaluated these polymorphisms in DNA samples from 125 endometrial cancer cases and 200 controls using polymerase chain reaction-based restriction fragment length polymorphism. The association of each genetic polymorphism with endometrial cancer was examined by the odds ratio and 95% confidence interval, which were obtained using logistic regression analysis. The SNP309 GG genotype non-significantly increased the risk of endometrial cancer. The 95% confidence interval for the GG genotype vs. the TT genotype of MDM2 SNP309 was 1.76 (0.93–3.30). Endometrial cancer was not associated with tested SNP genotypes for TP53, ESR1 and p21. The combination of SNP309 GG + TG and TP53 codon 72 Arg/Arg significantly increased endometrial cancer risk. The adjusted OR was 2.53 (95% confidence interval, 1.03–6.21) and P for the interaction was 0.04. This result was supported by in vitro data showing that endometrial cancer cell lines with the SNP309 G allele failed to show growth inhibition by treatment with RITA, which reduces p53-MDM2 binding. The presence of the SNP309 G allele and TP53 codon 72 Arg/Arg genotype is associated with an increased risk of endometrial cancer in Japanese women. PMID:23624782

  1. Imputation of microsatellite alleles from dense SNP genotypes for parentage verification across multiple Bos taurus and Bos indicus breeds

    PubMed Central

    McClure, Matthew C.; Sonstegard, Tad S.; Wiggans, George R.; Van Eenennaam, Alison L.; Weber, Kristina L.; Penedo, Cecilia T.; Berry, Donagh P.; Flynn, John; Garcia, Jose F.; Carmo, Adriana S.; Regitano, Luciana C. A.; Albuquerque, Milla; Silva, Marcos V. G. B.; Machado, Marco A.; Coffey, Mike; Moore, Kirsty; Boscher, Marie-Yvonne; Genestout, Lucie; Mazza, Raffaele; Taylor, Jeremy F.; Schnabel, Robert D.; Simpson, Barry; Marques, Elisa; McEwan, John C.; Cromie, Andrew; Coutinho, Luiz L.; Kuehn, Larry A.; Keele, John W.; Piper, Emily K.; Cook, Jim; Williams, Robert; Van Tassell, Curtis P.

    2013-01-01

    To assist cattle producers transition from microsatellite (MS) to single nucleotide polymorphism (SNP) genotyping for parental verification we previously devised an effective and inexpensive method to impute MS alleles from SNP haplotypes. While the reported method was verified with only a limited data set (N = 479) from Brown Swiss, Guernsey, Holstein, and Jersey cattle, some of the MS-SNP haplotype associations were concordant across these phylogenetically diverse breeds. This implied that some haplotypes predate modern breed formation and remain in strong linkage disequilibrium. To expand the utility of MS allele imputation across breeds, MS and SNP data from more than 8000 animals representing 39 breeds (Bos taurus and B. indicus) were used to predict 9410 SNP haplotypes, incorporating an average of 73 SNPs per haplotype, for which alleles from 12 MS markers could be accurately be imputed. Approximately 25% of the MS-SNP haplotypes were present in multiple breeds (N = 2 to 36 breeds). These shared haplotypes allowed for MS imputation in breeds that were not represented in the reference population with only a small increase in Mendelian inheritance inconsistancies. Our reported reference haplotypes can be used for any cattle breed and the reported methods can be applied to any species to aid the transition from MS to SNP genetic markers. While ~91% of the animals with imputed alleles for 12 MS markers had ≤1 Mendelian inheritance conflicts with their parents' reported MS genotypes, this figure was 96% for our reference animals, indicating potential errors in the reported MS genotypes. The workflow we suggest autocorrects for genotyping errors and rare haplotypes, by MS genotyping animals whose imputed MS alleles fail parentage verification, and then incorporating those animals into the reference dataset. PMID:24065982

  2. Somatic Mutation of the SNP rs11614913 and Its Association with Increased MIR 196A2 Expression in Breast Cancer.

    PubMed

    Zhao, Huanhuan; Xu, Jingman; Zhao, Dan; Geng, Meijuan; Ge, Haize; Fu, Li; Zhu, Zhengmao

    2016-02-01

    Common genetic variants (single-nucleotide polymorphisms [SNPs]) in microRNA genes may alter their maturation or expression, resulting in varied functional consequences. Several studies have evaluated the association between the SNP rs11614913 and cancer risk in diverse populations and in a range of cancers, with contradictory outcomes. In this study, we examined 114 paired samples (tumor and normal tissues) from breast cancer patients to study the genotype distribution and somatic mutation of the SNP in MIR 196A2 (rs11614913 C-T). In addition, we evaluated their influence on the mature MIR 196A2 expression. We found that 14% (16/114) of tumors underwent somatic mutation of the SNP rs11614913. Moreover, the CT heterozygous and the CC homozygous states of SNP rs11614913 were more prone to mutation, while the TT homozygous state appeared to be resistant. We further detected a significant increase (p = 0.002) in mature MIR 196A2 expression in breast cancer. In particular, we found a significant association between the occurrence of SNP rs11614913 mutation and high expression (p = 0.0002). In addition, the mature MIR 196A2 expression level was significantly associated with the higher tumor grade (p = 0.004). Taken together, our results seem to demonstrate that somatic mutation of SNP rs11614913 in MIR 196A2 can have an influence on its expression. In addition, it indicated that an unknown mechanism is responsible for both the mutation of SNP rs11614913 and the dysregulation of mature MIR 196A2 expression.

  3. Deriving Gene Networks from SNP Associated with Triacylglycerol and Phospholipid Fatty Acid Fractions from Ribeyes of Angus Cattle.

    PubMed

    Buchanan, Justin W; Reecy, James M; Garrick, Dorian J; Duan, Qing; Beitz, Don C; Koltes, James E; Saatchi, Mahdi; Koesterke, Lars; Mateescu, Raluca G

    2016-01-01

    The fatty acid profile of beef is a complex trait that can benefit from gene-interaction network analysis to understand relationships among loci that contribute to phenotypic variation. Phenotypic measures of fatty acid profile from triacylglycerol and phospholipid fractions of longissimus muscle, pedigree information, and Illumina 54 k bovine SNP genotypes were utilized to derive an annotated gene network associated with fatty acid composition in 1,833 Angus beef cattle. The Bayes-B statistical model was utilized to perform a genome wide association study to estimate associations between 54 k SNP genotypes and 39 individual fatty acid phenotypes within each fraction. Posterior means of the effects were estimated for each of the 54 k SNP and for the collective effects of all the SNP in every 1-Mb genomic window in terms of the proportion of genetic variance explained by the window. Windows that explained the largest proportions of genetic variance for individual lipids were found in the triacylglycerol fraction. There was almost no overlap in the genomic regions explaining variance between the triacylglycerol and phospholipid fractions. Partial correlations were used to identify correlated regions of the genome for the set of largest 1 Mb windows that explained up to 35% genetic variation in either fatty acid fraction. SNP were allocated to windows based on the bovine UMD3.1 assembly. Gene network clusters were generated utilizing a partial correlation and information theory algorithm. Results were used in conjunction with network scoring and visualization software to analyze correlated SNP across 39 fatty acid phenotypes to identify SNP of significance. Significant pathways implicated in fatty acid metabolism through GO term enrichment analysis included homeostasis of number of cells, homeostatic process, coenzyme/cofactor activity, and immunoglobulin. These results suggest different metabolic pathways regulate the development of different types of lipids found in

  4. SNP genotyping of animal and human derived isolates of Mycobacterium avium subsp. paratuberculosis.

    PubMed

    Wynne, James W; Beller, Christie; Boyd, Victoria; Francis, Barry; Gwoźdź, Jacek; Carajias, Marios; Heine, Hans G; Wagner, Josef; Kirkwood, Carl D; Michalski, Wojtek P

    2014-08-27

    Mycobacterium avium subsp. paratuberculosis (MAP) is the aetiological agent of Johne's disease (JD), a chronic granulomatous enteritis that affects ruminants worldwide. While the ability of MAP to cause disease in animals is clear, the role of this bacterium in human inflammatory bowel diseases remains unresolved. Previous whole genome sequencing of MAP isolates derived from human and three animal hosts showed that human isolates were genetically similar and showed a close phylogenetic relationship to one bovine isolate. In contrast, other animal derived isolates were more genetically diverse. The present study aimed to investigate the frequency of this human strain across 52 wild-type MAP isolates, collected predominantly from Australia. A Luminex based SNP genotyping approach was utilised to genotype SNPs that had previously been shown to be specific to the human, bovine or ovine isolate types. Fourteen SNPs were initially evaluated across a reference panel of isolates with known genotypes. A subset of seven SNPs was chosen for analysis within the wild-type collection. Of the seven SNPs, three were found to be unique to paediatric human isolates. No wild-type isolates contain these SNP alleles. Interestingly, and in contrast to the paediatric isolates, three additional adult human isolates (derived from adult Crohn's disease patients) also did not contain these SNP alleles. Furthermore we identified two SNPs, which demonstrate extensive polymorphism within the animal-derived MAP isolates. One of which appears unique to ovine and a single camel isolate. From this study we suggest the existence of genetic heterogeneity between human derived MAP isolates, some of which are highly similar to those derived from bovine hosts, but others of which are more divergent.

  5. [Study on relieving effects of exogenous SNP, Spd on Belamcanda chinensis under salt-alkalline stress].

    PubMed

    Xu, Meng-Ping; He, Ping; Duan, Cai-Xu; Yang, Mou

    2014-12-01

    The study is aimed to provide the theoretical basis for exploiting and utilization of salt-alkaline soil and cultivating Belamcanda chinensis. In this study, we exerted exogenous substances SNP, Spd to relieve the damage of the mixing salt-alkaline stress on B. chinensis seedling which is NaCl, Na2SO4, NaHCO3 and Na2CO3 four kinds of salt molar ratio of 9: 1: 9: 1, salt concentration of 100 mmol x L(-1). The result illustrated that high pH stress is a major factor caused the salt-alkaline stress, the interaction between time and the concentration of each, treatment was observed, what is more, there are synergies between the salt and alkali stress. The content of B. chinensis seedling leaves' membrane peroxidation index (MDA, O2-*) and metabolites (soluble protein, soluble sugars, organic acids) are showing an upward trend in varying degrees under 100 mmol x L(-1) salt-alkaline stress. It is effective to reduce the content of MDA and O2-*. and improve the levels of metabolites, in which the SNP (0.05 mmol x L(-1)) and Spd (0.5 mmol x L(-1)) to alleviate damage effects is the best. Therefore we can hold the conclusion that SNP and Spd can effectively mitigate the damage of B. chinensis seedling on salt-alkaline stress, improve the resistance ability of B. chinensis seedling which can provide the scientific basis for the utilization of salt-alkaline soil, and the cultivation of B. chinensis.

  6. Role of an SNP in Alternative Splicing of Bovine NCF4 and Mastitis Susceptibility.

    PubMed

    Ju, Zhihua; Wang, Changfa; Wang, Xiuge; Yang, Chunhong; Sun, Yan; Jiang, Qiang; Wang, Fei; Li, Mengjiao; Zhong, Jifeng; Huang, Jinming

    2015-01-01

    Neutrophil cytosolic factor 4 (NCF4) is component of the nicotinamide dinucleotide phosphate oxidase complex, a key factor in biochemical pathways and innate immune responses. In this study, splice variants and functional single-nucleotide polymorphism (SNP) of NCF4 were identified to determine the variability and association of the gene with susceptibility to bovine mastitis characterized by inflammation. A novel splice variant, designated as NCF4-TV and characterized by the retention of a 48 bp sequence in intron 9, was detected in the mammary gland tissues of infected cows. The expression of the NCF4-reference main transcript in the mastitic mammary tissues was higher than that in normal tissues. A novel SNP, g.18174 A>G, was also found in the retained 48 bp region of intron 9. To determine whether NCF4-TV could be due to the g.18174 A>G mutation, we constructed two mini-gene expression vectors with the wild-type or mutant NCF4 g.18174 A>G fragment. The vectors were then transiently transfected into 293T cells, and alternative splicing of NCF4 was analyzed by reverse transcription-PCR and sequencing. Mini-gene splicing assay demonstrated that the aberrantly spliced NCF4-TV with 48 bp retained fragment in intron 9 could be due to g.18174 A>G, which was associated with milk somatic count score and increased risk of mastitis infection in cows. NCF4 expression was also regulated by alternative splicing. This study proposes that NCF4 splice variants generated by functional SNP are important risk factors for mastitis susceptibility in dairy cows.

  7. PredictSNP: Robust and Accurate Consensus Classifier for Prediction of Disease-Related Mutations

    PubMed Central

    Bendl, Jaroslav; Stourac, Jan; Salanda, Ondrej; Pavelka, Antonin; Wieben, Eric D.; Zendulka, Jaroslav; Brezovsky, Jan; Damborsky, Jiri

    2014-01-01

    Single nucleotide variants represent a prevalent form of genetic variation. Mutations in the coding regions are frequently associated with the development of various genetic diseases. Computational tools for the prediction of the effects of mutations on protein function are very important for analysis of single nucleotide variants and their prioritization for experimental characterization. Many computational tools are already widely employed for this purpose. Unfortunately, their comparison and further improvement is hindered by large overlaps between the training datasets and benchmark datasets, which lead to biased and overly optimistic reported performances. In this study, we have constructed three independent datasets by removing all duplicities, inconsistencies and mutations previously used in the training of evaluated tools. The benchmark dataset containing over 43,000 mutations was employed for the unbiased evaluation of eight established prediction tools: MAPP, nsSNPAnalyzer, PANTHER, PhD-SNP, PolyPhen-1, PolyPhen-2, SIFT and SNAP. The six best performing tools were combined into a consensus classifier PredictSNP, resulting into significantly improved prediction performance, and at the same time returned results for all mutations, confirming that consensus prediction represents an accurate and robust alternative to the predictions delivered by individual tools. A user-friendly web interface enables easy access to all eight prediction tools, the consensus classifier PredictSNP and annotations from the Protein Mutant Database and the UniProt database. The web server and the datasets are freely available to the academic community at http://loschmidt.chemi.muni.cz/predictsnp. PMID:24453961

  8. [Study on relieving effects of exogenous SNP, Spd on Belamcanda chinensis under salt-alkalline stress].

    PubMed

    Xu, Meng-Ping; He, Ping; Duan, Cai-Xu; Yang, Mou

    2014-12-01

    The study is aimed to provide the theoretical basis for exploiting and utilization of salt-alkaline soil and cultivating Belamcanda chinensis. In this study, we exerted exogenous substances SNP, Spd to relieve the damage of the mixing salt-alkaline stress on B. chinensis seedling which is NaCl, Na2SO4, NaHCO3 and Na2CO3 four kinds of salt molar ratio of 9: 1: 9: 1, salt concentration of 100 mmol x L(-1). The result illustrated that high pH stress is a major factor caused the salt-alkaline stress, the interaction between time and the concentration of each, treatment was observed, what is more, there are synergies between the salt and alkali stress. The content of B. chinensis seedling leaves' membrane peroxidation index (MDA, O2-*) and metabolites (soluble protein, soluble sugars, organic acids) are showing an upward trend in varying degrees under 100 mmol x L(-1) salt-alkaline stress. It is effective to reduce the content of MDA and O2-*. and improve the levels of metabolites, in which the SNP (0.05 mmol x L(-1)) and Spd (0.5 mmol x L(-1)) to alleviate damage effects is the best. Therefore we can hold the conclusion that SNP and Spd can effectively mitigate the damage of B. chinensis seedling on salt-alkaline stress, improve the resistance ability of B. chinensis seedling which can provide the scientific basis for the utilization of salt-alkaline soil, and the cultivation of B. chinensis. PMID:25911800

  9. High-density SNP assay development for genetic analysis in maritime pine (Pinus pinaster).

    PubMed

    Plomion, C; Bartholomé, J; Lesur, I; Boury, C; Rodríguez-Quilón, I; Lagraulet, H; Ehrenmann, F; Bouffier, L; Gion, J M; Grivet, D; de Miguel, M; de María, N; Cervera, M T; Bagnoli, F; Isik, F; Vendramin, G G; González-Martínez, S C

    2016-03-01

    Maritime pine provides essential ecosystem services in the south-western Mediterranean basin, where it covers around 4 million ha. Its scattered distribution over a range of environmental conditions makes it an ideal forest tree species for studies of local adaptation and evolutionary responses to climatic change. Highly multiplexed single nucleotide polymorphism (SNP) genotyping arrays are increasingly used to study genetic variation in living organisms and for practical applications in plant and animal breeding and genetic resource conservation. We developed a 9k Illumina Infinium SNP array and genotyped maritime pine trees from (i) a three-generation inbred (F2) pedigree, (ii) the French breeding population and (iii) natural populations from Portugal and the French Atlantic coast. A large proportion of the exploitable SNPs (2052/8410, i.e. 24.4%) segregated in the mapping population and could be mapped, providing the densest ever gene-based linkage map for this species. Based on 5016 SNPs, natural and breeding populations from the French gene pool exhibited similar level of genetic diversity. Population genetics and structure analyses based on 3981 SNP markers common to the Portuguese and French gene pools revealed high levels of differentiation, leading to the identification of a set of highly differentiated SNPs that could be used for seed provenance certification. Finally, we discuss how the validated SNPs could facilitate the identification of ecologically and economically relevant genes in this species, improving our understanding of the demography and selective forces shaping its natural genetic diversity, and providing support for new breeding strategies. PMID:26358548

  10. Plastid DNA sequencing and nuclear SNP genotyping help resolve the puzzle of central American Platanus

    PubMed Central

    De Castro, Olga; Di Maio, Antonietta; Lozada García, José Armando; Piacenti, Danilo; Vázquez-Torres, Mario; De Luca, Paolo

    2013-01-01

    Background and Aims Recent research on the history of Platanus reveals that hybridization phenomena occurred in the central American species. This study has two goals: to help resolve the evolutive puzzle of central American Platanus, and to test the potential of real-time polymerase chain reaction (PCR) for detecting ancient hybridization. Methods Sequencing of a uniparental plastid DNA marker [psbA-trnH(GUG) intergenic spacer] and qualitative and quantitative single nucleotide polymorphism (SNP) genotyping of biparental nuclear ribosomal DNA (nrDNA) markers [LEAFY intron 2 (LFY-i2) and internal transcribed spacer 2 (ITS2)] were used. Key Results Based on the SNP genotyping results, several Platanus accessions show the presence of hybridization/introgression, including some accessions of P. rzedowskii and of P. mexicana var. interior and one of P. mexicana var. mexicana from Oaxaca (= P. oaxacana). Based on haplotype analyses of the psbA-trnH spacer, five haplotypes were detected. The most common of these is present in taxa belonging to P. orientalis, P. racemosa sensu lato, some accessions of P. occidentalis sensu stricto (s.s.) from Texas, P. occidentalis var. palmeri, P. mexicana s.s. and P. rzedowskii. This is highly relevant to genetic relationships with the haplotypes present in P. occidentalis s.s. and P. mexicana var. interior. Conclusions Hybridization and introgression events between lineages ancestral to modern central and eastern North American Platanus species occurred. Plastid haplotypes and qualitative and quantitative SNP genotyping provide information critical for understanding the complex history of Mexican Platanus. Compared with the usual molecular techniques of sub-cloning, sequencing and genotyping, real-time PCR assay is a quick and sensitive technique for analysing complex evolutionary patterns. PMID:23798602

  11. An EST-derived SNP and SSR genetic linkage map of cassava (Manihot esculenta Crantz).

    PubMed

    Rabbi, Ismail Yusuf; Kulembeka, Heneriko Philbert; Masumba, Esther; Marri, Pradeep Reddy; Ferguson, Morag

    2012-07-01

    Cassava (Manihot esculenta Crantz) is one of the most important food security crops in the tropics and increasingly being adopted for agro-industrial processing. Genetic improvement of cassava can be enhanced through marker-assisted breeding. For this, appropriate genomic tools are required to dissect the genetic architecture of economically important traits. Here, a genome-wide SNP-based genetic map of cassava anchored in SSRs is presented. An outbreeder full-sib (F1) family was genotyped on two independent SNP assay platforms: an array of 1,536 SNPs on Illumina's GoldenGate platform was used to genotype a first batch of 60 F1. Of the 1,358 successfully converted SNPs, 600 which were polymorphic in at least one of the parents and was subsequently converted to KBiosciences' KASPar assay platform for genotyping 70 additional F1. High-precision genotyping of 163 informative SSRs using capillary electrophoresis was also carried out. Linkage analysis resulted in a final linkage map of 1,837 centi-Morgans (cM) containing 568 markers (434 SNPs and 134 SSRs) distributed across 19 linkage groups. The average distance between adjacent markers was 3.4 cM. About 94.2% of the mapped SNPs and SSRs have also been localized on scaffolds of version 4.1 assembly of the cassava draft genome sequence. This more saturated genetic linkage map of cassava that combines SSR and SNP markers should find several applications in the improvement of cassava including aligning scaffolds of the cassava genome sequence, genetic analyses of important agro-morphological traits, studying the linkage disequilibrium landscape and comparative genomics.

  12. Role of an SNP in Alternative Splicing of Bovine NCF4 and Mastitis Susceptibility.

    PubMed

    Ju, Zhihua; Wang, Changfa; Wang, Xiuge; Yang, Chunhong; Sun, Yan; Jiang, Qiang; Wang, Fei; Li, Mengjiao; Zhong, Jifeng; Huang, Jinming

    2015-01-01

    Neutrophil cytosolic factor 4 (NCF4) is component of the nicotinamide dinucleotide phosphate oxidase complex, a key factor in biochemical pathways and innate immune responses. In this study, splice variants and functional single-nucleotide polymorphism (SNP) of NCF4 were identified to determine the variability and association of the gene with susceptibility to bovine mastitis characterized by inflammation. A novel splice variant, designated as NCF4-TV and characterized by the retention of a 48 bp sequence in intron 9, was detected in the mammary gland tissues of infected cows. The expression of the NCF4-reference main transcript in the mastitic mammary tissues was higher than that in normal tissues. A novel SNP, g.18174 A>G, was also found in the retained 48 bp region of intron 9. To determine whether NCF4-TV could be due to the g.18174 A>G mutation, we constructed two mini-gene expression vectors with the wild-type or mutant NCF4 g.18174 A>G fragment. The vectors were then transiently transfected into 293T cells, and alternative splicing of NCF4 was analyzed by reverse transcription-PCR and sequencing. Mini-gene splicing assay demonstrated that the aberrantly spliced NCF4-TV with 48 bp retained fragment in intron 9 could be due to g.18174 A>G, which was associated with milk somatic count score and increased risk of mastitis infection in cows. NCF4 expression was also regulated by alternative splicing. This study proposes that NCF4 splice variants generated by functional SNP are important risk factors for mastitis susceptibility in dairy cows. PMID:26600390

  13. High-throughput genomics in sorghum: from whole-genome resequencing to a SNP screening array.

    PubMed

    Bekele, Wubishet A; Wieckhorst, Silke; Friedt, Wolfgang; Snowdon, Rod J

    2013-12-01

    With its small, diploid and completely sequenced genome, sorghum (Sorghum bicolor L. Moench) is highly amenable to genomics-based breeding approaches. Here, we describe the development and testing of a robust single-nucleotide polymorphism (SNP) array platform that enables polymorphism screening for genome-wide and trait-linked polymorphisms in genetically diverse S. bicolor populations. Whole-genome sequences with 6× to 12× coverage from five genetically diverse S. bicolor genotypes, including three sweet sorghums and two grain sorghums, were aligned to the sorghum reference genome. From over 1 million high-quality SNPs, we selected 2124 Infinium Type II SNPs that were informative in all six source genomes, gave an optimal Assay Design Tool (ADT) score, had allele frequencies of 50% in the six genotypes and were evenly spaced throughout the S. bicolor genome. Furthermore, by phenotype-based pool sequencing, we selected an additional 876 SNPs with a phenotypic association to early-stage chilling tolerance, a key trait for European sorghum breeding. The 3000 attempted bead types were used to populate half of a dual-species Illumina iSelect SNP array. The array was tested using 564 Sorghum spp. genotypes, including offspring from four unrelated recombinant inbred line (RIL) and F2 populations and a genetic diversity collection. A high call rate of over 80% enabled validation of 2620 robust and polymorphic sorghum SNPs, underlining the efficiency of the array development scheme for whole-genome SNP selection and screening, with diverse applications including genetic mapping, genome-wide association studies and genomic selection.

  14. Role of an SNP in Alternative Splicing of Bovine NCF4 and Mastitis Susceptibility

    PubMed Central

    Wang, Xiuge; Yang, Chunhong; Sun, Yan; Jiang, Qiang; Wang, Fei; Li, Mengjiao; Zhong, Jifeng; Huang, Jinming

    2015-01-01

    Neutrophil cytosolic factor 4 (NCF4) is component of the nicotinamide dinucleotide phosphate oxidase complex, a key factor in biochemical pathways and innate immune responses. In this study, splice variants and functional single-nucleotide polymorphism (SNP) of NCF4 were identified to determine the variability and association of the gene with susceptibility to bovine mastitis characterized by inflammation. A novel splice variant, designated as NCF4-TV and characterized by the retention of a 48 bp sequence in intron 9, was detected in the mammary gland tissues of infected cows. The expression of the NCF4-reference main transcript in the mastitic mammary tissues was higher than that in normal tissues. A novel SNP, g.18174 A>G, was also found in the retained 48 bp region of intron 9. To determine whether NCF4-TV could be due to the g.18174 A>G mutation, we constructed two mini-gene expression vectors with the wild-type or mutant NCF4 g.18174 A>G fragment. The vectors were then transiently transfected into 293T cells, and alternative splicing of NCF4 was analyzed by reverse transcription-PCR and sequencing. Mini-gene splicing assay demonstrated that the aberrantly spliced NCF4-TV with 48 bp retained fragment in intron 9 could be due to g.18174 A>G, which was associated with milk somatic count score and increased risk of mastitis infection in cows. NCF4 expression was also regulated by alternative splicing. This study proposes that NCF4 splice variants generated by functional SNP are important risk factors for mastitis susceptibility in dairy cows. PMID:26600390

  15. High-density SNP assay development for genetic analysis in maritime pine (Pinus pinaster).

    PubMed

    Plomion, C; Bartholomé, J; Lesur, I; Boury, C; Rodríguez-Quilón, I; Lagraulet, H; Ehrenmann, F; Bouffier, L; Gion, J M; Grivet, D; de Miguel, M; de María, N; Cervera, M T; Bagnoli, F; Isik, F; Vendramin, G G; González-Martínez, S C

    2016-03-01

    Maritime pine provides essential ecosystem services in the south-western Mediterranean basin, where it covers around 4 million ha. Its scattered distribution over a range of environmental conditions makes it an ideal forest tree species for studies of local adaptation and evolutionary responses to climatic change. Highly multiplexed single nucleotide polymorphism (SNP) genotyping arrays are increasingly used to study genetic variation in living organisms and for practical applications in plant and animal breeding and genetic resource conservation. We developed a 9k Illumina Infinium SNP array and genotyped maritime pine trees from (i) a three-generation inbred (F2) pedigree, (ii) the French breeding population and (iii) natural populations from Portugal and the French Atlantic coast. A large proportion of the exploitable SNPs (2052/8410, i.e. 24.4%) segregated in the mapping population and could be mapped, providing the densest ever gene-based linkage map for this species. Based on 5016 SNPs, natural and breeding populations from the French gene pool exhibited similar level of genetic diversity. Population genetics and structure analyses based on 3981 SNP markers common to the Portuguese and French gene pools revealed high levels of differentiation, leading to the identification of a set of highly differentiated SNPs that could be used for seed provenance certification. Finally, we discuss how the validated SNPs could facilitate the identification of ecologically and economically relevant genes in this species, improving our understanding of the demography and selective forces shaping its natural genetic diversity, and providing support for new breeding strategies.

  16. CLUSTAG & WCLUSTAG: Hierarchical Clustering Algorithms for Efficient Tag-SNP Selection

    NASA Astrophysics Data System (ADS)

    Ao, Sio-Iong

    More than 6 million single nucleotide polymorphisms (SNPs) in the human genome have been genotyped by the HapMap project. Although only a pro portion of these SNPs are functional, all can be considered as candidate markers for indirect association studies to detect disease-related genetic variants. The complete screening of a gene or a chromosomal region is nevertheless an expensive undertak ing for association studies. A key strategy for improving the efficiency of association studies is to select a subset of informative SNPs, called tag SNPs, for analysis. In the chapter, hierarchical clustering algorithms have been proposed for efficient tag SNP selection.

  17. Rare coding SNP in DZIP1 gene associated with late-onset sporadic Parkinson's disease

    PubMed Central

    Valente, André X. C. N.; Shin, Joo H.; Sarkar, Abhijit; Gao, Yuan

    2012-01-01

    An association between a rare, coding, non-synonymous SNP variant in the gene DZIP1 and Parkinson's disease was found, based on an analysis of the existing NGRC genome-wide association study dataset. The statistical analysis utilized the hypothesis-rich, targeted search unbiased assessment approach, rather than the hypothesis-free, genome-wide agnostic search paradigm. The association of DZIP1 with Parkinson's disease is discussed in the context of a Parkinson's disease stem-cell ageing theory. PMID:22355768

  18. Benefits and burdens of using a SNP array in pregnancies at increased risk for the common aneuploidies.

    PubMed

    Van Opstal, Diane; de Vries, Femke; Govaerts, Lutgarde; Boter, Marjan; Lont, Debora; van Veen, Stefanie; Joosten, Marieke; Diderich, Karin; Galjaard, Robert-Jan; Srebniak, Malgorzata I

    2015-03-01

    We present the nature of pathogenic SNP array findings in pregnancies without ultrasound (US) abnormalities and show the additional diagnostic value of SNP array as compared with rapid aneuploidy detection and karyotyping. 1,330 prenatal samples were investigated with a 0.5-Mb SNP array after the exclusion of the most common aneuploidies. In 2.7% (36/1,330) of the cases, pathogenic chromosome aberrations were found; a microscopically detectable abnormality in 0.7% and a submicroscopic aberration in 2%. Our results show that in addition to the age- or screening-related aneuploidy risk, in pregnancies without US abnormalities, there is a risk of 1:148 (9/1,330) for a (sub)microscopic abnormality associated with an early-onset often severe disease, 1:222 (6/1,330) for a submicroscopic aberration causing an early-onset disease, 1:74 (18/1,330) for carrying a susceptibility locus for a neurodevelopmental disorder, and 1:443 (3/1,330) for a late-onset disorder (hereditary neuropathy with liability to pressure palsies in all three cases). These risk figures are important for adequate pretest counseling so that prospective parents can make informed individualized choices between targeted prenatal testing and broad testing with SNP array. Based on our results, we believe if invasive testing is performed, SNP array should be the preferred cytogenetic technique irrespective of the indication.

  19. Single-cell SNP analyses and interpretations based on RNA-Seq data for colon cancer research

    PubMed Central

    Chen, Jiahuan; Zhou, Qian; Wang, Yangfan; Ning, Kang

    2016-01-01

    Single-cell sequencing is useful for illustrating the cellular heterogeneities inherent in many intricate biological systems, particularly in human cancer. However, owing to the difficulties in acquiring, amplifying and analyzing single-cell genetic material, obstacles remain for single-cell diversity assessments such as single nucleotide polymorphism (SNP) analyses, rendering biological interpretations of single-cell omics data elusive. We used RNA-Seq data from single-cell and bulk colon cancer samples to analyze the SNP profiles for both structural and functional comparisons. Colon cancer-related pathways with single-cell level SNP enrichment, including the TGF-β and p53 signaling pathways, were also investigated based on both their SNP enrichment patterns and gene expression. We also detected a certain number of fusion transcripts, which may promote tumorigenesis, at the single-cell level. Based on these results, single-cell analyses not only recapitulated the SNP analysis results from the bulk samples but also detected cell-to-cell and cell-to-bulk variations, thereby aiding in early diagnosis and in identifying the precise mechanisms underlying cancers at the single-cell level. PMID:27677461

  20. SNP annotation-based whole genomic prediction and selection: an application to feed efficiency and its component traits in pigs.

    PubMed

    Do, D N; Janss, L L G; Jensen, J; Kadarmideen, H N

    2015-05-01

    The study investigated genetic architecture and predictive ability using genomic annotation of residual feed intake (RFI) and its component traits (daily feed intake [DFI], ADG, and back fat [BF]). A total of 1,272 Duroc pigs had both genotypic and phenotypic records, and the records were split into a training (968 pigs) and a validation dataset (304 pigs) by assigning records as before and after January 1, 2012, respectively. SNP were annotated by 14 different classes using Ensembl variant effect prediction. Predictive accuracy and prediction bias were calculated using Bayesian Power LASSO, Bayesian A, B, and Cπ, and genomic BLUP (GBLUP) methods. Predictive accuracy ranged from 0.508 to 0.531, 0.506 to 0.532, 0.276 to 0.357, and 0.308 to 0.362 for DFI, RFI, ADG, and BF, respectively. BayesCπ100.1 increased accuracy slightly compared to the GBLUP model and other methods. The contribution per SNP to total genomic variance was similar among annotated classes across different traits. Predictive performance of SNP classes did not significantly differ from randomized SNP groups. Genomic prediction has accuracy comparable to observed phenotype, and use of genomic prediction can be cost effective by replacing feed intake measurement. Genomic annotation had less impact on predictive accuracy traits considered here but may be different for other traits. It is the first study to provide useful insights into biological classes of SNP driving the whole genomic prediction for complex traits in pigs.

  1. Studies of Energy Recovery Linacs at Jefferson Laboratory: 1 GeV Demonstration of Energy Recovery at CEBAF and Studies of the Multibunch, Multipass Beam Breakup Instability in the 10 kW FEL Upgrade Driver

    SciTech Connect

    Tennant, Christopher D.

    2006-10-01

    An energy recovering linac (ERL) offers an attractive alternative for generating intense beams of charged particles by approaching the operational efficiency of a storage ring while maintaining the superior beam quality typical of a linear accelerator. Two primary physics challenges exist in pushing the frontier of ERL performance. The first is energy recovering a high energy beam while demonstrating operational control of two coupled beams in a common transport channel. The second is controlling the high average current effects in ERLs, specifically a type of beam instability called multipass beam breakup (BBU). This work addresses both of these issues. A successful 1 GeV energy recovery demonstration with a maximum-to-injection energy ratio of 51:1 was carried out on the Continuous Electron Beam Accelerator Facility at Jefferson Laboratory in an effort to address issues related to beam quality preservation in a large scale system. With a 1.3 km recirculation length and containing 312 superconducting radio frequency (SRF) cavities, this experiment has demonstrated energy recovery on the largest scale, and through the largest SRF environment, to date. The BBU instability imposes a potentially severe limitation to the average current that can be accelerated in an ERL. Simulation results for Jefferson Laboratory's 10 kW free electron laser (FEL) Upgrade Driver predict the occurrence of BBU below the nominal operating current. Measurements of the threshold current are described and shown to agree to within 10% of predictions from BBU simulation codes. This represents the first time the codes have been benchmarked with experimental data. With BBU limiting the beam current, several suppression schemes were developed. These include direct damping of the higher-order mode using two different cavity-based feedbacks and modifying the electron beam optics to reduce the coupling between the beam and mode. Specifically the effect of implementing (1) point-to-point focusing (2

  2. GStream: improving SNP and CNV coverage on genome-wide association studies.

    PubMed

    Alonso, Arnald; Marsal, Sara; Tortosa, Raül; Canela-Xandri, Oriol; Julià, Antonio

    2013-01-01

    We present GStream, a method that combines genome-wide SNP and CNV genotyping in the Illumina microarray platform with unprecedented accuracy. This new method outperforms previous well-established SNP genotyping software. More importantly, the CNV calling algorithm of GStream dramatically improves the results obtained by previous state-of-the-art methods and yields an accuracy that is close to that obtained by purely CNV-oriented technologies like Comparative Genomic Hybridization (CGH). We demonstrate the superior performance of GStream using microarray data generated from HapMap samples. Using the reference CNV calls generated by the 1000 Genomes Project (1KGP) and well-known studies on whole genome CNV characterization based either on CGH or genotyping microarray technologies, we show that GStream can increase the number of reliably detected variants up to 25% compared to previously developed methods. Furthermore, the increased genome coverage provided by GStream allows the discovery of CNVs in close linkage disequilibrium with SNPs, previously associated with disease risk in published Genome-Wide Association Studies (GWAS). These results could provide important insights into the biological mechanism underlying the detected disease risk association. With GStream, large-scale GWAS will not only benefit from the combined genotyping of SNPs and CNVs at an unprecedented accuracy, but will also take advantage of the computational efficiency of the method.

  3. GStream: Improving SNP and CNV Coverage on Genome-Wide Association Studies

    PubMed Central

    Alonso, Arnald; Marsal, Sara; Tortosa, Raül; Canela-Xandri, Oriol; Julià, Antonio

    2013-01-01

    We present GStream, a method that combines genome-wide SNP and CNV genotyping in the Illumina microarray platform with unprecedented accuracy. This new method outperforms previous well-established SNP genotyping software. More importantly, the CNV calling algorithm of GStream dramatically improves the results obtained by previous state-of-the-art methods and yields an accuracy that is close to that obtained by purely CNV-oriented technologies like Comparative Genomic Hybridization (CGH). We demonstrate the superior performance of GStream using microarray data generated from HapMap samples. Using the reference CNV calls generated by the 1000 Genomes Project (1KGP) and well-known studies on whole genome CNV characterization based either on CGH or genotyping microarray technologies, we show that GStream can increase the number of reliably detected variants up to 25% compared to previously developed methods. Furthermore, the increased genome coverage provided by GStream allows the discovery of CNVs in close linkage disequilibrium with SNPs, previously associated with disease risk in published Genome-Wide Association Studies (GWAS). These results could provide important insights into the biological mechanism underlying the detected disease risk association. With GStream, large-scale GWAS will not only benefit from the combined genotyping of SNPs and CNVs at an unprecedented accuracy, but will also take advantage of the computational efficiency of the method. PMID:23844243

  4. Varietal identification of tea (Camellia sinensis) using nanofluidic array of single nucleotide polymorphism (SNP) markers

    PubMed Central

    Fang, Wan-Ping; Meinhardt, Lyndel W; Tan, Hua-Wei; Zhou, Lin; Mischke, Sue; Zhang, Dapeng

    2014-01-01

    Apart from water, tea is the world’s most widely consumed beverage. Tea is produced in more than 50 countries with an annual production of approximately 4.7 million tons. The market segment for specialty tea has been expanding rapidly owing to increased demand, resulting in higher revenues and profits for tea growers and the industry. Accurate varietal identification is critically important to ensure traceability and authentication of premium tea products, which in turn contribute to on-farm conservation of tea genetic diversity. Using a set of single nucleotide polymorphism (SNP) markers developed from the expressed sequence tag (EST) database of Camilla senensis, we genotyped deoxyribonucleic acid (DNA) samples extracted from a diverse group of tea varieties, including both fresh and processed commercial loose-leaf teas. The validation led to the designation of 60 SNPs that unambiguously identified all 40 tested tea varieties with high statistical rigor (p<0.0001). Varietal authenticity and genetic relationships among the analyzed cultivars were further characterized by ordination and Bayesian clustering analysis. These SNP markers, in combination with a high-throughput genotyping protocol, effectively established and verified specific DNA fingerprints for all tested tea varieties. This method provides a powerful tool for variety authentication and quality control for the tea industry. It is also highly useful for the management of tea genetic resources and breeding, where accurate and efficient genotype identification is essential. PMID:26504544

  5. Fast and Rigorous Computation of Gene and Pathway Scores from SNP-Based Summary Statistics.

    PubMed

    Lamparter, David; Marbach, Daniel; Rueedi, Rico; Kutalik, Zoltán; Bergmann, Sven

    2016-01-01

    Integrating single nucleotide polymorphism (SNP) p-values from genome-wide association studies (GWAS) across genes and pathways is a strategy to improve statistical power and gain biological insight. Here, we present Pascal (Pathway scoring algorithm), a powerful tool for computing gene and pathway scores from SNP-phenotype association summary statistics. For gene score computation, we implemented analytic and efficient numerical solutions to calculate test statistics. We examined in particular the sum and the maximum of chi-squared statistics, which measure the strongest and the average association signals per gene, respectively. For pathway scoring, we use a modified Fisher method, which offers not only significant power improvement over more traditional enrichment strategies, but also eliminates the problem of arbitrary threshold selection inherent in any binary membership based pathway enrichment approach. We demonstrate the marked increase in power by analyzing summary statistics from dozens of large meta-studies for various traits. Our extensive testing indicates that our method not only excels in rigorous type I error control, but also results in more biologically meaningful discoveries.

  6. Testing the performance of mtSNP minisequencing in forensic samples.

    PubMed

    Mosquera-Miguel, A; Alvarez-Iglesias, V; Cerezo, M; Lareu, M V; Carracedo, A; Salas, A

    2009-09-01

    There is a growing interest among forensic geneticists in developing efficient protocols for genotyping coding region mitochondrial DNA (mtDNA) SNPs (mtSNPs). Minisequencing is becoming a popular method for SNP genotyping, but it is still used by few forensic laboratories. In part, this is due to the lack of studies testing its efficiency and reproducibility when applied to real and complex forensic samples. Here we tested a minisequencing design that consists of 71 mtSNPs (in three multiplexes) that are diagnostic of known branches of the R0 phylogeny, in real forensic samples, including degraded bones and teeth, hair shafts, and serial dilutions. The fact that amplicons are short coupled with the natural efficiency of the minisequencing technique allow these assays to perform well with all the samples tested either degraded and/or those containing low DNA amount. We did not observe phylogenetic inconsistencies in the 71 mtSNP haplotypes generated, indicating that the technique is robust against potential artefacts that could arise from unintended contamination and/or spurious amplification of nuclear mtDNA pseudogenes (NUMTs).

  7. Transcriptome sequencing to produce SNP-based genetic maps of onion.

    PubMed

    Duangjit, J; Bohanec, B; Chan, A P; Town, C D; Havey, M J

    2013-08-01

    We used the Roche-454 platform to sequence from normalized cDNA libraries from each of two inbred lines of onion (OH1 and 5225). From approximately 1.6 million reads from each inbred, 27,065 and 33,254 cDNA contigs were assembled from OH1 and 5225, respectively. In total, 3,364 well supported single nucleotide polymorphisms (SNPs) on 1,716 cDNA contigs were identified between these two inbreds. One SNP on each of 1,256 contigs was randomly selected for genotyping. OH1 and 5225 were crossed and 182 gynogenic haploids extracted from hybrid plants were used for SNP mapping. A total of 597 SNPs segregated in the OH1 × 5225 haploid family and a genetic map of ten linkage groups (LOD ≥8) was constructed. Three hundred and thirty-nine of the newly identified SNPs were also mapped using a previously developed segregating family from BYG15-23 × AC43, and 223 common SNPs were used to join the two maps. Because these new SNPs are in expressed regions of the genome and commonly occur among onion germplasms, they will be useful for genetic mapping, gene tagging, marker-aided selection, quality control of seed lots, and fingerprinting of cultivars.

  8. Linkage Disequilibrium Estimation of Chinese Beef Simmental Cattle Using High-density SNP Panels

    PubMed Central

    Zhu, M.; Zhu, B.; Wang, Y. H.; Wu, Y.; Xu, L.; Guo, L. P.; Yuan, Z. R.; Zhang, L. P.; Gao, X.; Gao, H. J.; Xu, S. Z.; Li, J. Y.

    2013-01-01

    Linkage disequilibrium (LD) plays an important role in genomic selection and mapping quantitative trait loci (QTL). In this study, the pattern of LD and effective population size (Ne) were investigated in Chinese beef Simmental cattle. A total of 640 bulls were genotyped with IlluminaBovinSNP50BeadChip and IlluminaBovinHDBeadChip. We estimated LD for each autosomal chromosome at the distance between two random SNPs of <0 to 25 kb, 25 to 50 kb, 50 to 100 kb, 100 to 500 kb, 0.5 to 1 Mb, 1 to 5 Mb and 5 to 10 Mb. The mean values of r2 were 0.30, 0.16 and 0.08, when the separation between SNPs ranged from 0 to 25 kb to 50 to 100 kb and then to 0.5 to 1 Mb, respectively. The LD estimates decreased as the distance increased in SNP pairs, and increased with the increase of minor allelic frequency (MAF) and with the decrease of sample sizes. Estimates of effective population size for Chinese beef Simmental cattle decreased in the past generations and Ne was 73 at five generations ago. PMID:25049849

  9. PrimerMapper: high throughput primer design and graphical assembly for PCR and SNP detection

    PubMed Central

    O’Halloran, Damien M.

    2016-01-01

    Primer design represents a widely employed gambit in diverse molecular applications including PCR, sequencing, and probe hybridization. Variations of PCR, including primer walking, allele-specific PCR, and nested PCR provide specialized validation and detection protocols for molecular analyses that often require screening large numbers of DNA fragments. In these cases, automated sequence retrieval and processing become important features, and furthermore, a graphic that provides the user with a visual guide to the distribution of designed primers across targets is most helpful in quickly ascertaining primer coverage. To this end, I describe here, PrimerMapper, which provides a comprehensive graphical user interface that designs robust primers from any number of inputted sequences while providing the user with both, graphical maps of primer distribution for each inputted sequence, and also a global assembled map of all inputted sequences with designed primers. PrimerMapper also enables the visualization of graphical maps within a browser and allows the user to draw new primers directly onto the webpage. Other features of PrimerMapper include allele-specific design features for SNP genotyping, a remote BLAST window to NCBI databases, and remote sequence retrieval from GenBank and dbSNP. PrimerMapper is hosted at GitHub and freely available without restriction. PMID:26853558

  10. SNPsplit: Allele-specific splitting of alignments between genomes with known SNP genotypes

    PubMed Central

    Krueger, Felix; Andrews, Simon R.

    2016-01-01

    Sequencing reads overlapping polymorphic sites in diploid mammalian genomes may be assigned to one allele or the other. This holds the potential to detect gene expression, chromatin modifications, DNA methylation or nuclear interactions in an allele-specific fashion. SNPsplit is an allele-specific alignment sorter designed to read files in SAM/BAM format and determine the allelic origin of reads or read-pairs that cover known single nucleotide polymorphic (SNP) positions. For this to work libraries must have been aligned to a genome in which all known SNP positions were masked with the ambiguity base 'N' and aligned using a suitable mapping program such as Bowtie2, TopHat, STAR, HISAT2, HiCUP or Bismark. SNPsplit also provides an automated solution to generate N-masked reference genomes for hybrid mouse strains based on the variant call information provided by the Mouse Genomes Project. The unique ability of SNPsplit to work with various different kinds of sequencing data including RNA-Seq, ChIP-Seq, Bisulfite-Seq or Hi-C opens new avenues for the integrative exploration of allele-specific data. PMID:27429743

  11. Human Y-chromosome SNP characterization by multiplex amplified product-length polymorphism analysis.

    PubMed

    Medina, Laura Smeldy Jurado; Muzzio, Marina; Schwab, Marisol; Costantino, María Leticia Bravi; Barreto, Guillermo; Bailliet, Graciela

    2014-09-01

    We designed an allele-specific amplification protocol to optimize Y-chromosome SNP typing, which is an unavoidable step for defining the phylogenetic status of paternal lineages. It allows the simultaneous highly specific definition of up to six mutations in a single reaction by amplification fragment length polymorphism (AFLP) without the need of specialized equipment, at a considerably lower cost than that based on single-base primer extension (SNaPshot™) technology or PCR-RFLP systems, requiring as little as 0.5 ng DNA and compatible with the small fragments characteristic of low-quality DNA. By designation of two primers recognizing the derived and ancestral state for each SNP, which can be differentiated by size by the addition of a noncomplementary nucleotide tail, we could define major Y clades E, F, K, R, Q, and subhaplogroups R1, R1a, R1b, R1b1b, R1b1c, J1, J2, G1, G2, I1, Q1a3, and Q1a3a1 through amplification fragments that ranged between 60 and 158bp. PMID:24846779

  12. Coding region SNP analysis to enhance dog mtDNA discrimination power in forensic casework.

    PubMed

    Verscheure, Sophie; Backeljau, Thierry; Desmyter, Stijn

    2015-01-01

    The high population frequencies of three control region haplotypes contribute to the low discrimination power of the dog mtDNA control region. It also diminishes the evidential power of a match with one of these haplotypes in forensic casework. A mitochondrial genome study of 214 Belgian dogs suggested 26 polymorphic coding region sites that successfully resolved dogs with the three most frequent control region haplotypes. In this study, three SNP assays were developed to determine the identity of the 26 informative sites. The control region of 132 newly sampled dogs was sequenced and added to the study of 214 dogs. The assays were applied to 58 dogs of the haplotypes of interest, which confirmed their suitability for enhancing dog mtDNA discrimination power. In the Belgian population study of 346 dogs, the set of 26 sites divided the dogs into 25 clusters of mtGenome sequences with substantially lower population frequency estimates than their control region sequences. In case of a match with one of the three control region haplotypes, using these three SNP assays in conjunction with control region sequencing would augment the exclusion probability of dog mtDNA analysis from 92.9% to 97.0%.

  13. Uncovering hidden variance: pair-wise SNP analysis accounts for additional variance in nicotine dependence

    PubMed Central

    Culverhouse, Robert C.; Saccone, Nancy L.; Stitzel, Jerry A.; Wang, Jen C.; Steinbach, Joseph H.; Goate, Alison M.; Schwantes-An, Tae-Hwi; Grucza, Richard A.; Stevens, Victoria L.; Bierut, Laura J.

    2010-01-01

    Results from genome-wide association studies of complex traits account for only a modest proportion of the trait variance predicted to be due to genetics. We hypothesize that joint analysis of polymorphisms may account for more variance. We evaluated this hypothesis on a case–control smoking phenotype by examining pairs of nicotinic receptor single-nucleotide polymorphisms (SNPs) using the Restricted Partition Method (RPM) on data from the Collaborative Genetic Study of Nicotine Dependence (COGEND). We found evidence of joint effects that increase explained variance. Four signals identified in COGEND were testable in independent American Cancer Society (ACS) data, and three of the four signals replicated. Our results highlight two important lessons: joint effects that increase the explained variance are not limited to loci displaying substantial main effects, and joint effects need not display a significant interaction term in a logistic regression model. These results suggest that the joint analyses of variants may indeed account for part of the genetic variance left unexplained by single SNP analyses. Methodologies that limit analyses of joint effects to variants that demonstrate association in single SNP analyses, or require a significant interaction term, will likely miss important joint effects. PMID:21079997

  14. Three clinical experiences with SNP array results consistent with parental incest: a narrative with lessons learned.

    PubMed

    Helm, Benjamin M; Langley, Katherine; Spangler, Brooke; Vergano, Samantha

    2014-08-01

    Single nucleotide polymorphism microarrays have the ability to reveal parental consanguinity which may or may not be known to healthcare providers. Consanguinity can have significant implications for the health of patients and for individual and family psychosocial well-being. These results often present ethical and legal dilemmas that can have important ramifications. Unexpected consanguinity can be confounding to healthcare professionals who may be unprepared to handle these results or to communicate them to families or other appropriate representatives. There are few published accounts of experiences with consanguinity and SNP arrays. In this paper we discuss three cases where molecular evidence of parental incest was identified by SNP microarray. We hope to further highlight consanguinity as a potential incidental finding, how the cases were handled by the clinical team, and what resources were found to be most helpful. This paper aims to contribute further to professional discourse on incidental findings with genomic technology and how they were addressed clinically. These experiences may provide some guidance on how others can prepare for these findings and help improve practice. As genetic and genomic testing is utilized more by non-genetics providers, we also hope to inform about the importance of engaging with geneticists and genetic counselors when addressing these findings.

  15. Heritability of Recurrent Exertional Rhabdomyolysis in Standardbred and Thoroughbred Racehorses Derived From SNP Genotyping Data.

    PubMed

    Norton, Elaine M; Mickelson, James R; Binns, Matthew M; Blott, Sarah C; Caputo, Paul; Isgren, Cajsa M; McCoy, Annette M; Moore, Alison; Piercy, Richard J; Swinburne, June E; Vaudin, Mark; McCue, Molly E

    2016-11-01

    Recurrent exertional rhabdomyolysis (RER) in Thoroughbred and Standardbred racehorses is characterized by episodes of muscle rigidity and cell damage that often recur upon strenuous exercise. The objective was to evaluate the importance of genetic factors in RER by obtaining an unbiased estimate of heritability in cohorts of unrelated Thoroughbred and Standardbred racehorses. Four hundred ninety-one Thoroughbred and 196 Standardbred racehorses were genotyped with the 54K or 74K SNP genotyping arrays. Heritability was calculated from genome-wide SNP data with a mixed linear and Bayesian model, utilizing the standard genetic relationship matrix (GRM). Both the mixed linear and Bayesian models estimated heritability of RER in Thoroughbreds to be approximately 0.34 and in Standardbred racehorses to be approximately 0.45 after adjusting for disease prevalence and sex. To account for potential differences in the genetic architecture of the underlying causal variants, heritability estimates were adjusted based on linkage disequilibrium weighted kinship matrix, minor allele frequency and variant effect size, yielding heritability estimates that ranged between 0.41-0.46 (Thoroughbreds) and 0.39-0.49 (Standardbreds). In conclusion, between 34-46% and 39-49% of the variance in RER susceptibility in Thoroughbred and Standardbred racehorses, respectively, can be explained by the SNPs present on these 2 genotyping arrays, indicating that RER is moderately heritable. These data provide further rationale for the investigation of genetic mutations associated with RER susceptibility.

  16. SNP Miniplexes for Individual Identification of Random-Bred Domestic Cats.

    PubMed

    Brooks, Ashley; Creighton, Erica K; Gandolfi, Barbara; Khan, Razib; Grahn, Robert A; Lyons, Leslie A

    2016-05-01

    Phenotypic and genotypic characteristics of the cat can be obtained from single nucleotide polymorphisms (SNPs) analyses of fur. This study developed miniplexes using SNPs with high discriminating power for random-bred domestic cats, focusing on individual and phenotypic identification. Seventy-eight SNPs were investigated using a multiplex PCR followed by a fluorescently labeled single base extension (SBE) technique (SNaPshot(®) ). The SNP miniplexes were evaluated for reliability, reproducibility, sensitivity, species specificity, detection limitations, and assignment accuracy. Six SNPplexes were developed containing 39 intergenic SNPs and 26 phenotypic SNPs, including a sex identification marker, ZFXY. The combined random match probability (cRMP) was 6.58 × 10(-19) across all Western cat populations and the likelihood ratio was 1.52 × 10(18) . These SNPplexes can distinguish individual cats and their phenotypic traits, which could provide insight into crime reconstructions. A SNP database of 237 cats from 13 worldwide populations is now available for forensic applications.

  17. Coding region SNP analysis to enhance dog mtDNA discrimination power in forensic casework.

    PubMed

    Verscheure, Sophie; Backeljau, Thierry; Desmyter, Stijn

    2015-01-01

    The high population frequencies of three control region haplotypes contribute to the low discrimination power of the dog mtDNA control region. It also diminishes the evidential power of a match with one of these haplotypes in forensic casework. A mitochondrial genome study of 214 Belgian dogs suggested 26 polymorphic coding region sites that successfully resolved dogs with the three most frequent control region haplotypes. In this study, three SNP assays were developed to determine the identity of the 26 informative sites. The control region of 132 newly sampled dogs was sequenced and added to the study of 214 dogs. The assays were applied to 58 dogs of the haplotypes of interest, which confirmed their suitability for enhancing dog mtDNA discrimination power. In the Belgian population study of 346 dogs, the set of 26 sites divided the dogs into 25 clusters of mtGenome sequences with substantially lower population frequency estimates than their control region sequences. In case of a match with one of the three control region haplotypes, using these three SNP assays in conjunction with control region sequencing would augment the exclusion probability of dog mtDNA analysis from 92.9% to 97.0%. PMID:25299153

  18. SNP diversity within and among Brassica rapa accessions reveals no geographic differentiation.

    PubMed

    Tanhuanpää, P; Erkkilä, M; Tenhola-Roininen, T; Tanskanen, J; Manninen, O

    2016-01-01

    Genetic diversity was studied in a collection of 61 accessions of Brassica rapa, which were mostly oil-type turnip rapes but also included two oil-type subsp. dichotoma and five subsp. trilocularis accessions, as well as three leaf-type subspecies (subsp. japonica, pekinensis, and chinensis) and five turnip cultivars (subsp. rapa). Two-hundred and nine SNP markers, which had been discovered by amplicon resequencing, were used to genotype 893 plants from the B. rapa collection using Illumina BeadXpress. There was great variation in the diversity indices between accessions. With STRUCTURE analysis, the plant collection could be divided into three groups that seemed to correspond to morphotype and flowering habit but not to geography. According to AMOVA analysis, 65% of the variation was due to variation within accessions, 25% among accessions, and 10% among groups. A smaller subset of the plant collection, 12 accessions, was also studied with 5727 GBS-SNPs. Diversity indices obtained with GBS-SNPs correlated well with those obtained with Illumina BeadXpress SNPs. The developed SNP markers have already been used and will be used in future plant breeding programs as well as in mapping and diversity studies.

  19. Identification of close relatives in the HUGO Pan-Asian SNP database.

    PubMed

    Yang, Xiong; Xu, Shuhua

    2011-01-01

    The HUGO Pan-Asian SNP Consortium has recently released a genome-wide dataset, which consists of 1,719 DNA samples collected from 71 Asian populations. For studies of human population genetics such as genetic structure and migration history, this provided the most comprehensive large-scale survey of genetic variation to date in East and Southeast Asia. However, although considered in the analysis, close relatives were not clearly reported in the original paper. Here we performed a systematic analysis of genetic relationships among individuals from the Pan-Asian SNP (PASNP) database and identified 3 pairs of monozygotic twins or duplicate samples, 100 pairs of first-degree and 161 second-degree of relationships. Three standardized subsets with different levels of unrelated individuals were suggested here for future applications of the samples in most types of population-genetics studies (denoted by PASNP1716, PASNP1640 and PASNP1583 respectively) based on the relationships inferred in this study. In addition, we provided gender information for PASNP samples, which were not included in the original dataset, based on analysis of X chromosome data.

  20. PrimerMapper: high throughput primer design and graphical assembly for PCR and SNP detection.

    PubMed

    O'Halloran, Damien M

    2016-01-01

    Primer design represents a widely employed gambit in diverse molecular applications including PCR, sequencing, and probe hybridization. Variations of PCR, including primer walking, allele-specific PCR, and nested PCR provide specialized validation and detection protocols for molecular analyses that often require screening large numbers of DNA fragments. In these cases, automated sequence retrieval and processing become important features, and furthermore, a graphic that provides the user with a visual guide to the distribution of designed primers across targets is most helpful in quickly ascertaining primer coverage. To this end, I describe here, PrimerMapper, which provides a comprehensive graphical user interface that designs robust primers from any number of inputted sequences while providing the user with both, graphical maps of primer distribution for each inputted sequence, and also a global assembled map of all inputted sequences with designed primers. PrimerMapper also enables the visualization of graphical maps within a browser and allows the user to draw new primers directly onto the webpage. Other features of PrimerMapper include allele-specific design features for SNP genotyping, a remote BLAST window to NCBI databases, and remote sequence retrieval from GenBank and dbSNP. PrimerMapper is hosted at GitHub and freely available without restriction. PMID:26853558

  1. Fast and Rigorous Computation of Gene and Pathway Scores from SNP-Based Summary Statistics

    PubMed Central

    Rueedi, Rico; Kutalik, Zoltán; Bergmann, Sven

    2016-01-01

    Integrating single nucleotide polymorphism (SNP) p-values from genome-wide association studies (GWAS) across genes and pathways is a strategy to improve statistical power and gain biological insight. Here, we present Pascal (Pathway scoring algorithm), a powerful tool for computing gene and pathway scores from SNP-phenotype association summary statistics. For gene score computation, we implemented analytic and efficient numerical solutions to calculate test statistics. We examined in particular the sum and the maximum of chi-squared statistics, which measure the strongest and the average association signals per gene, respectively. For pathway scoring, we use a modified Fisher method, which offers not only significant power improvement over more traditional enrichment strategies, but also eliminates the problem of arbitrary threshold selection inherent in any binary membership based pathway enrichment approach. We demonstrate the marked increase in power by analyzing summary statistics from dozens of large meta-studies for various traits. Our extensive testing indicates that our method not only excels in rigorous type I error control, but also results in more biologically meaningful discoveries. PMID:26808494

  2. Differentiation of drug and non-drug Cannabis using a single nucleotide polymorphism (SNP) assay.

    PubMed

    Rotherham, D; Harbison, S A

    2011-04-15

    Cannabis sativa is both an illegal drug and a legitimate crop. The differentiation of illegal drug Cannabis from non-drug forms of Cannabis is relevant in the context of the growth of fibre and seed oil varieties of Cannabis for commercial purposes. This differentiation is currently determined based on the levels of tetrahydrocannabinol (THC) in adult plants. DNA based methods have the potential to assay Cannabis material unsuitable for analysis using conventional means including seeds, pollen and severely degraded material. The purpose of this research was to develop a single nucleotide polymorphism (SNP) assay for the differentiation of "drug" and "non-drug"Cannabis plants. An assay was developed based on four polymorphisms within a 399 bp fragment of the tetrahydrocannabinolic acid (THCA) synthase gene, utilising the snapshot multiplex kit. This SNP assay was tested on 94 Cannabis plants, which included 10 blind samples, and was able to differentiate between "drug" and "non-drug"Cannabis in all cases, while also differentiating between Cannabis and other species. Non-drug plants were found to be homozygous at the four sites assayed while drug Cannabis plants were either homozygous or heterozygous.

  3. Cancer Gene Prioritization for Targeted Resequencing Using FitSNP Scores

    PubMed Central

    Fieuw, Annelies; De Wilde, Bram; Speleman, Frank

    2012-01-01

    Background Although the throughput of next generation sequencing is increasing and at the same time the cost is substantially reduced, for the majority of laboratories whole genome sequencing of large cohorts of cancer samples is still not feasible. In addition, the low number of genomes that are being sequenced is often problematic for the downstream interpretation of the significance of the variants. Targeted resequencing can partially circumvent this problem; by focusing on a limited number of candidate cancer genes to sequence, more samples can be included in the screening, hence resulting in substantial improvement of the statistical power. In this study, a successful strategy for prioritizing candidate genes for targeted resequencing of cancer genomes is presented. Results Four prioritization strategies were evaluated on six different cancer types: genes were ranked using these strategies, and the positive predictive value (PPV) or mutation rate within the top-ranked genes was compared to the baseline mutation rate in each tumor type. Successful strategies generate gene lists in which the top is enriched for known mutated genes, as evidenced by an increase in PPV. A clear example of such an improvement is seen in colon cancer, where the PPV is increased by 2.3 fold compared to the baseline level when 100 top fitSNP genes are sequenced. Conclusions A gene prioritization strategy based on the fitSNP scores appears to be most successful in identifying mutated cancer genes across different tumor entities, with variance of gene expression levels as a good second best. PMID:22396732

  4. Screening for replication of genome-wide SNP associations in sporadic ALS

    PubMed Central

    Cronin, Simon; Tomik, Barbara; Bradley, Daniel G; Slowik, Agnieszka; Hardiman, Orla

    2009-01-01

    We recently reported a joint analysis of genome-wide association (GWA) data on 958 sporadic amyotrophic lateral sclerosis (ALS) cases and 932 controls from Ireland and the publicly available data sets from the United States and the Netherlands. The strongest pooled association was rs10260404 in the dipeptidyl-peptidase 6 (DPP6) gene. Here, we sought confirmation of joint analysis signals in both an expanded Irish and a Polish ALS cohort. Among 287 522 autosomal single-nucleotide polymorphisms (SNPs), 27 were commonly associated on joint analysis of the Irish, US and Dutch GWAs. These 27 SNPs were genotyped in an expanded Irish cohort (312 patients with SALS; 259 controls) and an additional Polish cohort (218 patients; 356 controls). Eleven SNPs, including rs10260404, reached a final P-value below 0.05 in the Irish cohort. In the Polish cohort, only one SNP, rs6299711, showed nominal association with ALS. Pooling of data for 1267 patients with ALS and 1336 control subjects did not identify any association reaching Bonferroni significance (P<1.74 × 10−7). The present strategy did not reveal any consistently associated SNP across four populations. The result for DPP6 is surprising, as it has been replicated elsewhere. We discuss the possible interpretations and implications of these findings for future ALS GWA studies both within and between populations. PMID:18987618

  5. Diversity in 113 cowpea [Vigna unguiculata (L) Walp] accessions assessed with 458 SNP markers.

    PubMed

    Egbadzor, Kenneth F; Ofori, Kwadwo; Yeboah, Martin; Aboagye, Lawrence M; Opoku-Agyeman, Michael O; Danquah, Eric Y; Offei, Samuel K

    2014-01-01

    Single Nucleotide Polymorphism (SNP) markers were used in characterization of 113 cowpea accessions comprising of 108 from Ghana and 5 from abroad. Leaf tissues from plants cultivated at the University of Ghana were genotyped at KBioscience in the United Kingdom. Data was generated for 477 SNPs, out of which 458 revealed polymorphism. The results were used to analyze genetic dissimilarity among the accessions using Darwin 5 software. The markers discriminated among all of the cowpea accessions and the dissimilarity values which ranged from 0.006 to 0.63 were used for factorial plot. Unexpected high levels of heterozygosity were observed on some of the accessions. Accessions known to be closely related clustered together in a dendrogram drawn with WPGMA method. A maximum length sub-tree which comprised of 48 core accessions was constructed. The software package structure was used to separate accessions into three groups, and the programme correctly identified varieties that were known hybrids. The hybrids were those accessions with numerous heterozygous loci. The structure plot showed closely related accessions with similar genome patterns. The SNP markers were more efficient in discriminating among the cowpea germplasm than morphological, seed protein polymorphism and simple sequence repeat studies reported earlier on the same collection. PMID:25332852

  6. SNP genotyping and population genomics from expressed sequences - current advances and future possibilities.

    PubMed

    De Wit, Pierre; Pespeni, Melissa H; Palumbi, Stephen R

    2015-05-01

    With the rapid increase in production of genetic data from new sequencing technologies, a myriad of new ways to study genomic patterns in nonmodel organisms are currently possible. Because genome assembly still remains a complicated procedure, and because the functional role of much of the genome is unclear, focusing on SNP genotyping from expressed sequences provides a cost-effective way to reduce complexity while still retaining functionally relevant information. This review summarizes current methods, identifies ways that using expressed sequence data benefits population genomic inference and explores how current practitioners evaluate and overcome challenges that are commonly encountered. We focus particularly on the additional power of functional analysis provided by expressed sequence data and how these analyses push beyond allele pattern data available from nonfunction genomic approaches. The massive data sets generated by these approaches create opportunities and problems as well - especially false positives. We discuss methods available to validate results from expressed SNP genotyping assays, new approaches that sidestep use of mRNA and review follow-up experiments that can focus on evolutionary mechanisms acting across the genome.

  7. Heritability of Recurrent Exertional Rhabdomyolysis in Standardbred and Thoroughbred Racehorses Derived From SNP Genotyping Data.

    PubMed

    Norton, Elaine M; Mickelson, James R; Binns, Matthew M; Blott, Sarah C; Caputo, Paul; Isgren, Cajsa M; McCoy, Annette M; Moore, Alison; Piercy, Richard J; Swinburne, June E; Vaudin, Mark; McCue, Molly E

    2016-11-01

    Recurrent exertional rhabdomyolysis (RER) in Thoroughbred and Standardbred racehorses is characterized by episodes of muscle rigidity and cell damage that often recur upon strenuous exercise. The objective was to evaluate the importance of genetic factors in RER by obtaining an unbiased estimate of heritability in cohorts of unrelated Thoroughbred and Standardbred racehorses. Four hundred ninety-one Thoroughbred and 196 Standardbred racehorses were genotyped with the 54K or 74K SNP genotyping arrays. Heritability was calculated from genome-wide SNP data with a mixed linear and Bayesian model, utilizing the standard genetic relationship matrix (GRM). Both the mixed linear and Bayesian models estimated heritability of RER in Thoroughbreds to be approximately 0.34 and in Standardbred racehorses to be approximately 0.45 after adjusting for disease prevalence and sex. To account for potential differences in the genetic architecture of the underlying causal variants, heritability estimates were adjusted based on linkage disequilibrium weighted kinship matrix, minor allele frequency and variant effect size, yielding heritability estimates that ranged between 0.41-0.46 (Thoroughbreds) and 0.39-0.49 (Standardbreds). In conclusion, between 34-46% and 39-49% of the variance in RER susceptibility in Thoroughbred and Standardbred racehorses, respectively, can be explained by the SNPs present on these 2 genotyping arrays, indicating that RER is moderately heritable. These data provide further rationale for the investigation of genetic mutations associated with RER susceptibility. PMID:27489252

  8. Diversity in 113 cowpea [Vigna unguiculata (L) Walp] accessions assessed with 458 SNP markers.

    PubMed

    Egbadzor, Kenneth F; Ofori, Kwadwo; Yeboah, Martin; Aboagye, Lawrence M; Opoku-Agyeman, Michael O; Danquah, Eric Y; Offei, Samuel K

    2014-01-01

    Single Nucleotide Polymorphism (SNP) markers were used in characterization of 113 cowpea accessions comprising of 108 from Ghana and 5 from abroad. Leaf tissues from plants cultivated at the University of Ghana were genotyped at KBioscience in the United Kingdom. Data was generated for 477 SNPs, out of which 458 revealed polymorphism. The results were used to analyze genetic dissimilarity among the accessions using Darwin 5 software. The markers discriminated among all of the cowpea accessions and the dissimilarity values which ranged from 0.006 to 0.63 were used for factorial plot. Unexpected high levels of heterozygosity were observed on some of the accessions. Accessions known to be closely related clustered together in a dendrogram drawn with WPGMA method. A maximum length sub-tree which comprised of 48 core accessions was constructed. The software package structure was used to separate accessions into three groups, and the programme correctly identified varieties that were known hybrids. The hybrids were those accessions with numerous heterozygous loci. The structure plot showed closely related accessions with similar genome patterns. The SNP markers were more efficient in discriminating among the cowpea germplasm than morphological, seed protein polymorphism and simple sequence repeat studies reported earlier on the same collection.

  9. Whole-Genome Analysis of Diversity and SNP-Major Gene Association in Peach Germplasm

    PubMed Central

    Micheletti, Diego; Dettori, Maria Teresa; Micali, Sabrina; Aramini, Valeria; Pacheco, Igor; Da Silva Linge, Cassia; Foschi, Stefano; Banchi, Elisa; Barreneche, Teresa; Quilot-Turion, Bénédicte; Lambert, Patrick; Pascal, Thierry; Iglesias, Ignasi; Carbó, Joaquim; Wang, Li-rong; Ma, Rui-juan; Li, Xiong-wei; Gao, Zhong-shan; Nazzicari, Nelson; Troggio, Michela; Bassi, Daniele; Rossini, Laura; Verde, Ignazio; Laurens, François; Arús, Pere; Aranzana, Maria José

    2015-01-01

    Peach was domesticated in China more than four millennia ago and from there it spread world-wide. Since the middle of the last century, peach breeding programs have been very dynamic generating hundreds of new commercial varieties, however, in most cases such varieties derive from a limited collection of parental lines (founders). This is one reason for the observed low levels of variability of the commercial gene pool, implying that knowledge of the extent and distribution of genetic variability in peach is critical to allow the choice of adequate parents to confer enhanced productivity, adaptation and quality to improved varieties. With this aim we genotyped 1,580 peach accessions (including a few closely related Prunus species) maintained and phenotyped in five germplasm collections (four European and one Chinese) with the International Peach SNP Consortium 9K SNP peach array. The study of population structure revealed the subdivision of the panel in three main populations, one mainly made up of Occidental varieties from breeding programs (POP1OCB), one of Occidental landraces (POP2OCT) and the third of Oriental accessions (POP3OR). Analysis of linkage disequilibrium (LD) identified differential patterns of genome-wide LD blocks in each of the populations. Phenotypic data for seven monogenic traits were integrated in a genome-wide association study (GWAS). The significantly associated SNPs were always in the regions predicted by linkage analysis, forming haplotypes of markers. These diagnostic haplotypes could be used for marker-assisted selection (MAS) in modern breeding programs. PMID:26352671

  10. SNP discovery in complex allotetraploid genomes (Gossypium spp., Malvaceae) using genotyping by sequencing1

    PubMed Central

    Logan-Young, Carla Jo; Yu, John Z.; Verma, Surender K.; Percy, Richard G.; Pepper, Alan E.

    2015-01-01

    Premise of the study: Single-nucleotide polymorphism (SNP) marker discovery in plants with complex allotetraploid genomes is often confounded by the presence of homeologous loci (along with paralogous and orthologous loci). Here we present a strategy to filter for SNPs representing orthologous loci. Methods and Results: Using Illumina next-generation sequencing, 54 million reads were collected from restriction enzyme–digested DNA libraries of a diversity of Gossypium taxa. Loci with one to three SNPs were discovered using the Stacks software package, yielding 25,529 new cotton SNP combinations, including those that are polymorphic at both interspecific and intraspecific levels. Frequencies of predicted dual-homozygous (aa/bb) marker polymorphisms ranged from 6.7–11.6% of total shared fragments in intraspecific comparisons and from 15.0–16.4% in interspecific comparisons. Conclusions: This resource provides dual-homozygous (aa/bb) marker polymorphisms. Both in silico and experimental validation efforts demonstrated that these markers are enriched for single orthologous loci that are homozygous for alternative alleles. PMID:25798340

  11. Lack of Association of the CD247 SNP rs2056626 with Systemic Sclerosis in Han Chinese

    PubMed Central

    Wang, Jiucun; Yi, Lin; Guo, Xinjian; He, Dongyi; Li, Hongyi; Guo, Gang; Wang, Yi; Zou, Hejian; Gu, Yuanhui; Tu, Wenzhen; Wu, Wenyu; Yang, Li; Xiao, Rong; Lai, Syeling; Assassi, Shervin; Mayes, Maureen D; Zhou, Xiaodong

    2014-01-01

    Systemic sclerosis (SSc) is a complex disease involving multiple genetic factors. A recent genome-wide association study (GWAS) indicated that CD247 was strongly associated with SSc, which was subsequently confirmed in a SSc cohort of European population. However, genetic heterogeneity in different ethnic populations may significantly impact the complex trait of SSc. The studies herein aimed to examine whether the SSc-associated SNP rs2056626 of CD247 identified in Caucasian is also associated with Han Chinese SSc. A Han Chinese cohort consisting of 387 SSc patients and 523 healthy controls were examined in the studies. TaqMan assays were performed to examine the SNP. Exact p-values were obtained (Fisher’s test) from 2x2 tables of allele counts and disease status. The results showed that there was no association between rs2056626 of CD247 and SSc or any SSc subtypes of Han Chinese. The negative results are important in understanding genetics of SSc in different ethnic populations, which further suggest complex nature of genetics of SSc. PMID:25317213

  12. Performance of different SNP panels for parentage testing in two East Asian cattle breeds.

    PubMed

    Strucken, E M; Gudex, B; Ferdosi, M H; Lee, H K; Song, K D; Gibson, J P; Kelly, M; Piper, E K; Porto-Neto, L R; Lee, S H; Gondro, C

    2014-08-01

    The International Society for Animal Genetics (ISAG) proposed a panel of single nucleotide polymorphisms (SNPs) for parentage testing in cattle (a core panel of 100 SNPs and an additional list of 100 SNPs). However, markers specific to East Asian taurine cattle breeds were not included, and no information is available as to whether the ISAG panel performs adequately for these breeds. We tested ISAG's core (100 SNP) and full (200 SNP) panels on two East Asian taurine breeds: the Korean Hanwoo and the Japanese Wagyu, the latter from the Australian herd. Even though the power of exclusion was high at 0.99 for both ISAG panels, the core panel performed poorly with 3.01% false-positive assignments in the Hanwoo population and 3.57% in the Wagyu. The full ISAG panel identified all sire-offspring relations correctly in both populations with 0.02% of relations wrongly excluded in the Hanwoo population. Based on these results, we created and tested two population-specific marker panels: one for the Wagyu population, which showed no false-positive assignments with either 100 or 200 SNPs, and a second panel for the Hanwoo, which still had some false-positive assignments with 100 SNPs but no false positives using 200 SNPs. In conclusion, for parentage assignment in East Asian cattle breeds, only the full ISAG panel is adequate for parentage testing. If fewer markers should be used, it is advisable to use population-specific markers rather than the ISAG panel.

  13. SNPsplit: Allele-specific splitting of alignments between genomes with known SNP genotypes.

    PubMed

    Krueger, Felix; Andrews, Simon R

    2016-01-01

    Sequencing reads overlapping polymorphic sites in diploid mammalian genomes may be assigned to one allele or the other. This holds the potential to detect gene expression, chromatin modifications, DNA methylation or nuclear interactions in an allele-specific fashion. SNPsplit is an allele-specific alignment sorter designed to read files in SAM/BAM format and determine the allelic origin of reads or read-pairs that cover known single nucleotide polymorphic (SNP) positions. For this to work libraries must have been aligned to a genome in which all known SNP positions were masked with the ambiguity base 'N' and aligned using a suitable mapping program such as Bowtie2, TopHat, STAR, HISAT2, HiCUP or Bismark. SNPsplit also provides an automated solution to generate N-masked reference genomes for hybrid mouse strains based on the variant call information provided by the Mouse Genomes Project. The unique ability of SNPsplit to work with various different kinds of sequencing data including RNA-Seq, ChIP-Seq, Bisulfite-Seq or Hi-C opens new avenues for the integrative exploration of allele-specific data. PMID:27429743

  14. Development of genetic markers in abalone through construction of a SNP database.

    PubMed

    Kang, J-H; Appleyard, S A; Elliott, N G; Jee, Y-J; Lee, J B; Kang, S W; Baek, M K; Han, Y S; Choi, T-J; Lee, Y S

    2011-06-01

    In the absence of a reference genome, single-nucleotide polymorphisms (SNP) discovery in a group of abalone species was undertaken by random sequence assembly. A web-based interface was constructed, and 11 932 DNA sequences from the genus Haliotis were assembled, with 1321 contigs built. Of these, 118 contigs that consisted of at least ten annotation groups were selected. The 1577 putative SNPs were identified from the 118 contigs, with SNPs in several HSP70 gene contigs confirmed by PCR amplification of an 809-bp DNA fragment. SNPs in the HSP70 gene were compared across eight abalone species. A total of 129 polymorphic sites, including heterozygote sites within and among species, were observed. Phylogenetic analysis of the partial HSP70 gene region showed separation of the tested abalone into two groups, one reflecting the southern hemisphere species and the other the northern hemisphere species. Interestingly, Haliotis iris from New Zealand showed a closer relationship to species distributed in the northern Pacific region. Although HSP genes are known to be highly conserved among taxa, the validation of polymorphic SNPs from HSP70 in this mollusc demonstrates the applicability of cross-species SNP markers in abalone and the first step towards universal nuclear markers in Haliotis.

  15. PrimerMapper: high throughput primer design and graphical assembly for PCR and SNP detection.

    PubMed

    O'Halloran, Damien M

    2016-01-01

    Primer design represents a widely employed gambit in diverse molecular applications including PCR, sequencing, and probe hybridization. Variations of PCR, including primer walking, allele-specific PCR, and nested PCR provide specialized validation and detection protocols for molecular analyses that often require screening large numbers of DNA fragments. In these cases, automated sequence retrieval and processing become important features, and furthermore, a graphic that provides the user with a visual guide to the distribution of designed primers across targets is most helpful in quickly ascertaining primer coverage. To this end, I describe here, PrimerMapper, which provides a comprehensive graphical user interface that designs robust primers from any number of inputted sequences while providing the user with both, graphical maps of primer distribution for each inputted sequence, and also a global assembled map of all inputted sequences with designed primers. PrimerMapper also enables the visualization of graphical maps within a browser and allows the user to draw new primers directly onto the webpage. Other features of PrimerMapper include allele-specific design features for SNP genotyping, a remote BLAST window to NCBI databases, and remote sequence retrieval from GenBank and dbSNP. PrimerMapper is hosted at GitHub and freely available without restriction.

  16. Publishing SNP genotypes of human embryonic stem cell lines: policy statement of the International Stem Cell Forum Ethics Working Party.

    PubMed

    Knoppers, Bartha M; Isasi, Rosario; Benvenisty, Nissim; Kim, Ock-Joo; Lomax, Geoffrey; Morris, Clive; Murray, Thomas H; Lee, Eng Hin; Perry, Margery; Richardson, Genevra; Sipp, Douglas; Tanner, Klaus; Wahlström, Jan; de Wert, Guido; Zeng, Fanyi

    2011-09-01

    Novel methods and associated tools permitting individual identification in publicly accessible SNP databases have become a debatable issue. There is growing concern that current technical and ethical safeguards to protect the identities of donors could be insufficient. In the context of human embryonic stem cell research, there are no studies focusing on the probability that an hESC line donor could be identified by analyzing published SNP profiles and associated genotypic and phenotypic information. We present the International Stem Cell Forum (ISCF) Ethics Working Party's Policy Statement on "Publishing SNP Genotypes of Human Embryonic Stem Cell Lines (hESC)". The Statement prospectively addresses issues surrounding the publication of genotypic data and associated annotations of hESC lines in open access databases. It proposes a balanced approach between the goals of open science and data sharing with the respect for fundamental bioethical principles (autonomy, privacy, beneficence, justice and research merit and integrity).

  17. Assignment of SNP allelic configuration in polyploids using competitive allele-specific PCR: application to citrus triploid progeny

    PubMed Central

    Cuenca, José; Aleza, Pablo; Navarro, Luis; Ollitrault, Patrick

    2013-01-01

    Background Polyploidy is a major component of eukaryote evolution. Estimation of allele copy numbers for molecular markers has long been considered a challenge for polyploid species, while this process is essential for most genetic research. With the increasing availability and whole-genome coverage of single nucleotide polymorphism (SNP) markers, it is essential to implement a versatile SNP genotyping method to assign allelic configuration efficiently in polyploids. Scope This work evaluates the usefulness of the KASPar method, based on competitive allele-specific PCR, for the assignment of SNP allelic configuration. Citrus was chosen as a model because of its economic importance, the ongoing worldwide polyploidy manipulation projects for cultivar and rootstock breeding, and the increasing availability of SNP markers. Conclusions Fifteen SNP markers were successfully designed that produced clear allele signals that were in agreement with previous genotyping results at the diploid level. The analysis of DNA mixes between two haploid lines (Clementine and pummelo) at 13 different ratios revealed a very high correlation (average = 0·9796; s.d. = 0·0094) between the allele ratio and two parameters [θ angle = tan−1 (y/x) and y′ = y/(x + y)] derived from the two normalized allele signals (x and y) provided by KASPar. Separated cluster analysis and analysis of variance (ANOVA) from mixed DNA simulating triploid and tetraploid hybrids provided 99·71 % correct allelic configuration. Moreover, triploid populations arising from 2n gametes and interploid crosses were easily genotyped and provided useful genetic information. This work demonstrates that the KASPar SNP genotyping technique is an efficient way to assign heterozygous allelic configurations within polyploid populations. This method is accurate, simple and cost-effective. Moreover, it may be useful for quantitative studies, such as relative allele-specific expression analysis and bulk segregant analysis

  18. Frequency of SNP -336A/G in the promoter region of CD209 in a population from northeastern Brazil.

    PubMed

    Costa, P N; Ferreira-Fernandes, H; de Oliveira, J S; Pereira, A C T C; Pinto, G R; Ferreira, G P

    2015-08-14

    Dendritic cells (DCs) mediate the initiation of the immune response against a variety of pathogens. The DC-SIGN receptor is encoded by the gene CD209 and is expressed on the surface of DCs. It binds to mannose-rich carbohydrates and enables the recognition of bacteria, fungi, parasites, and viruses. SNP -336A/G in the promoter region of CD209 influences the expression of the DC-SIGN receptor. Several studies have associated this SNP with an increased susceptibility to infectious diseases and the development of more severe forms of disease. Therefore, the aim of this study was to determine the prevalence of SNP -336A/G in a population from northeastern Brazil. We analyzed 181 individuals from the general population of Parnaíba, Piauí, Brazil, of which 37% were men and 63% were women. SNP -336A/G was detected by polymerase chain reaction and treatment with the restriction enzyme MscI and visualized by electrophoresis on an 8% polyacrylamide gel stained with silver nitrate. Of the individuals analyzed, 116 (64.1%) were homozygous AA, 57 (31.5%) were heterozygous (AG), and 8 (4.4%) were homozygous GG. The allele frequency of -336G was 20.2%. Genotype frequencies were in Hardy-Weinberg equilibrium. To the best of our knowledge, this is the first report to describe the frequency of the CD209 SNP -336A/G in a population in the State of Piauí. Further studies are needed to determine the relationship between this SNP and the vulnerability of this population to major infectious diseases.

  19. Comparison of whole-genome (13X) and capture (87X) resequencing methods for SNP and genotype callings.

    PubMed

    Roux, P F; Marthey, S; Djari, A; Moroldo, M; Esquerré, D; Estellé, J; Klopp, C; Lagarrigue, S; Demeure, O

    2015-02-01

    The number of polymorphisms identified with next-generation sequencing approaches depends directly on the sequencing depth and therefore on the experimental cost. Although higher levels of depth ensure more sensitive and more specific SNP calls, economic constraints limit the increase of depth for whole-genome resequencing (WGS). For this reason, capture resequencing is used for studies focusing on only some specific regions of the genome. However, several biases in capture resequencing are known to have a negative impact on the sensitivity of SNP detection. Within this framework, the aim of this study was to compare the accuracy of WGS and capture resequencing on SNP detection and genotype calling, which differ in terms of both sequencing depth and biases. Indeed, we have evaluated the SNP calling and genotyping accuracy in a WGS dataset (13X) and in a capture resequencing dataset (87X) performed on 11 individuals. The percentage of SNPs not identified due to a sevenfold sequencing depth decrease was estimated at 7.8% using a down-sampling procedure on the capture sequencing dataset. A comparison of the 87X capture sequencing dataset with the WGS dataset revealed that capture-related biases were leading with the loss of 5.2% of SNPs detected with WGS. Nevertheless, when considering the SNPs detected by both approaches, capture sequencing appears to achieve far better SNP genotyping, with about 4.4% of the WGS genotypes that can be considered as erroneous and even 10% focusing on heterozygous genotypes. In conclusion, WGS and capture deep sequencing can be considered equivalent strategies for SNP detection, as the rate of SNPs not identified because of a low sequencing depth in the former is quite similar to SNPs missed because of method biases of the latter. On the other hand, capture deep sequencing clearly appears more adapted for studies requiring great accuracy in genotyping. PMID:25515399

  20. Safety considerations for magnetic fields of 10 mT to 100 mT amplitude in the frequency range of 10 kHz to 100 kHz for magnetic particle imaging.

    PubMed

    Dössel, Olaf; Bohnert, Julia

    2013-12-01

    Magnetic particle imaging (MPI) is a new imaging modality using oscillating magnetic fields in the frequency range of 10 kHz to 100 kHz. The duration of data acquisition becomes smaller, and signal-to-noise ratio improves if the amplitude of these fields is increased - technically amplitudes of up to 100 mT might be feasible for human-sized systems. On the other hand, with increasing field strength, adverse health effects must be expected: oscillating magnetic fields can stimulate nerves and muscle and heat up tissue. Thresholds for stimulation with magnetic fields in this frequency range are not precisely known, neither is the local temperature rise following exposure. The ICNIRP guidelines define reference levels for magnetic field exposure for the general public that contain large safety factors - for medical diagnostics, they might be exceeded for a short time. In this article, research and guidelines in this field are briefly reviewed, and new results are presented in order to contribute to a future definition of safety limits for oscillating magnetic fields in MPI. PMID:24176960

  1. Safety considerations for magnetic fields of 10 mT to 100 mT amplitude in the frequency range of 10 kHz to 100 kHz for magnetic particle imaging.

    PubMed

    Dössel, Olaf; Bohnert, Julia

    2013-12-01

    Magnetic particle imaging (MPI) is a new imaging modality using oscillating magnetic fields in the frequency range of 10 kHz to 100 kHz. The duration of data acquisition becomes smaller, and signal-to-noise ratio improves if the amplitude of these fields is increased - technically amplitudes of up to 100 mT might be feasible for human-sized systems. On the other hand, with increasing field strength, adverse health effects must be expected: oscillating magnetic fields can stimulate nerves and muscle and heat up tissue. Thresholds for stimulation with magnetic fields in this frequency range are not precisely known, neither is the local temperature rise following exposure. The ICNIRP guidelines define reference levels for magnetic field exposure for the general public that contain large safety factors - for medical diagnostics, they might be exceeded for a short time. In this article, research and guidelines in this field are briefly reviewed, and new results are presented in order to contribute to a future definition of safety limits for oscillating magnetic fields in MPI.

  2. SNP Analysis and Whole Exome Sequencing: Their Application in the Analysis of a Consanguineous Pedigree Segregating Ataxia

    PubMed Central

    Nickerson, Sarah L.; Marquis-Nicholson, Renate; Claxton, Karen; Ashton, Fern; Leong, Ivone U. S.; Prosser, Debra O.; Love, Jennifer M.; George, Alice M.; Taylor, Graham; Wilson, Callum; McKinlay Gardner, R. J.; Love, Donald R.

    2015-01-01

    Autosomal recessive cerebellar ataxia encompasses a large and heterogeneous group of neurodegenerative disorders. We employed single nucleotide polymorphism (SNP) analysis and whole exome sequencing to investigate a consanguineous Maori pedigree segregating ataxia. We identified a novel mutation in exon 10 of the SACS gene: c.7962T>G p.(Tyr2654*), establishing the diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Our findings expand both the genetic and phenotypic spectrum of this rare disorder, and highlight the value of high-density SNP analysis and whole exome sequencing as powerful and cost-effective tools in the diagnosis of genetically heterogeneous disorders such as the hereditary ataxias.

  3. SNiPloid: A Utility to Exploit High-Throughput SNP Data Derived from RNA-Seq in Allopolyploid Species

    PubMed Central

    Peralta, Marine; Combes, Marie-Christine; Lashermes, Philippe; Dereeper, Alexis

    2013-01-01

    High-throughput sequencing is a common approach to discover SNP variants, especially in plant species. However, methods to analyze predicted SNPs are often optimized for diploid plant species whereas many crop species are allopolyploids and combine related but divergent subgenomes (homoeologous chromosome sets). We created a software tool, SNiPloid, that exploits and interprets putative SNPs in the context of allopolyploidy by comparing SNPs from an allopolyploid with those obtained in its modern-day diploid progenitors. SNiPloid can compare SNPs obtained from a sample to estimate the subgenome contribution to the transcriptome or SNPs obtained from two polyploid accessions to search for SNP divergence. PMID:24163691

  4. SNP Regulation of microRNA Expression and Subsequent Colon Cancer Risk

    PubMed Central

    Mullany, Lila E.; Wolff, Roger K.; Herrick, Jennifer S.; Buas, Matthew F.; Slattery, Martha L.

    2015-01-01

    Introduction MicroRNAs (miRNAs) regulate messenger RNAs (mRNAs) and as such have been implicated in a variety of diseases, including cancer. MiRNAs regulate mRNAs through binding of the miRNA 5’ seed sequence (~7–8 nucleotides) to the mRNA 3’ UTRs; polymorphisms in these regions have the potential to alter miRNA-mRNA target associations. SNPs in miRNA genes as well as miRNA-target genes have been proposed to influence cancer risk through altered miRNA expression levels. Methods MiRNA-SNPs and miRNA-target gene-SNPs were identified through the literature. We used SNPs from Genome-Wide Association Study (GWAS) data that were matched to individuals with miRNA expression data generated from an Agilent platform for colon tumor and non-tumor paired tissues. These samples were used to evaluate 327 miRNA-SNP pairs for associations between SNPs and miRNA expression levels as well as for SNP associations with colon cancer. Results Twenty-two miRNAs expressed in non-tumor tissue were significantly different by genotype and 21 SNPs were associated with altered tumor/non-tumor differential miRNA expression across genotypes. Two miRNAs were associated with SNP genotype for both non-tumor and tumor/non-tumor differential expression. Of the 41 miRNAs significantly associated with SNPs all but seven were significantly differentially expressed in colon tumor tissue. Two of the 41 SNPs significantly associated with miRNA expression levels were associated with colon cancer risk: rs8176318 (BRCA1), ORAA 1.31 95% CI 1.01, 1.78, and rs8905 (PRKAR1A), ORGG 2.31 95% CI 1.11, 4.77. Conclusion Of the 327 SNPs identified in the literature as being important because of their potential regulation of miRNA expression levels, 12.5% had statistically significantly associations with miRNA expression. However, only two of these SNPs were significantly associated with colon cancer. PMID:26630397

  5. Genes of the RNASE5 pathway contain SNP associated with milk production traits in dairy cattle

    PubMed Central

    2013-01-01

    Background Identification of the processes and mutations responsible for the large genetic variation in milk production among dairy cattle has proved challenging. One approach is to identify a biological process potentially involved in milk production and to determine the genetic influence of all the genes included in the process or pathway. Angiogenin encoded by angiogenin, ribonuclease, RNase A family 5 (RNASE5) is relatively abundant in milk, and has been shown to regulate protein synthesis and act as a growth factor in epithelial cells in vitro. However, little is known about the role of angiogenin in the mammary gland or if the polymorphisms present in the bovine RNASE5 gene are associated with lactation and milk production traits in dairy cattle. Given the high economic value of increased protein in milk, we have tested the hypothesis that RNASE5 or genes in the RNASE5 pathway are associated with milk production traits. First, we constructed a “RNASE5 pathway” based on upstream and downstream interacting genes reported in the literature. We then tested SNP in close proximity to the genes of this pathway for association with milk production traits in a large dairy cattle dataset. Results The constructed RNASE5 pathway consisted of 11 genes. Association analysis between SNP in 1 Mb regions surrounding these genes and milk production traits revealed that more SNP than expected by chance were associated with milk protein percent (P < 0.05 significance). There was no significant association with other traits such as milk fat content or fertility. Conclusions These results support a role for the RNASE5 pathway in milk production, specifically milk protein percent, and indicate that polymorphisms in or near these genes explain a proportion of the variation for this trait. This method provides a novel way of understanding the underlying biology of lactation with implications for milk production and can be applied to any pathway or gene set to test whether

  6. Genome-Wide SNP Discovery from Transcriptome of Four Common Carp Strains

    PubMed Central

    Xu, Jian; Ji, Peifeng; Zhao, Zixia; Zhang, Yan; Feng, Jianxin; Wang, Jian; Li, Jiongtang; Zhang, Xiaofeng; Zhao, Lan; Liu, Guangzan; Xu, Peng; Sun, Xiaowen

    2012-01-01

    Background Single nucleotide polymorphisms (SNPs) have been used as genetic marker for genome-wide association studies in many species. Gene-associated SNPs could offer sufficient coverage in trait related research and further more could themselves be causative SNPs for traits. Common carp (Cyprinus carpio) is one of the most important aquaculture species in the world accounting for nearly 14% of freshwater aquaculture production. There are various strains of common carp with different economic traits, however, the genetic mechanism underlying the different traits have not been elucidated yet. In this project, we identified a large number of gene-associated SNPs from four strains of common carp using next-generation sequencing. Results Transcriptome sequencing of four strains of common carp (mirror carp, purse red carp, Xingguo red carp, Yellow River carp) was performed with Solexa HiSeq2000 platform. De novo assembled transcriptome was used as reference for alignments, and SNP calling was done through BWA and SAMtools. A total of 712,042 Intra-strain SNPs were discovered in four strains, of which 483,276 SNPs for mirror carp, 486,629 SNPs for purse red carp, 478,028 SNPs for Xingguo red carp and 488,281 SNPs for Yellow River carp were discovered, respectively. Besides, 53,893 inter-SNPs were identified. Strain-specific SNPs of four strains were 53,938, 53,866, 48,701, 40,131 in mirror carp, purse red carp, Xingguo red carp and Yellow River carp, respectively. GO and KEGG pathway analysis were done to reveal strain-specific genes affected by strain-specific non-synonymous SNPs. Validation of selected SNPs revealed that 48% percent of SNPs (12 of 25) were tested to be true SNPs. Conclusions Transcriptome analysis of common carp using RNA-Seq is a cost-effective way of generating numerous reads for SNP discovery. After validation of identified SNPs, these data will provide a solid base for SNP array designing and genome-wide association studies. PMID:23110192

  7. Genome wide SNP discovery in flax through next generation sequencing of reduced representation libraries

    PubMed Central

    2012-01-01

    Background Flax (Linum usitatissimum L.) is a significant fibre and oilseed crop. Current flax molecular markers, including isozymes, RAPDs, AFLPs and SSRs are of limited use in the construction of high density linkage maps and for association mapping applications due to factors such as low reproducibility, intense labour requirements and/or limited numbers. We report here on the use of a reduced representation library strategy combined with next generation Illumina sequencing for rapid and large scale discovery of SNPs in eight flax genotypes. SNP discovery was performed through in silico analysis of the sequencing data against the whole genome shotgun sequence assembly of flax genotype CDC Bethune. Genotyping-by-sequencing of an F6-derived recombinant inbred line population provided validation of the SNPs. Results Reduced representation libraries of eight flax genotypes were sequenced on the Illumina sequencing platform resulting in sequence coverage ranging from 4.33 to 15.64X (genome equivalents). Depending on the relatedness of the genotypes and the number and length of the reads, between 78% and 93% of the reads mapped onto the CDC Bethune whole genome shotgun sequence assembly. A total of 55,465 SNPs were discovered with the largest number of SNPs belonging to the genotypes with the highest mapping coverage percentage. Approximately 84% of the SNPs discovered were identified in a single genotype, 13% were shared between any two genotypes and the remaining 3% in three or more. Nearly a quarter of the SNPs were found in genic regions. A total of 4,706 out of 4,863 SNPs discovered in Macbeth were validated using genotyping-by-sequencing of 96 F6 individuals from a recombinant inbred line population derived from a cross between CDC Bethune and Macbeth, corresponding to a validation rate of 96.8%. Conclusions Next generation sequencing of reduced representation libraries was successfully implemented for genome-wide SNP discovery from flax. The genotyping

  8. Global Phylogeny of Mycobacterium tuberculosis Based on Single Nucleotide Polymorphism (SNP) Analysis: Insights into Tuberculosis Evolution, Phylogenetic Accuracy of Other DNA Fingerprinting Systems, and Recommendations for a Minimal Standard SNP Set†

    PubMed Central

    Filliol, Ingrid; Motiwala, Alifiya S.; Cavatore, Magali; Qi, Weihong; Hazbón, Manzour Hernando; Bobadilla del Valle, Miriam; Fyfe, Janet; García-García, Lourdes; Rastogi, Nalin; Sola, Christophe; Zozio, Thierry; Guerrero, Marta Inírida; León, Clara Inés; Crabtree, Jonathan; Angiuoli, Sam; Eisenach, Kathleen D.; Durmaz, Riza; Joloba, Moses L.; Rendón, Adrian; Sifuentes-Osornio, José; Ponce de León, Alfredo; Cave, M. Donald; Fleischmann, Robert; Whittam, Thomas S.; Alland, David

    2006-01-01

    We analyzed a global collection of Mycobacterium tuberculosis strains using 212 single nucleotide polymorphism (SNP) markers. SNP nucleotide diversity was high (average across all SNPs, 0.19), and 96% of the SNP locus pairs were in complete linkage disequilibrium. Cluster analyses identified six deeply branching, phylogenetically distinct SNP cluster groups (SCGs) and five subgroups. The SCGs were strongly associated with the geographical origin of the M. tuberculosis samples and the birthplace of the human hosts. The most ancestral cluster (SCG-1) predominated in patients from the Indian subcontinent, while SCG-1 and another ancestral cluster (SCG-2) predominated in patients from East Asia, suggesting that M. tuberculosis first arose in the Indian subcontinent and spread worldwide through East Asia. Restricted SCG diversity and the prevalence of less ancestral SCGs in indigenous populations in Uganda and Mexico suggested a more recent introduction of M. tuberculosis into these regions. The East African Indian and Beijing spoligotypes were concordant with SCG-1 and SCG-2, respectively; X and Central Asian spoligotypes were also associated with one SCG or subgroup combination. Other clades had less consistent associations with SCGs. Mycobacterial interspersed repetitive unit (MIRU) analysis provided less robust phylogenetic information, and only 6 of the 12 MIRU microsatellite loci were highly differentiated between SCGs as measured by GST. Finally, an algorithm was devised to identify two minimal sets of either 45 or 6 SNPs that could be used in future investigations to enable global collaborations for studies on evolution, strain differentiation, and biological differences of M. tuberculosis. PMID:16385065

  9. The human lactase persistence-associated SNP -13910*T enables in vivo functional persistence of lactase promoter-reporter transgene expression.

    PubMed

    Fang, Lin; Ahn, Jong Kun; Wodziak, Dariusz; Sibley, Eric

    2012-07-01

    Lactase is the intestinal enzyme responsible for digestion of the milk sugar lactose. Lactase gene expression declines dramatically upon weaning in mammals and during early childhood in humans (lactase nonpersistence). In various ethnic groups, however, lactase persists in high levels throughout adulthood (lactase persistence). Genetic association studies have identified that lactase persistence in northern Europeans is strongly associated with a single nucleotide polymorphism (SNP) located 14 kb upstream of the lactase gene: -13910*C/T. To determine whether the -13910*T SNP can function in vivo to mediate lactase persistence, we generated transgenic mice harboring human DNA fragments with the -13910*T SNP or the ancestral -13910*C SNP cloned upstream of a 2-kb rat lactase gene promoter in a luciferase reporter construct. We previously reported that the 2-kb rat lactase promoter directs a post-weaning decline of luciferase transgene expression similar to that of the endogenous lactase gene. In the present study, the post-weaning decline directed by the rat lactase promoter is impeded by addition of the -13910*T SNP human DNA fragment, but not by addition of the -13910*C ancestral SNP fragment. Persistence of transgene expression associated with the -13910*T SNP represents the first in vivo data in support of a functional role for the -13910*T SNP in mediating the human lactase persistence phenotype. PMID:22258180

  10. A high-density SNP map of sunflower derived from RAD-sequencing facilitating fine-mapping of the rust resistance gene R12

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A high-resolution genetic map of sunflower was constructed by integrating SNP data from three F2 mapping populations (HA 89/ RHA 464, B-line/ RHA 464, and CR 29/ RHA 468). The consensus map spanned a total length of 1443.84 cM, and consisted of 5,019 SNP markers derived from RAD tag sequencing and 1...

  11. The human lactase persistence-associated SNP -13910*T enables in vivo functional persistence of lactase promoter-reporter transgene expression.

    PubMed

    Fang, Lin; Ahn, Jong Kun; Wodziak, Dariusz; Sibley, Eric

    2012-07-01

    Lactase is the intestinal enzyme responsible for digestion of the milk sugar lactose. Lactase gene expression declines dramatically upon weaning in mammals and during early childhood in humans (lactase nonpersistence). In various ethnic groups, however, lactase persists in high levels throughout adulthood (lactase persistence). Genetic association studies have identified that lactase persistence in northern Europeans is strongly associated with a single nucleotide polymorphism (SNP) located 14 kb upstream of the lactase gene: -13910*C/T. To determine whether the -13910*T SNP can function in vivo to mediate lactase persistence, we generated transgenic mice harboring human DNA fragments with the -13910*T SNP or the ancestral -13910*C SNP cloned upstream of a 2-kb rat lactase gene promoter in a luciferase reporter construct. We previously reported that the 2-kb rat lactase promoter directs a post-weaning decline of luciferase transgene expression similar to that of the endogenous lactase gene. In the present study, the post-weaning decline directed by the rat lactase promoter is impeded by addition of the -13910*T SNP human DNA fragment, but not by addition of the -13910*C ancestral SNP fragment. Persistence of transgene expression associated with the -13910*T SNP represents the first in vivo data in support of a functional role for the -13910*T SNP in mediating the human lactase persistence phenotype.

  12. Electrochemical detection of type 2 diabetes mellitus-related SNP via DNA-mediated growth of silver nanoparticles on single walled carbon nanotubes.

    PubMed

    Tao, Jia; Zhao, Peng; Zheng, Jing; Wu, Cuichen; Shi, Muling; Li, Jishan; Li, Yinhui; Yang, Ronghua

    2015-11-01

    Herein, we proposed a new electrochemical sensing strategy for T2DM-related SNP detection via DNA-mediated growth of AgNPs on a SWCNT-modified electrode. Coupled with RNase HII enzyme assisted amplification, this approach could realize T2DM-related SNP assay and be applied in crude extracts of carcinoma pancreatic β-cell lines.

  13. Electrochemical detection of type 2 diabetes mellitus-related SNP via DNA-mediated growth of silver nanoparticles on single walled carbon nanotubes.

    PubMed

    Tao, Jia; Zhao, Peng; Zheng, Jing; Wu, Cuichen; Shi, Muling; Li, Jishan; Li, Yinhui; Yang, Ronghua

    2015-11-01

    Herein, we proposed a new electrochemical sensing strategy for T2DM-related SNP detection via DNA-mediated growth of AgNPs on a SWCNT-modified electrode. Coupled with RNase HII enzyme assisted amplification, this approach could realize T2DM-related SNP assay and be applied in crude extracts of carcinoma pancreatic β-cell lines. PMID:26365891

  14. A review on SNP and other types of molecular markers and their use in animal genetics

    PubMed Central

    Vignal, Alain; Milan, Denis; SanCristobal, Magali; Eggen, André

    2002-01-01

    During the last ten years, the use of molecular markers, revealing polymorphism at the DNA level, has been playing an increasing part in animal genetics studies. Amongst others, the microsatellite DNA marker has been the most widely used, due to its easy use by simple PCR, followed by a denaturing gel electrophoresis for allele size determination, and to the high degree of information provided by its large number of alleles per locus. Despite this, a new marker type, named SNP, for Single Nucleotide Polymorphism, is now on the scene and has gained high popularity, even though it is only a bi-allelic type of marker. In this review, we will discuss the reasons for this apparent step backwards, and the pertinence of the use of SNPs in animal genetics, in comparison with other marker types. PMID:12081799

  15. Olive oil DNA fingerprinting by multiplex SNP genotyping on fluorescent microspheres.

    PubMed

    Kalogianni, Despina P; Bazakos, Christos; Boutsika, Lemonia M; Targem, Mehdi Ben; Christopoulos, Theodore K; Kalaitzis, Panagiotis; Ioannou, Penelope C

    2015-04-01

    Olive oil cultivar verification is of primary importance for the competitiveness of the product and the protection of consumers and producers from fraudulence. Single-nucleotide polymorphisms (SNPs) have emerged as excellent DNA markers for authenticity testing. This paper reports the first multiplex SNP genotyping assay for olive oil cultivar identification that is performed on a suspension of fluorescence-encoded microspheres. Up to 100 sets of microspheres, with unique "fluorescence signatures", are available. Allele discrimination was accomplished by primer extension reaction. The reaction products were captured via hybridization on the microspheres and analyzed, within seconds, by a flow cytometer. The "fluorescence signature" of each microsphere is assigned to a specific allele, whereas the signal from a reporter fluorophore denotes the presence of the allele. As a model, a panel of three SNPs was chosen that enabled identification of five common Greek olive cultivars (Adramytini, Chondrolia Chalkidikis, Kalamon, Koroneiki, and Valanolia).

  16. [Mechanism of genuineness of Glycyrrhiza uralensis based on SNP of β-Amyrin synthase gene].

    PubMed

    Zang, Yi-mei; Li, Yan-peng; Qiao, Jing; Chen, Hong-hao; Liu, Chun-sheng

    2015-07-01

    β-Amyrin synthase (β-AS) genes of Glycyrrhiza uralensis from 6 different regions were analyzed by PCR-SSCP and sequenced, then the correlationship between β-AS SNP and regions of Glycyrrhiza uralensis were determined. According to the 1 coding single nucleotide polymorphism on the first exon of β-AS gene at 94 bp site, Glycyrrhiza uralensis could be divided into 3 genotypes. In these genotypes, the percentage of 94A type in genuine regions was much higher, and it had significant differences with the percentage in non-genuine regions (P < 0.001). The results of the experiment proved that different β-AS genotypes at 94 bp site from different regions may be one of the important reasons to result in the genuineness of Glycyrrhiza uralensis. PMID:26552155

  17. To Cheat or Not To Cheat: Tryptophan Hydroxylase 2 SNP Variants Contribute to Dishonest Behavior

    PubMed Central

    Shen, Qiang; Teo, Meijun; Winter, Eyal; Hart, Einav; Chew, Soo H.; Ebstein, Richard P.

    2016-01-01

    Although, lying (bear false witness) is explicitly prohibited in the Decalogue and a focus of interest in philosophy and theology, more recently the behavioral and neural mechanisms of deception are gaining increasing attention from diverse fields especially economics, psychology, and neuroscience. Despite the considerable role of heredity in explaining individual differences in deceptive behavior, few studies have investigated which specific genes contribute to the heterogeneity of lying behavior across individuals. Also, little is known concerning which specific neurotransmitter pathways underlie deception. Toward addressing these two key questions, we implemented a neurogenetic strategy and modeled deception by an incentivized die-under-cup task in a laboratory setting. The results of this exploratory study provide provisional evidence that SNP variants across the tryptophan hydroxylase 2 (TPH2) gene, that encodes the rate-limiting enzyme in the biosynthesis of brain serotonin, contribute to individual differences in deceptive behavior. PMID:27199691

  18. Design and synthesis of the superionic conductor Na10SnP2S12

    NASA Astrophysics Data System (ADS)

    Richards, William D.; Tsujimura, Tomoyuki; Miara, Lincoln J.; Wang, Yan; Kim, Jae Chul; Ong, Shyue Ping; Uechi, Ichiro; Suzuki, Naoki; Ceder, Gerbrand

    2016-03-01

    Sodium-ion batteries are emerging as candidates for large-scale energy storage due to their low cost and the wide variety of cathode materials available. As battery size and adoption in critical applications increases, safety concerns are resurfacing due to the inherent flammability of organic electrolytes currently in use in both lithium and sodium battery chemistries. Development of solid-state batteries with ionic electrolytes eliminates this concern, while also allowing novel device architectures and potentially improving cycle life. Here we report the computation-assisted discovery and synthesis of a high-performance solid-state electrolyte material: Na10SnP2S12, with room temperature ionic conductivity of 0.4 mS cm-1 rivalling the conductivity of the best sodium sulfide solid electrolytes to date. We also computationally investigate the variants of this compound where tin is substituted by germanium or silicon and find that the latter may achieve even higher conductivity.

  19. SNP in starch biosynthesis genes associated with nutritional and functional properties of rice

    PubMed Central

    Kharabian-Masouleh, Ardashir; Waters, Daniel L. E.; Reinke, Russell F.; Ward, Rachelle; Henry, Robert J.

    2012-01-01

    Starch is a major component of human diets. The relative contribution of variation in the genes of starch biosynthesis to the nutritional and functional properties of the rice was evaluated in a rice breeding population. Sequencing 18 genes involved in starch synthesis in a population of 233 rice breeding lines discovered 66 functional SNPs in exonic regions. Five genes, AGPS2b, Isoamylase1, SPHOL, SSIIb and SSIVb showed no polymorphism. Association analysis found 31 of the SNP were associated with differences in pasting and cooking quality properties of the rice lines. Two genes appear to be the major loci controlling traits under human selection in rice, GBSSI (waxy gene) and SSIIa. GBSSI influenced amylose content and retrogradation. Other genes contributing to retrogradation were GPT1, SSI, BEI and SSIIIa. SSIIa explained much of the variation in cooking characteristics. Other genes had relatively small effects. PMID:22870386

  20. Individual Genome of the Russian Male: SNP Calling and a de novo Assembly of Unmapped Reads.

    PubMed

    Chekanov, N N; Boulygina, E S; Beletskiy, A V; Prokhortchouk, E B; Skryabin, K G

    2010-07-01

    A somatic cell genome was recently resequenced for a patient with renal cancer. The data were submitted to the NCBI Sequence Read Archive under the accession number SRA012240. Here, we have performed SNP calling for the genome and compared it with several published genomes. We have found 2, 921, 724 SNPs, including 1, 472, 679 newly described ones. Among them, 63, 462 SNPs have been mapped to the Y chromosome and, based on 18 markers, the genome has been ascribed to the R1a1a haplogroup predominant in Russian males. The mitochondrial haplogroup has been determined as U5a, which is also common in the European part of Russia. Short reads unmapped to the human genome were used for thede novoassembly of DNA sequences. This resulted in genome-specific contigs (more than 100 bp in length) with an overall length of 154 kbp (for GAII) and 4.7 kbp (for SOLiD).

  1. Use of SNP-arrays for ChIP assays: computational aspects.

    PubMed

    Muro, Enrique M; McCann, Jennifer A; Rudnicki, Michael A; Andrade-Navarro, Miguel A

    2009-01-01

    The simultaneous genotyping of thousands of single nucleotide polymorphisms (SNPs) in a genome using SNP-Arrays is a very important tool that is revolutionizing genetics and molecular biology. We expanded the utility of this technique by using it following chromatin immunoprecipitation (ChIP) to assess the multiple genomic locations protected by a protein complex recognized by an antibody. The power of this technique is illustrated through an analysis of the changes in histone H4 acetylation, a marker of open chromatin and transcriptionally active genomic regions, which occur during differentiation of human myoblasts into myotubes. The findings have been validated by the observation of a significant correlation between the detected histone modifications and the expression of the nearby genes, as measured by DNA expression microarrays. This chapter focuses on the computational analysis of the data.

  2. Final Report on the Torque Key Comparison CCM.T-K2 Measurand Torque: 0 kN·m, 10 kN·m, 20 kN·m

    NASA Astrophysics Data System (ADS)

    Röske, D.; Ogushi, K.

    2016-01-01

    The purpose of the CIPM comparison CCM.T-K2 was to compare the measuring capabilities up to 20 kN m of deadweight torque standard machines with supported lever and reference-type torque standard machines in national metrology institutes. Five institutes participated, with the Physikalisch-Technische Bundesanstalt (PTB, Braunschweig, Germany) acting as the pilot laboratory. Two very stable torque transducers with well-known properties were used as travelling standards. The circulation of these transducers started in October 2008 and ended in May 2010. According to the technical protocol, torque steps of 10 kN m and 20 kN m had to be measured both in clockwise and anticlockwise directions. Corrections had to be applied to the results reported by the participants taking into account the use of different amplifiers, the creep (due to different loading times of the machines) and the environmental conditions in the laboratories (temperature and relative humidity of the ambient air). For each of the two torque steps and both senses of direction of the torque vector, a key comparison reference value was calculated. One participant had a problem with the own machine and the measurement results could not be used for the calculation of the corresponding reference values. The agreement between the results of the other participants is very good. The smallest relative standard uncertainty of the machines stated by the participants is between 1 × 10-5 and 2.5 × 10-4. The results of the comparison support these uncertainty statements. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  3. PPLine: An Automated Pipeline for SNP, SAP, and Splice Variant Detection in the Context of Proteogenomics.

    PubMed

    Krasnov, George Sergeevich; Dmitriev, Alexey Alexandrovich; Kudryavtseva, Anna Viktorovna; Shargunov, Alexander Valerievich; Karpov, Dmitry Sergeevich; Uroshlev, Leonid Andreevich; Melnikova, Natalya Vladimirovna; Blinov, Vladimir Mikhailovich; Poverennaya, Ekaterina Vladimirovna; Archakov, Alexander Ivanovich; Lisitsa, Andrey Valerievich; Ponomarenko, Elena Alexandrovna

    2015-09-01

    The fundamental mission of the Chromosome-Centric Human Proteome Project (C-HPP) is the research of human proteome diversity, including rare variants. Liver tissues, HepG2 cells, and plasma were selected as one of the major objects for C-HPP studies. The proteogenomic approach, a recently introduced technique, is a powerful method for predicting and validating proteoforms coming from alternative splicing, mutations, and transcript editing. We developed PPLine, a Python-based proteogenomic pipeline providing automated single-amino-acid polymorphism (SAP), indel, and alternative-spliced-variants discovery based on raw transcriptome and exome sequence data, single-nucleotide polymorphism (SNP) annotation and filtration, and the prediction of proteotypic peptides (available at https://sourceforge.net/projects/ppline). In this work, we performed deep transcriptome sequencing of HepG2 cells and liver tissues using two platforms: Illumina HiSeq and Applied Biosystems SOLiD. Using PPLine, we revealed 7756 SAP and indels for HepG2 cells and liver (including 659 variants nonannotated in dbSNP). We found 17 indels in transcripts associated with the translation of alternate reading frames (ARF) longer than 300 bp. The ARF products of two genes, SLMO1 and TMEM8A, demonstrate signatures of caspase-binding domain and Gcn5-related N-acetyltransferase. Alternative splicing analysis predicted novel proteoforms encoded by 203 (liver) and 475 (HepG2) genes according to both Illumina and SOLiD data. The results of the present work represent a basis for subsequent proteomic studies by the C-HPP consortium. PMID:26147802

  4. RNA-Seq Identifies SNP Markers for Growth Traits in Rainbow Trout

    PubMed Central

    Salem, Mohamed; Vallejo, Roger L.; Leeds, Timothy D.; Palti, Yniv; Liu, Sixin; Sabbagh, Annas; Rexroad, Caird E.; Yao, Jianbo

    2012-01-01

    Fast growth is an important and highly desired trait, which affects the profitability of food animal production, with feed costs accounting for the largest proportion of production costs. Traditional phenotype-based selection is typically used to select for growth traits; however, genetic improvement is slow over generations. Single nucleotide polymorphisms (SNPs) explain 90% of the genetic differences between individuals; therefore, they are most suitable for genetic evaluation and strategies that employ molecular genetics for selective breeding. SNPs found within or near a coding sequence are of particular interest because they are more likely to alter the biological function of a protein. We aimed to use SNPs to identify markers and genes associated with genetic variation in growth. RNA-Seq whole-transcriptome analysis of pooled cDNA samples from a population of rainbow trout selected for improved growth versus unselected genetic cohorts (10 fish from 1 full-sib family each) identified SNP markers associated with growth-rate. The allelic imbalances (the ratio between the allele frequencies of the fast growing sample and that of the slow growing sample) were considered at scores >5.0 as an amplification and <0.2 as loss of heterozygosity. A subset of SNPs (n = 54) were validated and evaluated for association with growth traits in 778 individuals of a three-generation parent/offspring panel representing 40 families. Twenty-two SNP markers and one mitochondrial haplotype were significantly associated with growth traits. Polymorphism of 48 of the markers was confirmed in other commercially important aquaculture stocks. Many markers were clustered into genes of metabolic energy production pathways and are suitable candidates for genetic selection. The study demonstrates that RNA-Seq at low sequence coverage of divergent populations is a fast and effective means of identifying SNPs, with allelic imbalances between phenotypes. This technique is suitable for marker

  5. Identifying Litchi (Litchi chinensis Sonn.) Cultivars and Their Genetic Relationships Using Single Nucleotide Polymorphism (SNP) Markers

    PubMed Central

    Liu, Wei; Xiao, Zhidan; Bao, Xiuli; Yang, Xiaoyan; Fang, Jing; Xiang, Xu

    2015-01-01

    Litchi is an important fruit tree in tropical and subtropical areas of the world. However, there is widespread confusion regarding litchi cultivar nomenclature and detailed information of genetic relationships among litchi germplasm is unclear. In the present study, the potential of single nucleotide polymorphism (SNP) for the identification of 96 representative litchi accessions and their genetic relationships in China was evaluated using 155 SNPs that were evenly spaced across litchi genome. Ninety SNPs with minor allele frequencies above 0.05 and a good genotyping success rate were used for further analysis. A relatively high level of genetic variation was observed among litchi accessions, as quantified by the expected heterozygosity (He = 0.305). The SNP based multilocus matching identified two synonymous groups, ‘Heiye’ and ‘Wuye’, and ‘Chengtuo’ and ‘Baitangli 1’. A subset of 14 SNPs was sufficient to distinguish all the non-redundant litchi genotypes, and these SNPs were proven to be highly stable by repeated analyses of a selected group of cultivars. Unweighted pair-group method of arithmetic averages (UPGMA) cluster analysis divided the litchi accessions analyzed into four main groups, which corresponded to the traits of extremely early-maturing, early-maturing, middle-maturing, and late-maturing, indicating that the fruit maturation period should be considered as the primary criterion for litchi taxonomy. Two subpopulations were detected among litchi accessions by STRUCTURE analysis, and accessions with extremely early- and late-maturing traits showed membership coefficients above 0.99 for Cluster 1 and Cluster 2, respectively. Accessions with early- and middle-maturing traits were identified as admixture forms with varying levels of membership shared between the two clusters, indicating their hybrid origin during litchi domestication. The results of this study will benefit litchi germplasm conservation programs and facilitate maximum

  6. Transcriptome sequencing for high throughput SNP development and genetic mapping in Pea

    PubMed Central

    2014-01-01

    Background Pea has a complex genome of 4.3 Gb for which only limited genomic resources are available to date. Although SNP markers are now highly valuable for research and modern breeding, only a few are described and used in pea for genetic diversity and linkage analysis. Results We developed a large resource by cDNA sequencing of 8 genotypes representative of modern breeding material using the Roche 454 technology, combining both long reads (400 bp) and high coverage (3.8 million reads, reaching a total of 1,369 megabases). Sequencing data were assembled and generated a 68 K unigene set, from which 41 K were annotated from their best blast hit against the model species Medicago truncatula. Annotated contigs showed an even distribution along M. truncatula pseudochromosomes, suggesting a good representation of the pea genome. 10 K pea contigs were found to be polymorphic among the genetic material surveyed, corresponding to 35 K SNPs. We validated a subset of 1538 SNPs through the GoldenGate assay, proving their ability to structure a diversity panel of breeding germplasm. Among them, 1340 were genetically mapped and used to build a new consensus map comprising a total of 2070 markers. Based on blast analysis, we could establish 1252 bridges between our pea consensus map and the pseudochromosomes of M. truncatula, which provides new insight on synteny between the two species. Conclusions Our approach created significant new resources in pea, i.e. the most comprehensive genetic map to date tightly linked to the model species M. truncatula and a large SNP resource for both academic research and breeding. PMID:24521263

  7. SNP microarray-based 24 chromosome aneuploidy screening is significantly more consistent than FISH

    PubMed Central

    Treff, Nathan R.; Levy, Brynn; Su, Jing; Northrop, Lesley E.; Tao, Xin; Scott, Richard T.

    2010-01-01

    Many studies estimate that chromosomal mosaicism within the cleavage-stage human embryo is high. However, comparison of two unique methods of aneuploidy screening of blastomeres within the same embryo has not been conducted and may indicate whether mosaicism has been overestimated due to technical inconsistency rather than the biological phenomena. The present study investigates the prevalence of chromosomal abnormality and mosaicism found with two different single cell aneuploidy screening techniques. Thirteen arrested cleavage-stage embryos were studied. Each was biopsied into individual cells (n = 160). The cells from each embryo were randomized into two groups. Those destined for FISH-based aneuploidy screening (n = 75) were fixed, one cell per slide. Cells for SNP microarray-based aneuploidy screening (n = 85) were put into individual tubes. Microarray was significantly more reliable (96%) than FISH (83%) for providing an interpretable result (P = 0.004). Markedly different results were obtained when comparing microarray and FISH results from individual embryos. Mosaicism was significantly less commonly observed by microarray (31%) than by FISH (100%) (P = 0.0005). Although FISH evaluated fewer chromosomes per cell and fewer cells per embryo, FISH still displayed significantly more unique genetic diagnoses per embryo (3.2 ± 0.2) than microarray (1.3 ± 0.2) (P < 0.0001). This is the first prospective, randomized, blinded and paired comparison between microarray and FISH-based aneuploidy screening. SNP microarray-based 24 chromosome aneuploidy screening provides more complete and consistent results than FISH. These results also suggest that FISH technology may overestimate the contribution of mitotic error to the origin of aneuploidy at the cleavage stage of human embryogenesis. PMID:20484246

  8. JAM: A Scalable Bayesian Framework for Joint Analysis of Marginal SNP Effects

    PubMed Central

    Conti, David V.; Richardson, Sylvia

    2016-01-01

    ABSTRACT Recently, large scale genome‐wide association study (GWAS) meta‐analyses have boosted the number of known signals for some traits into the tens and hundreds. Typically, however, variants are only analysed one‐at‐a‐time. This complicates the ability of fine‐mapping to identify a small set of SNPs for further functional follow‐up. We describe a new and scalable algorithm, joint analysis of marginal summary statistics (JAM), for the re‐analysis of published marginal summary stactistics under joint multi‐SNP models. The correlation is accounted for according to estimates from a reference dataset, and models and SNPs that best explain the complete joint pattern of marginal effects are highlighted via an integrated Bayesian penalized regression framework. We provide both enumerated and Reversible Jump MCMC implementations of JAM and present some comparisons of performance. In a series of realistic simulation studies, JAM demonstrated identical performance to various alternatives designed for single region settings. In multi‐region settings, where the only multivariate alternative involves stepwise selection, JAM offered greater power and specificity. We also present an application to real published results from MAGIC (meta‐analysis of glucose and insulin related traits consortium) – a GWAS meta‐analysis of more than 15,000 people. We re‐analysed several genomic regions that produced multiple significant signals with glucose levels 2 hr after oral stimulation. Through joint multivariate modelling, JAM was able to formally rule out many SNPs, and for one gene, ADCY5, suggests that an additional SNP, which transpired to be more biologically plausible, should be followed up with equal priority to the reported index. PMID:27027514

  9. PPLine: An Automated Pipeline for SNP, SAP, and Splice Variant Detection in the Context of Proteogenomics.

    PubMed

    Krasnov, George Sergeevich; Dmitriev, Alexey Alexandrovich; Kudryavtseva, Anna Viktorovna; Shargunov, Alexander Valerievich; Karpov, Dmitry Sergeevich; Uroshlev, Leonid Andreevich; Melnikova, Natalya Vladimirovna; Blinov, Vladimir Mikhailovich; Poverennaya, Ekaterina Vladimirovna; Archakov, Alexander Ivanovich; Lisitsa, Andrey Valerievich; Ponomarenko, Elena Alexandrovna

    2015-09-01

    The fundamental mission of the Chromosome-Centric Human Proteome Project (C-HPP) is the research of human proteome diversity, including rare variants. Liver tissues, HepG2 cells, and plasma were selected as one of the major objects for C-HPP studies. The proteogenomic approach, a recently introduced technique, is a powerful method for predicting and validating proteoforms coming from alternative splicing, mutations, and transcript editing. We developed PPLine, a Python-based proteogenomic pipeline providing automated single-amino-acid polymorphism (SAP), indel, and alternative-spliced-variants discovery based on raw transcriptome and exome sequence data, single-nucleoti