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Sample records for affymetrix 10k snp

  1. Evaluating the performance of Affymetrix SNP Array 6.0 platform with 400 Japanese individuals

    PubMed Central

    Nishida, Nao; Koike, Asako; Tajima, Atsushi; Ogasawara, Yuko; Ishibashi, Yoshimi; Uehara, Yasuka; Inoue, Ituro; Tokunaga, Katsushi

    2008-01-01

    Background With improvements in genotyping technologies, genome-wide association studies with hundreds of thousands of SNPs allow the identification of candidate genetic loci for multifactorial diseases in different populations. However, genotyping errors caused by genotyping platforms or genotype calling algorithms may lead to inflation of false associations between markers and phenotypes. In addition, the number of SNPs available for genome-wide association studies in the Japanese population has been investigated using only 45 samples in the HapMap project, which could lead to an inaccurate estimation of the number of SNPs with low minor allele frequencies. We genotyped 400 Japanese samples in order to estimate the number of SNPs available for genome-wide association studies in the Japanese population and to examine the performance of the current SNP Array 6.0 platform and the genotype calling algorithm "Birdseed". Results About 20% of the 909,622 SNP markers on the array were revealed to be monomorphic in the Japanese population. Consequently, 661,599 SNPs were available for genome-wide association studies in the Japanese population, after excluding the poorly behaving SNPs. The Birdseed algorithm accurately determined the genotype calls of each sample with a high overall call rate of over 99.5% and a high concordance rate of over 99.8% using more than 48 samples after removing low-quality samples by adjusting QC criteria. Conclusion Our results confirmed that the SNP Array 6.0 platform reached the level reported by the manufacturer, and thus genome-wide association studies using the SNP Array 6.0 platform have considerable potential to identify candidate susceptibility or resistance genetic factors for multifactorial diseases in the Japanese population, as well as in other populations. PMID:18803882

  2. A Single-Array-Based Method for Detecting Copy Number Variants Using Affymetrix High Density SNP Arrays and its Application to Breast Cancer

    PubMed Central

    Li, Ming; Wen, Yalu; Fu, Wenjiang

    2014-01-01

    Cumulative evidence has shown that structural variations, due to insertions, deletions, and inversions of DNA, may contribute considerably to the development of complex human diseases, such as breast cancer. High-throughput genotyping technologies, such as Affymetrix high density single-nucleotide polymorphism (SNP) arrays, have produced large amounts of genetic data for genome-wide SNP genotype calling and copy number estimation. Meanwhile, there is a great need for accurate and efficient statistical methods to detect copy number variants. In this article, we introduce a hidden-Markov-model (HMM)-based method, referred to as the PICR-CNV, for copy number inference. The proposed method first estimates copy number abundance for each single SNP on a single array based on the raw fluorescence values, and then standardizes the estimated copy number abundance to achieve equal footing among multiple arrays. This method requires no between-array normalization, and thus, maintains data integrity and independence of samples among individual subjects. In addition to our efforts to apply new statistical technology to raw fluorescence values, the HMM has been applied to the standardized copy number abundance in order to reduce experimental noise. Through simulations, we show our refined method is able to infer copy number variants accurately. Application of the proposed method to a breast cancer dataset helps to identify genomic regions significantly associated with the disease. PMID:26279618

  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. An Affymetrix Microarray Design for Microbial Genotyping

    DTIC Science & Technology

    2009-10-01

    Clostridium botulinum APRT Okra 5 Clostridium botulinum A str. ATCC 19397 5 Clostridium botulinum ATCC 3502 40 Clostridium botulinum B str. Eklund 17B 5...Clostridium botulinum SNP B1 str. Okra plasmid pCLD 20 Clostridium botulinum B1 str. Okra plasmid pCLD 5 Clostridium botulinum Bf 5 Clostridium...botulinum HPT Eklund 17B 10 Clostridium botulinum HPT Loch Maree 20 Clostridium botulinum HPT Okra 5 Clostridium botulinum A3 str. Loch Maree 5

  6. 10 K Spacecraft Cryocooler Development Program

    DTIC Science & Technology

    1996-07-01

    PL-TR-96-1115 PL-TR- 96-1115 10 K SPACECRAFT CRYOCOOLER DEVELOPMENT PROGRAM Larry D. Crawford Aerojet Electronic Systems Division P. 0. Box 296 Azusa...covered (from... to) July 1996 Final 09/92 to 11/94 4. Title & subtitle 5a. Contract or Grant # 10 K Spacecraft Cryocooler Development Program F29601...reports were not followed for this technical report. 14. Abstract The purpose of this project was to develop cryocooler technology capable of providing

  7. SNP Arrays

    PubMed Central

    Louhelainen, Jari

    2016-01-01

    The papers published in this Special Issue “SNP arrays” (Single Nucleotide Polymorphism Arrays) focus on several perspectives associated with arrays of this type. The range of papers vary from a case report to reviews, thereby targeting wider audiences working in this field. The research focus of SNP arrays is often human cancers but this Issue expands that focus to include areas such as rare conditions, animal breeding and bioinformatics tools. Given the limited scope, the spectrum of papers is nothing short of remarkable and even from a technical point of view these papers will contribute to the field at a general level. Three of the papers published in this Special Issue focus on the use of various SNP array approaches in the analysis of three different cancer types. Two of the papers concentrate on two very different rare conditions, applying the SNP arrays slightly differently. Finally, two other papers evaluate the use of the SNP arrays in the context of genetic analysis of livestock. The findings reported in these papers help to close gaps in the current literature and also to give guidelines for future applications of SNP arrays. PMID:27792140

  8. Celsius: a community resource for Affymetrix microarray data.

    PubMed

    Day, Allen; Carlson, Marc R J; Dong, Jun; O'Connor, Brian D; Nelson, Stanley F

    2007-01-01

    Celsius is a data warehousing system to aggregate Affymetrix CEL files and associated metadata. It provides mechanisms for importing, storing, querying, and exporting large volumes of primary and pre-processed microarray data. Celsius contains ten billion assay measurements and affiliated metadata. It is the largest publicly available source of Affymetrix microarray data, and through sheer volume it allows a sophisticated, broad view of transcription that has not previously been possible.

  9. Inference of kinship coefficients from Korean SNP genotyping data.

    PubMed

    Park, Seong-Jin; Yang, Jin Ok; Kim, Sang Cheol; Kwon, Jekeun; Lee, Sanghyuk; Lee, Byungwook

    2013-06-01

    The determination of relatedness between individuals in a family is crucial in analysis of common complex diseases. We present a method to infer close inter-familial relationships based on SNP genotyping data and provide the relationship coefficient of kinship in Korean families. We obtained blood samples from 43 Korean individuals in two families. SNP data was obtained using the Affymetrix Genome-wide Human SNP array 6.0 and the Illumina Human 1M-Duo chip. To measure the kinship coefficient with the SNP genotyping data, we considered all possible pairs of individuals in each family. The genetic distance between two individuals in a pair was determined using the allele sharing distance method. The results show that genetic distance is proportional to the kinship coefficient and that a close degree of kinship can be confirmed with SNP genotyping data. This study represents the first attempt to identify the genetic distance between very closely related individuals.

  10. Automated SNP genotype clustering algorithm to improve data completeness in high-throughput SNP genotyping datasets from custom arrays.

    PubMed

    Smith, Edward M; Littrell, Jack; Olivier, Michael

    2007-12-01

    High-throughput SNP genotyping platforms use automated genotype calling algorithms to assign genotypes. While these algorithms work efficiently for individual platforms, they are not compatible with other platforms, and have individual biases that result in missed genotype calls. Here we present data on the use of a second complementary SNP genotype clustering algorithm. The algorithm was originally designed for individual fluorescent SNP genotyping assays, and has been optimized to permit the clustering of large datasets generated from custom-designed Affymetrix SNP panels. In an analysis of data from a 3K array genotyped on 1,560 samples, the additional analysis increased the overall number of genotypes by over 45,000, significantly improving the completeness of the experimental data. This analysis suggests that the use of multiple genotype calling algorithms may be advisable in high-throughput SNP genotyping experiments. The software is written in Perl and is available from the corresponding author.

  11. Starburst Driven Superbubbles Radiating to 10 K

    NASA Astrophysics Data System (ADS)

    Tanner, Ryan; Cecil, Gerald; Heitsch, Fabian

    2016-01-01

    Starburst driven superbubbles can produce large scale galactic outflows. Whether any given starburst can create an outflow depends on several variables including the rate at which energy and mass are injected into the interstellar medium (ISM), the radiative cooling prescription used, and the overall density distribution of the ISM. We investigate the effect that two different temperature floors in our radiative cooling prescription have on wind kinematics and content. We find that cooling to 10 K instead of to 104 K increases the mass fraction of cold neutral and hot X-ray gas in the galactic wind while halving that in warm Hα. For sufficiently powerful starbursts our cooling prescription does not affect the terminal velocity of gas within the superbubble. Filaments embedded in the hot galactic wind contain warm and cold gas which moves slower than the surrounding wind, with the coldest gas hardly moving with respect to the galaxy. Optically bright filaments form at the edge of merging superbubbles and if anchored to a star forming complex will persist and grow to > 400 pc in length. These filaments are the main source of warm and cold gas being transported into the galactic halo. Using synthetic absorption profiles we measure the velocity of the warm and hot gas phases and find vwarm ∝ vhot0.5. We also find that vhot ∝ SFR0.5, which implies vwarm ∝ SFR0.25. Warm and cold gas embedded in the galactic wind show asymmetric absorption profiles consistent with observations and theoretical predictions. These asymmetries can be used to infer the kinematics of the filaments and associated dense cores.

  12. 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.

  13. SKM-SNP: SNP markers detection method.

    PubMed

    Liu, Yang; Li, Mark; Cheung, Yiu M; Sham, Pak C; Ng, Michael K

    2010-04-01

    SKM-SNP, SNP markers detection program, is proposed to identify a set of relevant SNPs for the association between a disease and multiple marker genotypes. We employ a subspace categorical clustering algorithm to compute a weight for each SNP in the group of patient samples and the group of normal samples, and use the weights to identify the subsets of relevant SNPs that categorize these two groups. The experiments on both Schizophrenia and Parkinson Disease data sets containing genome-wide SNPs are reported to demonstrate the program. Results indicate that our method can find some relevant SNPs that categorize the disease samples. The online SKM-SNP program is available at http://www.math.hkbu.edu.hk/~mng/SKM-SNP/SKM-SNP.html.

  14. 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

  15. Qualitative assessment of gene expression in affymetrix genechip arrays

    NASA Astrophysics Data System (ADS)

    Nagarajan, Radhakrishnan; Upreti, Meenakshi

    2007-01-01

    Affymetrix Genechip microarrays are used widely to determine the simultaneous expression of genes in a given biological paradigm. Probes on the Genechip array are atomic entities which by definition are randomly distributed across the array and in turn govern the gene expression. In the present study, we make several interesting observations. We show that there is considerable correlation between the probe intensities across the array which defy the independence assumption. While the mechanism behind such correlations is unclear, we show that scaling behavior and the profiles of perfect match (PM) as well as mismatch (MM) probes are similar and immune-to-background subtraction. We believe that the observed correlations are possibly an outcome of inherent non-stationarities or patchiness in the array devoid of biological significance. This is demonstrated by inspecting their scaling behavior and profiles of the PM and MM probe intensities obtained from publicly available Genechip arrays from three eukaryotic genomes, namely: Drosophila melanogaster (fruit fly), Homo sapiens (humans) and Mus musculus (house mouse) across distinct biological paradigms and across laboratories, with and without background subtraction. The fluctuation functions were estimated using detrended fluctuation analysis (DFA) with fourth-order polynomial detrending. The results presented in this study provide new insights into correlation signatures of PM and MM probe intensities and suggests the choice of DFA as a tool for qualitative assessment of Affymetrix Genechip microarrays prior to their analysis. A more detailed investigation is necessary in order to understand the source of these correlations.

  16. CEL_INTERROGATOR: A FREE AND OPEN SOURCE PACKAGE FOR AFFYMETRIX CEL FILE PARSING

    Technology Transfer Automated Retrieval System (TEKTRAN)

    CEL_Interrogator Package is a suite of programs designed to extract the average probe intensity and other information for each probe sequence from an Affymetrix GeneChip CEL file and unite them with their human-readable Affymetrix consensus sequence names. The resulting text file is suitable for di...

  17. High correspondence between Affymetrix exon and standard expression arrays.

    PubMed

    Okoniewski, Michał J; Hey, Yvonne; Pepper, Stuart D; Miller, Crispin J

    2007-02-01

    Exon arrays aim to provide comprehensive gene expression data at the level of individual exons, similar to that provided on a per-gene basis by existing expression arrays. This report describes the performance of Affymetrix GeneChip Human Exon 1.0 ST array by using replicated RNA samples from two human cell lines, MCF7 and MCF10A, hybridized both to Exon 1.0 ST and to HG-U133 Plus2 arrays. Cross-comparison between array types requires an appropriate mapping to be found between individual probe sets. Three possible mappings were considered, reflecting different strategies for dealing with probe sets that target different parts of the same transcript. Irrespective of the mapping used, Exon 1.0 ST and HG-U133 Plus2 arrays show a high degree of correspondence. More than 80% of HG-U133 Plus2 probe sets may be mapped to the Exon chip, and fold changes are found well preserved for over 96% of those probe sets detected present. Since HG-U133 Plus2 arrays have already been extensively validated, these results lend a significant degree of confidence to exon arrays.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Ultratight crystal packing of a 10 kDa protein

    SciTech Connect

    Trillo-Muyo, Sergio; Chruszcz, Maksymilian; Minor, Wladek; Kuisiene, Nomeda

    2013-03-01

    The crystal structure of the C-terminal domain of a putative U32 peptidase from G. thermoleovorans is reported; it is one of the most tightly packed protein structures reported to date. While small organic molecules generally crystallize forming tightly packed lattices with little solvent content, proteins form air-sensitive high-solvent-content crystals. Here, the crystallization and full structure analysis of a novel recombinant 10 kDa protein corresponding to the C-terminal domain of a putative U32 peptidase are reported. The orthorhombic crystal contained only 24.5% solvent and is therefore among the most tightly packed protein lattices ever reported.

  4. SNP panels/Imputation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Participants from thirteen countries discussed services that Interbull can perform or recommendations that Interbull can make to promote harmonization and assist member countries in improving their genomic evaluations in regard to SNP panels and imputation. The panel recommended: A mechanism to shar...

  5. 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.

  6. SFP Genotyping from Affymetrix Arrays is Robust but Largely Detects Cis-acting Expression Regulators

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The recent development of Affymetrix chips designed from assembled EST sequences has spawned considerable interest in identifying single-feature polymorphisms (SFPs) from transcriptome data. SFPs are valuable genetic markers that potentially offer a physical link to the structural genes themselves....

  7. Discovery and mapping of single feature polymorphisms in wheat using affymetrix arrays

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Single feature polymorphisms (SFPs) can be a rich source of markers for gene mapping and function studies. To explore the feasibility of using the Affymetrix GeneChip to discover and map SFPs in the large hexaploid wheat genome, six wheat varieties of diverse origins were analyzed for significant pr...

  8. Starburst-driven Galactic Superbubbles Radiating to 10 K

    NASA Astrophysics Data System (ADS)

    Tanner, Ryan; Cecil, Gerald; Heitsch, Fabian

    2016-04-01

    Our three-dimensional hydrodynamical simulations of starbursts examine the formation of superbubbles over a range of driving luminosities and mass loadings that determine superbubble growth and wind velocity. From this we determine the relationship between the velocity of a galactic wind (GW) and the power of the starburst. We find a threshold for the formation of a wind, above which the speed of the wind is not affected by grid resolution or the temperature floor of our radiative cooling. We investigate the effect that two different temperature floors in our radiative cooling prescription have on wind kinematics and content. We find that cooling to 10 K instead of to 104 K increases the mass fraction of cold neutral and hot X-ray gas in the GW, while halving that in warm Hα. Our simulations show that the mass of cold gas transported into the lower halo does not depend on the starburst strength. Optically bright filaments form at the edge of merging superbubbles, or where a cold dense cloud has been disrupted by the wind. Filaments formed by merging superbubbles will persist and grow to \\gt 400 pc in length if anchored to a star forming complex. Filaments embedded in the hot GW contain warm and cold gas that moves 300-1200 km s-1 slower than the surrounding wind, with the coldest gas hardly moving with respect to the Galaxy. Warm and cold matter in the GW show asymmetric absorption profiles consistent with observations, with a thin tail up to the wind velocity.

  9. Genome-Wide Association Mapping for Intelligence in Military Working Dogs: Canine Cohort, Canine Intelligence Assessment Regimen, Genome-Wide Single Nucleotide Polymorphism (SNP) Typing, and Unsupervised Classification Algorithm for Genome-Wide Association Data Analysis

    DTIC Science & Technology

    2011-09-01

    were down-selected and successfully genotyped for whole genome (WG) single nucleotide polymorphism (SNP) markers by means of the Affymetrix Canine...SUBJECT TERMS Military working dog genome-wide association study genetic marker intelligence... marker , intelligence, Canine Intelligence Testing Protocol, classification technique, clustering analysis Technical Report: September 2011 2

  10. 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

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

    PubMed Central

    Huang, Jie; Howie, Bryan; McCarthy, Shane; Memari, Yasin; Walter, Klaudia; Min, Josine L.; Danecek, Petr; Malerba, Giovanni; Trabetti, Elisabetta; Zheng, Hou-Feng; Al Turki, Saeed; Amuzu, Antoinette; Anderson, Carl A.; Anney, Richard; Antony, Dinu; Artigas, María Soler; Ayub, Muhammad; Bala, Senduran; Barrett, Jeffrey C.; Barroso, Inês; Beales, Phil; Benn, Marianne; Bentham, Jamie; Bhattacharya, Shoumo; Birney, Ewan; Blackwood, Douglas; Bobrow, Martin; Bochukova, Elena; Bolton, Patrick F.; Bounds, Rebecca; Boustred, Chris; Breen, Gerome; Calissano, Mattia; Carss, Keren; Pablo Casas, Juan; Chambers, John C.; Charlton, Ruth; Chatterjee, Krishna; Chen, Lu; Ciampi, Antonio; Cirak, Sebahattin; Clapham, Peter; Clement, Gail; Coates, Guy; Cocca, Massimiliano; Collier, David A.; Cosgrove, Catherine; Cox, Tony; Craddock, Nick; Crooks, Lucy; Curran, Sarah; Curtis, David; Daly, Allan; Day, Ian N. M.; Day-Williams, Aaron; Dedoussis, George; Down, Thomas; Du, Yuanping; van Duijn, Cornelia M.; Dunham, Ian; Edkins, Sarah; Ekong, Rosemary; Ellis, Peter; Evans, David M.; Farooqi, I. Sadaf; Fitzpatrick, David R.; Flicek, Paul; Floyd, James; Foley, A. Reghan; Franklin, Christopher S.; Futema, Marta; Gallagher, Louise; Gasparini, Paolo; Gaunt, Tom R.; Geihs, Matthias; Geschwind, Daniel; Greenwood, Celia; Griffin, Heather; Grozeva, Detelina; Guo, Xiaosen; Guo, Xueqin; Gurling, Hugh; Hart, Deborah; Hendricks, Audrey E.; Holmans, Peter; Huang, Liren; Hubbard, Tim; Humphries, Steve E.; Hurles, Matthew E.; Hysi, Pirro; Iotchkova, Valentina; Isaacs, Aaron; Jackson, David K.; Jamshidi, Yalda; Johnson, Jon; Joyce, Chris; Karczewski, Konrad J.; Kaye, Jane; Keane, Thomas; Kemp, John P.; Kennedy, Karen; Kent, Alastair; Keogh, Julia; Khawaja, Farrah; Kleber, Marcus E.; van Kogelenberg, Margriet; Kolb-Kokocinski, Anja; Kooner, Jaspal S.; Lachance, Genevieve; Langenberg, Claudia; Langford, Cordelia; Lawson, Daniel; Lee, Irene; van Leeuwen, Elisabeth M.; Lek, Monkol; Li, Rui; Li, Yingrui; Liang, Jieqin; Lin, Hong; Liu, Ryan; Lönnqvist, Jouko; Lopes, Luis R.; Lopes, Margarida; Luan, Jian'an; MacArthur, Daniel G.; Mangino, Massimo; Marenne, Gaëlle; März, Winfried; Maslen, John; Matchan, Angela; Mathieson, Iain; McGuffin, Peter; McIntosh, Andrew M.; McKechanie, Andrew G.; McQuillin, Andrew; Metrustry, Sarah; Migone, Nicola; Mitchison, Hannah M.; Moayyeri, Alireza; Morris, James; Morris, Richard; Muddyman, Dawn; Muntoni, Francesco; Nordestgaard, Børge G.; Northstone, Kate; O'Donovan, Michael C.; O'Rahilly, Stephen; Onoufriadis, Alexandros; Oualkacha, Karim; Owen, Michael J.; Palotie, Aarno; Panoutsopoulou, Kalliope; Parker, Victoria; Parr, Jeremy R.; Paternoster, Lavinia; Paunio, Tiina; Payne, Felicity; Payne, Stewart J.; Perry, John R. B.; Pietilainen, Olli; Plagnol, Vincent; Pollitt, Rebecca C.; Povey, Sue; Quail, Michael A.; Quaye, Lydia; Raymond, Lucy; Rehnström, Karola; Ridout, Cheryl K.; Ring, Susan; Ritchie, Graham R. S.; Roberts, Nicola; Robinson, Rachel L.; Savage, David B.; Scambler, Peter; Schiffels, Stephan; Schmidts, Miriam; Schoenmakers, Nadia; Scott, Richard H.; Scott, Robert A.; Semple, Robert K.; Serra, Eva; Sharp, Sally I.; Shaw, Adam; Shihab, Hashem A.; Shin, So-Youn; Skuse, David; Small, Kerrin S.; Smee, Carol; Smith, George Davey; Southam, Lorraine; Spasic-Boskovic, Olivera; Spector, Timothy D.; St Clair, David; St Pourcain, Beate; Stalker, Jim; Stevens, Elizabeth; Sun, Jianping; Surdulescu, Gabriela; Suvisaari, Jaana; Syrris, Petros; Tachmazidou, Ioanna; Taylor, Rohan; Tian, Jing; Tobin, Martin D.; Toniolo, Daniela; Traglia, Michela; Tybjaerg-Hansen, Anne; Valdes, Ana M.; Vandersteen, Anthony M.; Varbo, Anette; Vijayarangakannan, Parthiban; Visscher, Peter M.; Wain, Louise V.; Walters, James T. R.; Wang, Guangbiao; Wang, Jun; Wang, Yu; Ward, Kirsten; Wheeler, Eleanor; Whincup, Peter; Whyte, Tamieka; Williams, Hywel J.; Williamson, Kathleen A.; Wilson, Crispian; Wilson, Scott G.; Wong, Kim; Xu, ChangJiang; Yang, Jian; Zaza, Gianluigi; Zeggini, Eleftheria; Zhang, Feng; Zhang, Pingbo; Zhang, Weihua; 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. PMID:26368830

  12. 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

  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.

  14. Etiological yield of SNP microarrays in idiopathic intellectual disability.

    PubMed

    Utine, G Eda; Haliloğlu, Göknur; Volkan-Salancı, Bilge; Çetinkaya, Arda; Kiper, Pelin Ö; Alanay, Yasemin; Aktaş, Dilek; Anlar, Banu; Topçu, Meral; Boduroğlu, Koray; Alikaşifoğlu, Mehmet

    2014-05-01

    Intellectual disability (ID) has a prevalence of 3% and is classified according to its severity. An underlying etiology cannot be determined in 75-80% in mild ID, and in 20-50% of severe ID. After it has been shown that copy number variations involving short DNA segments may cause ID, genome-wide SNP microarrays are being used as a tool for detecting submicroscopic copy number changes and uniparental disomy. This study was performed to investigate the presence of copy number changes in patients with ID of unidentified etiology. Affymetrix(®) 6.0 SNP microarray platform was used for analysis of 100 patients and their healthy parents, and data were evaluated using various databases and literature. Etiological diagnoses were made in 12 patients (12%). Homozygous deletion in NRXN1 gene and duplication in IL1RAPL1 gene were detected for the first time. Two separate patients had deletions in FOXP2 and UBE2A genes, respectively, for which only few patients have recently been reported. Interstitial and subtelomeric copy number changes were described in 6 patients, in whom routine cytogenetic tools revealed normal results. In one patient uniparental disomy type of Angelman syndrome was diagnosed. SNP microarrays constitute a screening test able to detect very small genomic changes, with a high etiological yield even in patients already evaluated using traditional cytogenetic tools, offer analysis for uniparental disomy and homozygosity, and thereby are helpful in finding novel disease-causing genes: for these reasons they should be considered as a first-tier genetic screening test in the evaluation of patients with ID and autism.

  15. Genome-wide SNP typing reveals signatures of population history.

    PubMed

    Hughes, Austin L; Welch, Robert; Puri, Vinita; Matthews, Casey; Haque, Kashif; Chanock, Stephen J; Yeager, Meredith

    2008-07-01

    Single-nucleotide polymorphism (SNP) arrays have become a popular technology for disease-association studies, but they also have potential for studying the genetic differentiation of human populations. Application of the Affymetrix GeneChip Human Mapping 500K Array Set to a population of 102 individuals representing the major ethnic groups in the United States (African, Asian, European, and Hispanic) revealed patterns of gene diversity and genetic distance that reflected population history. We analyzed allelic frequencies at 388,654 autosomal SNP sites that showed some variation in our study population and 10% or fewer missing values. Despite the small size (23-31 individuals) of each subpopulation, there were no fixed differences at any site between any two subpopulations. As expected from the African origin of modern humans, greater gene diversity was seen in Africans than in either Asians or Europeans, and the genetic distance between the Asian and the European populations was significantly lower than that between either of these two populations and Africans. Principal components analysis applied to a correlation matrix among individuals was able to separate completely the major continental groups of humans (Africans, Asians, and Europeans), while Hispanics overlapped all three of these groups. Genes containing two or more markers with extraordinarily high genetic distance between subpopulations were identified as candidate genes for health differences between subpopulations. The results show that, even with modest sample sizes, genome-wide SNP genotyping technologies have great promise for capturing signatures of gene frequency difference between human subpopulations, with applications in areas as diverse as forensics and the study of ethnic health disparities.

  16. An annotation infrastructure for the analysis and interpretation of Affymetrix exon array data.

    PubMed

    Okoniewski, Michał J; Yates, Tim; Dibben, Siân; Miller, Crispin J

    2007-01-01

    Affymetrix exon arrays contain probesets intended to target every known and predicted exon in the entire genome, posing significant challenges for high-throughput genome-wide data analysis. X:MAP http://xmap.picr.man.ac.uk, an annotation database, and exonmap http://www.bioconductor.org/packages/2.0/bioc/html/exonmap.html, a BioConductor/R package, are designed to support fine-grained analysis of exon array data. The system supports the application of standard statistical techniques, prior to the use of genome scale annotation to provide gene-, transcript- and exon-level summaries and visualization tools.

  17. An annotation infrastructure for the analysis and interpretation of Affymetrix exon array data

    PubMed Central

    Okoniewski, Michał J; Yates, Tim; Dibben, Siân; Miller, Crispin J

    2007-01-01

    Affymetrix exon arrays contain probesets intended to target every known and predicted exon in the entire genome, posing significant challenges for high-throughput genome-wide data analysis. X:MAP , an annotation database, and exonmap , a BioConductor/R package, are designed to support fine-grained analysis of exon array data. The system supports the application of standard statistical techniques, prior to the use of genome scale annotation to provide gene-, transcript- and exon-level summaries and visualization tools. PMID:17498294

  18. 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

  19. Exon array data analysis using Affymetrix power tools and R statistical software

    PubMed Central

    2011-01-01

    The use of microarray technology to measure gene expression on a genome-wide scale has been well established for more than a decade. Methods to process and analyse the vast quantity of expression data generated by a typical microarray experiment are similarly well-established. The Affymetrix Exon 1.0 ST array is a relatively new type of array, which has the capability to assess expression at the individual exon level. This allows a more comprehensive analysis of the transcriptome, and in particular enables the study of alternative splicing, a gene regulation mechanism important in both normal conditions and in diseases. Some aspects of exon array data analysis are shared with those for standard gene expression data but others present new challenges that have required development of novel tools. Here, I will introduce the exon array and present a detailed example tutorial for analysis of data generated using this platform. PMID:21498550

  20. X:Map: annotation and visualization of genome structure for Affymetrix exon array analysis

    PubMed Central

    Yates, Tim; Okoniewski, Michał J.; Miller, Crispin J.

    2008-01-01

    Affymetrix exon arrays aim to target every known and predicted exon in the human, mouse or rat genomes, and have reporters that extend beyond protein coding regions to other areas of the transcribed genome. This combination of increased coverage and precision is important because a substantial proportion of protein coding genes are predicted to be alternatively spliced, and because many non-coding genes are known also to be of biological significance. In order to fully exploit these arrays, it is necessary to associate each reporter on the array with the features of the genome it is targeting, and to relate these to gene and genome structure. X:Map is a genome annotation database that provides this information. Data can be browsed using a novel Google-maps based interface, and analysed and further visualized through an associated BioConductor package. The database can be found at http://xmap.picr.man.ac.uk. PMID:17932061

  1. Understanding the physics of oligonucleotide microarrays: the Affymetrix spike-in data reanalysed

    NASA Astrophysics Data System (ADS)

    Burden, Conrad J.

    2008-03-01

    The Affymetrix U95 and U133 Latin-Square spike-in datasets are reanalysed, together with a dataset from a version of the U95 spike-in experiment without a complex non-specific background. The approach uses a physico-chemical model which includes the effects of the specific and non-specific hybridization and probe folding at the microarray surface, target folding and hybridization in the bulk RNA target solution and duplex dissociation during the post-hybridization washing phase. The model predicts a three-parameter hyperbolic response function that fits well with fluorescence intensity data from all the three datasets. The importance of the various hybridization and washing effects in determining each of the three parameters is examined, and some guidance is given as to how a practical algorithm for determining specific target concentrations might be developed.

  2. Exon array data analysis using Affymetrix power tools and R statistical software.

    PubMed

    Lockstone, Helen E

    2011-11-01

    The use of microarray technology to measure gene expression on a genome-wide scale has been well established for more than a decade. Methods to process and analyse the vast quantity of expression data generated by a typical microarray experiment are similarly well-established. The Affymetrix Exon 1.0 ST array is a relatively new type of array, which has the capability to assess expression at the individual exon level. This allows a more comprehensive analysis of the transcriptome, and in particular enables the study of alternative splicing, a gene regulation mechanism important in both normal conditions and in diseases. Some aspects of exon array data analysis are shared with those for standard gene expression data but others present new challenges that have required development of novel tools. Here, I will introduce the exon array and present a detailed example tutorial for analysis of data generated using this platform.

  3. 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

  4. 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.

  5. Design and optimization of the combination film in 10kW diode laser cladding source

    NASA Astrophysics Data System (ADS)

    Zhu, Hong-bo; Lin, Xing-chen; Hao, Ming-ming; Zhang, Jin-sheng; Ning, Yong-qiang

    2015-08-01

    According to the special requirements of combination film in 10kW diode laser cladding source, the polarization combination film at 915nm was designed and grew. Film system is designed at different film materials based on the design theory. The non-QWOT film is optimized using the needle optimization and double sided coating by Optilayer software. The film was used in the 10kW diode laser source after high temperature aging testing. The film formed by Ta2O5 is very stable under IBAD, which can meet the reliability of 10kW diode laser cladding source in industry

  6. 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.

  7. Elucidation of the ‘Honeycrisp’ pedigree through haplotype analysis with a multi-family integrated SNP linkage map and a large apple (Malus×domestica) pedigree-connected SNP data set

    PubMed Central

    Howard, Nicholas P; van de Weg, Eric; Bedford, David S; Peace, Cameron P; Vanderzande, Stijn; Clark, Matthew D; Teh, Soon Li; Cai, Lichun; Luby, James J

    2017-01-01

    The apple (Malus×domestica) cultivar Honeycrisp has become important economically and as a breeding parent. An earlier study with SSR markers indicated the original recorded pedigree of ‘Honeycrisp’ was incorrect and ‘Keepsake’ was identified as one putative parent, the other being unknown. The objective of this study was to verify ‘Keepsake’ as a parent and identify and genetically describe the unknown parent and its grandparents. A multi-family based dense and high-quality integrated SNP map was created using the apple 8 K Illumina Infinium SNP array. This map was used alongside a large pedigree-connected data set from the RosBREED project to build extended SNP haplotypes and to identify pedigree relationships. ‘Keepsake’ was verified as one parent of ‘Honeycrisp’ and ‘Duchess of Oldenburg’ and ‘Golden Delicious’ were identified as grandparents through the unknown parent. Following this finding, siblings of ‘Honeycrisp’ were identified using the SNP data. Breeding records from several of these siblings suggested that the previously unreported parent is a University of Minnesota selection, MN1627. This selection is no longer available, but now is genetically described through imputed SNP haplotypes. We also present the mosaic grandparental composition of ‘Honeycrisp’ for each of its 17 chromosome pairs. This new pedigree and genetic information will be useful in future pedigree-based genetic studies to connect ‘Honeycrisp’ with other cultivars used widely in apple breeding programs. The created SNP linkage map will benefit future research using the data from the Illumina apple 8 and 20 K and Affymetrix 480 K SNP arrays. PMID:28243452

  8. 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.

  9. 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

  10. UASIS: Universal Automatic SNP Identification System

    PubMed Central

    2011-01-01

    Background SNP (Single Nucleotide Polymorphism), the most common genetic variations between human beings, is believed to be a promising way towards personalized medicine. As more and more research on SNPs are being conducted, non-standard nomenclatures may generate potential problems. The most serious issue is that researchers cannot perform cross referencing among different SNP databases. This will result in more resources and time required to track SNPs. It could be detrimental to the entire academic community. Results UASIS (Universal Automated SNP Identification System) is a web-based server for SNP nomenclature standardization and translation at DNA level. Three utilities are available. They are UASIS Aligner, Universal SNP Name Generator and SNP Name Mapper. UASIS maps SNPs from different databases, including dbSNP, GWAS, HapMap and JSNP etc., into an uniform view efficiently using a proposed universal nomenclature and state-of-art alignment algorithms. UASIS is freely available at http://www.uasis.tk with no requirement of log-in. Conclusions UASIS is a helpful platform for SNP cross referencing and tracking. By providing an informative, unique and unambiguous nomenclature, which utilizes unique position of a SNP, we aim to resolve the ambiguity of SNP nomenclatures currently practised. Our universal nomenclature is a good complement to mainstream SNP notations such as rs# and HGVS guidelines. UASIS acts as a bridge to connect heterogeneous representations of SNPs. PMID:22369494

  11. Linear reduction methods for tag SNP selection.

    PubMed

    He, Jingwu; Zelikovsky, Alex

    2004-01-01

    It is widely hoped that constructing a complete human haplotype map will help to associate complex diseases with certain SNP's. Unfortunately, the number of SNP's is huge and it is very costly to sequence many individuals. Therefore, it is desirable to reduce the number of SNP's that should be sequenced to considerably small number of informative representatives, so called tag SNP's. In this paper, we propose a new linear algebra based method for selecting and using tag SNP's. Our method is purely combinatorial and can be combined with linkage disequilibrium (LD) and block based methods. We measure the quality of our tag SNP selection algorithm by comparing actual SNP's with SNP's linearly predicted from linearly chosen tag SNP's. We obtain an extremely good compression and prediction rates. For example, for long haplotypes (>25000 SNP's), knowing only 0.4% of all SNP's we predict the entire unknown haplotype with 2% accuracy while the prediction method is based on a 10% sample of the population.

  12. The 10 kDa protein of Taenia solium metacestodes shows genus specific antigenicity.

    PubMed

    Park, S K; Yun, D H; Chung, J Y; Kong, Y; Cho, S Y

    2000-09-01

    Genus specific antigenicity of the 10 kDa protein in cyst fluid (CF) of Taenia solium metacestodes was demonstrated by comparative immunoblot analysis. When CFs from taeniid metacestodes of T. saginata, T. solium, T. taeniaeformis and T. crassiceps were probed with specific monoclonal antibody (mAb) raised against 150 kDa protein of T. solium metacestodes, specific antibody reactions were observed in 7 and 10 kDa proteins of T. solium and in 7/8 kDa of T. saginata, T. taeniaeformis and T. crassiceps. The mAb did not react with any protein in hydatid fluid of Echinococcus granulosus and E. multilocularis. This result revealed that the 10 kDa peptide of T. solium metacestodes and its equivalent proteins of different Taenia metacestodes are genus specific antigens that are shared among different Taenia species.

  13. 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.

  14. 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.

  15. 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).

  16. 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...

  17. A 10kW series resonant converter design, transistor characterization, and base-drive optimization

    NASA Technical Reports Server (NTRS)

    Robson, R.; Hancock, D.

    1981-01-01

    Transistors are characterized for use as switches in resonant circuit applications. A base drive circuit to provide the optimal base drive to these transistors under resonant circuit conditions is developed and then used in the design, fabrication and testing of a breadboard, spaceborne type 10 kW series resonant converter.

  18. Girth welding of X-60 pipeline with a 10kW laser

    NASA Astrophysics Data System (ADS)

    Megaw, J. H. P. C.; Hill, M.,; Osbourn, S. J.

    1986-10-01

    Single-pass autogeneous welding by 10kW laser of API 5LX X60 pipeline samples, of 760mm diameter and with wall thickness up to 19mm, in a configuration appropriate 4to J-lay operations, is described. The results of mechanical testing, including Charpy impact properties and their dependence on process conditions, are presented and discussed.

  19. 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.

  20. Genome-wide SNP analysis of the Systemic Capillary Leak Syndrome (Clarkson disease)

    PubMed Central

    Xie, Zhihui; Nagarajan, Vijayaraj; Sturdevant, Daniel E; Iwaki, Shoko; Chan, Eunice; Wisch, Laura; Young, Michael; Nelson, Celeste M; Porcella, Stephen F; Druey, Kirk M

    2013-01-01

    The Systemic Capillary Leak Syndrome (SCLS) is an extremely rare, orphan disease that resembles, and is frequently erroneously diagnosed as, systemic anaphylaxis. The disorder is characterized by repeated, transient, and seemingly unprovoked episodes of hypotensive shock and peripheral edema due to transient endothelial hyperpermeability. SCLS is often accompanied by a monoclonal gammopathy of unknown significance (MGUS). Using Affymetrix Single Nucleotide Polymorphism (SNP) microarrays, we performed the first genome-wide SNP analysis of SCLS in a cohort of 12 disease subjects and 18 controls. Exome capture sequencing was performed on genomic DNA from nine of these patients as validation for the SNP-chip discoveries and de novo data generation. We identified candidate susceptibility loci for SCLS, which included a region flanking CAV3 (3p25.3) as well as SNP clusters in PON1 (7q21.3), PSORS1C1 (6p21.3), and CHCHD3 (7q33). Among the most highly ranked discoveries were gene-associated SNPs in the uncharacterized LOC100130480 gene (rs6417039, rs2004296). Top case-associated SNPs were observed in BTRC (rs12355803, 3rs4436485), ARHGEF18 (rs11668246), CDH13 (rs4782779), and EDG2 (rs12552348), which encode proteins with known or suspected roles in B cell function and/or vascular integrity. 61 SNPs that were significantly associated with SCLS by microarray analysis were also detected and validated by exome deep sequencing. Functional annotation of highly ranked SNPs revealed enrichment of cell projections, cell junctions and adhesion, and molecules containing pleckstrin homology, Ras/Rho regulatory, and immunoglobulin Ig-like C2/fibronectin type III domains, all of which involve mechanistic functions that correlate with the SCLS phenotype. These results highlight SNPs with potential relevance to SCLS. PMID:24808988

  1. 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.

  2. Design and Development of a 3 to 10 kW Ammonia Arcjet

    NASA Technical Reports Server (NTRS)

    Goodfellow, K. D.; Polk, J. E.

    1993-01-01

    An ammonia arcjet capable of throttling between 3 and 10 kW and producing a specific impulse of 600 s is required for the SSTAR flight experiment. Testing was performed to evaluate the performance of two nozzle configurations on ammonia arcjet performance over this power range. One of the objectives of these tests was to quantify the effect small nozzle changes have on performance. The smaller constrictor engine (2.54 mm diameter) produced a specific impulse of about 650 s over the range of 3 to 10 kW at a specific power of 60 kJ/g exceeding the 500-600 s requirement for the SSTAR flight experiment.

  3. A crystal structure prediction enigma solved: the gallic acid monohydrate system - surprises at 10 K.

    PubMed

    Hoser, A A; Sovago, I; Lanza, A; Madsen, A Ø

    2017-01-10

    The seemingly unpredictable structure of gallic acid monohydrate form IV has been investigated using accurate X-ray diffraction measurements at temperatures of 10 and 123 K. The measurements demonstrate that the structure is commensurately modulated at 10 K and disordered at higher temperatures. Aided by charge-density modeling and periodic DFT calculations we show that the disorder gives a substantial stabilization of the structure.

  4. '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.

  5. 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.

  6. 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.

  7. 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.

  8. Study on 10 kVDC powered junction box for a cabled ocean observatory system

    NASA Astrophysics Data System (ADS)

    Chen, Yan-hu; Yang, Can-jun; Li, De-jun; Jin, Bo; Chen, Ying

    2013-04-01

    A cabled ocean observatory system that can provide abundant power and broad bandwidth communication for undersea instruments is developed. A 10 kV direct current (kVDC) with up to 10 kW power, along with 1 Gigabit/sec Ethernet communication, can be transmitted from the shore to the seafloor through an umbilical armored cable. A subsea junction box is fixed at a cable terminal, enabling the extension of up to nine connections. The box consists of three main pressure vessels that perform power conversion, power distribution, and real-time communication functions. A method of stacking modules is used to design the power conversion system in order to reduce the 10 kV voltage to levels that can power the attached instruments. A power distribution system and an Ethernet communication system are introduced to control the power supply and transmit data or commands between the terminals and the shore station, respectively. Specific validations of all sections were qualified in a laboratory environment prior to the sea trial. The ocean observatory system was then deployed at the coast of the East China Sea along with three in situ instruments for a 14-day test. The results show that this high voltage-powered observatory system is effective for subsea long-term and real-time observations.

  9. Development of 10-kWe preferential oxidation system for fuel cell vehicles

    NASA Astrophysics Data System (ADS)

    Lee, Seong Ho; Han, Jaesung; Lee, Kwan-Young

    A preferential oxidation (PROX) reactor for a 10-kWe polymer electrolyte membrane fuel cell (PEMFC) system is developed. Pt-Ru/Al 2O 3 catalyst powder, with a size of 300-600 μm is applied for the PROX reaction. To minimize pressure drop and to avoid hot spots in the catalyst bed, the reactor is designed as a dual-staged, multi-tube system. The performance of the 10-kWe PROX unit is evaluated by feeding simulated gasoline reformate which contains 1.2 wt.% carbon monoxide (CO). The CO concentration of the treated reformate is lower than 20 ppm in the steady-state and is under 30 ppm at 65% load change. Hydrogen loss in the steady-state is about 1.5% and the pressure drop across the reactor is 4 psi. Start-up characteristics of the 10-kWe PROX system are also investigated. It takes 3 min to reduce the CO concentration to below 20 ppm. Several controllable factors are found to shorten the start-up time.

  10. 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

  11. Analysis of a claimed distant relationship in a deficient pedigree using high density SNP data.

    PubMed

    Lareu, M V; García-Magariños, M; Phillips, C; Quintela, I; Carracedo, A; Salas, A

    2012-05-01

    DNA markers are routinely used to reveal both simple and complex family relationships. Likelihood based approaches have been traditionally used to estimate relationships using relatively few unlinked markers. However it is widely recognized that when using such limited numbers of loci distant relationships between two individuals cannot be distinguished from the average level of allele sharing found in random pairwise comparisons in the same population. As a real example, we demonstrate the usefulness of genome-wide SNP genotyping to analyze a claimed second cousin relationship that could not be resolved using standard forensic markers, confirming theoretical expectations for very distant relationships. Genome profiles derived from Affymetrix 6.0 SNP arrays obtained from the claimed second cousins were compared to profiles obtained from unrelated individuals and simulated data. Significance of the high estimated probabilities in favor of the second cousin relationship hypothesis was proved from the results obtained with both real and simulated unrelated pairs. As a final cautionary note, it is important to consider that successful identification of the claimed distant relationship reported here is largely due to a well-founded hypothesis being compared to the alternative hypothesis of the claimants being unrelated, but where there are several possible alternative hypotheses, the approach we outline here can yield false indications of unfounded alternative relationships.

  12. 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.

  13. The Development and Demonstration of a 360m/10 kA HTS DC Power Cable

    NASA Astrophysics Data System (ADS)

    Xiao, Liye

    With the quick development of renewable energy, it is expected that the electric power from renewable energy would be the dominant one for the future power grid. Due to the specialty of the renewable energy, the HVDC power transmission would be very useful for the transmission of electric power from renewable energy. DC power cable made of High Tc Superconductor (HTS) would be a possible alternative for the construction of HVDC power transmission system. In this chapter, we report the development and demonstration of a 360 m/10 kA HTS DC power cable and the test results.

  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. Ammonia arcjet engine behavior in a cyclic endurance test at 10 kW

    NASA Technical Reports Server (NTRS)

    Polk, J. E.; Goodfellow, K. D.; Pless, L. C.

    1992-01-01

    The behavior of a 30 kWe-class ammonia arcjet operated at 10 kWe during the 707 successful cycles of an endurance test is described. The propellant flow rate was 0.170 g/s, and the measured performance was about 630 s specific impulse at an efficiency of 0.34. Data obtained indicate that the terminal voltage increased over the first 300 cycles, and then remained approximately constant for the remainder of the test, which suggests that the cathode eroded initially and then reached a stable geometry. No major changes were observed in thruster performance. The test was terminated by a series of external arcs.

  16. Affymetrix Whole-Transcript Human Gene 1.0 ST array is highly concordant with standard 3' expression arrays.

    PubMed

    Pradervand, Sylvain; Paillusson, Alexandra; Thomas, Jérôme; Weber, Johann; Wirapati, Pratyaksha; Hagenbüchle, Otto; Harshman, Keith

    2008-05-01

    The recently released Affymetrix Human Gene 1.0 ST array has two major differences compared with standard 3' based arrays: (i) it interrogates the entire mRNA transcript, and (ii) it uses DNA targets. To assess the impact of these differences on array performance, we performed a series of comparative hybridizations between the Human Gene 1.0 ST and the Affymetrix HG-U133 Plus 2.0 and the Illumina HumanRef-8 BeadChip arrays. Additionally, both RNA and DNA targets were hybridized on HG-U133 Plus 2.0 arrays. The results show that the overall reproducibility of the Gene 1.0 ST array is best. When looking only at the high intensity probes, the reproducibility of the Gene 1.0 ST array and the Illumina BeadChip array is equally good. Concordance of array results was assessed using different inter-platform mappings. Agreements are best between the two labeling protocols using HG-U133 Plus 2.0 array. The Gene 1.0 ST array is most concordant with the HG-U133 array hybridized with cDNA targets. This may reflect the impact of the target type. Overall, the high degree of correspondence provides strong evidence for the reliability of the Gene 1.0 ST array.

  17. Mining Affymetrix microarray data for long non-coding RNAs: altered expression in the nucleus accumbens of heroin abusers.

    PubMed

    Michelhaugh, Sharon K; Lipovich, Leonard; Blythe, Jason; Jia, Hui; Kapatos, Gregory; Bannon, Michael J

    2011-02-01

    Although recent data suggest that some long non-coding RNAs (lncRNAs) exert widespread effects on gene expression and organelle formation, lncRNAs as a group constitute a sizable but poorly characterized fraction of the human transcriptome. We investigated whether some human lncRNA sequences were fortuitously represented on commonly used microarrays, then used this annotation to assess lncRNA expression in human brain. A computational and annotation pipeline was developed to identify lncRNA transcripts represented on Affymetrix U133 arrays. A previously published dataset derived from human nucleus accumbens was then examined for potential lncRNA expression. Twenty-three lncRNAs were determined to be represented on U133 arrays. Of these, dataset analysis revealed that five lncRNAs were consistently detected in samples of human nucleus accumbens. Strikingly, the abundance of these lncRNAs was up-regulated in human heroin abusers compared to matched drug-free control subjects, a finding confirmed by quantitative PCR. This study presents a paradigm for examining existing Affymetrix datasets for the detection and potential regulation of lncRNA expression, including changes associated with human disease. The finding that all detected lncRNAs were up-regulated in heroin abusers is consonant with the proposed role of lncRNAs as mediators of widespread changes in gene expression as occur in drug abuse.

  18. 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

  19. Construction and evaluation of a high-density SNP array for the Pacific oyster (Crassostrea gigas)

    PubMed Central

    Li, Chunyan; Wang, Wei; Li, Busu; Li, Li

    2017-01-01

    Single nucleotide polymorphisms (SNPs) are widely used in genetics and genomics research. The Pacific oyster (Crassostrea gigas) is an economically and ecologically important marine bivalve, and it possesses one of the highest levels of genomic DNA variation among animal species. Pacific oyster SNPs have been extensively investigated; however, the mechanisms by which these SNPs may be used in a high-throughput, transferable, and economical manner remain to be elucidated. Here, we constructed an oyster 190K SNP array using Affymetrix Axiom genotyping technology. We designed 190,420 SNPs on the chip; these SNPs were selected from 54 million SNPs identified through re-sequencing of 472 Pacific oysters collected in China, Japan, Korea, and Canada. Our genotyping results indicated that 133,984 (70.4%) SNPs were polymorphic and successfully converted on the chip. The SNPs were distributed evenly throughout the oyster genome, located in 3,595 scaffolds with a length of ~509.4 million; the average interval spacing was 4,210 bp. In addition, 111,158 SNPs were distributed in 21,050 coding genes, with an average of 5.3 SNPs per gene. In comparison with genotypes obtained through re-sequencing, ~69% of the converted SNPs had a concordance rate of >0.971; the mean concordance rate was 0.966. Evaluation based on genotypes of full-sib family individuals revealed that the average genotyping accuracy rate was 0.975. Carrying 133 K polymorphic SNPs, our oyster 190K SNP array is the first commercially available high-density SNP chip for mollusks, with the highest throughput. It represents a valuable tool for oyster genome-wide association studies, fine linkage mapping, and population genetics. PMID:28328985

  20. 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.

  1. SNP Cutter: a comprehensive tool for SNP PCR–RFLP assay design

    PubMed Central

    Zhang, Ruifang; Zhu, Zanhua; Zhu, Hongming; Nguyen, Tu; Yao, Fengxia; Xia, Kun; Liang, Desheng; Liu, Chunyu

    2005-01-01

    The Polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) is a relatively simple and inexpensive method for genotyping single nucleotide polymorphisms (SNPs). It requires minimal investment in instrumentation. Here, we describe a web application, ‘SNP Cutter,’ which designs PCR–RFLP assays on a batch of SNPs from the human genome. NCBI dbSNP rs IDs or formatted SNPs are submitted into the SNP Cutter which then uses restriction enzymes from a pre-selected list to perform enzyme selection. The program is capable of designing primers for either natural PCR–RFLP or mismatch PCR–RFLP, depending on the SNP sequence data. SNP Cutter generates the information needed to evaluate and perform genotyping experiments, including a PCR primers list, sizes of original amplicons and different allelic fragment after enzyme digestion. Some output data is tab-delimited, therefore suitable for database archiving. The SNP Cut-ter is available at . PMID:15980518

  2. SNP genotyping by DNA photoligation: application to SNP detection of genes from food crops

    NASA Astrophysics Data System (ADS)

    Yoshimura, Yoshinaga; Ohtake, Tomoko; Okada, Hajime; Ami, Takehiro; Tsukaguchi, Tadashi; Fujimoto, Kenzo

    2009-06-01

    We describe a simple and inexpensive single-nucleotide polymorphism (SNP) typing method, using DNA photoligation with 5-carboxyvinyl-2'-deoxyuridine and two fluorophores. This SNP-typing method facilitates qualitative determination of genes from indica and japonica rice, and showed a high degree of single nucleotide specificity up to 10 000. This method can be used in the SNP typing of actual genomic DNA samples from food crops.

  3. Design and testing of the HTS bearing for a 10 kWh flywheel system

    NASA Astrophysics Data System (ADS)

    Day, A. C.; Strasik, M.; McCrary, K. E.; Johnson, P. E.; Gabrys, J. W.; Schindler, J. R.; Hawkins, R. A.; Carlson, D. L.; Higgins, M. D.; Hull, J. R.

    2002-05-01

    Flywheels are of interest for a wide range of energy storage applications, from support of renewable resources to distributed power applications and uninterruptible power systems (UPS) (Day et al 2000 Proc. EESAT 2000 (Orlando, FL, Sept. 2000)). The use of high-temperature superconducting (HTS) bearings for such systems has significant advantages for applications requiring large amounts of energy to be stored with low parasitic losses and with minimal system maintenance. As flywheel systems increase in size, it becomes a significant challenge to provide adequate stiffness in these bearings without exceeding the strength limits of rotating magnet assemblies. The Boeing Company is designing and building a prototype flywheel of 10 kWh total stored energy and has focused much effort on the HTS bearing system. This paper will describe the general structure of the bearing and the steps taken to optimize its magnetic and structural performance and show recent test results.

  4. 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.

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

    NASA Astrophysics Data System (ADS)

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

    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.

  6. Reliability and availability analysis of a 10 kW@20 K helium refrigerator

    NASA Astrophysics Data System (ADS)

    Li, J.; Xiong, L. Y.; Liu, L. Q.; Wang, H. R.; Wang, B. M.

    2017-02-01

    A 10 kW@20 K helium refrigerator has been established in the Technical Institute of Physics and Chemistry, Chinese Academy of Sciences. To evaluate and improve this refrigerator’s reliability and availability, a reliability and availability analysis is performed. According to the mission profile of this refrigerator, a functional analysis is performed. The failure data of the refrigerator components are collected and failure rate distributions are fitted by software Weibull++ V10.0. A Failure Modes, Effects & Criticality Analysis (FMECA) is performed and the critical components with higher risks are pointed out. Software BlockSim V9.0 is used to calculate the reliability and the availability of this refrigerator. The result indicates that compressors, turbine and vacuum pump are the critical components and the key units of this refrigerator. The mitigation actions with respect to design, testing, maintenance and operation are proposed to decrease those major and medium risks.

  7. Regeneration experiments below 10K in a regenerative-cycle cryocooler

    NASA Technical Reports Server (NTRS)

    Sager, R. E.; Paulson, D. N.

    1983-01-01

    At temperatures below 10K, regenerative cycle cryocoolers are limited by regeneration losses in the helium working fluid which result from the decreasing heat capacity of the regenerating material and the increasing density of helium. Experiments examining several approaches to improving the low-temperature regeneration in a four-stage regenerative cycle cooler constructed primarily of fiberglass materials are discussed. Using an interchangeable fourth stage, the experiments included configurations with multiple regeneration passages, and a static helium volume for increased heat capacity. Experiments using helium-3 as the working fluid and a Malone stage are planned. Results indicate that, using these techniques, it should be possible to construct a regenerative cycle cooler which will operate below 6K.

  8. 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.

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

    PubMed Central

    Lubke, GH; Laurin, C; Walters, R; Eriksson, N; Hysi, P; Spector, TD; Montgomery, GW; Martin, NG; Medland, SE; Boomsma, DI

    2013-01-01

    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

  10. EzArray: A web-based highly automated Affymetrix expression array data management and analysis system

    PubMed Central

    Zhu, Yuerong; Zhu, Yuelin; Xu, Wei

    2008-01-01

    Background Though microarray experiments are very popular in life science research, managing and analyzing microarray data are still challenging tasks for many biologists. Most microarray programs require users to have sophisticated knowledge of mathematics, statistics and computer skills for usage. With accumulating microarray data deposited in public databases, easy-to-use programs to re-analyze previously published microarray data are in high demand. Results EzArray is a web-based Affymetrix expression array data management and analysis system for researchers who need to organize microarray data efficiently and get data analyzed instantly. EzArray organizes microarray data into projects that can be analyzed online with predefined or custom procedures. EzArray performs data preprocessing and detection of differentially expressed genes with statistical methods. All analysis procedures are optimized and highly automated so that even novice users with limited pre-knowledge of microarray data analysis can complete initial analysis quickly. Since all input files, analysis parameters, and executed scripts can be downloaded, EzArray provides maximum reproducibility for each analysis. In addition, EzArray integrates with Gene Expression Omnibus (GEO) and allows instantaneous re-analysis of published array data. Conclusion EzArray is a novel Affymetrix expression array data analysis and sharing system. EzArray provides easy-to-use tools for re-analyzing published microarray data and will help both novice and experienced users perform initial analysis of their microarray data from the location of data storage. We believe EzArray will be a useful system for facilities with microarray services and laboratories with multiple members involved in microarray data analysis. EzArray is freely available from . PMID:18218103

  11. 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 ...

  12. 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...

  13. 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.

  14. 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.

  15. 10-kHz High-Frequency SCS Therapy: A Clinical Summary

    PubMed Central

    Russo, Marc; Van Buyten, Jean-Pierre

    2015-01-01

    Objective Chronic pain remains a serious public health problem worldwide. A spinal cord stimulation (SCS) therapy called HF10 SCS uses 10-kHz high-frequency stimulation to provide pain relief without paresthesia. In this article, we describe the therapy, device, and the methods of implant and then review the safety and effectiveness data for this therapy. Results HF10 SCS uses a charge-balanced stimulation waveform that has been shown to be safe in both animal and human studies. Data from a multicenter, prospective clinical trial shows that the therapy provides substantial back and leg pain relief. Numerous additional reports suggest improved pain relief in other body areas and for complex pain patterns, even for patients who have previously failed other neuromodulation therapies. Conclusions The clinical experience reported in this article supports the efficacy and pain relief provided by HF10 SCS therapy. Clinical studies have also concluded that HF10 SCS does not generate paresthesia nor was it necessary to provide adequate coverage for pain relief. As clinical evidence accumulates and technological innovation improves patient outcomes, neuromodulatory techniques will be sought earlier in the treatment continuum to reduce the suffering for the many with otherwise intractable chronic pain. PMID:25377278

  16. 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.

  17. Thermodynamic Properties of He Gas in the Temperature Range 4.2-10 K

    NASA Astrophysics Data System (ADS)

    Mosameh, S. M.; Sandouqa, A. S.; Ghassib, H. B.; Joudeh, B. R.

    2014-05-01

    The thermodynamic properties of He gas are investigated in the temperature-range 4.2-10 K, with special emphasis on the second virial coefficient in both the classical and quantum regimes. The main input in computing the quantum coefficient is the `effective' phase shifts. These are calculated within the framework of the Galitskii-Migdal-Feynman (GMF) formalism, using the HFDHE2 and Sposito potentials. The virial equation of state is constructed. Extensive calculations are carried out for the pressure-volume-temperature (P-V-T) behavior, as well as chemical potential, and nonideality of the system. The following results are obtained. First, the validity of the GMF formalism for the present system is demonstrated beyond any doubt. Second, the boiling point (phase-transition point) of He gas is determined from the P-V behavior using the virial equation of state, its value being closest than all previous results to the experimental value. Third, the chemical potential is evaluated from the quantum second virial coefficient. It is found that increases (becomes less negative) as the temperature decreases or the number density n increases. Further, shows no sensitivity to the differences between the potentials used up to n = 10 m. Finally, the compressibility Z is computed and discussed as a measure of the nonideality of the system.

  18. 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.

  19. Numerical analysis of the wake of a 10kW HAWT

    NASA Astrophysics Data System (ADS)

    Gong, S. G.; Deng, Y. B.; Xie, G. L.; Zhang, J. P.

    2017-01-01

    With the rising of wind power industry and the ever-growing scale of wind farm, the research for the wake performance of wind turbine has an important guiding significance for the overall arrangement of wind turbines in the large wind farm. The wake simulation model of 10kW horizontal-axis wind turbine is presented on the basis of Averaged Navier-Stokes (RANS) equations and the RNG k-ε turbulence model for applying to the rotational fluid flow. The sliding mesh technique in ANSYS CFX software is used to solve the coupling equation of velocity and pressure. The characters of the average velocity in the wake zone under rated inlet wind speed and different rotor rotational speeds have been investigated. Based on the analysis results, it is proposed that the horizontal spacing between the wind turbines is less than two times radius of rotor, and its longitudinal spacing is less than five times of radius. And other results have also been obtained, which are of great importance for large wind farms.

  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. Measurements on a FET based 1 MHz, 10 kV pulse generator

    SciTech Connect

    Wait, G.D.; Barnes, M.J.

    1995-08-01

    A prototype pulser, which incorporates thirty-two 1 kV Field-Effect Transistor (FET) modules, has been built and tested at TRIUMF. The pulser has been developed for application in a scheme for pulsed extraction from the TRIUMF 500 MeV cyclotron. Deflection of the beam will be provided by an electric field between a set of 1 in long deflector plates. The pulser generates a continuous, unipolar, pulse train at a fundamental frequency of approximately 1 MHz and a magnitude of 10 kV. The pulses have 38 ns rise and fall times and are stored on a low-loss coaxial cable which interconnects the pulse generator and the deflector plates. The circuit performance was evaluated with the aid of PSpice in the design stage and confirmed by measurements on the prototype. Temperature measurements have been performed on 1 kV FET modules under DC conditions and compared with temperatures under operating conditions to ensure that switching losses are acceptable. Results of various measurements are presented and compared with simulations.

  2. Managing clinically significant findings in research: the UK10K example.

    PubMed

    Kaye, Jane; Hurles, Matthew; Griffin, Heather; Grewal, Jasote; Bobrow, Martin; Timpson, Nic; Smee, Carol; Bolton, Patrick; Durbin, Richard; Dyke, Stephanie; Fitzpatrick, David; Kennedy, Karen; Kent, Alastair; Muddyman, Dawn; Muntoni, Francesco; Raymond, Lucy F; Semple, Robert; Spector, Tim

    2014-09-01

    Recent advances in sequencing technology allow data on the human genome to be generated more quickly and in greater detail than ever before. Such detail includes findings that may be of significance to the health of the research participant involved. Although research studies generally do not feed back information on clinically significant findings (CSFs) to participants, this stance is increasingly being questioned. There may be difficulties and risks in feeding clinically significant information back to research participants, however, the UK10K consortium sought to address these by creating a detailed management pathway. This was not intended to create any obligation upon the researchers to feed back any CSFs they discovered. Instead, it provides a mechanism to ensure that any such findings can be passed on to the participant where appropriate. This paper describes this mechanism and the specific criteria, which must be fulfilled in order for a finding and participant to qualify for feedback. This mechanism could be used by future research consortia, and may also assist in the development of sound principles for dealing with CSFs.

  3. Managing clinically significant findings in research: the UK10K example

    PubMed Central

    Kaye, Jane; Hurles, Matthew; Griffin, Heather; Grewal, Jasote; Bobrow, Martin; Timpson, Nic; Smee, Carol; Bolton, Patrick; Durbin, Richard; Dyke, Stephanie; Fitzpatrick, David; Kennedy, Karen; Kent, Alastair; Muddyman, Dawn; Muntoni, Francesco; Raymond, Lucy F; Semple, Robert; Spector, Tim

    2014-01-01

    Recent advances in sequencing technology allow data on the human genome to be generated more quickly and in greater detail than ever before. Such detail includes findings that may be of significance to the health of the research participant involved. Although research studies generally do not feed back information on clinically significant findings (CSFs) to participants, this stance is increasingly being questioned. There may be difficulties and risks in feeding clinically significant information back to research participants, however, the UK10K consortium sought to address these by creating a detailed management pathway. This was not intended to create any obligation upon the researchers to feed back any CSFs they discovered. Instead, it provides a mechanism to ensure that any such findings can be passed on to the participant where appropriate. This paper describes this mechanism and the specific criteria, which must be fulfilled in order for a finding and participant to qualify for feedback. This mechanism could be used by future research consortia, and may also assist in the development of sound principles for dealing with CSFs. PMID:24424120

  4. 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 eroison was not quantified in this test. There were no measurable changes in the accelerator grid thickness or the accelerator grid hole diameters.

  5. 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.

  6. Calculation method for line loss in 10kV distribution grid planning

    NASA Astrophysics Data System (ADS)

    Xiao, Ming-hui; Lin, Ling-xue; Liu, Si-yuan

    2017-01-01

    Distribution grid line loss index is an important indicator of running and managing a distribution grid. A general feature in distribution network is its difficulty in gathering data about structure and operation. Based on its feature, this paper proposed a method for calculating line loss in 10kV distribution grid from the perspective of planning. According to the characteristics of power consumption on different location of the feeder, line loss can be divided into three parts, including the main line loss, the loss of branch line and the loss of distribution transformer. The proposed method achieved quick calculation and component analysis. Distributed coefficient was calculated by analyzing different distributed situation of load on feeder and the equivalent loss power on main line was calculated. Branch line and distribution transformer were equivalent to a resistance located at the head of the line to match the real power consumption. With the data acquirement, accuracy can be improved. Finally, the example of different power supply zone was calculated based on the method. The comparison between the calculated results and technical guidelines of southern power grid indicated the components of the line loss and put forward solutions for loss reduction. The method proposed overcame disadvantage of strong dependence on complete and precise data, which fits for planning work.

  7. Characterization of the Streptomyces sp. Strain C5 snp Locus and Development of snp-Derived Expression Vectors

    PubMed Central

    DeSanti, Charles L.; Strohl, William R.

    2003-01-01

    The Streptomyces sp. strain C5 snp locus is comprised of two divergently oriented genes: snpA, a metalloproteinase gene, and snpR, which encodes a LysR-like activator of snpA transcription. The transcriptional start point of snpR is immediately downstream of a strong T-N11-A inverted repeat motif likely to be the SnpR binding site, while the snpA transcriptional start site overlaps the ATG start codon, generating a leaderless snpA transcript. By using the aphII reporter gene of pIJ486 as a reporter, the plasmid-borne snpR-activated snpA promoter was ca. 60-fold more active than either the nonactivated snpA promoter or the melC1 promoter of pIJ702. The snpR-activated snpA promoter produced reporter protein levels comparable to those of the up-mutated ermE∗ promoter. The SnpR-activated snpA promoter was built into a set of transcriptional and translational fusion expression vectors which have been used for the intracellular expression of numerous daunomycin biosynthesis pathway genes from Streptomyces sp. strain C5 as well as the expression and secretion of soluble recombinant human endostatin. PMID:12620855

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

    SciTech Connect

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

    2016-02-07

    The lattice constants of hydrogenated and deuterated CH{sub 4}-, CO{sub 2}-, Xe- (clathrate structure type I) and N{sub 2}-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 CO{sub 2} as compared to methane, CO{sub 2}-hydrate has the smaller lattice constants at low temperatures, which is ascribed to the larger attractive guest-host interaction of the CO{sub 2}-water system. (3) The expansivity of CO{sub 2}-hydrate is larger than for CH{sub 4}-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 CO{sub 2} guest molecules. (4) The cage occupancies of Xe- and CO{sub 2}-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 CO{sub 2}- and Xe-hydrates.

  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. 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

  11. Acquisition of biologically relevant gene expression data by Affymetrix microarray analysis of archival formalin-fixed paraffin-embedded tumours

    PubMed Central

    Linton, K M; Hey, Y; Saunders, E; Jeziorska, M; Denton, J; Wilson, C L; Swindell, R; Dibben, S; Miller, C J; Pepper, S D; Radford, J A; Freemont, A J

    2008-01-01

    Robust protocols for microarray gene expression profiling of archival formalin-fixed paraffin-embedded tissue (FFPET) are needed to facilitate research when availability of fresh-frozen tissue is limited. Recent reports attest to the feasibility of this approach, but the clinical value of these data is poorly understood. We employed state-of-the-art RNA extraction and Affymetrix microarray technology to examine 34 archival FFPET primary extremity soft tissue sarcomas. Nineteen arrays met stringent QC criteria and were used to model prognostic signatures for metastatic recurrence. Arrays from two paired frozen and FFPET samples were compared: although FFPET sensitivity was low (∼50%), high specificity (95%) and positive predictive value (92%) suggest that transcript detection is reliable. Good agreement between arrays and real time (RT)–PCR was confirmed, especially for abundant transcripts, and RT–PCR validated the regulation pattern for 19 of 24 candidate genes (overall R2=0.4662). RT–PCR and immunohistochemistry on independent cases validated prognostic significance for several genes including RECQL4, FRRS1, CFH and MET – whose combined expression carried greater prognostic value than tumour grade – and cmet and TRKB proteins. These molecules warrant further evaluation in larger series. Reliable clinically relevant data can be obtained from archival FFPET, but protocol amendments are needed to improve the sensitivity and broad application of this approach. PMID:18382428

  12. Acquisition of biologically relevant gene expression data by Affymetrix microarray analysis of archival formalin-fixed paraffin-embedded tumours.

    PubMed

    Linton, K M; Hey, Y; Saunders, E; Jeziorska, M; Denton, J; Wilson, C L; Swindell, R; Dibben, S; Miller, C J; Pepper, S D; Radford, J A; Freemont, A J

    2008-04-22

    Robust protocols for microarray gene expression profiling of archival formalin-fixed paraffin-embedded tissue (FFPET) are needed to facilitate research when availability of fresh-frozen tissue is limited. Recent reports attest to the feasibility of this approach, but the clinical value of these data is poorly understood. We employed state-of-the-art RNA extraction and Affymetrix microarray technology to examine 34 archival FFPET primary extremity soft tissue sarcomas. Nineteen arrays met stringent QC criteria and were used to model prognostic signatures for metastatic recurrence. Arrays from two paired frozen and FFPET samples were compared: although FFPET sensitivity was low ( approximately 50%), high specificity (95%) and positive predictive value (92%) suggest that transcript detection is reliable. Good agreement between arrays and real time (RT)-PCR was confirmed, especially for abundant transcripts, and RT-PCR validated the regulation pattern for 19 of 24 candidate genes (overall R(2)=0.4662). RT-PCR and immunohistochemistry on independent cases validated prognostic significance for several genes including RECQL4, FRRS1, CFH and MET - whose combined expression carried greater prognostic value than tumour grade - and cmet and TRKB proteins. These molecules warrant further evaluation in larger series. Reliable clinically relevant data can be obtained from archival FFPET, but protocol amendments are needed to improve the sensitivity and broad application of this approach.

  13. Effects of leakage through clearance seals on the performance of a 10 K Stirling-cycle refrigerator

    NASA Technical Reports Server (NTRS)

    Keung, C. S.; Lindale, E.

    1985-01-01

    The use of clearance seals is essential to achieve long life, wear free operation of Stirling cycle cryogenic refrigerators. The effect of leakage through clearance seals on the performance of such a refrigerator operating at temperatures ranging from 20 K down to 10 K was determined. The ability of a Stirling cycle refrigerator to achieve 10 K with clearance seals was successfully demonstrated. It is indicated that the leakage flow undergoes gap regeneration before reaching the cold expansion volume. A simple model of gap regeneration was used to estimate the regeneration loss due to the leakage flow. This regeneration process minimizes the loss in refrigerator performance caused by the clearance seal leakage. It is found that clearance seals remain effective down to a refrigeration temperature of 10 K.

  14. A major T cell antigen of Mycobacterium leprae is a 10-kD heat-shock cognate protein

    PubMed Central

    1992-01-01

    Several mycobacterial antigens, identified by monoclonal antibodies and patient sera, have been found to be homologous to stress or heat-shock proteins (hsp) defined in Escherichia coli and yeast. A major antigen recognized by most Mycobacterium leprae-reactive human T cell lines and cell wall-reactive T cell clones is a 10-kD protein that has now been cloned and sequenced. The predicted amino acid sequence of this protein is 44% homologous to the hsp 10 (GroES) of E. coli. The purified native and recombinant 10-kD protein was found to be a stronger stimulator of peripheral blood T cell proliferation than other native and recombinant M. leprae proteins tested. The degree of reactivity paralleled the response to intact M. leprae throughout the spectrum of leprosy. Limiting-dilution analysis of peripheral blood lymphocytes from a patient contact and a tuberculoid patient indicated that approximately one third of M. leprae-reactive T cell precursors responded to the 10- kD antigen. T cell lines derived from lepromin skin tests were strongly responsive to the 10-kD protein. T cell clones reactive to both the purified native and recombinant 10-kD antigens recognized M. leprae- specific epitopes as well as epitopes crossreactive with the cognate antigen of M. tuberculosis. Further, the purified hsp 10 elicited strong delayed-type hypersensitivity reactions in guinea pigs sensitized to M. leprae. The strong T cell responses against the M. leprae 10-kD protein suggest a role for this heat-shock cognate protein in the protective/resistant responses to infection. PMID:1730920

  15. [Research progress on the phenotype informative SNP in forensic science].

    PubMed

    Liu, Yu-Xuan; Hu, Qing-Qing; Ma, Hong-Du; Huang, Dai-Xin

    2014-10-01

    Single nucleotide polymorphism (SNP) refers to the single base sequence variation in specific location of the human genome. Phenotype informative SNP has gradually become one of the research hot spots in forensic science. In this paper, the forensic research situation and application prospect of phenotype informative SNP in the characteristics of hair, eye and skin color, height, and facial feature are reviewed.

  16. A novel TCF7L2 type 2 diabetes SNP identified from fine mapping in African American women

    PubMed Central

    Haddad, Stephen A.; Palmer, Julie R.; Lunetta, Kathryn L.; Ng, Maggie C. Y.; Ruiz-Narváez, Edward A.

    2017-01-01

    SNP rs7903146 in the Wnt pathway’s TCF7L2 gene is the variant most significantly associated with type 2 diabetes to date, with associations observed across diverse populations. We sought to determine whether variants in other Wnt pathway genes are also associated with this disease. We evaluated 69 genes involved in the Wnt pathway, including TCF7L2, for associations with type 2 diabetes in 2632 African American cases and 2596 controls from the Black Women’s Health Study. Tag SNPs for each gene region were genotyped on a custom Affymetrix Axiom Array, and imputation was performed to 1000 Genomes Phase 3 data. Gene-based analyses were conducted using the adaptive rank truncated product (ARTP) statistic. The PSMD2 gene was significantly associated with type 2 diabetes after correction for multiple testing (corrected p = 0.016), based on the nine most significant single variants in the +/- 20 kb region surrounding the gene, which includes nearby genes EIF4G1, ECE2, and EIF2B5. Association data on four of the nine variants were available from an independent sample of 8284 African American cases and 15,543 controls; associations were in the same direction, but weak and not statistically significant. TCF7L2 was the only other gene associated with type 2 diabetes at nominal p <0.01 in our data. One of the three variants in the best gene-based model for TCF7L2, rs114770437, was not correlated with the GWAS index SNP rs7903146 and may represent an independent association signal seen only in African ancestry populations. Data on this SNP were not available in the replication sample. PMID:28253288

  17. Beam dynamics in the ETA and ATA 10 kA linear induction accelerators: observations and issues

    SciTech Connect

    Briggs, R.J.; Birx, D.L.; Caporaso, G.J.; Fessenden, T.J.; Hester, R.E.; Melendez, R.; Neil, V.K.; Paul, A.C.; Struve, K.W.

    1981-03-06

    The 10 kA ETA and ATA linear induction accelerators are described. Beam instability is the major concern in these high current machines, and the current status of theoretical understanding, and experimental investigations with the 8 cavity ETA, are reviewed. Modifications to the induction cavities are described that have essentially eliminated the transverse resonant modes seen in the ETA.

  18. 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.

  19. 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...

  20. 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.

  1. Secretion of 10-kDa and 12-kDa thioredoxin species from blood monocytes and transformed leukocytes.

    PubMed

    Sahaf, B; Rosén, A

    2000-01-01

    Thioredoxins (TRX) are ubiquitous, small redox-active proteins with multiple functions, including antioxidant, cytoprotective, and chemoattractant activities. In addition to a 12-kDa intracellular form, extracellular 10-kDa and 12-kDa TRX have been defined. The biological activities of the 10-kDa TRX were previously measured as eosinophil cytotoxicity enhancing activity or B-cell stimulatory activity. Cytotrophoblastic cell lines also release a 10-kDa TRX form. To study the biological role of 10-kDa TRX, we established two highly sensitive enzyme-linked immuno-spot assays (ELISPOT), which detect secreted truncated 10-kDa and full-length 12-kDa TRX at the single cell level. TRX secretion was investigated in several cell lines including the T-helper cell hybridoma MP6, the Jurkat T-cell leukemia, the U-937 myelomonocytic leukemia, and the 3B6, EBV-transformed, lymphoblastoid B-cell line. The highest number of secreting cells was found in 3B6 cultures, median = 34 (quartiles, 27-39) per well (10(5) cells). Peripheral blood monocytes isolated from healthy donors secreted significantly more TRX after stimulation with ionomycin, phorbol myristate acetate (PMA), fMLP, and lipopolysaccharide (LPS), compared to unstimulated cells. Oxidative stress induced by thioloxidant diamide also induced the secretion of both truncated and full-length TRX measured in ELISPOT (p = 0.047 and p = 0.031, respectively). The biological activity of the truncated and full-length forms was tested in a cell migration assay. Truncated TRX was devoid of protein disulfide reductase activity, but retained strong chemoattractant activity for human monocytes, in the same range as full-length TRX, as previously reported (Bertini et al., 1999).

  2. is-rSNP: a novel technique for in silico regulatory SNP detection

    PubMed Central

    Macintyre, Geoff; Bailey, James; Haviv, Izhak; Kowalczyk, Adam

    2010-01-01

    Motivation: Determining the functional impact of non-coding disease-associated single nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) is challenging. Many of these SNPs are likely to be regulatory SNPs (rSNPs): variations which affect the ability of a transcription factor (TF) to bind to DNA. However, experimental procedures for identifying rSNPs are expensive and labour intensive. Therefore, in silico methods are required for rSNP prediction. By scoring two alleles with a TF position weight matrix (PWM), it can be determined which SNPs are likely rSNPs. However, predictions in this manner are noisy and no method exists that determines the statistical significance of a nucleotide variation on a PWM score. Results: We have designed an algorithm for in silico rSNP detection called is-rSNP. We employ novel convolution methods to determine the complete distributions of PWM scores and ratios between allele scores, facilitating assignment of statistical significance to rSNP effects. We have tested our method on 41 experimentally verified rSNPs, correctly predicting the disrupted TF in 28 cases. We also analysed 146 disease-associated SNPs with no known functional impact in an attempt to identify candidate rSNPs. Of the 11 significantly predicted disrupted TFs, 9 had previous evidence of being associated with the disease in the literature. These results demonstrate that is-rSNP is suitable for high-throughput screening of SNPs for potential regulatory function. This is a useful and important tool in the interpretation of GWAS. Availability: is-rSNP software is available for use at: www.genomics.csse.unimelb.edu.au/is-rSNP Contact: gmaci@csse.unimelb.edu.au; adam.kowalczyk@nicta.com.au Supplementary information: Supplementary data are available at Bioinformatics online. PMID:20823317

  3. Analyzing cancer samples with SNP arrays.

    PubMed

    Van Loo, Peter; Nilsen, Gro; Nordgard, Silje H; Vollan, Hans Kristian Moen; Børresen-Dale, Anne-Lise; Kristensen, Vessela N; Lingjærde, Ole Christian

    2012-01-01

    Single nucleotide polymorphism (SNP) arrays are powerful tools to delineate genomic aberrations in cancer genomes. However, the analysis of these SNP array data of cancer samples is complicated by three phenomena: (a) aneuploidy: due to massive aberrations, the total DNA content of a cancer cell can differ significantly from its normal two copies; (b) nonaberrant cell admixture: samples from solid tumors do not exclusively contain aberrant tumor cells, but always contain some portion of nonaberrant cells; (c) intratumor heterogeneity: different cells in the tumor sample may have different aberrations. We describe here how these phenomena impact the SNP array profile, and how these can be accounted for in the analysis. In an extended practical example, we apply our recently developed and further improved ASCAT (allele-specific copy number analysis of tumors) suite of tools to analyze SNP array data using data from a series of breast carcinomas as an example. We first describe the structure of the data, how it can be plotted and interpreted, and how it can be segmented. The core ASCAT algorithm next determines the fraction of nonaberrant cells and the tumor ploidy (the average number of DNA copies), and calculates an ASCAT profile. We describe how these ASCAT profiles visualize both copy number aberrations as well as copy-number-neutral events. Finally, we touch upon regions showing intratumor heterogeneity, and how they can be detected in ASCAT profiles. All source code and data described here can be found at our ASCAT Web site ( http://www.ifi.uio.no/forskning/grupper/bioinf/Projects/ASCAT/).

  4. 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.

  5. Statistical evaluation of transcriptomic data generated using the Affymetrix one-cycle, two-cycle and IVT-Express RNA labelling protocols with the Arabidopsis ATH1 microarray

    PubMed Central

    2010-01-01

    Background Microarrays are a powerful tool used for the determination of global RNA expression. There is an increasing requirement to focus on profiling gene expression in tissues where it is difficult to obtain large quantities of material, for example individual tissues within organs such as the root, or individual isolated cells. From such samples, it is difficult to produce the amount of RNA required for labelling and hybridisation in microarray experiments, thus a process of amplification is usually adopted. Despite the increasing use of two-cycle amplification for transcriptomic analyses on the Affymetrix ATH1 array, there has been no report investigating any potential bias in gene representation that may occur as a result. Results Here we compare transcriptomic data generated using Affymetrix one-cycle (standard labelling protocol), two-cycle (small-sample protocol) and IVT-Express protocols with the Affymetrix ATH1 array using Arabidopsis root samples. Results obtained with each protocol are broadly similar. However, we show that there are 35 probe sets (of a total of 22810) that are misrepresented in the two-cycle data sets. Of these, 33 probe sets were classed as mis-amplified when comparisons of two independent publicly available data sets were undertaken. Conclusions Given the unreliable nature of the highlighted probes, we caution against using data associated with the corresponding genes in analyses involving transcriptomic data generated with two-cycle amplification protocols. We have shown that the Affymetrix IVT-E labelling protocol produces data with less associated bias than the two-cycle protocol, and as such, would recommend this kit for new experiments that involve small samples. PMID:20230623

  6. Variable Selection in Logistic Regression for Detecting SNP-SNP Interactions: the Rheumatoid Arthritis Example

    PubMed Central

    Lin, H. Y.; Desmond, R.; Liu, Y. H.; Bridges, S. L.; Soong, S. J.

    2013-01-01

    Summary Many complex disease traits are observed to be associated with single nucleotide polymorphism (SNP) interactions. In testing small-scale SNP-SNP interactions, variable selection procedures in logistic regressions are commonly used. The empirical evidence of variable selection for testing interactions in logistic regressions is limited. This simulation study was designed to compare nine variable selection procedures in logistic regressions for testing SNP-SNP interactions. Data on 10 SNPs were simulated for 400 and 1000 subjects (case/control ratio=1). The simulated model included one main effect and two 2-way interactions. The variable selection procedures included automatic selection (stepwise, forward and backward), common 2-step selection, AIC- and BIC-based selection. The hierarchical rule effect, in which all main effects and lower order terms of the highest-order interaction term are included in the model regardless of their statistical significance, was also examined. We found that the stepwise variable selection without the hierarchical rule which had reasonably high authentic (true positive) proportion and low noise (false positive) proportion, is a better method compared to other variable selection procedures. The procedure without the hierarchical rule requires fewer terms in testing interactions, so it can accommodate more SNPs than the procedure with the hierarchical rule. For testing interactions, the procedures without the hierarchical rule had higher authentic proportion and lower noise proportion compared with ones with the hierarchical rule. These variable selection procedures were also applied and compared in a rheumatoid arthritis study. PMID:18231122

  7. Numerical Study of a 10 K Two Stage Pulse Tube Cryocooler with Precooling Inside the Pulse Tube

    NASA Astrophysics Data System (ADS)

    Xiaomin, Pang; Xiaotao, Wang; Wei, Dai; Jianyin, Hu; Ercang, Luo

    2017-02-01

    High efficiency cryocoolers working below 10 K have many applications such as cryo-pump, superconductor cooling and cryogenic electronics. This paper presents a thermally coupled two-stage pulse tube cryocooler system and its numeric analysis. The simulation results indicate that temperature distribution in the pulse tube has a significant impact on the system performance. So a precooling heat exchanger is put inside the second stage pulse tube for a deep investigation on its influence on the system performance. The influences of operating parameters such as precooling temperature, location of the precooling heat exchanger are discussed. Comparison of energy losses apparently show the advantages of the configuration which leads to an improvement on the efficiency. Finally, the cryocooler is predicted to be able to reach a relative Carnot efficiency of 10.7% at 10 K temperature.

  8. A high-density SNP genome-wide linkage scan in a large autism extended pedigree.

    PubMed

    Allen-Brady, K; Miller, J; Matsunami, N; Stevens, J; Block, H; Farley, M; Krasny, L; Pingree, C; Lainhart, J; Leppert, M; McMahon, W M; Coon, H

    2009-06-01

    We performed a high-density, single nucleotide polymorphism (SNP), genome-wide scan on a six-generation pedigree from Utah with seven affected males, diagnosed with autism spectrum disorder. Using a two-stage linkage design, we first performed a nonparametric analysis on the entire genome using a 10K SNP chip to identify potential regions of interest. To confirm potentially interesting regions, we eliminated SNPs in high linkage disequilibrium (LD) using a principal components analysis (PCA) method and repeated the linkage results. Three regions met genome-wide significance criteria after controlling for LD: 3q13.2-q13.31 (nonparametric linkage (NPL), 5.58), 3q26.31-q27.3 (NPL, 4.85) and 20q11.21-q13.12 (NPL, 5.56). Two regions met suggestive criteria for significance 7p14.1-p11.22 (NPL, 3.18) and 9p24.3 (NPL, 3.44). All five chromosomal regions are consistent with other published findings. Haplotype sharing results showed that five of the affected subjects shared more than a single chromosomal region of interest with other affected subjects. Although no common autism susceptibility genes were found for all seven autism cases, these results suggest that multiple genetic loci within these regions may contribute to the autism phenotype in this family, and further follow-up of these chromosomal regions is warranted.

  9. dbSNP: the NCBI database of genetic variation.

    PubMed

    Sherry, S T; Ward, M H; Kholodov, M; Baker, J; Phan, L; Smigielski, E M; Sirotkin, K

    2001-01-01

    In response to a need for a general catalog of genome variation to address the large-scale sampling designs required by association studies, gene mapping and evolutionary biology, the National Center for Biotechnology Information (NCBI) has established the dbSNP database [S.T.Sherry, M.Ward and K. Sirotkin (1999) Genome Res., 9, 677-679]. Submissions to dbSNP will be integrated with other sources of information at NCBI such as GenBank, PubMed, LocusLink and the Human Genome Project data. The complete contents of dbSNP are available to the public at website: http://www.ncbi.nlm.nih.gov/SNP. The complete contents of dbSNP can also be downloaded in multiple formats via anonymous FTP at ftp://ncbi.nlm.nih.gov/snp/.

  10. TRM: a powerful two-stage machine learning approach for identifying SNP-SNP interactions.

    PubMed

    Lin, Hui-Yi; Chen, Y Ann; Tsai, Ya-Yu; Qu, Xiaotao; Tseng, Tung-Sung; Park, Jong Y

    2012-01-01

    Studies have shown that interactions of single nucleotide polymorphisms (SNPs) may play an important role in understanding the causes of complex disease. We have proposed an integrated machine learning method that combines two machine-learning methods-Random Forests (RF) and Multivariate Adaptive Regression Splines (MARS)-to identify a subset of important SNPs and detect interaction patterns more effectively and efficiently. In this two-stage RF-MARS (TRM) approach, RF is first applied to detect a predictive subset of SNPs, and then MARS is used to identify the interaction patterns. We evaluated the TRM performances in four models. RF variable selection was based on out-of-bag classification error rate (OOB) and variable important spectrum (IS). Our results support that RF(OOB) had better performance than MARS and RF(IS) in detecting important variables. This study demonstrates that TRM(OOB) , which is RF(OOB) plus MARS, has combined the strengths of RF and MARS in identifying SNP-SNP interactions in a scenario of 100 candidate SNPs. TRM(OOB) had greater true positive rate and lower false positive rate compared with MARS, particularly for searching interactions with a strong association with the outcome. Therefore, the use of TRM(OOB) is favored for exploring SNP-SNP interactions in a large-scale genetic variation study.

  11. SNP2CAPS: a SNP and INDEL analysis tool for CAPS marker development.

    PubMed

    Thiel, Thomas; Kota, Raja; Grosse, Ivo; Stein, Nils; Graner, Andreas

    2004-01-02

    With the influx of various SNP genotyping assays in recent years, there has been a need for an assay that is robust, yet cost effective, and could be performed using standard gel-based procedures. In this context, CAPS markers have been shown to meet these criteria. However, converting SNPs to CAPS markers can be a difficult process if done manually. In order to address this problem, we describe a computer program, SNP2CAPS, that facilitates the computational conversion of SNP markers into CAPS markers. 413 multiple aligned sequences derived from barley ESTs were analysed for the presence of polymorphisms in 235 distinct restriction sites. 282 (90%) of 314 alignments that contain sequence variation due to SNPs and InDels revealed at least one polymorphic restriction site. After reducing the number of restriction enzymes from 235 to 10, 31% of the polymorphic sites could still be detected. In order to demonstrate the usefulness of this tool for marker development, we experimentally validated some of the results predicted by SNP2CAPS.

  12. 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.

  13. 10K Force Analysis

    DTIC Science & Technology

    1993-06-01

    operation will be joint, and the Army will share airlift capabilities with other services; (2) the Air Mobility Command’s (AMC) sustained airlift...4-1 4-2 Daily fuel consumption range for intensity of combat (kgal) ................................. 4-2 4-3 Daily ammunition... consumption range for intensity of combat (STONs) ............... 4-2 4-4 Daily sorties required for sustainment in a high usage environment

  14. Topology and dynamics of the 10 kDa C-terminal domain of DnaK in solution.

    PubMed Central

    Bertelsen, E. B.; Zhou, H.; Lowry, D. F.; Flynn, G. C.; Dahlquist, F. W.

    1999-01-01

    Hsp70 molecular chaperones contain three distinct structural domains, a 44 kDa N-terminal ATPase domain, a 17 kDa peptide-binding domain, and a 10 kDa C-terminal domain. The ATPase and peptide binding domains are conserved in sequence and are functionally well characterized. The function of the 10 kDa variable C-terminal domain is less well understood. We have characterized the secondary structure and dynamics of the C-terminal domain from the Escherichia coli Hsp70, DnaK, in solution by high-resolution NMR. The domain was shown to be comprised of a rigid structure consisting of four helices and a flexible C-terminal subdomain of approximately 33 amino acids. The mobility of the flexible region is maintained in the context of the full-length protein and does not appear to be modulated by the nucleotide state. The flexibility of this region appears to be a conserved feature of Hsp70 architecture and may have important functional implications. We also developed a method to analyze 15N nuclear spin relaxation data, which allows us to extract amide bond vector directions relative to a unique diffusion axis. The extracted angles and rotational correlation times indicate that the helices form an elongated, bundle-like structure in solution. PMID:10048327

  15. 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.

  16. 10 kHz repetition rate solid-state dye laser pumped by diode-pumped solid-state laser

    NASA Astrophysics Data System (ADS)

    Abedin, K. M.; Álvarez, M.; Costela, A.; García-Moreno, I.; García, O.; Sastre, R.; Coutts, D. W.; Webb, C. E.

    2003-04-01

    We describe the operation of an all solid-state pulsed dye laser of high repetition rate (10 kHz) pumped by a diode-pumped laser. Three different active media in the form of coin-sized disks were investigated: the dye rhodamine 6G doped in a copolymer of methyl methacrylate (MMA) and 2-hydroxyethyl methacrylate (HEMA) [Rh6G/P(MMA:HEMA)], and the dye pyrromethene 567 (PM567) doped in copolymers of MMA with pentaerythritol triacrylate (PETA) and with pentaerythritol tetraacrylate (PETRA) [PM567/P(MMA:PETA) and PM567/P(MMA:PETRA)]. Pump radiation at 527nm was provided by a frequency-doubled diode-pumped Nd:YLF laser Q-switched at 10 kHz. Laser output was observed with an initial average power of 560 mW for Rh6G in P(MMA:HEMA), and with an initial average power of 430 mW for PM567 in P(MMA:PETRA) and 220 mW for PM567 in P(MMA:PETA). In the case of Rh6G/P(MMA:HEMA), the output decreased to about half the initial value after about 6.6 min (or about 4.0 million shots) due to dye degradation. The device constitutes a tunable, all solid-state, high repetition rate laser system possibly suitable for biomedical and dermatological applications.

  17. Magnetically coupled gear based drive mechanism for contactless continuous rotation using superconducting magnetic bearing below 10 K

    NASA Astrophysics Data System (ADS)

    Matsumura, T.; Sakurai, Y.; Kataza, H.; Utsunomiya, S.; Yamamoto, R.

    2016-11-01

    We present the design and mechanical performances of a magnetically coupled gear mechanism to drive a levitating rotor magnet of a superconducting magnetic bearing (SMB). The SMB consists of a ring-shaped high-temperature superconducting array (YBCO) and a ring-shaped permanent magnet. This rotational system is designed to operate below 10 K, and thus the design philosophy is to minimize any potential source of heat dissipation. While an SMB provides only a functionality of namely a bearing, it requires a mechanism to drive a rotational motion. We introduce a simple implementation of a magnetically coupled gears between a stator and a rotor. This enables to achieve enough torque to drive a levitating rotor without slip at the rotation frequency of about 1 Hz below 10 K. The rotational variation between the rotor and the drive gear is synchronised within σ = 0.019 Hz. The development of this mechanism is a part of the program to develop a testbed in order to evaluate a prototype half-wave plate based polarization modulator for future space missions. The successful development allows this modulator to be a candidate for an instrument to probe the cosmic inflation by measuring the cosmic microwave background polarization.

  18. 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.

  19. SNIT: SNP identification for strain typing

    PubMed Central

    2011-01-01

    With ever-increasing numbers of microbial genomes being sequenced, efficient tools are needed to perform strain-level identification of any newly sequenced genome. Here, we present the SNP identification for strain typing (SNIT) pipeline, a fast and accurate software system that compares a newly sequenced bacterial genome with other genomes of the same species to identify single nucleotide polymorphisms (SNPs) and small insertions/deletions (indels). Based on this information, the pipeline analyzes the polymorphic loci present in all input genomes to identify the genome that has the fewest differences with the newly sequenced genome. Similarly, for each of the other genomes, SNIT identifies the input genome with the fewest differences. Results from five bacterial species show that the SNIT pipeline identifies the correct closest neighbor with 75% to 100% accuracy. The SNIT pipeline is available for download at http://www.bhsai.org/snit.html PMID:21902825

  20. 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.

  1. 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.

  2. Exercise improves adiponectin concentrations irrespective of the adiponectin gene polymorphisms SNP45 and the SNP276 in obese Korean women.

    PubMed

    Lee, Kyoung-Young; Kang, Hyun-Sik; Shin, Yun-A

    2013-03-10

    The effects of exercise on adiponectin levels have been reported to be variable and may be attributable to an interaction between environmental and genetic factors. The single nucleotide polymorphisms (SNP) 45 (T>G) and SNP276 (G>T) of the adiponectin gene are associated with metabolic risk factors including adiponectin levels. We examined whether SNP45 and SNP276 would differentially influence the effect of exercise training in middle-aged women with uncomplicated obesity. We conducted a prospective study in the general community that included 90 Korean women (age 47.0±5.1 years) with uncomplicated obesity. The intervention was aerobic exercise training for 3 months. Body composition, adiponectin levels, and other metabolic risk factors were measured. Prior to exercise training, only body weight differed among the SNP276 genotypes. Exercise training improved body composition, systolic blood pressure, maximal oxygen consumption, high-density lipoprotein cholesterol, and leptin levels. In addition, exercise improved adiponectin levels irrespective of weight gain or loss. However, after adjustments for age, BMI, body fat (%), and waist circumference, no differences were found in obesity-related characteristics (e.g., adiponectin) following exercise training among the SNP45 and the 276 genotypes. Our findings suggest that aerobic exercise affects adiponectin levels regardless of weight loss and this effect would not be influenced by SNP45 and SNP276 in the adiponectin gene.

  3. 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).

  4. Adiabatic quantum-flux-parametron cell library designed using a 10 kA cm-2 niobium fabrication process

    NASA Astrophysics Data System (ADS)

    Takeuchi, Naoki; Nagasawa, Shuichi; China, Fumihiro; Ando, Takumi; Hidaka, Mutsuo; Yamanashi, Yuki; Yoshikawa, Nobuyuki

    2017-03-01

    Adiabatic quantum-flux-parametron (AQFP) logic is an energy-efficient superconductor logic with zero static power consumption and very small switching energy. In this paper, we report a new AQFP cell library designed using the AIST 10 kA cm-2 Nb high-speed standard process (HSTP), which is a high-critical-current-density version of the AIST 2.5 kA cm-2 Nb standard process (STP2). Since the intrinsic damping of the Josephson junction (JJ) of HSTP is relatively strong, shunt resistors for JJs were removed and the energy efficiency improved significantly. Also, excitation transformers in the new cells were redesigned so that the cells can operate in a four-phase excitation mode. We described the detail of HSTP and the AQFP cell library designed using HSTP, and showed experimental results of cell test circuits.

  5. Fluorescence excitation and emission spectra of 1,5-dihydroxyanthraquinone-d2 in n-hexane at 10 K

    NASA Astrophysics Data System (ADS)

    Smulevich, Giulietta; Foggi, Paolo

    1987-11-01

    The fluorescence excitation, between 430 and 505 nm, and emission, between 505 and 725 nm, spectra in n-hexane of 1,5-dihydroxyanthraquinone-d0 and -d2 at 10 K have been measured. Dual excitation and emission associated to excited state proton transfer were observed. Apart from the long wavelength emission, well resolved vibrational structures were obtained. A remarkable spectral shift (684 cm-1) of the origin of the high frequency transition was observed upon deuteration. The energy gaps between the transition origins both in excitation and emission as well as the isotopic shifts of the origins, were interpreted in terms of Lippincott-Schroeder asymmetric double minimum potential functions along the OH coordinate. An extra fluorescence occurs in the low frequency range, vanishing upon deuteration. It was explained as due to the ν(OH) stretching mode of the high frequency emission enhanced via vibronic coupling between the two ground states.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Haplotype assembly from aligned weighted SNP fragments.

    PubMed

    Zhao, Yu-Ying; Wu, Ling-Yun; Zhang, Ji-Hong; Wang, Rui-Sheng; Zhang, Xiang-Sun

    2005-08-01

    Given an assembled genome of a diploid organism the haplotype assembly problem can be formulated as retrieval of a pair of haplotypes from a set of aligned weighted SNP fragments. Known computational formulations (models) of this problem are minimum letter flips (MLF) and the weighted minimum letter flips (WMLF; Greenberg et al. (INFORMS J. Comput. 2004, 14, 211-213)). In this paper we show that the general WMLF model is NP-hard even for the gapless case. However the algorithmic solutions for selected variants of WMFL can exist and we propose a heuristic algorithm based on a dynamic clustering technique. We also introduce a new formulation of the haplotype assembly problem that we call COMPLETE WMLF (CWMLF). This model and algorithms for its implementation take into account a simultaneous presence of multiple kinds of data errors. Extensive computational experiments indicate that the algorithmic implementations of the CWMLF model achieve higher accuracy of haplotype reconstruction than the WMLF-based algorithms, which in turn appear to be more accurate than those based on MLF.

  11. 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

  12. Gene Expression Analysis of Cultured Rat-Endothelial Cells after Nd:YAG Laser Irradiation by Affymetrix GeneChip Array

    PubMed Central

    MASUDA, YOSHIKO; YOKOSE, SATOSHI; SAKAGAMI, HIROSHI

    2017-01-01

    Endothelial cells and dental pulp cells enhance osteo-/odontogenic and angiogenic differentiation. In our previous study, rat pulp cells migrated to Nd:YAG laser-irradiated endothelial cells in an insert cell culture system. The purpose of this study was to examine the possible changes in the gene expression of cultured rat aortic endothelial cells after Nd:YAG laser irradiation using affymetrix GeneChip Array. Total RNA was extracted from the cells at 5 h after laser irradiation. Gene expressions were evaluated by DNA array chip. Up-regulated genes were related to cell migration and cell structure (membrane stretch, actin regulation and junctional complexes), neurotransmission and inflammation. Heat-shock 70 kDa protein (Hsp70) was related to the development of tooth germ. This study offers candidate genes for understanding the relationship between the laser-stimulated endothelial cells and dental pulp cells. PMID:28064220

  13. 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

  14. A scan statistic for identifying chromosomal patterns of SNP association.

    PubMed

    Sun, Yan V; Levin, Albert M; Boerwinkle, Eric; Robertson, Henry; Kardia, Sharon L R

    2006-11-01

    We have developed a single nucleotide polymorphism (SNP) association scan statistic that takes into account the complex distribution of the human genome variation in the identification of chromosomal regions with significant SNP associations. This scan statistic has wide applicability for genetic analysis, whether to identify important chromosomal regions associated with common diseases based on whole-genome SNP association studies or to identify disease susceptibility genes based on dense SNP positional candidate studies. To illustrate this method, we analyzed patterns of SNP associations on chromosome 19 in a large cohort study. Among 2,944 SNPs, we found seven regions that contained clusters of significantly associated SNPs. The average width of these regions was 35 kb with a range of 10-72 kb. We compared the scan statistic results to Fisher's product method using a sliding window approach, and detected 22 regions with significant clusters of SNP associations. The average width of these regions was 131 kb with a range of 10.1-615 kb. Given that the distances between SNPs are not taken into consideration in the sliding window approach, it is likely that a large fraction of these regions represents false positives. However, all seven regions detected by the scan statistic were also detected by the sliding window approach. The linkage disequilibrium (LD) patterns within the seven regions were highly variable indicating that the clusters of SNP associations were not due to LD alone. The scan statistic developed here can be used to make gene-based or region-based SNP inferences about disease association.

  15. A Novel Test for Detecting SNP-SNP Interactions in Case-Only Trio Studies.

    PubMed

    Balliu, Brunilda; Zaitlen, Noah

    2016-04-01

    Epistasis plays a significant role in the genetic architecture of many complex phenotypes in model organisms. To date, there have been very few interactions replicated in human studies due in part to the multiple-hypothesis burden implicit in genome-wide tests of epistasis. Therefore, it is of paramount importance to develop the most powerful tests possible for detecting interactions. In this work we develop a new SNP-SNP interaction test for use in case-only trio studies called the trio correlation (TC) test. The TC test computes the expected joint distribution of marker pairs in offspring conditional on parental genotypes. This distribution is then incorporated into a standard 1 d.f. correlation test of interaction. We show via extensive simulations under a variety of disease models that our test substantially outperforms existing tests of interaction in case-only trio studies. We also demonstrate a bias in a previous case-only trio interaction test and identify its origin. Finally, we show that a previously proposed permutation scheme in trio studies mitigates the known biases of case-only tests in the presence of population stratification. We conclude that the TC test shows improved power to identify interactions in existing, as well as emerging, trio association studies. The method is publicly available at www.github.com/BrunildaBalliu/TrioEpi.

  16. In vitro electrical conductivity of seizing and non-seizing mouse brain slices at 10 kHz

    NASA Astrophysics Data System (ADS)

    Elbohouty, M.; Wilson, M. T.; Voss, L. J.; Steyn-Ross, D. A.; Hunt, L. A.

    2013-06-01

    The electrical conductivity of small samples of mouse cortex (in vitro) has been measured at 10 kHz through the four-electrode method of van der Pauw. Brain slices from three mice were prepared under seizing and non-seizing conditions by changing the concentration of magnesium in the artificial cerebrospinal fluid used to maintain the tissue. These slices provided 121 square samples of cortical tissue; the conductivity of these samples was measured with an Agilent E4980A four-point impedance monitor. Of these, 73 samples were considered acceptable on the grounds of having good electrical contact between electrodes and tissue excluding outlier measurements. Results show that there is a significant difference (p = 0.03) in the conductivities of the samples under the two conditions. The seizing and non-seizing samples have mean conductivities of 0.33 and 0.36 S m-1, respectively; however, these quantitative values should be used with caution as they are both subject to similar systematic uncertainties due to non-ideal temperature conditions and non-ideal placement of electrodes. We hypothesize that the difference between them, which is more robust to uncertainty, is due to the changing gap junction connectivity during seizures.

  17. Test results from a 10 kW{sub t} solar/natural gas hybrid pool boiler receiver

    SciTech Connect

    Noble, J.E.; Olan, R.W.; White, M.A.; Kesseli, J.B.; Bohn, M.S.; Scholl, K.L.

    1995-12-31

    Dispatchability of solar-electric energy conversion systems which utilize fossil fuel to augment solar energy has major economic benefits over systems utilizing solar energy only. For hybridization to be effective, the combustion system must be durable, low cost, produce a low level of emissions, and operate over a wide power range. Thermal energy must be delivered uniformly and reliably to the engine during varied operating conditions, such as intermittent cloud cover. A 10 kW{sub t} hybrid solar receiver using a natural gas burner to augment solar energy was built and tested. The program objective was met with on-sun testing at the National Renewable Energy Laboratory (NREL) High-Flux Solar Furnace test facility in Golden, Colorado. Constant power was delivered to a thermal load at constant temperature over a wide range of solar insolation, with natural and simulated cloud cover. Pool temperature varied by less than 10 C when solar inputs varied from 6 kW to zero. Stable boiling and good overall performance was also demonstrated over a wide range of steady-state and transient conditions.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. A SNP resource for Douglas-fir: de novo transcriptome assembly and SNP detection and validation

    PubMed Central

    2013-01-01

    Background Douglas-fir (Pseudotsuga menziesii), one of the most economically and ecologically important tree species in the world, also has one of the largest tree breeding programs. Although the coastal and interior varieties of Douglas-fir (vars. menziesii and glauca) are native to North America, the coastal variety is also widely planted for timber production in Europe, New Zealand, Australia, and Chile. Our main goal was to develop a SNP resource large enough to facilitate genomic selection in Douglas-fir breeding programs. To accomplish this, we developed a 454-based reference transcriptome for coastal Douglas-fir, annotated and evaluated the quality of the reference, identified putative SNPs, and then validated a sample of those SNPs using the Illumina Infinium genotyping platform. Results We assembled a reference transcriptome consisting of 25,002 isogroups (unique gene models) and 102,623 singletons from 2.76 million 454 and Sanger cDNA sequences from coastal Douglas-fir. We identified 278,979 unique SNPs by mapping the 454 and Sanger sequences to the reference, and by mapping four datasets of Illumina cDNA sequences from multiple seed sources, genotypes, and tissues. The Illumina datasets represented coastal Douglas-fir (64.00 and 13.41 million reads), interior Douglas-fir (80.45 million reads), and a Yakima population similar to interior Douglas-fir (8.99 million reads). We assayed 8067 SNPs on 260 trees using an Illumina Infinium SNP genotyping array. Of these SNPs, 5847 (72.5%) were called successfully and were polymorphic. Conclusions Based on our validation efficiency, our SNP database may contain as many as ~200,000 true SNPs, and as many as ~69,000 SNPs that could be genotyped at ~20,000 gene loci using an Infinium II array—more SNPs than are needed to use genomic selection in tree breeding programs. Ultimately, these genomic resources will enhance Douglas-fir breeding and allow us to better understand landscape-scale patterns of genetic variation

  5. Cardiovascular pharmacogenetics in the SNP era.

    PubMed

    Mooser, V; Waterworth, D M; Isenhour, T; Middleton, L

    2003-07-01

    In the past pharmacological agents have contributed to a significant reduction in age-adjusted incidence of cardiovascular events. However, not all patients treated with these agents respond favorably, and some individuals may develop side-effects. With aging of the population and the growing prevalence of cardiovascular risk factors worldwide, it is expected that the demand for cardiovascular drugs will increase in the future. Accordingly, there is a growing need to identify the 'good' responders as well as the persons at risk for developing adverse events. Evidence is accumulating to indicate that responses to drugs are at least partly under genetic control. As such, pharmacogenetics - the study of variability in drug responses attributed to hereditary factors in different populations - may significantly assist in providing answers toward meeting this challenge. Pharmacogenetics mostly relies on associations between a specific genetic marker like single nucleotide polymorphisms (SNPs), either alone or arranged in a specific linear order on a certain chromosomal region (haplotypes), and a particular response to drugs. Numerous associations have been reported between selected genotypes and specific responses to cardiovascular drugs. Recently, for instance, associations have been reported between specific alleles of the apoE gene and the lipid-lowering response to statins, or the lipid-elevating effect of isotretinoin. Thus far, these types of studies have been mostly limited to a priori selected candidate genes due to restricted genotyping and analytical capacities. Thanks to the large number of SNPs now available in the public domain through the SNP Consortium and the newly developed technologies (high throughput genotyping, bioinformatics software), it is now possible to interrogate more than 200,000 SNPs distributed over the entire human genome. One pharmacogenetic study using this approach has been launched by GlaxoSmithKline to identify the approximately 4% of

  6. Test results from a 10 kW{sub t} solar/natural gas hybrid pool boiler receiver

    SciTech Connect

    Noble, J.E.; Olan, R.W.; White, M.A.; Kesseli, J.; Bohn, M.S.; Scholl, K.L.; Becker, E.W.

    1995-11-01

    Studies have shown that the ability to dispatch solar-electric energy conversion systems which utilize fossil fuel to augment solar energy has major economic benefits over systems utilizing solar energy only. For hybridization to be effective, the combustion system must be durable, low cost, produce a low level of emissions, and operate over a wide power range. Thermal energy must be delivered uniformly and reliably to the engine during varied operating conditions, such as intermittent cloud cover. A 10 kW, hybrid solar receiver using a natural gas burner to augment solar energy was built and tested. The objective was to demonstrate the concept of using a gas burner to supplement solar energy in providing a constant flow of heat to a heat engine under transient conditions of changing cloud cover with automatic control. In the approach pursued, a natural gas combustor is fitted to a pool boiler solar receiver. The burner delivers radiant heat directly to existing boiler surfaces with recovery of exhaust gas energy to achieve high overall efficiency at relatively low combustor temperatures with low emission. Stable boiling and good overall performance were demonstrated over a wide range of steady-state and transient operating conditions. The program objective was met with on-sun tests conducted at the National Renewable Energy Laboratory (NREL) High Flux Solar Furnace test facility in Golden, Colorado, with constant power delivered to a thermal load at constant temperature over a wide range of solar insolation. In this paper, the basic principles and test hardware are presented and test results discussed.

  7. 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.

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

    PubMed

    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

    2015-10-01

    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.

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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

    ... timely file all or any required portion of a Form 10-K, 20-F, 11-K, N-SAR, N-CSR, 10-Q, or 10-D. 240.12b... timely file all or any required portion of a Form 10-K, 20-F, 11-K, N-SAR, N-CSR, 10-Q, or 10-D. (a) If..., annual or transition report on Form N-CSR (17 CFR 249.331; 17 CFR 274.128) or Form N-SAR (17 CFR...

  14. PanSNPdb: the Pan-Asian SNP genotyping database.

    PubMed

    Ngamphiw, Chumpol; Assawamakin, Anunchai; Xu, Shuhua; Shaw, Philip J; Yang, Jin Ok; Ghang, Ho; Bhak, Jong; Liu, Edison; Tongsima, Sissades

    2011-01-01

    The HUGO Pan-Asian SNP consortium conducted the largest survey to date of human genetic diversity among Asians by sampling 1,719 unrelated individuals among 71 populations from China, India, Indonesia, Japan, Malaysia, the Philippines, Singapore, South Korea, Taiwan, and Thailand. We have constructed a database (PanSNPdb), which contains these data and various new analyses of them. PanSNPdb is a research resource in the analysis of the population structure of Asian peoples, including linkage disequilibrium patterns, haplotype distributions, and copy number variations. Furthermore, PanSNPdb provides an interactive comparison with other SNP and CNV databases, including HapMap3, JSNP, dbSNP and DGV and thus provides a comprehensive resource of human genetic diversity. The information is accessible via a widely accepted graphical interface used in many genetic variation databases. Unrestricted access to PanSNPdb and any associated files is available at: http://www4a.biotec.or.th/PASNP.

  15. Forensic SNP Genotyping using Nanopore MinION Sequencing

    PubMed Central

    Cornelis, Senne; Gansemans, Yannick; Deleye, Lieselot; Deforce, Dieter; Van Nieuwerburgh, Filip

    2017-01-01

    One of the latest developments in next generation sequencing is the Oxford Nanopore Technologies’ (ONT) MinION nanopore sequencer. We studied the applicability of this system to perform forensic genotyping of the forensic female DNA standard 9947 A using the 52 SNP-plex assay developed by the SNPforID consortium. All but one of the loci were correctly genotyped. Several SNP loci were identified as problematic for correct and robust genotyping using nanopore sequencing. All these loci contained homopolymers in the sequence flanking the forensic SNP and most of them were already reported as problematic in studies using other sequencing technologies. When these problematic loci are avoided, correct forensic genotyping using nanopore sequencing is technically feasible. PMID:28155888

  16. Forensic SNP Genotyping using Nanopore MinION Sequencing.

    PubMed

    Cornelis, Senne; Gansemans, Yannick; Deleye, Lieselot; Deforce, Dieter; Van Nieuwerburgh, Filip

    2017-02-03

    One of the latest developments in next generation sequencing is the Oxford Nanopore Technologies' (ONT) MinION nanopore sequencer. We studied the applicability of this system to perform forensic genotyping of the forensic female DNA standard 9947 A using the 52 SNP-plex assay developed by the SNPforID consortium. All but one of the loci were correctly genotyped. Several SNP loci were identified as problematic for correct and robust genotyping using nanopore sequencing. All these loci contained homopolymers in the sequence flanking the forensic SNP and most of them were already reported as problematic in studies using other sequencing technologies. When these problematic loci are avoided, correct forensic genotyping using nanopore sequencing is technically feasible.

  17. 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.

  18. A sequence-based identification of the genes detected by probesets on the Affymetrix U133 plus 2.0 array.

    PubMed

    Harbig, Jeremy; Sprinkle, Robert; Enkemann, Steven A

    2005-02-18

    One of the biggest problems facing microarray experiments is the difficulty of translating results into other microarray formats or comparing microarray results to other biochemical methods. We believe that this is largely the result of poor gene identification. We re-identified the probesets on the Affymetrix U133 plus 2.0 GeneChip array. This identification was based on the sequence of the probes and the sequence of the human genome. Using the BLAST program, we matched probes with documented and postulated human transcripts. This resulted in the redefinition of approximately 37% of the probes on the U133 plus 2.0 array. This updated identification specifically points out where the identification is complicated by cross-hybridization from splice variants or closely related genes. More than 5000 probesets detect multiple transcripts and therefore the exact protein affected cannot be readily concluded from the performance of one probeset alone. This makes naming difficult and impacts any downstream analysis such as associating gene ontologies, mapping affected pathways or simply validating expression changes. We have now automated the sequence-based identification and can more appropriately annotate any array where the sequence on each spot is known.

  19. 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

  20. 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.

  1. 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).

  2. Evidence for SNP-SNP interaction identified through targeted sequencing of cleft case-parent trios.

    PubMed

    Xiao, Yanzi; Taub, Margaret A; Ruczinski, Ingo; Begum, Ferdouse; Hetmanski, Jacqueline B; Schwender, Holger; Leslie, Elizabeth J; Koboldt, Daniel C; Murray, Jeffrey C; Marazita, Mary L; Beaty, Terri H

    2017-04-01

    Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is the most common craniofacial birth defect in humans, affecting 1 in 700 live births. This malformation has a complex etiology where multiple genes and several environmental factors influence risk. At least a dozen different genes have been confirmed to be associated with risk of NSCL/P in previous studies. However, all the known genetic risk factors cannot fully explain the observed heritability of NSCL/P, and several authors have suggested gene-gene (G × G) interaction may be important in the etiology of this complex and heterogeneous malformation. We tested for G × G interactions using common single nucleotide polymorphic (SNP) markers from targeted sequencing in 13 regions identified by previous studies spanning 6.3 Mb of the genome in a study of 1,498 NSCL/P case-parent trios. We used the R-package trio to assess interactions between polymorphic markers in different genes, using a 1 degree of freedom (1df) test for screening, and a 4 degree of freedom (4df) test to assess statistical significance of epistatic interactions. To adjust for multiple comparisons, we performed permutation tests. The most significant interaction was observed between rs6029315 in MAFB and rs6681355 in IRF6 (4df P = 3.8 × 10(-8) ) in case-parent trios of European ancestry, which remained significant after correcting for multiple comparisons. However, no significant interaction was detected in trios of Asian ancestry.

  3. 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.

  4. Target SNP selection in complex disease association studies

    PubMed Central

    Wjst, Matthias

    2004-01-01

    Background The massive amount of SNP data stored at public internet sites provides unprecedented access to human genetic variation. Selecting target SNP for disease-gene association studies is currently done more or less randomly as decision rules for the selection of functional relevant SNPs are not available. Results We implemented a computational pipeline that retrieves the genomic sequence of target genes, collects information about sequence variation and selects functional motifs containing SNPs. Motifs being considered are gene promoter, exon-intron structure, AU-rich mRNA elements, transcription factor binding motifs, cryptic and enhancer splice sites together with expression in target tissue. As a case study, 396 genes on chromosome 6p21 in the extended HLA region were selected that contributed nearly 20,000 SNPs. By computer annotation ~2,500 SNPs in functional motifs could be identified. Most of these SNPs are disrupting transcription factor binding sites but only those introducing new sites had a significant depressing effect on SNP allele frequency. Other decision rules concern position within motifs, the validity of SNP database entries, the unique occurrence in the genome and conserved sequence context in other mammalian genomes. Conclusion Only 10% of all gene-based SNPs have sequence-predicted functional relevance making them a primary target for genotyping in association studies. PMID:15248903

  5. 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...

  6. Genetic mapping in grapevine using a SNP microarray: intensity values

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genotyping microarrays are widely used for genome wide association studies, but in high-diversity organisms, the quality of SNP calls can be diminished by genetic variation near the assayed nucleotide. To address this limitation in grapevine, we developed a simple heuristic that uses hybridization i...

  7. High throughput SNP detection system based on magnetic nanoparticles separation.

    PubMed

    Liu, Bin; Jia, Yingying; Ma, Man; Li, Zhiyang; Liu, Hongna; Li, Song; Deng, Yan; Zhang, Liming; Lu, Zhuoxuan; Wang, Wei; He, Nongyue

    2013-02-01

    Single-nucleotide polymorphism (SNP) was one-base variations in DNA sequence that can often be helpful to find genes associations for hereditary disease, communicable disease and so on. We developed a high throughput SNP detection system based on magnetic nanoparticles (MNPs) separation and dual-color hybridization or single base extension. This system includes a magnetic separation unit for sample separation, three high precision robot arms for pipetting and microtiter plate transferring respectively, an accurate temperature control unit for PCR and DNA hybridization and a high accurate and sensitive optical signal detection unit for fluorescence detection. The cyclooxygenase-2 gene promoter region--65G > C polymorphism locus SNP genotyping experiment for 48 samples from the northern Jiangsu area has been done to verify that if this system can simplify manual operation of the researchers, save time and improve efficiency in SNP genotyping experiments. It can realize sample preparation, target sequence amplification, signal detection and data analysis automatically and can be used in clinical molecule diagnosis and high throughput fluorescence immunological detection and so on.

  8. Weighted SNP set analysis in genome-wide association study.

    PubMed

    Dai, Hui; Zhao, Yang; Qian, Cheng; Cai, Min; Zhang, Ruyang; Chu, Minjie; Dai, Juncheng; Hu, Zhibin; Shen, Hongbing; Chen, Feng

    2013-01-01

    Genome-wide association studies (GWAS) are popular for identifying genetic variants which are associated with disease risk. Many approaches have been proposed to test multiple single nucleotide polymorphisms (SNPs) in a region simultaneously which considering disadvantages of methods in single locus association analysis. Kernel machine based SNP set analysis is more powerful than single locus analysis, which borrows information from SNPs correlated with causal or tag SNPs. Four types of kernel machine functions and principal component based approach (PCA) were also compared. However, given the loss of power caused by low minor allele frequencies (MAF), we conducted an extension work on PCA and used a new method called weighted PCA (wPCA). Comparative analysis was performed for weighted principal component analysis (wPCA), logistic kernel machine based test (LKM) and principal component analysis (PCA) based on SNP set in the case of different minor allele frequencies (MAF) and linkage disequilibrium (LD) structures. We also applied the three methods to analyze two SNP sets extracted from a real GWAS dataset of non-small cell lung cancer in Han Chinese population. Simulation results show that when the MAF of the causal SNP is low, weighted principal component and weighted IBS are more powerful than PCA and other kernel machine functions at different LD structures and different numbers of causal SNPs. Application of the three methods to a real GWAS dataset indicates that wPCA and wIBS have better performance than the linear kernel, IBS kernel and PCA.

  9. Comparative transcriptomic profiling of Vitis vinifera under high light using a custom-made array and the Affymetrix GeneChip.

    PubMed

    Carvalho, Luísa C; Vilela, Belmiro J; Mullineaux, Phil M; Amâncio, Sara

    2011-11-01

    Understanding abiotic stress responses is one of the most important issues in plant research nowadays. Abiotic stress, including excess light, can promote the onset of oxidative stress through the accumulation of reactive oxygen species. Oxidative stress also arises when in vitro propagated plants are exposed to high light upon transfer to ex vitro. To determine whether the underlying pathways activated at the transfer of in vitro grapevine to ex vitro conditions reflect the processes occurring upon light stress, we used Vitis vinifera Affymetrix GeneChip (VvGA) and a custom array of genes responsive to light stress (LSCA) detected by real-time reverse transcriptase PCR (qRT-PCR). When gene-expression profiles were compared, 'protein metabolism and modification', 'signaling', and 'anti-oxidative' genes were more represented in LSCA, while, in VvGA, 'cell wall metabolism' and 'secondary metabolism' were the categories in which gene expression varied more significantly. The above functional categories confirm previous studies involving other types of abiotic stresses, enhancing the common attributes of abiotic stress defense pathways. The LSCA analysis of our experimental system detected strong response of heat shock genes, particularly the protein rescuing mechanism involving the cooperation of two ATP-dependent chaperone systems, Hsp100 and Hsp70, which showed an unusually late response during the recovery period, of extreme relevance to remove non-functional, potentially harmful polypeptides arising from misfolding, denaturation, or aggregation brought about by stress. The success of LSCA also proves the feasibility of a custom-made qRT-PCR approach, particularly for species for which no GeneChip is available and for researchers dealing with a specific and focused problem.

  10. High throughput SNP discovery and validation in the pig: towards the development of a high density swine SNP chip

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recent developments in sequencing technology have allowed the generation of millions of short read sequences in a fast and inexpensive way. This enables the cost effective large scale identification of hundreds of thousands of SNPs needed for the development of high density SNP arrays. Currently, a ...

  11. 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

  12. 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.

  13. High-throughput SNP genotyping for breeding applications in rice using the BeadXpress platform

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Multiplexed single nucleotide polymorphism (SNP) markers have the potential to increase the speed and cost-effectiveness of genotyping, provided that an optimal SNP density is used for each application. To test the efficiency of multiplexed SNP genotyping for diversity, mapping and breeding applicat...

  14. Development of Single Nucleotide Polymorphism (SNP) Markers for Use in Commercial Maize (Zea Mays L.) Germplasm

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The development of single nucleotide polymorphism (SNP) markers in maize offer the opportunity to utilize DNA markers in many new areas of population genetics, gene discovery, plant breeding, and germplasm identification. However, the steps from sequencing and SNP discovery to SNP marker design and ...

  15. 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.

  16. 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.

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

    PubMed

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

    2013-09-01

    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.

  18. Dominant recognition of a cross-reactive B-cell epitope in Mycobacterium leprae 10 K antigen by immunoglobulin G1 antibodies across the disease spectrum in leprosy

    PubMed Central

    Hussain, R; Dockrell, H M; Chiang, T J

    1999-01-01

    Mycobacterium leprae-specific immunoglobulin G1 (IgG1) antibodies in patients with leprosy show a direct correlation with bacterial load (ρ=0·748; P < 0002) suggesting that IgG1 B-cell responses may be surrogate markers of disease progression. To investigate if this upregulation was a general feature of IgG1 responses to all M. leprae (ML) antigens, we analysed responses to several recombinant purified ML heat-shock proteins (HSP). Three recombinant HSPs (ML10 K, ML 18 K and ML 65 K) were tested for their ability to induce various IgG subclasses in patients with either the lepromatous (LL/BL, n = 26) or tuberculoid form (BT/TT, n = 39) of the disease as well as in healthy households (HC, n = 14) and endemic controls (EC = 19). Our major findings were: (1) selective augmentation of IgG1 antibody responses to ML10 K; (2) recognition of a restricted number of epitopes across the disease spectrum and healthy controls by IgG1 antibodies; (3) dominant recognition of cross-reactive epitopes which were common to both ML and MT 10 K. This response was not related to contamination with endotoxin. Epitope mapping using 15-mer overlapping peptides spanning the ML 10 000 MW revealed an immunodominant IgG1 binding peptide (aa41–55) in patients as well as healthy controls. This peptide is a shared epitope with M. tuberculosis 10 K suggesting that postswitched IgG1 B cells recognizing this epitope rather than naive B cells are being expanded. PMID:10233750

  19. 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.

  20. Development of a measurement and control system for a 10 kW@20 K refrigerator based on Siemens PLC S7-300

    NASA Astrophysics Data System (ADS)

    Li, J.; Liu, L. Q.; Liu, T.; Xu, X. D.; Dong, B.; Lu, W. H.; Pan, W.; Wu, J. H.; Xiong, L. Y.

    2017-02-01

    A 10 kW@20 K refrigerator has been established by the Technical Institute of Physics and Chemistry, Chinese Academy of Sciences. A measurement and control system based on Siemens PLC S7-300 for this 10 kW@20 K refrigerator is developed. According to the detailed measurement requirements, proper sensors and transmitters are adopted. Siemens S7-300 PLC CPU315-2 PN/DP operates as a master station. Two sets of ET200M DP remote expand I/O, one power meter, two compressors and one vacuum gauge operate as slave stations. Profibus-DP field communication and Modbus communication are used between the master station and the slave stations in this control system. The upper computer HMI (Human Machine Interface) is compiled using Siemens configuration software WinCC V7.0. The upper computer communicates with PLC by means of industrial Ethernet. After commissioning, this refrigerator has been operating with a 10 kW of cooling power at 20 K for more than 72 hours.

  1. 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.

  2. BEAT: Bioinformatics Exon Array Tool to store, analyze and visualize Affymetrix GeneChip Human Exon Array data from disease experiments

    PubMed Central

    2012-01-01

    Background It is known from recent studies that more than 90% of human multi-exon genes are subject to Alternative Splicing (AS), a key molecular mechanism in which multiple transcripts may be generated from a single gene. It is widely recognized that a breakdown in AS mechanisms plays an important role in cellular differentiation and pathologies. Polymerase Chain Reactions, microarrays and sequencing technologies have been applied to the study of transcript diversity arising from alternative expression. Last generation Affymetrix GeneChip Human Exon 1.0 ST Arrays offer a more detailed view of the gene expression profile providing information on the AS patterns. The exon array technology, with more than five million data points, can detect approximately one million exons, and it allows performing analyses at both gene and exon level. In this paper we describe BEAT, an integrated user-friendly bioinformatics framework to store, analyze and visualize exon arrays datasets. It combines a data warehouse approach with some rigorous statistical methods for assessing the AS of genes involved in diseases. Meta statistics are proposed as a novel approach to explore the analysis results. BEAT is available at http://beat.ba.itb.cnr.it. Results BEAT is a web tool which allows uploading and analyzing exon array datasets using standard statistical methods and an easy-to-use graphical web front-end. BEAT has been tested on a dataset with 173 samples and tuned using new datasets of exon array experiments from 28 colorectal cancer and 26 renal cell cancer samples produced at the Medical Genetics Unit of IRCCS Casa Sollievo della Sofferenza. To highlight all possible AS events, alternative names, accession Ids, Gene Ontology terms and biochemical pathways annotations are integrated with exon and gene level expression plots. The user can customize the results choosing custom thresholds for the statistical parameters and exploiting the available clinical data of the samples for a

  3. Pyrobayes: an improved base caller for SNP discovery in pyrosequences.

    PubMed

    Quinlan, Aaron R; Stewart, Donald A; Strömberg, Michael P; Marth, Gábor T

    2008-02-01

    Previously reported applications of the 454 Life Sciences pyrosequencing technology have relied on deep sequence coverage for accurate polymorphism discovery because of frequent insertion and deletion sequence errors. Here we report a new base calling program, Pyrobayes, for pyrosequencing reads. Pyrobayes permits accurate single-nucleotide polymorphism (SNP) calling in resequencing applications, even in shallow read coverage, primarily because it produces more confident base calls than the native base calling program.

  4. Development of SNP-genotyping arrays in two shellfish species.

    PubMed

    Lapègue, S; Harrang, E; Heurtebise, S; Flahauw, E; Donnadieu, C; Gayral, P; Ballenghien, M; Genestout, L; Barbotte, L; Mahla, R; Haffray, P; Klopp, C

    2014-07-01

    Use of SNPs has been favoured due to their abundance in plant and animal genomes, accompanied by the falling cost and rising throughput capacity for detection and genotyping. Here, we present in vitro (obtained from targeted sequencing) and in silico discovery of SNPs, and the design of medium-throughput genotyping arrays for two oyster species, the Pacific oyster, Crassostrea gigas, and European flat oyster, Ostrea edulis. Two sets of 384 SNP markers were designed for two Illumina GoldenGate arrays and genotyped on more than 1000 samples for each species. In each case, oyster samples were obtained from wild and selected populations and from three-generation families segregating for traits of interest in aquaculture. The rate of successfully genotyped polymorphic SNPs was about 60% for each species. Effects of SNP origin and quality on genotyping success (Illumina functionality Score) were analysed and compared with other model and nonmodel species. Furthermore, a simulation was made based on a subset of the C. gigas SNP array with a minor allele frequency of 0.3 and typical crosses used in shellfish hatcheries. This simulation indicated that at least 150 markers were needed to perform an accurate parental assignment. Such panels might provide valuable tools to improve our understanding of the connectivity between wild (and selected) populations and could contribute to future selective breeding programmes.

  5. Development of a forensic identity SNP panel for Indonesia.

    PubMed

    Augustinus, Daniel; Gahan, Michelle E; McNevin, Dennis

    2015-07-01

    Genetic markers included in forensic identity panels must exhibit Hardy-Weinberg and linkage equilibrium (HWE and LE). "Universal" panels designed for global use can fail these tests in regional jurisdictions exhibiting high levels of genetic differentiation such as the Indonesian archipelago. This is especially the case where a single DNA database is required for allele frequency estimates to calculate random match probabilities (RMPs) and associated likelihood ratios (LRs). A panel of 65 single nucleotide polymorphisms (SNPs) and a reduced set of 52 SNPs have been selected from 15 Indonesian subpopulations in the HUGO Pan Asian SNP database using a SNP selection strategy that could be applied to any panel of forensic identity markers. The strategy consists of four screening steps: (1) application of a G test for HWE; (2) ranking for high heterozygosity; (3) selection for LE; and (4) selection for low inbreeding depression. SNPs in our Indonesian panel perform well in comparison to some other universal SNP and short tandem repeat (STR) panels as measured by Fisher's exact test for HWE and LE and Wright's F statistics.

  6. 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

  7. Forensic SNP genotyping with SNaPshot: Technical considerations for the development and optimization of multiplexed SNP assays.

    PubMed

    Fondevila, M; Børsting, C; Phillips, C; de la Puente, M; Consortium, Euroforen-NoE; Carracedo, A; Morling, N; Lareu, M V

    2017-01-01

    This review explores the key factors that influence the optimization, routine use, and profile interpretation of the SNaPshot single-base extension (SBE) system applied to forensic single-nucleotide polymorphism (SNP) genotyping. Despite being a mainly complimentary DNA genotyping technique to routine STR profiling, use of SNaPshot is an important part of the development of SNP sets for a wide range of forensic applications with these markers, from genotyping highly degraded DNA with very short amplicons to the introduction of SNPs to ascertain the ancestry and physical characteristics of an unidentified contact trace donor. However, this technology, as resourceful as it is, displays several features that depart from the usual STR genotyping far enough to demand a certain degree of expertise from the forensic analyst before tackling the complex casework on which SNaPshot application provides an advantage. In order to provide the basis for developing such expertise, we cover in this paper the most challenging aspects of the SNaPshot technology, focusing on the steps taken to design primer sets, optimize the PCR and single-base extension chemistries, and the important features of the peak patterns observed in typical forensic SNP profiles using SNaPshot. With that purpose in mind, we provide guidelines and troubleshooting for multiplex-SNaPshot-oriented primer design and the resulting capillary electrophoresis (CE) profile interpretation (covering the most commonly observed artifacts and expected departures from the ideal conditions).

  8. Genomewide linkage analysis of bipolar disorder by use of a high-density single-nucleotide-polymorphism (SNP) genotyping assay: a comparison with microsatellite marker assays and finding of significant linkage to chromosome 6q22.

    PubMed

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

    2004-05-01

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

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

    PubMed Central

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

    2004-01-01

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

  10. Gamma-irradiated and nonirradiated Eimeria tenella sporozoites exhibit differential uracil uptake and expression of a 7- to 10-kDa metabolic antigen.

    PubMed

    Jenkins, M C; Chute, M B; Danforth, H D; Lillehoj, H S

    1995-06-01

    Eimeria tenella sporozoites were exposed in the oocyst form to either an optimum (15 kRad) or a high (25 kRad) dose of gamma irradiation and used to infect cultured chicken embryo fibroblasts (CEF). The sporozoite-infected CEF monolayer was pulsed at time of infection or 24 hr postinfection with [3H]uracil and harvested 24 hr later to measure sporozoite metabolic activity. Sporozoites exposed to either 0 or 15 kRad gamma irradiation incorporated similar (P > 0.05) amounts of [3H]uracil during the first and second 24-hr periods after infection. However, there was a significant decrease (P < 0.05) in [3H]uracil uptake by 25 kRad-exposed sporozoites compared to nonirradiated and 15 kRad-irradiated sporozoites. Indirect immunofluorescence (IFA) staining of E. tenella sporozoite-infected CEFs using monoclonal antibodies (MAb) specific for somatic or "metabolic" antigens showed that gamma irradiation also affected the release of intracellular metabolites. Regardless of irradiation dose, extracellular sporozoites exhibited similar intensity of immunofluorescence when stained with either somatic antigen- or metabolic antigen-reactive MAb. Also, somatic antigen expression was similar for intracellular parasites irrespective of radiation dose. However, metabolic 7- to 10-kDa antigen expression by 25 kRad-irradiated sporozoites was markedly reduced compared to nonirradiated or 15 kRad-irradiated intracellular sporozoites. These results were corroborated by immunostaining sporozoite/CEF protein-impregnated Immobilon membrane with somatic or metabolic 7- to 10-kDa antigen-reactive MAb. These findings may indicate that the metabolic 7- to 10-kDa antigen is involved in protective immunity elicited by nonirradiated and/or 15 kRad-irradiated E. tenella sporozoites.

  11. KEY COMPARISON: Force key comparison CCM.F-K1.a and CCM.F-K1.b: 5 kN and 10 kN

    NASA Astrophysics Data System (ADS)

    Pusa, Aimo

    2009-01-01

    This report describes the key comparisons named CCM.F-K1.a and CCM.F-K1.b, for force with loads of 5 kN and 10 kN. The Draft A Report, reporting the measurement results of the key comparisons, has been accepted at the force expert group meeting in Pretoria on 23 March 2004. This became Part 1 of the preliminary Draft B Report. Then, there have been several discussions to find the best way for the determination of the reference value for force values 5 kN and 10 kN in the key comparisons CCM.F-K1.a and CCM.F-K1.b. Following the meeting held in Queretaro, Mexico, by CENAM, from 3 to 5 December 2007, the reference values have been calculated for each single transducer (see chapter 2), and as one reference value for 5 kN and a second reference value for 10 kN (see chapter 3). To get a better consistency a linear model for the drift of transducers has been applied. The results have been evaluated according to the paper from M G Cox, 'The evaluation of key comparison data' (2002 Metrologia 39 589-595). 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 (MRA).

  12. 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.

  13. Comparison of the NIST and NPL Air Kerma Standards Used for X-Ray Measurements Between 10 kV and 80 kV.

    PubMed

    O'Brien, M; Lamperti, P; Williams, T; Sander, T

    2000-01-01

    A direct comparison was made between the air kerma primary standards used for the measurements of low-energy x rays at the National Institute of Standards and Technology (NIST) and the National Physical Laboratory (NPL). The comparison was conducted at the NPL using NPL reference radiation qualities between 10 kV and 80 kV. The results show the primary air-kerma standards to agree within 0.6 % of their values for beam qualities up to 80 kV.

  14. 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.

  15. Exploration of SNP variants affecting hair colour prediction in Europeans.

    PubMed

    Söchtig, Jens; Phillips, Chris; Maroñas, Olalla; Gómez-Tato, Antonio; Cruz, Raquel; Alvarez-Dios, Jose; de Cal, María-Ángeles Casares; Ruiz, Yarimar; Reich, Kristian; Fondevila, Manuel; Carracedo, Ángel; Lareu, María V

    2015-09-01

    DNA profiling is a key tool for forensic analysis; however, current methods identify a suspect either by direct comparison or from DNA database searches. In cases with unidentified suspects, prediction of visible physical traits e.g. pigmentation or hair distribution of the DNA donors can provide important probative information. This study aimed to explore single nucleotide polymorphism (SNP) variants for their effect on hair colour prediction. A discovery panel of 63 SNPs consisting of already established hair colour markers from the HIrisPlex hair colour phenotyping assay as well as additional markers for which associations to human pigmentation traits were previously identified was used to develop multiplex assays based on SNaPshot single-base extension technology. A genotyping study was performed on a range of European populations (n = 605). Hair colour phenotyping was accomplished by matching donor's hair to a graded colour category system of reference shades and photography. Since multiple SNPs in combination contribute in varying degrees to hair colour predictability in Europeans, we aimed to compile a compact marker set that could provide a reliable hair colour inference from the fewest SNPs. The predictive approach developed uses a naïve Bayes classifier to provide hair colour assignment probabilities for the SNP profiles of the key SNPs and was embedded into the Snipper online SNP classifier ( http://mathgene.usc.es/snipper/ ). Results indicate that red, blond, brown and black hair colours are predictable with informative probabilities in a high proportion of cases. Our study resulted in the identification of 12 most strongly associated SNPs to hair pigmentation variation in six genes.

  16. Computational tradeoffs in multiplex PCR assay design for SNP genotyping

    PubMed Central

    Rachlin, John; Ding, Chunming; Cantor, Charles; Kasif, Simon

    2005-01-01

    Background Multiplex PCR is a key technology for detecting infectious microorganisms, whole-genome sequencing, forensic analysis, and for enabling flexible yet low-cost genotyping. However, the design of a multiplex PCR assays requires the consideration of multiple competing objectives and physical constraints, and extensive computational analysis must be performed in order to identify the possible formation of primer-dimers that can negatively impact product yield. Results This paper examines the computational design limits of multiplex PCR in the context of SNP genotyping and examines tradeoffs associated with several key design factors including multiplexing level (the number of primer pairs per tube), coverage (the % of SNP whose associated primers are actually assigned to one of several available tube), and tube-size uniformity. We also examine how design performance depends on the total number of available SNPs from which to choose, and primer stringency criterial. We show that finding high-multiplexing/high-coverage designs is subject to a computational phase transition, becoming dramatically more difficult when the probability of primer pair interaction exceeds a critical threshold. The precise location of this critical transition point depends on the number of available SNPs and the level of multiplexing required. We also demonstrate how coverage performance is impacted by the number of available snps, primer selection criteria, and target multiplexing levels. Conclusion The presence of a phase transition suggests limits to scaling Multiplex PCR performance for high-throughput genomics applications. Achieving broad SNP coverage rapidly transitions from being very easy to very hard as the target multiplexing level (# of primer pairs per tube) increases. The onset of a phase transition can be "delayed" by having a larger pool of SNPs, or loosening primer selection constraints so as to increase the number of candidate primer pairs per SNP, though the latter

  17. 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).

  18. Dielectric constant dispersion of yttrium-doped (Ba,Sr)TiO3 films in the high-frequency (10 kHz-67 GHz) domain

    NASA Astrophysics Data System (ADS)

    Jeong, Doo Seok; Hwang, Cheol Seong; Baniecki, J. D.; Shioga, T.; Kurihara, K.; Kamehara, N.; Ishii, M.

    2005-12-01

    The frequency dispersion of the dielectric constant of yttrium (Y)-doped (Ba,Sr)TiO3 thin films (Y-BST) in the high-frequency domain (10kHz-67GHz) was investigated. In order to remove the substantial parasitic capacitances, inductances, and resistances from the measured impedance data, test samples, short-circuit standard, and open-circuit standard structures were fabricated and their frequency response was measured. Before removing parasitic components, the measured dielectric response showed a rolloff at approximately 4GHz. However, after circuit calibration, the dielectric constant was almost constant up to 40GHz where another rolloff was observed. However, this rolloff was due to the uncompensated small parasitic components. Therefore, the dielectric constant of the Y-BST films (170 with a film thickness of 30nm) showed small frequency dispersion corresponding to the Curie-von Schweidler dispersion, of which the exponent is -0.0131, up to 40GHz. Furthermore, the decrease of the capacitance was 17% in the frequency range from 10kHzto40GHz.

  19. A combined reference panel from the 1000 Genomes and UK10K projects improved rare variant imputation in European and Chinese samples.

    PubMed

    Chou, Wen-Chi; Zheng, Hou-Feng; Cheng, Chia-Ho; Yan, Han; Wang, Li; Han, Fang; Richards, J Brent; Karasik, David; Kiel, Douglas P; Hsu, Yi-Hsiang

    2016-12-22

    Imputation using the 1000 Genomes haplotype reference panel has been widely adapted to estimate genotypes in genome wide association studies. To evaluate imputation quality with a relatively larger reference panel and a reference panel composed of different ethnic populations, we conducted imputations in the Framingham Heart Study and the North Chinese Study using a combined reference panel from the 1000 Genomes (N = 1,092) and UK10K (N = 3,781) projects. For rare variants with 0.01% < MAF ≤ 0.5%, imputation in the Framingham Heart Study with the combined reference panel increased well-imputed genotypes (with imputation quality score ≥0.4) from 62.9% to 76.1% when compared to imputation with the 1000 Genomes. For the North Chinese samples, imputation of rare variants with 0.01% < MAF ≤ 0.5% with the combined reference panel increased well-imputed genotypes by from 49.8% to 61.8%. The predominant European ancestry of the UK10K and the combined reference panels may explain why there was less of an increase in imputation success in the North Chinese samples. Our results underscore the importance and potential of larger reference panels to impute rare variants, while recognizing that increasing ethnic specific variants in reference panels may result in better imputation for genotypes in some ethnic groups.

  20. A combined reference panel from the 1000 Genomes and UK10K projects improved rare variant imputation in European and Chinese samples

    PubMed Central

    Chou, Wen-Chi; Zheng, Hou-Feng; Cheng, Chia-Ho; Yan, Han; Wang, Li; Han, Fang; Richards, J. Brent; Karasik, David; Kiel, Douglas P.; Hsu, Yi-Hsiang

    2016-01-01

    Imputation using the 1000 Genomes haplotype reference panel has been widely adapted to estimate genotypes in genome wide association studies. To evaluate imputation quality with a relatively larger reference panel and a reference panel composed of different ethnic populations, we conducted imputations in the Framingham Heart Study and the North Chinese Study using a combined reference panel from the 1000 Genomes (N = 1,092) and UK10K (N = 3,781) projects. For rare variants with 0.01% < MAF ≤ 0.5%, imputation in the Framingham Heart Study with the combined reference panel increased well-imputed genotypes (with imputation quality score ≥0.4) from 62.9% to 76.1% when compared to imputation with the 1000 Genomes. For the North Chinese samples, imputation of rare variants with 0.01% < MAF ≤ 0.5% with the combined reference panel increased well-imputed genotypes by from 49.8% to 61.8%. The predominant European ancestry of the UK10K and the combined reference panels may explain why there was less of an increase in imputation success in the North Chinese samples. Our results underscore the importance and potential of larger reference panels to impute rare variants, while recognizing that increasing ethnic specific variants in reference panels may result in better imputation for genotypes in some ethnic groups. PMID:28004816

  1. Crystallization and X-ray data analysis of the 10 kDa C-terminal lid subdomain from Caenorhabditis elegans Hsp70

    SciTech Connect

    Worrall, Liam; Walkinshaw, Malcolm D.

    2006-09-01

    Crystals of the C-terminal 10 kDa lid subdomain from the C. elegans chaperone Hsp70 have been obtained that diffract X-rays to ∼3.5 Å and belong to space group I2{sub 1}2{sub 1}2{sub 1}. Analysis of X-ray data and initial heavy-atom phasing reveals 24 monomers in the asymmetric unit related by 432 non-crystallographic symmetry. Hsp70 is an important molecular chaperone involved in the regulation of protein folding. Crystals of the C-terminal 10 kDa helical lid domain (residues 542–640) from a Caenorhabditis elegans Hsp70 homologue have been produced that diffract X-rays to ∼3.4 Å. Crystals belong to space group I2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = b = 197, c = 200 Å. The Matthews coefficient, self-rotation function and Patterson map indicate 24 monomers in the asymmetric unit, showing non-crystallographic 432 symmetry. Molecular-replacement studies using the corresponding domain from rat, the only eukaryotic homologue with a known structure, failed and a mercury derivative was obtained. Preliminary MAD phasing using SHELXD and SHARP for location and refinement of the heavy-atom substructure and SOLOMON for density modification produced interpretable maps with a clear protein–solvent boundary. Further density-modification, model-building and refinement are currently under way.

  2. Genome-wide SNP discovery in walnut with an AGSNP pipeline updated for SNP discovery in allogamous organisms

    PubMed Central

    2012-01-01

    Background A genome-wide set of single nucleotide polymorphisms (SNPs) is a valuable resource in genetic research and breeding and is usually developed by re-sequencing a genome. If a genome sequence is not available, an alternative strategy must be used. We previously reported the development of a pipeline (AGSNP) for genome-wide SNP discovery in coding sequences and other single-copy DNA without a complete genome sequence in self-pollinating (autogamous) plants. Here we updated this pipeline for SNP discovery in outcrossing (allogamous) species and demonstrated its efficacy in SNP discovery in walnut (Juglans regia L.). Results The first step in the original implementation of the AGSNP pipeline was the construction of a reference sequence and the identification of single-copy sequences in it. To identify single-copy sequences, multiple genome equivalents of short SOLiD reads of another individual were mapped to shallow genome coverage of long Sanger or Roche 454 reads making up the reference sequence. The relative depth of SOLiD reads was used to filter out repeated sequences from single-copy sequences in the reference sequence. The second step was a search for SNPs between SOLiD reads and the reference sequence. Polymorphism within the mapped SOLiD reads would have precluded SNP discovery; hence both individuals had to be homozygous. The AGSNP pipeline was updated here for using SOLiD or other type of short reads of a heterozygous individual for these two principal steps. A total of 32.6X walnut genome equivalents of SOLiD reads of vegetatively propagated walnut scion cultivar ‘Chandler’ were mapped to 48,661 ‘Chandler’ bacterial artificial chromosome (BAC) end sequences (BESs) produced by Sanger sequencing during the construction of a walnut physical map. A total of 22,799 putative SNPs were initially identified. A total of 6,000 Infinium II type SNPs evenly distributed along the walnut physical map were selected for the construction of an Infinium Bead

  3. The Impact of a Common MDM2 SNP on the Sensitivity of Breast Cancer to Treatment

    DTIC Science & Technology

    2012-06-01

    could decrease the effectiveness of treatment. These outcomes are likely due to the increased expression of mdm2 protein in SNP309 individuals, which...expression at the protein level occur in the mdm2 SNP309 cell line. There was no association between the mdm2 SNP309 and clinical outcome of breast cancer...with chemotherapy, hormonal therapy and radiation therapy. 1S. SUBJECT TERMS mdm2, breast cancer, polymorphisms 16. SECURITY CLASSIFICATION OF: 17

  4. A genome-wide search for common SNP x SNP interactions on the risk of venous thrombosis

    PubMed Central

    2013-01-01

    Background Venous Thrombosis (VT) is a common multifactorial disease with an estimated heritability between 35% and 60%. Known genetic polymorphisms identified so far only explain ~5% of the genetic variance of the disease. This study was aimed to investigate whether pair-wise interactions between common single nucleotide polymorphisms (SNPs) could exist and modulate the risk of VT. Methods A genome-wide SNP x SNP interaction analysis on VT risk was conducted in a French case–control study and the most significant findings were tested for replication in a second independent French case–control sample. The results obtained in the two studies totaling 1,953 cases and 2,338 healthy subjects were combined into a meta-analysis. Results The smallest observed p-value for interaction was p = 6.00 10-11 but it did not pass the Bonferroni significance threshold of 1.69 10-12 correcting for the number of investigated interactions that was 2.96 1010. Among the 37 suggestive pair-wise interactions with p-value less than 10-8, one was further shown to involve two SNPs, rs9804128 (IGFS21 locus) and rs4784379 (IRX3 locus) that demonstrated significant interactive effects (p = 4.83 10-5) on the variability of plasma Factor VIII levels, a quantitative biomarker of VT risk, in a sample of 1,091 VT patients. Conclusion This study, the first genome-wide SNP interaction analysis conducted so far on VT risk, suggests that common SNPs are unlikely exerting strong interactive effects on the risk of disease. PMID:23509962

  5. 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

  6. 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.

  7. SNP Markers and Their Impact on Plant Breeding

    PubMed Central

    Mammadov, Jafar; Aggarwal, Rajat; Buyyarapu, Ramesh; Kumpatla, Siva

    2012-01-01

    The use of molecular markers has revolutionized the pace and precision of plant genetic analysis which in turn facilitated the implementation of molecular breeding of crops. The last three decades have seen tremendous advances in the evolution of marker systems and the respective detection platforms. Markers based on single nucleotide polymorphisms (SNPs) have rapidly gained the center stage of molecular genetics during the recent years due to their abundance in the genomes and their amenability for high-throughput detection formats and platforms. Computational approaches dominate SNP discovery methods due to the ever-increasing sequence information in public databases; however, complex genomes pose special challenges in the identification of informative SNPs warranting alternative strategies in those crops. Many genotyping platforms and chemistries have become available making the use of SNPs even more attractive and efficient. This paper provides a review of historical and current efforts in the development, validation, and application of SNP markers in QTL/gene discovery and plant breeding by discussing key experimental strategies and cases exemplifying their impact. PMID:23316221

  8. Eigenanalysis of SNP data with an identity by descent interpretation.

    PubMed

    Zheng, Xiuwen; Weir, Bruce S

    2016-02-01

    Principal component analysis (PCA) is widely used in genome-wide association studies (GWAS), and the principal component axes often represent perpendicular gradients in geographic space. The explanation of PCA results is of major interest for geneticists to understand fundamental demographic parameters. Here, we provide an interpretation of PCA based on relatedness measures, which are described by the probability that sets of genes are identical-by-descent (IBD). An approximately linear transformation between ancestral proportions (AP) of individuals with multiple ancestries and their projections onto the principal components is found. In addition, a new method of eigenanalysis "EIGMIX" is proposed to estimate individual ancestries. EIGMIX is a method of moments with computational efficiency suitable for millions of SNP data, and it is not subject to the assumption of linkage equilibrium. With the assumptions of multiple ancestries and their surrogate ancestral samples, EIGMIX is able to infer ancestral proportions (APs) of individuals. The methods were applied to the SNP data from the HapMap Phase 3 project and the Human Genome Diversity Panel. The APs of individuals inferred by EIGMIX are consistent with the findings of the program ADMIXTURE. In conclusion, EIGMIX can be used to detect population structure and estimate genome-wide ancestral proportions with a relatively high accuracy.

  9. 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

  10. Fabrication of an Ultra High Vacuum Compatible Faraday Cup for Qualification of Electron Gun for 10 kW Industrial LINAC

    NASA Astrophysics Data System (ADS)

    Kak, Ajay; Kher, A.; Vishwakarma, S. C.; Kumar, Abhay; Gandhi, Manoj; Radheshyam, Pramod; Kumar, Ajay; Abhinandan, Lala

    2012-11-01

    In this paper, we report fabrication and testing of a unique Faraday Cup designed for qualification of Electron Gun for a 10 kW industrial LINAC. This is a compact device consisting of a tapered copper cavity electrically isolated by a ceramic cylinder metalized at both ends. Kovar tubes matching with the diameter of ceramic isolator were used at both ends to facilitate high quality UHV compatible joints with copper cavity at one end and standard knife edge stainless steel flange at the other end. The Kovar tube was flared at both ends to form a collar matching with the outer diameter of the ceramic isolator. The joint between Kovar collar and ceramic isolator was done by hydrogen brazing using copper silver eutectic alloy. All the joints were tested with helium leak detector and leak rates were found to be below 1 × 10-10mbar.litre/second.

  11. Pilot Study EURAMET.AUV.V-P1: Bilateral comparison on magnitude of the complex charge sensitivity of accelerometers from 10 Hz to 10 kHz

    NASA Astrophysics Data System (ADS)

    Bartoli, Claire; Hermawanto, Denny

    2017-01-01

    The results of a Pilot Study EURAMET.AUV.V-P1 between LNE (France) and RCM-LIPI (Indonesia) are reported. This bilateral comparison of sinusoidal vibration was organized after the implementation of various improvements at RCM-LIPI following a previous (unpublished) comparison that had revealed discrepancies in their results at frequencies above 5 kHz. The results of this Pilot Study, using the same accelerometers as the earlier comparison, demonstrate that the discrepancies at high frequencies have been resolved. For both the back-to-back and the single-ended accelerometers tested, the sensitivities of the RCM-LIPI and the LNE over the frequency range from 10 Hz to 10 kHz now agree within their declared uncertainties. Main text To reach the main text of this paper, click on Final Report. The final report has been peer-reviewed and approved for publication by the CCAUV.

  12. 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.

  13. 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

  14. 10 kHz ps 1342 nm laser generation by an electro-optically cavity-dumped mode-locked Nd:YVO4 laser

    NASA Astrophysics Data System (ADS)

    Chen, Ying; Liu, Ke; He, Li-jiao; Yang, Jing; Zong, Nan; Yang, Feng; Gao, Hong-wei; Liu, Zhao; Yuan, Lei; Lan, Ying-jie; Bo, Yong; Peng, Qin-jun; Cui, Da-fu; Xu, Zu-yan

    2017-01-01

    We have demonstrated an electro-optically cavity-dumped mode-locked (CDML) picosecond Nd:YVO4 laser at 1342 nm with 880 nm diode-laser direct pumping. At a repetition rate of 10 kHz, an average output power of 0.119 W was achieved, corresponding to a pulse energy of 11.9 μJ. Compared with the continuous wave mode-locking pulse energy of 17.5 nJ, the CDML pulse energy was 680 times higher. The pulse width was measured to be 33.4 ps, resulting in the peak power of 356 kW. Meanwhile, the beam quality was nearly diffraction limited with an average beam quality factor M2 of 1.29.

  15. Calculation of Settings for the Control Systems of Insulation in Power Distribution Grids with Voltage of 6 or 10 kV in Conditions of Uncertainty

    NASA Astrophysics Data System (ADS)

    Sidorov, Aleksandr I.; Medvedeva, Yulia V.; Khanzhina, Olga A.

    2016-10-01

    The article deals with the calculation of setpoints for control systems insulation installed in all power distribution networks with voltage of 6 or 10 kV. It is shown that on the basis of fuzzy sets, the calculation of setpoints may be carried out even in the face of uncertainty. The efficiency of the system insulation monitoring based on measuring parameters of the electric network is largely determined by proper selection of the setpoint, i.e. the value of the insulation resistance of the network relative to the earth, in which it is necessary to disable a particular part of the network where a further reduction of the insulation resistance is unacceptable.

  16. Fluorescence excitation and emission spectra of 1,8-dihydroxyanthraquinone-d0 and -d2 in n-octane at 10 K

    NASA Astrophysics Data System (ADS)

    Smulevich, Giulietta; Foggi, Paolo; Feis, Alessandro; Marzocchi, Mario P.

    1987-11-01

    The fluorescence excitation and emission spectra in n-octane of 1,8-dihydroxyanthraquinone-d0 and -d2 at 10 K have been measured. Dual excitation and emission were observed as a consequence of excited state intramolecular proton transfer. A model, based on the Lippincott-Schroeder potential function, is proposed to predict the observed energy gaps and relative intensities of the transition. The isotopic effects are also explained. The Shpolskii matrices in n-octane show only one main site allowing a detailed vibrational analysis of the ground and the excited states. This furnished further evidence for the existence of excited state tautomers. The occurrence of an extra fluorescence was explained in terms of the ν(OH) stretching mode of the high frequency transition enhanced via vibronic coupling between the two ground states.

  17. A 10 kHz Sub-microsecond High-voltage Pulse Generator using SI Thyristor for Micro-plasma Jets Generation

    NASA Astrophysics Data System (ADS)

    Jia, Li; Sakai, Natsuko; Watanabe, Masato; Hotta, Eiki

    Employing an inductive energy storage system, a stable and high-repetitive sub-microsecond pulse generator is developed for generation of micro-plasma jets. Its operation is based on the current interruption by an SI Thyristor, coupled with MOSFETs connected in series. While being operated without loads, the pulse generator can reliably generate high-voltage pulses of ∼20 kV with pulse duration of about 400 ns at the repetition rate up to 10 kHz. At the operating frequency of 1 kHz, a maximal energy transfer efficiency of ∼57 % has been obtained with 3 kΩ resistor as a dummy load. Driven by this pulse generator, a 6 mm long N2 plasma plume at atmospheric pressure was successfully produced.

  18. A Genome-Wide Association Study for Agronomic Traits in Soybean Using SNP Markers and SNP-Based Haplotype Analysis

    PubMed Central

    de Oliveira, Marco Antônio Rott; Higashi, Wilson; Scapim, Carlos Alberto; Schuster, Ivan

    2017-01-01

    Mapping quantitative trait loci through the use of linkage disequilibrium (LD) in populations of unrelated individuals provides a valuable approach for dissecting the genetic basis of complex traits in soybean (Glycine max). The haplotype-based genome-wide association study (GWAS) has now been proposed as a complementary approach to intensify benefits from LD, which enable to assess the genetic determinants of agronomic traits. In this study a GWAS was undertaken to identify genomic regions that control 100-seed weight (SW), plant height (PH) and seed yield (SY) in a soybean association mapping panel using single nucleotide polymorphism (SNP) markers and haplotype information. The soybean cultivars (N = 169) were field-evaluated across four locations of southern Brazil. The genome-wide haplotype association analysis (941 haplotypes) identified eleven, seventeen and fifty-nine SNP-based haplotypes significantly associated with SY, SW and PH, respectively. Although most marker-trait associations were environment and trait specific, stable haplotype associations were identified for SY and SW across environments (i.e., haplotypes Gm12_Hap12). The haplotype block 42 on Chr19 (Gm19_Hap42) was confirmed to be associated with PH in two environments. These findings enable us to refine the breeding strategy for tropical soybean, which confirm that haplotype-based GWAS can provide new insights on the genetic determinants that are not captured by the single-marker approach. PMID:28152092

  19. 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

    2016-04-04

    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.

  20. SNP Discovery for mapping alien introgressions in wheat

    PubMed Central

    2014-01-01

    Background Monitoring alien introgressions in crop plants is difficult due to the lack of genetic and molecular mapping information on the wild crop relatives. The tertiary gene pool of wheat is a very important source of genetic variability for wheat improvement against biotic and abiotic stresses. By exploring the 5Mg short arm (5MgS) of Aegilops geniculata, we can apply chromosome genomics for the discovery of SNP markers and their use for monitoring alien introgressions in wheat (Triticum aestivum L). Results The short arm of chromosome 5Mg of Ae. geniculata Roth (syn. Ae. ovata L.; 2n = 4x = 28, UgUgMgMg) was flow-sorted from a wheat line in which it is maintained as a telocentric chromosome. DNA of the sorted arm was amplified and sequenced using an Illumina Hiseq 2000 with ~45x coverage. The sequence data was used for SNP discovery against wheat homoeologous group-5 assemblies. A total of 2,178 unique, 5MgS-specific SNPs were discovered. Randomly selected samples of 59 5MgS-specific SNPs were tested (44 by KASPar assay and 15 by Sanger sequencing) and 84% were validated. Of the selected SNPs, 97% mapped to a chromosome 5Mg addition to wheat (the source of t5MgS), and 94% to 5Mg introgressed from a different accession of Ae. geniculata substituting for chromosome 5D of wheat. The validated SNPs also identified chromosome segments of 5MgS origin in a set of T5D-5Mg translocation lines; eight SNPs (25%) mapped to TA5601 [T5DL · 5DS-5MgS(0.75)] and three (8%) to TA5602 [T5DL · 5DS-5MgS (0.95)]. SNPs (gsnp_5ms83 and gsnp_5ms94), tagging chromosome T5DL · 5DS-5MgS(0.95) with the smallest introgression carrying resistance to leaf rust (Lr57) and stripe rust (Yr40), were validated in two released germplasm lines with Lr57 and Yr40 genes. Conclusion This approach should be widely applicable for the identification of species/genome-specific SNPs. The development of a large number of SNP markers will facilitate the precise introgression and

  1. Development of maizeSNP3072, a high-throughput compatible SNP array, for DNA fingerprinting identification of Chinese maize varieties.

    PubMed

    Tian, Hong-Li; Wang, Feng-Ge; Zhao, Jiu-Ran; Yi, Hong-Mei; Wang, Lu; Wang, Rui; Yang, Yang; Song, Wei

    Single nucleotide polymorphisms (SNPs) are abundant and evenly distributed throughout the maize (Zea mays L.) genome. SNPs have several advantages over simple sequence repeats, such as ease of data comparison and integration, high-throughput processing of loci, and identification of associated phenotypes. SNPs are thus ideal for DNA fingerprinting, genetic diversity analysis, and marker-assisted breeding. Here, we developed a high-throughput and compatible SNP array, maizeSNP3072, containing 3072 SNPs developed from the maizeSNP50 array. To improve genotyping efficiency, a high-quality cluster file, maizeSNP3072_GT.egt, was constructed. All 3072 SNP loci were localized within different genes, where they were distributed in exons (43 %), promoters (21 %), 3' untranslated regions (UTRs; 22 %), 5' UTRs (9 %), and introns (5 %). The average genotyping failure rate using these SNPs was only 6 %, or 3 % using the cluster file to call genotypes. The genotype consistency of repeat sample analysis on Illumina GoldenGate versus Infinium platforms exceeded 96.4 %. The minor allele frequency (MAF) of the SNPs averaged 0.37 based on data from 309 inbred lines. The 3072 SNPs were highly effective for distinguishing among 276 examined hybrids. Comparative analysis using Chinese varieties revealed that the 3072SNP array showed a better marker success rate and higher average MAF values, evaluation scores, and variety-distinguishing efficiency than the maizeSNP50K array. The maizeSNP3072 array thus can be successfully used in DNA fingerprinting identification of Chinese maize varieties and shows potential as a useful tool for germplasm resource evaluation and molecular marker-assisted breeding.

  2. Linear reduction method for predictive and informative tag SNP selection.

    PubMed

    He, Jingwu; Westbrooks, Kelly; Zelikovsky, Alexander

    2005-01-01

    Constructing a complete human haplotype map is helpful when associating complex diseases with their related SNPs. Unfortunately, the number of SNPs is very large and it is costly to sequence many individuals. Therefore, it is desirable to reduce the number of SNPs that should be sequenced to a small number of informative representatives called tag SNPs. In this paper, we propose a new linear algebra-based method for selecting and using tag SNPs. We measure the quality of our tag SNP selection algorithm by comparing actual SNPs with SNPs predicted from selected linearly independent tag SNPs. Our experiments show that for sufficiently long haplotypes, knowing only 0.4% of all SNPs the proposed linear reduction method predicts an unknown haplotype with the error rate below 2% based on 10% of the population.

  3. Grouping preprocess for haplotype inference from SNP and CNV data

    NASA Astrophysics Data System (ADS)

    Shindo, Hiroyuki; Chigira, Hiroshi; Nagaoka, Tomoyo; Kamatani, Naoyuki; Inoue, Masato

    2009-12-01

    The method of statistical haplotype inference is an indispensable technique in the field of medical science. The authors previously reported Hardy-Weinberg equilibrium-based haplotype inference that could manage single nucleotide polymorphism (SNP) data. We recently extended the method to cover copy number variation (CNV) data. Haplotype inference from mixed data is important because SNPs and CNVs are occasionally in linkage disequilibrium. The idea underlying the proposed method is simple, but the algorithm for it needs to be quite elaborate to reduce the calculation cost. Consequently, we have focused on the details on the algorithm in this study. Although the main advantage of the method is accuracy, in that it does not use any approximation, its main disadvantage is still the calculation cost, which is sometimes intractable for large data sets with missing values.

  4. Authentication of medicinal plants by SNP-based multiplex PCR.

    PubMed

    Lee, Ok Ran; Kim, Min-Kyeoung; Yang, Deok-Chun

    2012-01-01

    Highly variable intergenic spacer and intron regions from nuclear and cytoplasmic DNA have been used for species identification. Noncoding internal transcribed spacers (ITSs) located in 18S-5.8S-26S, and 5S ribosomal RNA genes (rDNAs) represent suitable region for medicinal plant authentication. Noncoding regions from two cytoplasmic DNA, chloroplast DNA (trnT-F intergenic spacer region), and mitochondrial DNA (fourth intron region of nad7 gene) are also successfully applied for the proper identification of medicinal plants. Single-nucleotide polymorphism (SNP) sites obtained from the amplification of intergenic spacer and intron regions are properly utilized for the verification of medicinal plants in species level using multiplex PCR. Multiplex PCR as a variant of PCR technique used to amplify more than two loci simultaneously.

  5. Methods for the design, implementation, and analysis of illumina infinium™ SNP assays in plants.

    PubMed

    Chagné, David; Bianco, Luca; Lawley, Cindy; Micheletti, Diego; Jacobs, Jeanne M E

    2015-01-01

    The advent of Next-Generation sequencing-by-synthesis technologies has fuelled SNP discovery, genotyping, and screening of populations in myriad ways for many species, including various plant species. One technique widely applied to screening a large number of SNP markers over a large number of samples is the Illumina Infinium™ assay.

  6. A genome-wide SNP panel for genetic diversity, mapping and breeding studies in rice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A genome-wide SNP resource was developed for rice using the GoldenGate assay and used to genotype 400 landrace accessions of O. sativa. SNPs were originally discovered using Perlegen re-sequencing technology in 20 diverse landraces of O. sativa as part of OryzaSNP project (http://irfgc.irri.org). An...

  7. 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...

  8. 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.

  9. SNP uniqueness problem: a proof-of-principle in HapMap SNPs.

    PubMed

    Doron, Shany; Shweiki, Dorit

    2011-04-01

    SNP-based research strongly affects our biomedical and clinically associated knowledge. Nonunique and false-positive SNP existence in commonly used datasets may thus lead to biased, inaccurate clinically associated conclusions. We designed a computational study to reveal the degree of nonunique/false-positive SNPs in the HapMap dataset. Two sets of SNP flanking sequences were used as queries for BLAT analysis against the human genome. 4.2% and 11.9% of HapMap SNPs align to the genome nonuniquely (long and short, respectively). Furthermore, an average of 7.9% nonunique SNPs are included in common commercial genotyping arrays (according to our designed probes). Nonunique SNPs identified in this study are represented to various degrees in clinically associated databases, stressing the consequence of inaccurate SNP annotation and hence SNP utilization. Unfortunately, our results question some disease-related genotyping analyses, raising a worrisome concern on their validity.

  10. 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.

  11. Nitric-oxide planar laser-induced fluorescence at 10 kHz in a seeded flow, a plasma discharge, and a flame.

    PubMed

    Hammack, Stephen D; Carter, Campbell D; Gord, James R; Lee, Tonghun

    2012-12-20

    This study demonstrates high-repetition-rate planar laser-induced fluorescence (PLIF) imaging of both cold (~300 K) and hot (~2400 K) nitric oxide (NO) at a framing rate of 10 kHz. The laser system is composed of a frequency-doubled dye laser pumped by the third harmonic of a 10 kHz Nd:YAG laser to generate continuously pulsed laser radiation at 226 nm for excitation of NO. The laser-induced fluorescence signal is detected using a high-frame rate, intensified CMOS camera, yielding a continuous cinematographic propagation of the NO plume where data acquisition duration is limited only by camera memory. The pulse energy of the beam is ~20 μJ with a spectral width ~0.15 cm(-1), though energies as high as 40 μJ were generated. Hot NO is generated by passing air through a DC transient-arc plasma torch that dissociates air. The plasma torch is also used to ignite and sustain a CH(4)/air premixed flame. Cold NO is imaged from a 1% NO flow (buffered by nitrogen). The estimated signal-to-noise ratio (SNR) for the cold seeded flow and air plasma exceeds 50 with expected NO concentrations of 6000-8000 parts per million (ppm, volume basis). Images show distinct, high-contrast boundaries. The plasma-assisted flame images have an SNR of less than 10 for concentrations reaching 1000 ppm. For many combustion applications, the pulse energy is insufficient for PLIF measurements. However, the equipment and strategies herein could be applied to high-frequency line imaging of NO at concentrations of 10-100 ppm. Generation of 226 nm radiation was also performed using sum-frequency mixing of the 532 nm pumped dye laser and 355 nm Nd:YAG third harmonic but was limited in energy to 14 μJ. Frequency tripling a 532 nm pumped dye laser produced 226 nm radiation at energies comparable to the 355 nm pumping scheme.

  12. 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

  13. 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).

  14. Final report on key comparison CCAUV.A-K5: pressure calibration of laboratory standard microphones in the frequency range 2 Hz to 10 kHz

    NASA Astrophysics Data System (ADS)

    Avison, Janine; Barham, Richard

    2014-01-01

    This document and the accompanying spreadsheets constitute the final report for key comparison CCAUV.A-K5 on the pressure calibration of laboratory standard microphones in the frequency range from 2 Hz to 10 kHz. Twelve national measurement institutes took part in the key comparison and the National Physical Laboratory piloted the project. Two laboratory standard microphones IEC type LS1P were circulated to the participants and results in the form of regular calibration certificates were collected throughout the project. One of the microphones was subsequently deemed to have compromised stability for the purpose of deriving a reference value. Consequently the key comparison reference value (KCRV) has been made based on the weighted mean results for sensitivity level and for sensitivity phase from just one of the microphones. Corresponding degrees of equivalence (DoEs) have also been calculated and are presented. 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).

  15. Tissue-specific expression, hormonal regulation and 5'-flanking gene region of the rat Clara cell 10 kDa protein: comparison to rabbit uteroglobin.

    PubMed Central

    Hagen, G; Wolf, M; Katyal, S L; Singh, G; Beato, M; Suske, G

    1990-01-01

    The amino acid sequence of rat Clara Cell 10 kDa secretory protein (CC10) shows 55% identity to rabbit uteroglobin. In order to define the relationship between rat CC10 and rabbit uteroglobin in detail, the tissue-specific expression and hormonal regulation of rat CC10 mRNA was analyzed. We report that like rabbit uteroglobin, rat CC10 mRNA is expressed in lung and esophagus, as well as in uteri of estrogen- and progesterone-treated females. Expression of CC10 mRNA in lung is regulated by glucocorticoids. The similarity in expression pattern of rat CC10 mRNA and rabbit uteroglobin mRNA is reflected by a striking similarity in the 5'-flanking regions of the two genes. Despite this overall similarity, two regions of 0.3 kb and 2.1 kb are absent in the rat CC10 upstream gene region. The larger region includes a cluster of hormone receptor binding sites, believed to be responsible for differential regulation of rabbit uteroglobin by glucocorticoids and progesterone. Thus, while the sequence identities in the coding and 5'-flanking regions point towards a common ancestor for the uteroglobin and CC10 gene, later events (deletions/insertions) might have caused species-specific differences in their regulation. Images PMID:2349092

  16. Crystallization and X-ray data analysis of the 10 kDa C-terminal lid subdomain from Caenorhabditis elegans Hsp70.

    PubMed

    Worrall, Liam; Walkinshaw, Malcolm D

    2006-09-01

    Hsp70 is an important molecular chaperone involved in the regulation of protein folding. Crystals of the C-terminal 10 kDa helical lid domain (residues 542-640) from a Caenorhabditis elegans Hsp70 homologue have been produced that diffract X-rays to approximately 3.4 A. Crystals belong to space group I2(1)2(1)2(1), with unit-cell parameters a = b = 197, c = 200 A. The Matthews coefficient, self-rotation function and Patterson map indicate 24 monomers in the asymmetric unit, showing non-crystallographic 432 symmetry. Molecular-replacement studies using the corresponding domain from rat, the only eukaryotic homologue with a known structure, failed and a mercury derivative was obtained. Preliminary MAD phasing using SHELXD and SHARP for location and refinement of the heavy-atom substructure and SOLOMON for density modification produced interpretable maps with a clear protein-solvent boundary. Further density-modification, model-building and refinement are currently under way.

  17. Analysis of population structure and genetic history of cattle breeds based on high-density SNP data

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Advances in single nucleotide polymorphism (SNP) genotyping microarrays have facilitated a new understanding of population structure and evolutionary history for several species. Most existing studies in livestock were based on low density SNP arrays. The first wave of low density SNP studies on cat...

  18. Rice SNP-seek database update: new SNPs, indels, and queries

    PubMed Central

    Mansueto, Locedie; Fuentes, Roven Rommel; Borja, Frances Nikki; Detras, Jeffery; Abriol-Santos, Juan Miguel; Chebotarov, Dmytro; Sanciangco, Millicent; Palis, Kevin; Copetti, Dario; Poliakov, Alexandre; Dubchak, Inna; Solovyev, Victor; Wing, Rod A.; Hamilton, Ruaraidh Sackville; Mauleon, Ramil; McNally, Kenneth L.; Alexandrov, Nickolai

    2017-01-01

    We describe updates to the Rice SNP-Seek Database since its first release. We ran a new SNP-calling pipeline followed by filtering that resulted in complete, base, filtered and core SNP datasets. Besides the Nipponbare reference genome, the pipeline was run on genome assemblies of IR 64, 93-11, DJ 123 and Kasalath. New genotype query and display features are added for reference assemblies, SNP datasets and indels. JBrowse now displays BAM, VCF and other annotation tracks, the additional genome assemblies and an embedded VISTA genome comparison viewer. Middleware is redesigned for improved performance by using a hybrid of HDF5 and RDMS for genotype storage. Query modules for genotypes, varieties and genes are improved to handle various constraints. An integrated list manager allows the user to pass query parameters for further analysis. The SNP Annotator adds traits, ontology terms, effects and interactions to markers in a list. Web-service calls were implemented to access most data. These features enable seamless querying of SNP-Seek across various biological entities, a step toward semi-automated gene-trait association discovery. URL: http://snp-seek.irri.org. PMID:27899667

  19. Rice SNP-seek database update: new SNPs, indels, and queries.

    PubMed

    Mansueto, Locedie; Fuentes, Roven Rommel; Borja, Frances Nikki; Detras, Jeffery; Abriol-Santos, Juan Miguel; Chebotarov, Dmytro; Sanciangco, Millicent; Palis, Kevin; Copetti, Dario; Poliakov, Alexandre; Dubchak, Inna; Solovyev, Victor; Wing, Rod A; Hamilton, Ruaraidh Sackville; Mauleon, Ramil; McNally, Kenneth L; Alexandrov, Nickolai

    2017-01-04

    We describe updates to the Rice SNP-Seek Database since its first release. We ran a new SNP-calling pipeline followed by filtering that resulted in complete, base, filtered and core SNP datasets. Besides the Nipponbare reference genome, the pipeline was run on genome assemblies of IR 64, 93-11, DJ 123 and Kasalath. New genotype query and display features are added for reference assemblies, SNP datasets and indels. JBrowse now displays BAM, VCF and other annotation tracks, the additional genome assemblies and an embedded VISTA genome comparison viewer. Middleware is redesigned for improved performance by using a hybrid of HDF5 and RDMS for genotype storage. Query modules for genotypes, varieties and genes are improved to handle various constraints. An integrated list manager allows the user to pass query parameters for further analysis. The SNP Annotator adds traits, ontology terms, effects and interactions to markers in a list. Web-service calls were implemented to access most data. These features enable seamless querying of SNP-Seek across various biological entities, a step toward semi-automated gene-trait association discovery. URL: http://snp-seek.irri.org.

  20. Identification, validation and survey of a single nucleotide polymorphism (SNP) associated with pungency in Capsicum spp.

    PubMed

    Garcés-Claver, Ana; Fellman, Shanna Moore; Gil-Ortega, Ramiro; Jahn, Molly; Arnedo-Andrés, María S

    2007-11-01

    A single nucleotide polymorphism (SNP) associated with pungency was detected within an expressed sequence tag (EST) of 307 bp. This fragment was identified after expression analysis of the EST clone SB2-66 in placenta tissue of Capsicum fruits. Sequence alignments corresponding to this new fragment allowed us to identify an SNP between pungent and non-pungent accessions. Two methods were chosen for the development of the SNP marker linked to pungency: tetra-primer amplification refractory mutation system-PCR (tetra-primer ARMS-PCR) and cleaved amplified polymorphic sequence. Results showed that both methods were successful in distinguishing genotypes. Nevertheless, tetra-primer ARMS-PCR was chosen for SNP genotyping because it was more rapid, reliable and less cost-effective. The utility of this SNP marker for pungency was demonstrated by the ability to distinguish between 29 pungent and non-pungent cultivars of Capsicum annuum. In addition, the SNP was also associated with phenotypic pungent character in the tested genotypes of C. chinense, C. baccatum, C. frutescens, C. galapagoense, C. eximium, C. tovarii and C. cardenasi. This SNP marker is a faster, cheaper and more reproducible method for identifying pungent peppers than other techniques such as panel tasting, and allows rapid screening of the trait in early growth stages.

  1. QuickSNP: an automated web server for selection of tagSNPs

    PubMed Central

    Grover, Deepak; Woodfield, Alonzo S.; Verma, Ranjana; Zandi, Peter P.; Levinson, Douglas F.; Potash, James B.

    2007-01-01

    Although large-scale genetic association studies involving hundreds to thousands of SNPs have become feasible, the associated cost is substantial. Even with the increased efficiency introduced by the use of tagSNPs, researchers are often seeking ways to maximize resource utilization given a set of SNP-based gene-mapping goals. We have developed a web server named QuickSNP in order to provide cost-effective selection of SNPs, and to fill in some of the gaps in existing SNP selection tools. One useful feature of QuickSNP is the option to select only gene-centric SNPs from a chromosomal region in an automated fashion. Other useful features include automated selection of coding non-synonymous SNPs, SNP filtering based on inter-SNP distances and information regarding the availability of genotyping assays for SNPs and whether they are present on whole genome chips. The program produces user-friendly summary tables and results, and a link to a UCSC Genome Browser track illustrating the position of the selected tagSNPs in relation to genes and other genomic features. We hope the unique combination of features of this server will be useful for researchers aiming to select markers for their genotyping studies. The server is freely available and can be accessed at the URL http://bioinformoodics.jhmi.edu/quickSNP.pl. PMID:17517769

  2. Exploring of new Y-chromosome SNP loci using Pyrosequencing and the SNaPshot methods.

    PubMed

    Wei, Wei; Luo, Hai-Bo; Yan, Jing; Hou, Yi-Ping

    2012-11-01

    The single nucleotide polymorphisms on the Y chromosome (Y-SNP) have been considered to be important in forensic casework. However, Y-SNP loci were mostly population specific and lacked biallelic polymorphisms in the Asian population. In this study, we developed a strategy for seeking and genotyping new Y-SNP markers based on both Pyrosequencing and the SNaPshot methods. As results, 34 new biallelic markers were observed to be polymorphic in the Chinese Han population by estimation of allele frequencies of 103 candidate's Y-SNP loci in DNA pools using Pyrosequencing technology. Then, a multiplex system with 20 Y-SNP loci was genotyped using the SNaPshot™ multiplex kit. Twenty Y-SNP loci defined 56 different haplotypes, and the haplotype diversity was estimated to be 0.9539. Our result demonstrated that the strategy could be used as an efficient tool to search and genotype biallelic markers from a large amount of candidate loci. In addition, 20 Y-SNP loci constructed a multiplex system, which could provide supplementary information for forensic identification.

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

    PubMed Central

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

    2013-01-01

    Motivation: The use of dense single nucleotide polymorphism (SNP) data in genetic linkage analysis of large pedigrees is impeded by significant technical, methodological and computational challenges. Here we describe Superlink-Online SNP, a new powerful online system that streamlines the linkage analysis of SNP data. It features a fully integrated flexible processing workflow comprising both well-known and novel data analysis tools, including SNP clustering, erroneous data filtering, exact and approximate LOD calculations and maximum-likelihood haplotyping. The system draws its power from thousands of CPUs, performing data analysis tasks orders of magnitude faster than a single computer. By providing an intuitive interface to sophisticated state-of-the-art analysis tools coupled with high computing capacity, Superlink-Online SNP helps geneticists unleash the potential of SNP data for detecting disease genes. Results: Computations performed by Superlink-Online SNP are automatically parallelized using novel paradigms, and executed on unlimited number of private or public CPUs. One novel service is large-scale approximate Markov Chain–Monte Carlo (MCMC) analysis. The accuracy of the results is reliably estimated by running the same computation on multiple CPUs and evaluating the Gelman–Rubin Score to set aside unreliable results. Another service within the workflow is a novel parallelized exact algorithm for inferring maximum-likelihood haplotyping. The reported system enables genetic analyses that were previously infeasible. We demonstrate the system capabilities through a study of a large complex pedigree affected with metabolic syndrome. Availability: Superlink-Online SNP is freely available for researchers at http://cbl-hap.cs.technion.ac.il/superlink-snp. The system source code can also be downloaded from the system website. Contact: omerw@cs.technion.ac.il Supplementary information: Supplementary data are available at Bioinformatics online. PMID:23162081

  4. 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.

  5. SNP-SNP interactions between WNT4 and WNT5A were associated with obesity related traits in Han Chinese Population

    PubMed Central

    Dong, Shan-Shan; Hu, Wei-Xin; Yang, Tie-Lin; Chen, Xiao-Feng; Yan, Han; Chen, Xiang-Ding; Tan, Li-Jun; Tian, Qing; Deng, Hong-Wen; Guo, Yan

    2017-01-01

    Considering the biological roles of WNT4 and WNT5A involved in adipogenesis, we aimed to investigate whether SNPs in WNT4 and WNT5A contribute to obesity related traits in Han Chinese population. Targeted genomic sequence for WNT4 and WNT5A was determined in 100 Han Chinese subjects and tag SNPs were selected. Both single SNP and SNP × SNP interaction association analyses with body mass index (BMI) were evaluated in the 100 subjects and another independent sample of 1,627 Han Chinese subjects. Meta-analyses were performed and multiple testing corrections were carried out using the Bonferroni method. Consistent with the Genetic Investigation of ANthropometric Traits (GIANT) dataset results, we didn’t detect significant association signals in single SNP association analyses. However, the interaction between rs2072920 and rs11918967, was associated with BMI after multiple testing corrections (combined P = 2.20 × 10−4). The signal was also significant in each contributing data set. SNP rs2072920 is located in the 3′-UTR of WNT4 and SNP rs11918967 is located in the intron of WNT5A. Functional annotation results revealed that both SNPs might be involved in transcriptional regulation of gene expression. Our results suggest that a combined effect of SNPs via WNT4-WNT5A interaction may affect the variation of BMI in Han Chinese population. PMID:28272483

  6. 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.

  7. 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

  8. Rapid SNP Detection and Genotyping of Bacterial Pathogens by Pyrosequencing.

    PubMed

    Amoako, Kingsley K; Thomas, Matthew C; Janzen, Timothy W; Goji, Noriko

    2017-01-01

    Bacterial identification and typing are fixtures of microbiology laboratories and are vital aspects of our response mechanisms in the event of foodborne outbreaks and bioterrorist events. Whole genome sequencing (WGS) is leading the way in terms of expanding our ability to identify and characterize bacteria through the identification of subtle differences between genomes (e.g. single nucleotide polymorphisms (SNPs) and insertions/deletions). Modern high-throughput technologies such as pyrosequencing can facilitate the typing of bacteria by generating short-read sequence data of informative regions identified by WGS analyses, at a fraction of the cost of WGS. Thus, pyrosequencing systems remain a valuable asset in the laboratory today. Presented in this chapter are two methods developed in the Amoako laboratory that detail the identification and genotyping of bacterial pathogens. The first targets canonical single nucleotide polymorphisms (canSNPs) of evolutionary importance in Bacillus anthracis, the causative agent of Anthrax. The second assay detects Shiga-toxin (stx) genes, which are associated with virulence in Escherichia coli and Shigella spp., and differentiates the subtypes of stx-1 and stx-2 based on SNP loci. These rapid methods provide end users with important information regarding virulence traits as well as the evolutionary and biogeographic origin of isolates.

  9. SNP Markers as Additional Information to Resolve Complex Kinship Cases

    PubMed Central

    Pontes, M. Lurdes; Fondevila, Manuel; Laréu, Maria Victoria; Medeiros, Rui

    2015-01-01

    Summary Background DNA profiling with sets of highly polymorphic autosomal short tandem repeat (STR) markers has been applied in various aspects of human identification in forensic casework for nearly 20 years. However, in some cases of complex kinship investigation, the information provided by the conventionally used STR markers is not enough, often resulting in low likelihood ratio (LR) calculations. In these cases, it becomes necessary to increment the number of loci under analysis to reach adequate LRs. Recently, it has been proposed that single nucleotide polymorphisms (SNPs) could be used as a supportive tool to STR typing, eventually even replacing the methods/markers now employed. Methods In this work, we describe the results obtained in 7 revised complex paternity cases when applying a battery of STRs, as well as 52 human identification SNPs (SNPforID 52plex identification panel) using a SNaPshot methodology followed by capillary electrophoresis. Results Our results show that the analysis of SNPs, as complement to STR typing in forensic casework applications, would at least increase by a factor of 4 total PI values and correspondent Essen-Möller's W value. Conclusions We demonstrated that SNP genotyping could be a key complement to STR information in challenging casework of disputed paternity, such as close relative individualization or complex pedigrees subject to endogamous relations. PMID:26733770

  10. Using Mendelian inheritance to improve high-throughput SNP discovery.

    PubMed

    Chen, Nancy; Van Hout, Cristopher V; Gottipati, Srikanth; Clark, Andrew G

    2014-11-01

    Restriction site-associated DNA sequencing or genotyping-by-sequencing (GBS) approaches allow for rapid and cost-effective discovery and genotyping of thousands of single-nucleotide polymorphisms (SNPs) in multiple individuals. However, rigorous quality control practices are needed to avoid high levels of error and bias with these reduced representation methods. We developed a formal statistical framework for filtering spurious loci, using Mendelian inheritance patterns in nuclear families, that accommodates variable-quality genotype calls and missing data--both rampant issues with GBS data--and for identifying sex-linked SNPs. Simulations predict excellent performance of both the Mendelian filter and the sex-linkage assignment under a variety of conditions. We further evaluate our method by applying it to real GBS data and validating a subset of high-quality SNPs. These results demonstrate that our metric of Mendelian inheritance is a powerful quality filter for GBS loci that is complementary to standard coverage and Hardy-Weinberg filters. The described method, implemented in the software MendelChecker, will improve quality control during SNP discovery in nonmodel as well as model organisms.

  11. Imputation of KIR Types from SNP Variation Data

    PubMed Central

    Vukcevic, Damjan; Traherne, James A.; Næss, Sigrid; Ellinghaus, Eva; Kamatani, Yoichiro; Dilthey, Alexander; Lathrop, Mark; Karlsen, Tom H.; Franke, Andre; Moffatt, Miriam; Cookson, William; Trowsdale, John; McVean, Gil; Sawcer, Stephen; Leslie, Stephen

    2015-01-01

    Large population studies of immune system genes are essential for characterizing their role in diseases, including autoimmune conditions. Of key interest are a group of genes encoding the killer cell immunoglobulin-like receptors (KIRs), which have known and hypothesized roles in autoimmune diseases, resistance to viruses, reproductive conditions, and cancer. These genes are highly polymorphic, which makes typing expensive and time consuming. Consequently, despite their importance, KIRs have been little studied in large cohorts. Statistical imputation methods developed for other complex loci (e.g., human leukocyte antigen [HLA]) on the basis of SNP data provide an inexpensive high-throughput alternative to direct laboratory typing of these loci and have enabled important findings and insights for many diseases. We present KIR∗IMP, a method for imputation of KIR copy number. We show that KIR∗IMP is highly accurate and thus allows the study of KIRs in large cohorts and enables detailed investigation of the role of KIRs in human disease. PMID:26430804

  12. 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.

  13. 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.

  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. 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.

  16. 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.

  17. Development and Evaluation of a 9K SNP Array for Peach by Internationally Coordinated SNP Detection and Validation in Breeding Germplasm

    PubMed Central

    Scalabrin, Simone; Gilmore, Barbara; Lawley, Cynthia T.; Gasic, Ksenija; Micheletti, Diego; Rosyara, Umesh R.; Cattonaro, Federica; Vendramin, Elisa; Main, Dorrie; Aramini, Valeria; Blas, Andrea L.; Mockler, Todd C.; Bryant, Douglas W.; Wilhelm, Larry; Troggio, Michela; Sosinski, Bryon; Aranzana, Maria José; Arús, Pere; Iezzoni, Amy; Morgante, Michele; Peace, Cameron

    2012-01-01

    Although a large number of single nucleotide polymorphism (SNP) markers covering the entire genome are needed to enable molecular breeding efforts such as genome wide association studies, fine mapping, genomic selection and marker-assisted selection in peach [Prunus persica (L.) Batsch] and related Prunus species, only a limited number of genetic markers, including simple sequence repeats (SSRs), have been available to date. To address this need, an international consortium (The International Peach SNP Consortium; IPSC) has pursued a coordinated effort to perform genome-scale SNP discovery in peach using next generation sequencing platforms to develop and characterize a high-throughput Illumina Infinium® SNP genotyping array platform. We performed whole genome re-sequencing of 56 peach breeding accessions using the Illumina and Roche/454 sequencing technologies. Polymorphism detection algorithms identified a total of 1,022,354 SNPs. Validation with the Illumina GoldenGate® assay was performed on a subset of the predicted SNPs, verifying ∼75% of genic (exonic and intronic) SNPs, whereas only about a third of intergenic SNPs were verified. Conservative filtering was applied to arrive at a set of 8,144 SNPs that were included on the IPSC peach SNP array v1, distributed over all eight peach chromosomes with an average spacing of 26.7 kb between SNPs. Use of this platform to screen a total of 709 accessions of peach in two separate evaluation panels identified a total of 6,869 (84.3%) polymorphic SNPs. The almost 7,000 SNPs verified as polymorphic through extensive empirical evaluation represent an excellent source of markers for future studies in genetic relatedness, genetic mapping, and dissecting the genetic architecture of complex agricultural traits. The IPSC peach SNP array v1 is commercially available and we expect that it will be used worldwide for genetic studies in peach and related stone fruit and nut species. PMID:22536421

  18. 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.

  19. A user guide to the Brassica 60K Illumina Infinium™ SNP genotyping array.

    PubMed

    Mason, Annaliese S; Higgins, Erin E; Snowdon, Rod J; Batley, Jacqueline; Stein, Anna; Werner, Christian; Parkin, Isobel A P

    2017-02-20

    The Brassica napus 60K Illumina Infinium™ SNP array has had huge international uptake in the rapeseed community due to the revolutionary speed of acquisition and ease of analysis of this high-throughput genotyping data, particularly when coupled with the newly available reference genome sequence. However, further utilization of this valuable resource can be optimized by better understanding the promises and pitfalls of SNP arrays. We outline how best to analyze Brassica SNP marker array data for diverse applications, including linkage and association mapping, genetic diversity and genomic introgression studies. We present data on which SNPs are locus-specific in winter, semi-winter and spring B. napus germplasm pools, rather than amplifying both an A-genome and a C-genome locus or multiple loci. Common issues that arise when analyzing array data will be discussed, particularly those unique to SNP markers and how to deal with these for practical applications in Brassica breeding applications.

  20. Use of molecular variation in the NCBI dbSNP database.

    PubMed

    Sherry, S T; Ward, M; Sirotkin, K

    2000-01-01

    While high quality information regarding variation in genes is currently available in locus-specific or specialized mutation databases, the need remains for a general catalog of genome variation to address the large-scale sampling designs required by association studies, gene mapping, and evolutionary biology. In response to this need, the National Center for Biotechnology Information (NCBI) has established the dbSNP database http://ncbi. nlm.nih.gov/SNP/ to serve as a generalized, central variation database. Submissions to dbSNP will be integrated with other sources of information at NCBI such as GenBank, PubMed, LocusLink, and the Human Genome Project data, and the complete contents of dbSNP are available to the public via anonymous FTP. Hum Mutat 15:68-75, 2000. Published 2000 Wiley-Liss, Inc.

  1. Set up of cutoff thresholds for kinship determination using SNP loci.

    PubMed

    Cho, Sohee; Shin, Eun Soon; Yu, Hyung Jin; Lee, Ji Hyun; Seo, Hee Jin; Kim, Moon Young; Lee, Soong Deok

    2017-03-08

    The usefulness of single nucleotide polymorphism (SNP) loci for kinship testing has been demonstrated in many case works, and suggested as a promising marker for relationship identification. For interpreting results based on the calculation of the likelihood ratio (LR) in kinship testing, it is important to prepare cutoffs for respective relatives which are dependent on genetic relatedness. For this, analysis using true pedigree data is significant and reliable as it reflects the actual frequencies of markers in the population. In this study, the kinship index was explored through 1209 parent-child pairs, 1373 full sibling pairs, and 247 uncle-nephew pairs using 136 SNP loci. The cutoffs for LR were set up using different numbers of SNP loci with accuracy, sensitivity, and specificity. It is expected that this study can support the application of SNP loci-based kinship testing for various relationships.

  2. SNP discovery and genotyping using Genotyping-by-Sequencing in Pekin ducks

    PubMed Central

    Zhu, Feng; Cui, Qian-Qian; Hou, Zhuo-Cheng

    2016-01-01

    Genomic selection and genome-wide association studies need thousands to millions of SNPs. However, many non-model species do not have reference chips for detecting variation. Our goal was to develop and validate an inexpensive but effective method for detecting SNP variation. Genotyping by sequencing (GBS) can be a highly efficient strategy for genome-wide SNP detection, as an alternative to microarray chips. Here, we developed a GBS protocol for ducks and tested it to genotype 49 Pekin ducks. A total of 169,209 SNPs were identified from all animals, with a mean of 55,920 SNPs per individual. The average SNP density reached 1156 SNPs/MB. In this study, the first application of GBS to ducks, we demonstrate the power and simplicity of this method. GBS can be used for genetic studies in to provide an effective method for genome-wide SNP discovery. PMID:27845353

  3. Gene-Environment Interaction in the Etiology of Mathematical Ability Using SNP Sets

    PubMed Central

    Kovas, Yulia; Plomin, Robert

    2010-01-01

    Mathematics ability and disability is as heritable as other cognitive abilities and disabilities, however its genetic etiology has received relatively little attention. In our recent genome-wide association study of mathematical ability in 10-year-old children, 10 SNP associations were nominated from scans of pooled DNA and validated in an individually genotyped sample. In this paper, we use a ‘SNP set’ composite of these 10 SNPs to investigate gene-environment (GE) interaction, examining whether the association between the 10-SNP set and mathematical ability differs as a function of ten environmental measures in the home and school in a sample of 1888 children with complete data. We found two significant GE interactions for environmental measures in the home and the school both in the direction of the diathesis-stress type of GE interaction: The 10-SNP set was more strongly associated with mathematical ability in chaotic homes and when parents are negative. PMID:20978832

  4. Evaluation of breast cancer susceptibility using improved genetic algorithms to generate genotype SNP barcodes.

    PubMed

    Yang, Cheng-Hong; Lin, Yu-Da; Chuang, Li-Yeh; Chang, Hsueh-Wei

    2013-01-01

    Genetic association is a challenging task for the identification and characterization of genes that increase the susceptibility to common complex multifactorial diseases. To fully execute genetic studies of complex diseases, modern geneticists face the challenge of detecting interactions between loci. A genetic algorithm (GA) is developed to detect the association of genotype frequencies of cancer cases and noncancer cases based on statistical analysis. An improved genetic algorithm (IGA) is proposed to improve the reliability of the GA method for high-dimensional SNP-SNP interactions. The strategy offers the top five results to the random population process, in which they guide the GA toward a significant search course. The IGA increases the likelihood of quickly detecting the maximum ratio difference between cancer cases and noncancer cases. The study systematically evaluates the joint effect of 23 SNP combinations of six steroid hormone metabolisms, and signaling-related genes involved in breast carcinogenesis pathways were systematically evaluated, with IGA successfully detecting significant ratio differences between breast cancer cases and noncancer cases. The possible breast cancer risks were subsequently analyzed by odds-ratio (OR) and risk-ratio analysis. The estimated OR of the best SNP barcode is significantly higher than 1 (between 1.15 and 7.01) for specific combinations of two to 13 SNPs. Analysis results support that the IGA provides higher ratio difference values than the GA between breast cancer cases and noncancer cases over 3-SNP to 13-SNP interactions. A more specific SNP-SNP interaction profile for the risk of breast cancer is also provided.

  5. Prim-SNPing: a primer designer for cost-effective SNP genotyping.

    PubMed

    Chang, Hsueh-Wei; Chuang, Li-Yeh; Cheng, Yu-Huei; Hung, Yu-Chen; Wen, Cheng-Hao; Gu, De-Leung; Yang, Cheng-Hong

    2009-05-01

    Many kinds of primer design (PD) software tools have been developed, but most of them lack a single nucleotide polymorphism (SNP) genotyping service. Here, we introduce the web-based freeware "Prim-SNPing," which, in addition to general PD, provides three kinds of primer design functions for cost-effective SNP genotyping: natural PD, mutagenic PD, and confronting two-pair primers (CTPP) PD. The natural PD and mutagenic PD provide primers and restriction enzyme mining for polymerase chain reaction-restriction fragment of length polymorphism (PCR-RFLP), while CTPP PD provides primers for restriction enzyme-free SNP genotyping. The PCR specificity and efficiency of the designed primers are improved by BLAST searching and evaluating secondary structure (such as GC clamps, dimers, and hairpins), respectively. The length pattern of PCR-RFLP using natural PD is user-adjustable, and the restriction sites of the RFLP enzymes provided by Prim-SNPing are confirmed to be absent within the generated PCR product. In CTPP PD, the need for a separate digestion step in RFLP is eliminated, thus making it faster and cheaper. The output of Prim-SNPing includes the primer list, melting temperature (Tm) value, GC percentage, and amplicon size with enzyme digestion information. The reference SNP (refSNP, or rs) clusters from the Single Nucleotide Polymorphism database (dbSNP) at the National Center for Biotechnology Information (NCBI), and multiple other formats of human, mouse, and rat SNP sequences are acceptable input. In summary, Prim-SNPing provides interactive, user-friendly and cost-effective primer design for SNP genotyping. It is freely available at http://bio.kuas.edu.tw/prim-snping.

  6. 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

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

    NASA Astrophysics Data System (ADS)

    Park, Jae-Wan; Park, Cheol-Min

    2016-10-01

    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.

  8. SNP-based prediction of the human germ cell methylation landscape.

    PubMed

    Xie, Hehuang; Wang, Min; Bischof, Jared; Bonaldo, Maria de Fatima; Soares, Marcelo Bento

    2009-05-01

    Base substitution occurs at a high rate at CpG dinucleotides due to the frequent methylation of CpG and the deamination of methylated cytosine to thymine. If these substitutions occur in germ cells, they constitute a heritable mutation that may eventually rise to polymorphic frequencies, hence resulting in a SNP that is methylation associated. In this study, we sought to identify clusters of methylation associated SNPs as a basis for prediction of methylation landscapes of germ cell genomes. Genomic regions enriched with methylation associated SNPs, namely "methylation associated SNP clusters", were identified with an agglomerative hierarchical clustering algorithm. Repetitive elements, segmental duplications, and syntenic tandem DNA repeats were enriched in methylation associated SNP clusters. The frequency of methylation associated SNPs in Alu Y/S elements exhibited a gradient pattern suggestive of linear spreading, being higher in proximity to methylation associated SNP clusters and lower closer to CpG islands. Interestingly, methylation associated SNP clusters were over-represented near the transcriptional initiation sites of immune response genes. We propose a de novo DNA methylation model during germ cell development whereby a pattern is established by long-range chromatic interactions through syntenic repeats combined with regional methylation spreading from methylation associated SNP clusters.

  9. SNP2TFBS – a database of regulatory SNPs affecting predicted transcription factor binding site affinity

    PubMed Central

    Kumar, Sunil; Ambrosini, Giovanna; Bucher, Philipp

    2017-01-01

    SNP2TFBS is a computational resource intended to support researchers investigating the molecular mechanisms underlying regulatory variation in the human genome. The database essentially consists of a collection of text files providing specific annotations for human single nucleotide polymorphisms (SNPs), namely whether they are predicted to abolish, create or change the affinity of one or several transcription factor (TF) binding sites. A SNP's effect on TF binding is estimated based on a position weight matrix (PWM) model for the binding specificity of the corresponding factor. These data files are regenerated at regular intervals by an automatic procedure that takes as input a reference genome, a comprehensive SNP catalogue and a collection of PWMs. SNP2TFBS is also accessible over a web interface, enabling users to view the information provided for an individual SNP, to extract SNPs based on various search criteria, to annotate uploaded sets of SNPs or to display statistics about the frequencies of binding sites affected by selected SNPs. Homepage: http://ccg.vital-it.ch/snp2tfbs/. PMID:27899579

  10. 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.

  11. SNP2TFBS - a database of regulatory SNPs affecting predicted transcription factor binding site affinity.

    PubMed

    Kumar, Sunil; Ambrosini, Giovanna; Bucher, Philipp

    2017-01-04

    SNP2TFBS is a computational resource intended to support researchers investigating the molecular mechanisms underlying regulatory variation in the human genome. The database essentially consists of a collection of text files providing specific annotations for human single nucleotide polymorphisms (SNPs), namely whether they are predicted to abolish, create or change the affinity of one or several transcription factor (TF) binding sites. A SNP's effect on TF binding is estimated based on a position weight matrix (PWM) model for the binding specificity of the corresponding factor. These data files are regenerated at regular intervals by an automatic procedure that takes as input a reference genome, a comprehensive SNP catalogue and a collection of PWMs. SNP2TFBS is also accessible over a web interface, enabling users to view the information provided for an individual SNP, to extract SNPs based on various search criteria, to annotate uploaded sets of SNPs or to display statistics about the frequencies of binding sites affected by selected SNPs. Homepage: http://ccg.vital-it.ch/snp2tfbs/.

  12. The influence of 1-10 kD fraction from brains of the hibernating ground squirrel and the Yakut horse on proliferation and protein synthesizing system of Ehrlich ascitic carcinoma cells.

    PubMed

    Gulevsky, A K; Grischenko, V I; Tereschenko, O S; Shchenyavcky, I J

    2005-01-01

    The experimental data presented in the work testify to the cytostatic activity of 1-10 kD polypeptide fractions from brains of the hibernating ground squirrel and the Yakut horse towards Ehrlich ascitic carcinoma (EAC) cells. The experiments on the investigation of the inhibiting influence of 1-10 kD fractions from tissues of the hibernating and cold-adapted animals on protein-synthesizing system of EAC cells allow us to conclude that the cytostatic effect of the fractions is effected at the genetic level in the tumor cells.

  13. 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

  14. 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

  15. 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

  16. 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

  17. Generation of SNP datasets for orangutan population genomics using improved reduced-representation sequencing and direct comparisons of SNP calling algorithms

    PubMed Central

    2014-01-01

    Background High-throughput sequencing has opened up exciting possibilities in population and conservation genetics by enabling the assessment of genetic variation at genome-wide scales. One approach to reduce genome complexity, i.e. investigating only parts of the genome, is reduced-representation library (RRL) sequencing. Like similar approaches, RRL sequencing reduces ascertainment bias due to simultaneous discovery and genotyping of single-nucleotide polymorphisms (SNPs) and does not require reference genomes. Yet, generating such datasets remains challenging due to laboratory and bioinformatical issues. In the laboratory, current protocols require improvements with regards to sequencing homologous fragments to reduce the number of missing genotypes. From the bioinformatical perspective, the reliance of most studies on a single SNP caller disregards the possibility that different algorithms may produce disparate SNP datasets. Results We present an improved RRL (iRRL) protocol that maximizes the generation of homologous DNA sequences, thus achieving improved genotyping-by-sequencing efficiency. Our modifications facilitate generation of single-sample libraries, enabling individual genotype assignments instead of pooled-sample analysis. We sequenced ~1% of the orangutan genome with 41-fold median coverage in 31 wild-born individuals from two populations. SNPs and genotypes were called using three different algorithms. We obtained substantially different SNP datasets depending on the SNP caller. Genotype validations revealed that the Unified Genotyper of the Genome Analysis Toolkit and SAMtools performed significantly better than a caller from CLC Genomics Workbench (CLC). Of all conflicting genotype calls, CLC was only correct in 17% of the cases. Furthermore, conflicting genotypes between two algorithms showed a systematic bias in that one caller almost exclusively assigned heterozygotes, while the other one almost exclusively assigned homozygotes. Conclusions

  18. 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.

  19. 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

  20. SnpFilt: A pipeline for reference-free assembly-based identification of SNPs in bacterial genomes.

    PubMed

    Chan, Carmen H S; Octavia, Sophie; Sintchenko, Vitali; Lan, Ruiting

    2016-12-01

    De novo assembly of bacterial genomes from next-generation sequencing (NGS) data allows a reference-free discovery of single nucleotide polymorphisms (SNP). However, substantial rates of errors in genomes assembled by this approach remain a major barrier for the reference-free analysis of genome variations in medically important bacteria. The aim of this report was to improve the quality of SNP identification in bacterial genomes without closely related references. We developed a bioinformatics pipeline (SnpFilt) that constructs an assembly using SPAdes and then removes unreliable regions based on the quality and coverage of re-aligned reads at neighbouring regions. The performance of the pipeline was compared against reference-based SNP calling for Illumina HiSeq, MiSeq and NextSeq reads from a range of bacterial pathogens including Salmonella, which is one of the most common causes of food-borne disease. The SnpFilt pipeline removed all false SNP in all test NGS datasets consisting of paired-end Illumina reads. We also showed that for reliable and complete SNP calls, at least 40-fold coverage is required. Analysis of bacterial isolates associated with epidemiologically confirmed outbreaks using the SnpFilt pipeline produced results consistent with previously published findings. The SnpFilt pipeline improves the quality of de-novo assembly and precision of SNP calling in bacterial genomes by removal of regions of the assembly that may potentially contain assembly errors. SnpFilt is available from https://github.com/LanLab/SnpFilt.

  1. Explaining the disease phenotype of intergenic SNP through predicted long range regulation

    PubMed Central

    Chen, Jingqi; Tian, Weidong

    2016-01-01

    Thousands of disease-associated SNPs (daSNPs) are located in intergenic regions (IGR), making it difficult to understand their association with disease phenotypes. Recent analysis found that non-coding daSNPs were frequently located in or approximate to regulatory elements, inspiring us to try to explain the disease phenotypes of IGR daSNPs through nearby regulatory sequences. Hence, after locating the nearest distal regulatory element (DRE) to a given IGR daSNP, we applied a computational method named INTREPID to predict the target genes regulated by the DRE, and then investigated their functional relevance to the IGR daSNP's disease phenotypes. 36.8% of all IGR daSNP-disease phenotype associations investigated were possibly explainable through the predicted target genes, which were enriched with, were functionally relevant to, or consisted of the corresponding disease genes. This proportion could be further increased to 60.5% if the LD SNPs of daSNPs were also considered. Furthermore, the predicted SNP-target gene pairs were enriched with known eQTL/mQTL SNP-gene relationships. Overall, it's likely that IGR daSNPs may contribute to disease phenotypes by interfering with the regulatory function of their nearby DREs and causing abnormal expression of disease genes. PMID:27280978

  2. Objective evaluation measures of genetic marker selection in large-scale SNP genotyping.

    PubMed

    Kaminuma, Eli; Masuya, Hiroshi; Miura, Ikuo; Motegi, Hiromi; Takahasi, Kenzi R; Nakazawa, Miki; Matsui, Minami; Gondo, Yoichi; Noda, Tetsuo; Shiroishi, Toshihiko; Wakana, Shigeharu; Toyoda, Tetsuro

    2008-10-01

    High-throughput single nucleotide polymorphism (SNP) genotyping systems provide two kinds of fluorescent signals detected from different alleles. In current technologies, the process of genotype discrimination requires subjective judgments by expert operators, even when using clustering algorithms. Here, we propose two evaluation measures to manage fluorescent scatter data with nonclear plot aggregation. The first is the marker ranking measure, which provides a ranking system for the SNP markers based on the distance between the scatter plot distribution and a user-defined ideal distribution. The second measure, called individual genotype membership, uses the membership probability of each genotype related to an individual plot in the scatter data. In verification experiments, the marker ranking measure determined the ranking of SNP markers correlated with the subjective order of SNP markers judged by an expert operator. The experiment using the individual genotype membership measure clarified that the total number of unclassified individuals was remarkably reduced compared to that of manually unclassified ones. These two evaluation measures were implemented as the GTAssist software. GTAssist provides objective standards and avoids subjective biases in SNP genotyping workflows.

  3. Assessment of high resolution melting analysis as a potential SNP genotyping technique in forensic casework.

    PubMed

    Venables, Samantha J; Mehta, Bhavik; Daniel, Runa; Walsh, Simon J; van Oorschot, Roland A H; McNevin, Dennis

    2014-11-01

    High resolution melting (HRM) analysis is a simple, cost effective, closed tube SNP genotyping technique with high throughput potential. The effectiveness of HRM for forensic SNP genotyping was assessed with five commercially available HRM kits evaluated on the ViiA™ 7 Real Time PCR instrument. Four kits performed satisfactorily against forensically relevant criteria. One was further assessed to determine the sensitivity, reproducibility, and accuracy of HRM SNP genotyping. The manufacturer's protocol using 0.5 ng input DNA and 45 PCR cycles produced accurate and reproducible results for 17 of the 19 SNPs examined. Problematic SNPs had GC rich flanking regions which introduced additional melting domains into the melting curve (rs1800407) or included homozygotes that were difficult to distinguish reliably (rs16891982; a G to C SNP). A proof of concept multiplexing experiment revealed that multiplexing a small number of SNPs may be possible after further investigation. HRM enables genotyping of a number of SNPs in a large number of samples without extensive optimization. However, it requires more genomic DNA as template in comparison to SNaPshot®. Furthermore, suitably modifying pre-existing forensic intelligence SNP panels for HRM analysis may pose difficulties due to the properties of some SNPs.

  4. 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.

  5. snpGeneSets: An R Package for Genome-Wide Study Annotation

    PubMed Central

    Mei, Hao; Li, Lianna; Jiang, Fan; Simino, Jeannette; Griswold, Michael; Mosley, Thomas; Liu, Shijian

    2016-01-01

    Genome-wide studies (GWS) of SNP associations and differential gene expressions have generated abundant results; next-generation sequencing technology has further boosted the number of variants and genes identified. Effective interpretation requires massive annotation and downstream analysis of these genome-wide results, a computationally challenging task. We developed the snpGeneSets package to simplify annotation and analysis of GWS results. Our package integrates local copies of knowledge bases for SNPs, genes, and gene sets, and implements wrapper functions in the R language to enable transparent access to low-level databases for efficient annotation of large genomic data. The package contains functions that execute three types of annotations: (1) genomic mapping annotation for SNPs and genes and functional annotation for gene sets; (2) bidirectional mapping between SNPs and genes, and genes and gene sets; and (3) calculation of gene effect measures from SNP associations and performance of gene set enrichment analyses to identify functional pathways. We applied snpGeneSets to type 2 diabetes (T2D) results from the NHGRI genome-wide association study (GWAS) catalog, a Finnish GWAS, and a genome-wide expression study (GWES). These studies demonstrate the usefulness of snpGeneSets for annotating and performing enrichment analysis of GWS results. The package is open-source, free, and can be downloaded at: https://www.umc.edu/biostats_software/. PMID:27807048

  6. snpGeneSets: An R Package for Genome-Wide Study Annotation.

    PubMed

    Mei, Hao; Li, Lianna; Jiang, Fan; Simino, Jeannette; Griswold, Michael; Mosley, Thomas; Liu, Shijian

    2016-12-07

    Genome-wide studies (GWS) of SNP associations and differential gene expressions have generated abundant results; next-generation sequencing technology has further boosted the number of variants and genes identified. Effective interpretation requires massive annotation and downstream analysis of these genome-wide results, a computationally challenging task. We developed the snpGeneSets package to simplify annotation and analysis of GWS results. Our package integrates local copies of knowledge bases for SNPs, genes, and gene sets, and implements wrapper functions in the R language to enable transparent access to low-level databases for efficient annotation of large genomic data. The package contains functions that execute three types of annotations: (1) genomic mapping annotation for SNPs and genes and functional annotation for gene sets; (2) bidirectional mapping between SNPs and genes, and genes and gene sets; and (3) calculation of gene effect measures from SNP associations and performance of gene set enrichment analyses to identify functional pathways. We applied snpGeneSets to type 2 diabetes (T2D) results from the NHGRI genome-wide association study (GWAS) catalog, a Finnish GWAS, and a genome-wide expression study (GWES). These studies demonstrate the usefulness of snpGeneSets for annotating and performing enrichment analysis of GWS results. The package is open-source, free, and can be downloaded at: https://www.umc.edu/biostats_software/.

  7. 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

  8. 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

  9. Developing a new nonbinary SNP fluorescent multiplex detection system for forensic application in China.

    PubMed

    Liu, Yanfang; Liao, Huidan; Liu, Ying; Guo, Juanjuan; Sun, Yi; Fu, Xiaoliang; Xiao, Ding; Cai, Jifeng; Lan, Lingmei; Xie, Pingli; Zha, Lagabaiyila

    2017-02-06

    Nonbinary single-nucleotide polymorphisms (SNPs) are potential forensic genetic markers because their discrimination power is greater than that of normal binary SNPs, and that they can detect highly degraded samples. We previously developed a nonbinary SNP multiplex typing assay. In this study, we selected additional 20 nonbinary SNPs from the NCBI SNP database and verified them through pyrosequencing. These 20 nonbinary SNPs were analyzed using the fluorescent-labeled SNaPshot multiplex SNP typing method. The allele frequencies and genetic parameters of these 20 nonbinary SNPs were determined among 314 unrelated individuals from Han populations from China. The total power of discrimination was 0.9999999999994, and the cumulative probability of exclusion was 0.9986. Moreover, the result of the combination of this 20 nonbinary SNP assay with the 20 nonbinary SNP assay we previously developed demonstrated that the cumulative probability of exclusion of the 40 nonbinary SNPs was 0.999991 and that no significant linkage disequilibrium was observed in all 40 nonbinary SNPs. Thus, we concluded that this new system consisting of new 20 nonbinary SNPs could provide highly informative polymorphic data which would be further used in forensic application and would serve as a potentially valuable supplement to forensic DNA analysis.

  10. MDM2 SNP309 polymorphism is associated with colorectal cancer risk

    PubMed Central

    Wang, Weizhi; Du, Mulong; Gu, Dongying; Zhu, Lingjun; Chu, Haiyan; Tong, Na; Zhang, Zhengdong; Xu, Zekuan; Wang, Meilin

    2014-01-01

    The human murine double minute 2 (MDM2) is known as an oncoprotein through inhibiting P53 transcriptional activity and mediating P53 ubiquitination. Therefore, the amplification of MDM2 may attenuate the P53 pathway and promote tumorigenesis. The SNP309 T>G polymorphism (rs2279744), which is located in the intronic promoter of MDM2 gene, was reported to contribute to the increased level of MDM2 protein. In this hospital-based case-control study, which consisted of 573 cases and 588 controls, we evaluated the association between MDM2 SNP309 and the risk of colorectal cancer (CRC) in a Chinese population by using the TaqMan method to genotype the polymorphism. We found that the MDM2 SNP309 polymorphism was significantly associated with CRC risk. In addition, in our meta-analysis, we found a significant association between MDM2 SNP309 and CRC risk among Asians, which was consistent with our results. In conclusion, we demonstrated that the MDM2 SNP309 polymorphism increased the susceptibility of CRC in Asian populations. PMID:24797837

  11. SNP Discovery by Illumina-Based Transcriptome Sequencing of the Olive and the Genetic Characterization of Turkish Olive Genotypes Revealed by AFLP, SSR and SNP Markers

    PubMed Central

    Kaya, Hilal Betul; Cetin, Oznur; Kaya, Hulya; Sahin, Mustafa; Sefer, Filiz; Kahraman, Abdullah; Tanyolac, Bahattin

    2013-01-01

    Background The olive tree (Olea europaea L.) is a diploid (2n = 2x = 46) outcrossing species mainly grown in the Mediterranean area, where it is the most important oil-producing crop. Because of its economic, cultural and ecological importance, various DNA markers have been used in the olive to characterize and elucidate homonyms, synonyms and unknown accessions. However, a comprehensive characterization and a full sequence of its transcriptome are unavailable, leading to the importance of an efficient large-scale single nucleotide polymorphism (SNP) discovery in olive. The objectives of this study were (1) to discover olive SNPs using next-generation sequencing and to identify SNP primers for cultivar identification and (2) to characterize 96 olive genotypes originating from different regions of Turkey. Methodology/Principal Findings Next-generation sequencing technology was used with five distinct olive genotypes and generated cDNA, producing 126,542,413 reads using an Illumina Genome Analyzer IIx. Following quality and size trimming, the high-quality reads were assembled into 22,052 contigs with an average length of 1,321 bases and 45 singletons. The SNPs were filtered and 2,987 high-quality putative SNP primers were identified. The assembled sequences and singletons were subjected to BLAST similarity searches and annotated with a Gene Ontology identifier. To identify the 96 olive genotypes, these SNP primers were applied to the genotypes in combination with amplified fragment length polymorphism (AFLP) and simple sequence repeats (SSR) markers. Conclusions/Significance This study marks the highest number of SNP markers discovered to date from olive genotypes using transcriptome sequencing. The developed SNP markers will provide a useful source for molecular genetic studies, such as genetic diversity and characterization, high density quantitative trait locus (QTL) analysis, association mapping and map-based gene cloning in the olive. High levels of

  12. Breast cancer-associated high-order SNP-SNP interaction of CXCL12/CXCR4-related genes by an improved multifactor dimensionality reduction (MDR-ER).

    PubMed

    Fu, Ou-Yang; Chang, Hsueh-Wei; Lin, Yu-Da; Chuang, Li-Yeh; Hou, Ming-Feng; Yang, Cheng-Hong

    2016-09-01

    In association studies, the combined effects of single nucleotide polymorphism (SNP)-SNP interactions and the problem of imbalanced data between cases and controls are frequently ignored. In the present study, we used an improved multifactor dimensionality reduction (MDR) approach namely MDR-ER to detect the high order SNP‑SNP interaction in an imbalanced breast cancer data set containing seven SNPs of chemokine CXCL12/CXCR4 pathway genes. Most individual SNPs were not significantly associated with breast cancer. After MDR‑ER analysis, six significant SNP‑SNP interaction models with seven genes (highest cross‑validation consistency, 10; classification error rates, 41.3‑21.0; and prediction error rates, 47.4‑55.3) were identified. CD4 and VEGFA genes were associated in a 2‑loci interaction model (classification error rate, 41.3; prediction error rate, 47.5; odds ratio (OR), 2.069; 95% bootstrap CI, 1.40‑2.90; P=1.71E‑04) and it also appeared in all the best 2‑7‑loci models. When the loci number increased, the classification error rates and P‑values decreased. The powers in 2‑7‑loci in all models were >0.9. The minimum classification error rate of the MDR‑ER‑generated model was shown with the 7‑loci interaction model (classification error rate, 21.0; OR=15.282; 95% bootstrap CI, 9.54‑23.87; P=4.03E‑31). In the epistasis network analysis, the overall effect with breast cancer susceptibility was identified and the SNP order of impact on breast cancer was identified as follows: CD4 = VEGFA > KITLG > CXCL12 > CCR7 = MMP2 > CXCR4. In conclusion, the MDR‑ER can effectively and correctly identify the best SNP‑SNP interaction models in an imbalanced data set for breast cancer cases.

  13. 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

  14. Observation of perturbed 3snp double photoexcited Ryberg series of beryllium atoms

    SciTech Connect

    Yoshida, Fumiko; Matsuoka, Leo; Osaki, Hiroyuki; Kikkawa, Satoshi; Fukushima, Yu; Hasegawa, Shuichi; Nagata, Tetsuo; Azuma, Yoshiro; Obara, Satoshi

    2006-04-15

    We observed the 3snp autoionizing Rydberg series of the Be atom in order to investigate the double-photoexcitation processes in two-s-electron systems. We employed synchrotron radiation to photoexcite the Be atoms and measured the generated Be{sup +} photoions by the time-of-flight method. The 3snp (n=3-9) photoexcitation resonance peaks with interloper state of 3p4s that converges to Be{sup +}(3p) threshold were observed. We derived the resonance parameters of 3snp series from a fitting procedure and obtained the Fano parameter q, energy position E{sub 0}, and resonance width {gamma}. These parameters are in good agreement with theoretical values. In the vicinity of the 3s5p state these experimental results clearly revealed the influence of the interloper 3p4s state, and the comparison with the numerical calculations indicates that more detailed calculations might be required to fully explain this phenomenon.

  15. Multi-marker-LD based genetic algorithm for tag SNP selection.

    PubMed

    Mouawad, Amer E; Mansour, Nashat

    2014-12-01

    Despite the advances in genotyping technologies which have led to large reduction in genotyping cost, the Tag SNP Selection problem remains an important problem for computational biologists and geneticists. Selecting the smallest subset of tag SNPs that can predict the other SNPs would considerably minimize the complexity of genome-wide or block-based SNP-disease association studies. These studies would lead to better diagnosis and treatment of diseases. In this work, we propose three variations of a genetic algorithm based on two-marker linkage disequilibrium, multi-marker linkage disequilibrium, and a third measure that we denote by prediction power. The performance of the three algorithms are compared with those of a recognized tag SNP selection algorithm using three different real data sets from the HapMap project. The results indicate that the multi-marker linkage disequilibrium based genetic algorithm yields better prediction accuracy.

  16. 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

  17. 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

  18. SNP discrimination through proofreading and OFF-switch of exo+ polymerase.

    PubMed

    Zhang, Jia; Li, Kai; Pardinas, Jose R; Liao, Duan F; Li, Hong J; Zhang, Xu

    2004-05-01

    Single nucleotide polymorphisms (SNPs) are useful physical markers for genetic studies as well as the cause of some genetic diseases. To develop more reliable SNP assays, we examined the underlying molecular mechanisms by which deoxyribonucleic acid (DNA) polymerases with 3' exonuclease activity maintain the high fidelity of DNA replication. In addition to mismatch removal by proofreading, we have discovered a premature termination of polymerization mediated by a novel OFF-switch mechanism. Two SNP assays were developed, one based on proofreading using 3' end-labeled primer extension and the other based on the newly identified OFF-switch, respectively. These two new assays are well suited for conventional techniques, such as electrophoresis and microplates detection systems as well as the sophisticated microchips. Application of these reliable SNP assays will greatly facilitate genetic and biomedical studies in the postgenome era.

  19. 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.

  20. 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

  1. Using Hamming Distance as Information for SNP-Sets Clustering and Testing in Disease Association Studies.

    PubMed

    Wang, Charlotte; Kao, Wen-Hsin; Hsiao, Chuhsing Kate

    2015-01-01

    The availability of high-throughput genomic data has led to several challenges in recent genetic association studies, including the large number of genetic variants that must be considered and the computational complexity in statistical analyses. Tackling these problems with a marker-set study such as SNP-set analysis can be an efficient solution. To construct SNP-sets, we first propose a clustering algorithm, which employs Hamming distance to measure the similarity between strings of SNP genotypes and evaluates whether the given SNPs or SNP-sets should be clustered. A dendrogram can then be constructed based on such distance measure, and the number of clusters can be determined. With the resulting SNP-sets, we next develop an association test HDAT to examine susceptibility to the disease of interest. This proposed test assesses, based on Hamming distance, whether the similarity between a diseased and a normal individual differs from the similarity between two individuals of the same disease status. In our proposed methodology, only genotype information is needed. No inference of haplotypes is required, and SNPs under consideration do not need to locate in nearby regions. The proposed clustering algorithm and association test are illustrated with applications and simulation studies. As compared with other existing methods, the clustering algorithm is faster and better at identifying sets containing SNPs exerting a similar effect. In addition, the simulation studies demonstrated that the proposed test works well for SNP-sets containing a large proportion of neutral SNPs. Furthermore, employing the clustering algorithm before testing a large set of data improves the knowledge in confining the genetic regions for susceptible genetic markers.

  2. Viability of in-house datamarting approaches for population genetics analysis of SNP genotypes

    PubMed Central

    Amigo, Jorge; Phillips, Christopher; Salas, Antonio; Carracedo, Ángel

    2009-01-01

    Background Databases containing very large amounts of SNP (Single Nucleotide Polymorphism) data are now freely available for researchers interested in medical and/or population genetics applications. While many of these SNP repositories have implemented data retrieval tools for general-purpose mining, these alone cannot cover the broad spectrum of needs of most medical and population genetics studies. Results To address this limitation, we have built in-house customized data marts from the raw data provided by the largest public databases. In particular, for population genetics analysis based on genotypes we have built a set of data processing scripts that deal with raw data coming from the major SNP variation databases (e.g. HapMap, Perlegen), stripping them into single genotypes and then grouping them into populations, then merged with additional complementary descriptive information extracted from dbSNP. This allows not only in-house standardization and normalization of the genotyping data retrieved from different repositories, but also the calculation of statistical indices from simple allele frequency estimates to more elaborate genetic differentiation tests within populations, together with the ability to combine population samples from different databases. Conclusion The present study demonstrates the viability of implementing scripts for handling extensive datasets of SNP genotypes with low computational costs, dealing with certain complex issues that arise from the divergent nature and configuration of the most popular SNP repositories. The information contained in these databases can also be enriched with additional information obtained from other complementary databases, in order to build a dedicated data mart. Updating the data structure is straightforward, as well as permitting easy implementation of new external data and the computation of supplementary statistical indices of interest. PMID:19344481

  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. An Integrated SNP Mining and Utilization (ISMU) Pipeline for Next Generation Sequencing Data

    PubMed Central

    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

  5. 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

  6. Bilateral comparison of 1 Ω and 10 kΩ standards (ongoing BIPM key comparisons BIPM.EM-K13.a and 13.b) between the CMI (Czech Republic) and the BIPM

    NASA Astrophysics Data System (ADS)

    Rolland, B.; Fletcher, N.; Kučera, J.; Chrobok, P.; Vo&jacute; čko&vacute; , L.

    2017-01-01

    This report gives the result of a bilateral comparison of resistance between the CMI (Czech Republic) and the BIPM carried out in 2015. Two 1 Ω and two 10 kΩ travelling standards belonging to the BIPM were used. The comparison was carried out with an 'A-B-A' pattern of measurements; the standards were measured first at the BIPM for a period of about one month, then for a similar period at the BIM, and finally again at the BIPM. The measurand was the 4 terminal dc resistance at low power. The BIPM was the pilot laboratory, and the comparison forms part of the ongoing BIPM key comparisons BIPM.EM-K13.a (for 1 Ω) and BIPM.EM-K13b (for 10 kΩ). The results from the CMI and the BIPM were found to be in good agreement, with a difference smaller than the relative expanded uncertainty (95% confidence, k = 2) of 0.046 × 10-6 for 1 Ω and 0.034 × 10-6 for 10 kΩ. 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 (CIPM MRA).

  7. Bilateral comparison of 1 Ω and 10 kΩ standards (ongoing BIPM key comparisons BIPM.EM-K13.a and 13.b) between the NIMT (Thailand) and the BIPM

    NASA Astrophysics Data System (ADS)

    Rolland, B.; Fletcher, N.; Khumthukthit, N.; Jassadajin, C.

    2017-01-01

    This report gives the result of a bilateral comparison of resistance between the NIMT (Thailand) and the BIPM carried out in 2015. Two 1 Ω and two 10 kΩ travelling standards belonging to the BIPM were used. The comparison was carried out with an 'A-B-A' pattern of measurements; the standards were measured first at the BIPM for a period of about one month, then for a similar period at the BIM, and finally again at the BIPM. The measurand was the 4 terminal dc resistance at low power. The BIPM was the pilot laboratory, and the comparison forms part of the ongoing BIPM key comparisons BIPM.EM-K13.a (for 1 Ω) and BIPM.EM-K13b (for 10 kΩ). The results from the NIMT and the BIPM were found to be in good agreement, with a difference smaller than the relative expanded uncertainty (95% confidence, k = 2) of 0.20 × 10-6 for 1 Ω and 0.74 × 10-6 for 10 kΩ. 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 (CIPM MRA).

  8. Bilateral comparison of 1 Ω and 10 kΩ standards (ongoing BIPM key comparisons BIPM.EM-K13.a and 13.b) between the NSAI NML (Ireland) and the BIPM

    NASA Astrophysics Data System (ADS)

    Rolland, B.; Fletcher, N.; Power, O.

    2017-01-01

    This report gives the result of a bilateral comparison of resistance between the NSAI NML (Ireland) and the BIPM carried out in 2014-2015. Two 1 Ω and two 10 kΩ travelling standards belonging to the BIPM were used. The comparison was carried out with an 'A-B-A' pattern of measurements; the standards were measured first at the BIPM for a period of about one month, then for a similar period at the NSAI-NML, and finally again at the BIPM. The measurand was the 4 terminal dc resistance at low power. The BIPM was the pilot laboratory, and the comparison forms part of the ongoing BIPM key comparisons BIPM.EM-K13.a (for 1 Ω) and BIPM.EM-K13b (for 10 kΩ). The results from the NSAI NML and the BIPM were found to be in good agreement, with a difference smaller than the relative expanded uncertainties (95% confidence, k = 2) of 0.16 × 10-6 for 1 Ω and 0.42 × 10-6 for 10 kΩ. 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 (CIPM MRA).

  9. 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

  10. 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.

  11. 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

  12. 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...

  13. Multiplexed SNP genotyping using the Qbead™ system: a quantum dot-encoded microsphere-based assay

    PubMed Central

    Xu, Hongxia; Sha, Michael Y.; Wong, Edith Y.; Uphoff, Janet; Xu, Yanzhang; Treadway, Joseph A.; Truong, Anh; O’Brien, Eamonn; Asquith, Steven; Stubbins, Michael; Spurr, Nigel K.; Lai, Eric H.; Mahoney, Walt

    2003-01-01

    We have developed a new method using the Qbead™ system for high-throughput genotyping of single nucleotide polymorphisms (SNPs). The Qbead system employs fluorescent Qdot™ semiconductor nanocrystals, also known as quantum dots, to encode microspheres that subsequently can be used as a platform for multiplexed assays. By combining mixtures of quantum dots with distinct emission wavelengths and intensities, unique spectral ‘barcodes’ are created that enable the high levels of multiplexing required for complex genetic analyses. Here, we applied the Qbead system to SNP genotyping by encoding microspheres conjugated to allele-specific oligonucleotides. After hybridization of oligonucleotides to amplicons produced by multiplexed PCR of genomic DNA, individual microspheres are analyzed by flow cytometry and each SNP is distinguished by its unique spectral barcode. Using 10 model SNPs, we validated the Qbead system as an accurate and reliable technique for multiplexed SNP genotyping. By modifying the types of probes conjugated to microspheres, the Qbead system can easily be adapted to other assay chemistries for SNP genotyping as well as to other applications such as analysis of gene expression and protein–protein interactions. With its capability for high-throughput automation, the Qbead system has the potential to be a robust and cost-effective platform for a number of applications. PMID:12682378

  14. 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 ...

  15. 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

  16. 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...

  17. 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...

  18. 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...

  19. 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 ...

  20. SNP-based genotyping in lentil: linking sequence information with phenotypes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lentil (Lens culinaris) has been late to enter the world of high throughput molecular analysis due to a general lack of genomic resources. Using a 454 sequencing-based approach, SNPs have been identified in genes across the lentil genome. Several hundred have been turned into single SNP KASP assay...

  1. High-throughput RAD-SNP genotyping for characterization of sugar beet genotypes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    High-throughput SNP genotyping provides a rapid way of developing resourceful set of markers for delineating the genetic architecture and for effective species discrimination. In the presented research, we demonstrate a set of 192 SNPs for effective genotyping in sugar beet using high-throughput mar...

  2. 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.

  3. 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...

  4. Microsatellite Imputation for parental verification from SNP across multiple Bos taurus and indicus breeds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Microsatellite markers (MS) have traditionally been used for parental verification and are still the international standard in spite of their higher cost, error rate, and turnaround time compared with Single Nucleotide Polymorphisms (SNP)-based assays. Despite domestic and international demands fro...

  5. 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...

  6. 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...

  7. Mining for SNPs and SSRs using SNPServer, dbSNP and SSR taxonomy tree.

    PubMed

    Batley, Jacqueline; Edwards, David

    2009-01-01

    Molecular genetic markers represent one of the most powerful tools for the analysis of genomes and the association of heritable traits with underlying genetic variation. The development of high-throughput methods for the detection of single nucleotide polymorphisms (SNPs) and simple sequence repeats (SSRs) has led to a revolution in their use as molecular markers. The availability of large sequence data sets permits mining for these molecular markers, which may then be used for applications such as genetic trait mapping, diversity analysis and marker assisted selection in agriculture. Here we describe web-based automated methods for the discovery of SSRs using SSR taxonomy tree, the discovery of SNPs from sequence data using SNPServer and the identification of validated SNPs from within the dbSNP database. SSR taxonomy tree identifies pre-determined SSR amplification primers for virtually all species represented within the GenBank database. SNPServer uses a redundancy based approach to identify SNPs within DNA sequences. Following submission of a sequence of interest, SNPServer uses BLAST to identify similar sequences, CAP3 to cluster and assemble these sequences and then the SNP discovery software autoSNP to detect SNPs and insertion/deletion (indel) polymorphisms. The NCBI dbSNP database is a catalogue of molecular variation, hosting validated SNPs for several species within a public-domain archive.

  8. 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 ...

  9. 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...

  10. EvoSNP-DB: A database of genetic diversity in East Asian populations

    PubMed Central

    Kim, Young Uk; Kim, Young Jin; Lee, Jong-Young; Park, Kiejung

    2013-01-01

    Genome-wide association studies (GWAS) have become popular as an approach for the identification of large numbers of phenotype-associated variants. However, differences in genetic architecture and environmental factors mean that the effect of variants can vary across populations. Understanding population genetic diversity is valuable for the investigation of possible population specific and independent effects of variants. EvoSNP-DB aims to provide information regarding genetic diversity among East Asian populations, including Chinese, Japanese, and Korean. Non-redundant SNPs (1.6 million) were genotyped in 54 Korean trios (162 samples) and were compared with 4 million SNPs from HapMap phase II populations. EvoSNP-DB provides two user interfaces for data query and visualization, and integrates scores of genetic diversity (Fst and VarLD) at the level of SNPs, genes, and chromosome regions. EvoSNP-DB is a web-based application that allows users to navigate and visualize measurements of population genetic differences in an interactive manner, and is available online at [http://biomi.cdc.go.kr/EvoSNP/]. [BMB Reports 2013; 46(8): 416-421] PMID:23977990

  11. 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...

  12. 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

  13. 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.

  14. The identification of SNPs with indeterminate positions using the Equine SNP50 BeadChip.

    PubMed

    Corbin, L J; Blott, S C; Swinburne, J E; Vaudin, M; Bishop, S C; Woolliams, J A

    2012-06-01

    We have used linkage disequilibrium (LD) to identify single nucleotide polymorphisms (SNPs) on the Illumina Equine SNP50 BeadChip, which may be incorrectly positioned on the genome map. A total of 1201 Thoroughbred horses were genotyped using the Illumina Equine SNP50 BeadChip. LD was evaluated in a pairwise fashion between all autosomal SNPs, both within and across chromosomes. Filters were then applied to the data, firstly to identify SNPs that may have been mapped to the wrong chromosome and secondly to identify SNPs that may have been incorrectly positioned within chromosomes. We identified a single SNP on ECA28, which showed low LD with neighbouring SNPs but considerable LD with a group of SNPs on ECA10. Furthermore, a cluster of SNPs on ECA5 showed unusually low LD with surrounding SNPs. A total of 39 SNPs met the criteria for unusual within-chromosome LD. The results of this study indicate that some SNPs may be misplaced. This finding is significant, as misplaced SNPs may lead to difficulties in the application of genomic methods, such as homozygosity mapping, for which SNP order is important.

  15. Analysis of gene-derived SNP marker polymorphism in wheat (Triticum aestivum L.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this study, we analyzed 359 single nucleotide polymorphisms (SNPs) previously discovered in intron sequences of wheat genes to evaluate SNP marker polymorphism in common wheat (Triticum aestivum L.). These SNPs showed an average polymorphism information content (PIC) of 0.181 among 20 US wheat c...

  16. 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...

  17. 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

  18. 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.

  19. 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.

  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 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

  2. Detecting SNP combinations discriminating human populations from HapMap data.

    PubMed

    Ding, XiaoJun; Li, Min; Gu, HaiHua; Peng, XiaoQing; Zhang, Zhen; Wu, FangXiang

    2015-03-01

    The genomes of different human beings are similar. There are only a relatively small number of genetic differences between people. The genetic differences between people are very worthy of study. Researchers have proposed the fixation index FST measurement to find the single nucleotide polymorphisms (SNPs) which can reflect human population differences. However, most SNPs have interactions and they work together, which leads to the differences among human populations. The number of all possible m-locus combinations chosen from n SNPs grows exponentially. Most methods concern on 2-locus interactions. In this paper, we propose a novel method to find a new coordinate system under which the energy distributions of different populations are quite different. We select out candidate SNPs from n SNPs by using the information of the axes in the coordinate system. The number of candidate SNPs is small, thus SNP-SNP interactions can be searched efficiently. The method can also find interactions of more than two loci. These interactions should be able to reflect the evolution of human populations from another way. The numbers of SNP-SNP interactions are regarded as the differences between pairwise populations and a hierarchical clustering algorithm is used to construct the evolutionary tree. In the experiments, we apply the method to SNP data of four chromosomes separately and the trees constructed on these four chromosomes are highly consistent. Furthermore, the trees are also consistent with previous studies, which indicates that evolutionary information is well mined. The method provides a new insight to analyze the human population differences.

  3. MDM2 SNP309 polymorphism contributes to endometrial cancer susceptibility: evidence from a meta-analysis

    PubMed Central

    2013-01-01

    Objective The SNP309 polymorphism (T-G) in the promoter of MDM2 gene has been reported to be associated with enhanced MDM2 expression and tumor development. Studies investigating the association between MDM2 SNP309 polymorphism and endometrial cancer risk reported conflicting results. We performed a meta-analysis of all available studies to explore this association. Methods All studies published up to August 2013 on the association between MDM2 SNP309 polymorphism and endometrial cancer risk were identified by searching electronic databases PubMed, Web of Science, EMBASE, and Chinese Biomedical Literature database (CBM). The association between the MDM2 SNP309 polymorphism and endometrial cancer risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). Results Eight case–control studies with 2069 endometrial cancer cases and 4546 controls were identified. Overall, significant increase of endometrial cancer risk was found when all studies were pooled in the meta-analysis (GG vs. TT: OR = 1.464, 95% CI 1.246–1.721, P < 0.001; GG vs. TG + TT: OR = 1.726, 95% CI 1.251–2.380, P = 0.001; GG + TG vs. TT: OR = 1.169, 95% CI 1.048–1.304, P = 0.005). In subgroup analysis by ethnicity and HWE in controls, significant increase of endometrial cancer risks were observed in Caucasians and studies consistent with HWE. In subgroup analysis according to study quality, significant associations were observed in both high quality studies and low quality studies. Conclusions This meta-analysis suggests that MDM2 SNP309 polymorphism contributes to endometrial cancer susceptibility, especially in Caucasian populations. Further large and well-designed studies are needed to confirm this association. PMID:24423195

  4. SNP discovery in candidate adaptive genes using exon capture in a free-ranging alpine ungulate

    USGS Publications Warehouse

    Roffler, Gretchen H.; Amish, Stephen J.; Smith, Seth; Cosart, Ted F.; Kardos, Marty; Schwartz, Michael K.; Luikart, Gordon

    2016-01-01

    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.

  5. 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.

  6. 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.

  7. When whole-genome alignments just won't work: kSNP v2 software for alignment-free SNP discovery and phylogenetics of hundreds of microbial genomes.

    PubMed

    Gardner, Shea N; Hall, Barry G

    2013-01-01

    Effective use of rapid and inexpensive whole genome sequencing for microbes requires fast, memory efficient bioinformatics tools for sequence comparison. The kSNP v2 software finds single nucleotide polymorphisms (SNPs) in whole genome data. kSNP v2 has numerous improvements over kSNP v1 including SNP gene annotation; better scaling for draft genomes available as assembled contigs or raw, unassembled reads; a tool to identify the optimal value of k; distribution of packages of executables for Linux and Mac OS X for ease of installation and user-friendly use; and a detailed User Guide. SNP discovery is based on k-mer analysis, and requires no multiple sequence alignment or the selection of a single reference genome. Most target sets with hundreds of genomes complete in minutes to hours. SNP phylogenies are built by maximum likelihood, parsimony, and distance, based on all SNPs, only core SNPs, or SNPs present in some intermediate user-specified fraction of targets. The SNP-based trees that result are consistent with known taxonomy. kSNP v2 can handle many gigabases of sequence in a single run, and if one or more annotated genomes are included in the target set, SNPs are annotated with protein coding and other information (UTRs, etc.) from Genbank file(s). We demonstrate application of kSNP v2 on sets of viral and bacterial genomes, and discuss in detail analysis of a set of 68 finished E. coli and Shigella genomes and a set of the same genomes to which have been added 47 assemblies and four "raw read" genomes of H104:H4 strains from the recent European E. coli outbreak that resulted in both bloody diarrhea and hemolytic uremic syndrome (HUS), and caused at least 50 deaths.

  8. Identification of Mendelian inconsistencies between SNP and pedigree information of sibs

    PubMed Central

    2011-01-01

    Background Using SNP genotypes to apply genomic selection in breeding programs is becoming common practice. Tools to edit and check the quality of genotype data are required. Checking for Mendelian inconsistencies makes it possible to identify animals for which pedigree information and genotype information are not in agreement. Methods Straightforward tests to detect Mendelian inconsistencies exist that count the number of opposing homozygous marker (e.g. SNP) genotypes between parent and offspring (PAR-OFF). Here, we develop two tests to identify Mendelian inconsistencies between sibs. The first test counts SNP with opposing homozygous genotypes between sib pairs (SIBCOUNT). The second test compares pedigree and SNP-based relationships (SIBREL). All tests iteratively remove animals based on decreasing numbers of inconsistent parents and offspring or sibs. The PAR-OFF test, followed by either SIB test, was applied to a dataset comprising 2,078 genotyped cows and 211 genotyped sires. Theoretical expectations for distributions of test statistics of all three tests were calculated and compared to empirically derived values. Type I and II error rates were calculated after applying the tests to the edited data, while Mendelian inconsistencies were introduced by permuting pedigree against genotype data for various proportions of animals. Results Both SIB tests identified animal pairs for which pedigree and genomic relationships could be considered as inconsistent by visual inspection of a scatter plot of pairwise pedigree and SNP-based relationships. After removal of 235 animals with the PAR-OFF test, SIBCOUNT (SIBREL) identified 18 (22) additional inconsistent animals. Seventeen animals were identified by both methods. The numbers of incorrectly deleted animals (Type I error), were equally low for both methods, while the numbers of incorrectly non-deleted animals (Type II error), were considerably higher for SIBREL compared to SIBCOUNT. Conclusions Tests to remove

  9. Bilateral comparison of 1 Ω and 10 kΩ standards (ongoing BIPM key comparisons BIPM.EM-K13.a and 13.b) between the BIM (Bulgaria) and the BIPM

    NASA Astrophysics Data System (ADS)

    Rolland, B.; Fletcher, N.; Tenev, A.; Hadzhistoykova, R.

    2017-01-01

    This report gives the result of a bilateral comparison of resistance between the BIM (Bulgaria) and the BIPM carried out in 2013. Two 1 Ω and two 10 kΩ travelling standards belonging to the BIPM were used. The comparison was carried out with an 'A-B-A' pattern of measurements; the standards were measured first at the BIPM for a period of about one month, then for a similar period at the BIM, and finally again at the BIPM. The measurand was the 4 terminal dc resistance at low power. The BIPM was the pilot laboratory, and the comparison forms part of the ongoing BIPM key comparisons BIPM.EM-K13.a (for 1 Ω) and BIPM.EM-K13b (for 10 kΩ). The results from the BIM and the BIPM were found to be in good agreement, with a difference smaller than the relative expanded uncertainty (95% confidence, k = 2) of 0.30 × 10-6 at 10 kΩ and in reasonable agreement for 1 Ω with a relative difference of -0.18 × 10-6 with a relative expanded uncertainty of 0.17 × 10-6. 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 (CIPM MRA).

  10. Ecotoxicological assessment of PAHs and their dead-end metabolites after degradation by Mycobacterium sp. strain SNP11.

    PubMed

    Pagnout, Christophe; Rast, Claudine; Veber, Anne-Marie; Poupin, Pascal; Férard, Jean-François

    2006-10-01

    Mycobacterium sp. SNP11 has a high PAH biodegradation potential. In this paper, the toxicity of pyrene, fluoranthene, phenanthrene, and their dead-end metabolites, accumulated in the media after biodegradation by Mycobacterium sp. SNP11, were evaluated by a screening battery of acute, chronic, and genotoxic tests. According to the bioassays, performed on bacteria (Vibrio fischeri, Salmonella typhimurium strains TA1535/pSK1002, TA97a, TA98, TA100), algae (Pseudokirchneriella subcapitata), and crustaceans (Daphnia magna, Ceriodaphnia dubia), total disappearance or a very significant reduction of the (geno)toxic potential was observed after PAH degradation by Mycobacterium sp. SNP11.

  11. MA-SNP--A new genotype calling method for oligonucleotide SNP arrays modeling the batch effect with a normal mixture model.

    PubMed

    Wen, Yalu; Li, Ming; Fu, Wenjiang J

    2011-08-30

    Genome-wide association studies hold great promise in identifying disease-susceptibility variants and understanding the genetic etiology of complex diseases. Microarray technology enables the genotyping of millions of single nucleotide polymorphisms. Many factors in microarray studies, such as probe selection, sample quality, and experimental process and batch, have substantial effect on the genotype calling accuracy, which is crucial for downstream analyses. Failure to account for the variability of these sources may lead to inaccurate genotype calls and false positive and false negative findings. In this study, we develop a SNP-specific genotype calling algorithm based on the probe intensity composite representation (PICR) model, while using a normal mixture model to account for the variability of batch effect on the genotype calls. We demonstrate our method with SNP array data in a few studies, including the HapMap project, the coronary heart disease and the UK Blood Service Control studies by the Wellcome Trust Case-Control Consortium, and a methylation profiling study. Our single array based approach outperforms PICR and is comparable to the best multi-array genotype calling methods.

  12. Microfluidic linear hydrogel array for multiplexed single nucleotide polymorphism (SNP) detection.

    PubMed

    Jung, Yun Kyung; Kim, Jungkyu; Mathies, Richard A

    2015-03-17

    A PDMS-based microfluidic linear hydrogel array is developed for multiplexed single nucleotide polymorphism (SNP) detection. A sequence of three-dimensional (3D) hydrogel plugs containing the desired DNA probes is prepared by UV polymerization within a PDMS microchannel system. The fluorescently labeled target DNA is then electrophoresed through the sequence of hydrogel plugs for hybridization. Continued electrophoresis provides an electrophoretic wash that removes nonspecific binders. The capture gel array is imaged after washing at various temperatures (temperature gradient electrophoresis) to further distinguish perfect matches from mismatches. The ability of this microdevice to perform multiplex SNP genotyping is demonstrated by analyzing a mixture of model E. coli bacterial targets. This microfluidic hydrogel array is ∼1000 times more sensitive than planar microarrays due to the 3D gel capture, the hybridization time is much shorter due to electrophoretic control of the transport properties, and the stringent wash with temperature gradient electrophoresis enables analysis of single nucleotide mismatches with high specificity.

  13. Using false discovery rates to benchmark SNP-callers in next-generation sequencing projects.

    PubMed

    Farrer, Rhys A; Henk, Daniel A; MacLean, Dan; Studholme, David J; Fisher, Matthew C

    2013-01-01

    Sequence alignments form the basis for many comparative and population genomic studies. Alignment tools provide a range of accuracies dependent on the divergence between the sequences and the alignment methods. Despite widespread use, there is no standard method for assessing the accuracy of a dataset and alignment strategy after resequencing. We present a framework and tool for determining the overall accuracies of an input read dataset, alignment and SNP-calling method providing an isolate in that dataset has a corresponding, or closely related reference sequence available. In addition to this tool for comparing False Discovery Rates (FDR), we include a method for determining homozygous and heterozygous positions from an alignment using binomial probabilities for an expected error rate. We benchmark this method against other SNP callers using our FDR method with three fungal genomes, finding that it was able achieve a high level of accuracy. These tools are available at http://cfdr.sourceforge.net/.

  14. Using False Discovery Rates to Benchmark SNP-callers in next-generation sequencing projects

    PubMed Central

    Farrer, Rhys A.; Henk, Daniel A.; MacLean, Dan; Studholme, David J.; Fisher, Matthew C.

    2013-01-01

    Sequence alignments form the basis for many comparative and population genomic studies. Alignment tools provide a range of accuracies dependent on the divergence between the sequences and the alignment methods. Despite widespread use, there is no standard method for assessing the accuracy of a dataset and alignment strategy after resequencing. We present a framework and tool for determining the overall accuracies of an input read dataset, alignment and SNP-calling method providing an isolate in that dataset has a corresponding, or closely related reference sequence available. In addition to this tool for comparing False Discovery Rates (FDR), we include a method for determining homozygous and heterozygous positions from an alignment using binomial probabilities for an expected error rate. We benchmark this method against other SNP callers using our FDR method with three fungal genomes, finding that it was able achieve a high level of accuracy. These tools are available at http://cfdr.sourceforge.net/. PMID:23518929

  15. 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.

  16. Light whole genome sequence for SNP discovery across domestic cat breeds

    PubMed Central

    2010-01-01

    Background The domestic cat has offered enormous genomic potential in the veterinary description of over 250 hereditary disease models as well as the occurrence of several deadly feline viruses (feline leukemia virus -- FeLV, feline coronavirus -- FECV, feline immunodeficiency virus - FIV) that are homologues to human scourges (cancer, SARS, and AIDS respectively). However, to realize this bio-medical potential, a high density single nucleotide polymorphism (SNP) map is required in order to accomplish disease and phenotype association discovery. Description To remedy this, we generated 3,178,297 paired fosmid-end Sanger sequence reads from seven cats, and combined these data with the publicly available 2X cat whole genome sequence. All sequence reads were assembled together to form a 3X whole genome assembly allowing the discovery of over three million SNPs. To reduce potential false positive SNPs due to the low coverage assembly, a low upper-limit was placed on sequence coverage and a high lower-limit on the quality of the discrepant bases at a potential variant site. In all domestic cats of different breeds: female Abyssinian, female American shorthair, male Cornish Rex, female European Burmese, female Persian, female Siamese, a male Ragdoll and a female African wildcat were sequenced lightly. We report a total of 964 k common SNPs suitable for a domestic cat SNP genotyping array and an additional 900 k SNPs detected between African wildcat and domestic cats breeds. An empirical sampling of 94 discovered SNPs were tested in the sequenced cats resulting in a SNP validation rate of 99%. Conclusions These data provide a large collection of mapped feline SNPs across the cat genome that will allow for the development of SNP genotyping platforms for mapping feline diseases. PMID:20576142

  17. Sensitive Quantification of Mosaicism Using High Density SNP Arrays and the Cumulative Distribution Function

    PubMed Central

    Markello, Thomas C.; Carlson-Donohoe, Hannah; Sincan, Murat; Adams, David; Bodine, David M.; Farrar, Jason E.; Vlachos, Adrianna; Lipton, Jeffrey M.; Auerbach, Arleen D.; Ostrander, Elaine A.; Chandrasekharappa, Settara C.; Boerkoel, Cornelius F.; Gahl, William A.

    2012-01-01

    Medicine is rapidly applying exome and genome sequencing to the diagnosis and management of human disease. Somatic mosaicism, however, is not readily detectable by these means, and yet it accounts for a significant portion of undiagnosed disease. We present a rapid and sensitive method, the Continuous Distribution Function as applied to single nucleotide polymorphism (SNP) array data, to quantify somatic mosaicism throughout the genome. We also demonstrate application of the method to novel diseases and mechanisms. PMID:22277120

  18. 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

  19. Hydrogen maser oscillation at 10 K

    NASA Technical Reports Server (NTRS)

    Crampton, S. B.; Jones, K. M.; Souza, S. P.

    1984-01-01

    A low temperature atomic hydrogen maser was developed using frozen atomic neon as the storage surface. The maser has been operated in the pulsed mode at temperatures from 6 K to 11 K and as a self-excited oscillator from 9 K to 10.5 K.

  20. 10k Run for the Border Act

    THOMAS, 111th Congress

    Rep. Myrick, Sue Wilkins [R-NC-9

    2009-01-15

    03/16/2009 Referred to the Subcommittee on Immigration, Citizenship, Refugees, Border Security, and International Law. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  1. Evaluation of TP53 Pro72Arg and MDM2 SNP285-SNP309 polymorphisms in an Italian cohort of LFS suggestive patients lacking identifiable TP53 germline mutations.

    PubMed

    Ponti, Francesca; Corsini, Serena; Gnoli, Maria; Pedrini, Elena; Mordenti, Marina; Sangiorgi, Luca

    2016-10-01

    Li-Fraumeni syndrome (LFS) is a rare genetic cancer predisposition disease, partly determined by the presence of a TP53 germline mutation; lacking thereof, in presence of a typical LFS phenotype, defines a wide group of 'LFS Suggestive' patients. Alternative LFS susceptibility genes have been investigated without promising results, thus suggesting other genetic determinants involvement in cancer predisposition. Hence, this study explores the single and combined effects of cancer risk, age of onset and cancer type of three single nucleotide polymorphisms (SNPs)-TP53 Pro72Arg, MDM2 SNP285 and SNP309-already described as modifiers on TP53 mutation carriers but not properly investigated in LFS Suggestive patients. This case-control study examines 34 Italian LFS Suggestive lacking of germline TP53 mutations and 95 tumour-free subjects. A significant prevalence of homozygous MDM2 SNP309 G in the LFS Suggestive group (p < 0.0005) confirms its contribute to cancer susceptibility, also highlighted in LFS TP53 positive families. Conversely its anticipating role on tumour onset has not been confirmed, as in our results it was associated with the SNP309 T allele. A strong combined outcome with a 'dosage' effect has also been reported for TP53 P72 and MDM2 SNP309 G allele on cancer susceptibility (p < 0.0005). Whereas the MDM2 SNP285 C allele neutralizing effect on MDM2 SNP309 G variant is not evident in our population. Although it needs further evaluations, obtained results strengthen the role of MDM2 SNP309 as a genetic factor in hereditary predisposition to cancer, so improving LFS Suggestive patients management.

  2. 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).

  3. 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.

    PubMed

    Barragán, Patricia; Pérez de Tudela, Ricardo; Qu, Chen; Prosmiti, Rita; Bowman, Joel M

    2013-07-14

    Diffusion Monte Carlo (DMC) and path-integral Monte Carlo computations of the vibrational ground state and 10 K equilibrium state properties of the H7 (+)/D7 (+) cations are presented, using an ab initio full-dimensional potential energy surface. The DMC zero-point energies of dissociated fragments H5 (+)(D5 (+))+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 H7 (+) and D7 (+), 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 H7 (+) and D7 (+). These are qualitatively described as a central H3 (+)/D3 (+) core surrounded by "solvent" H2/D2 molecules that nearly freely rotate.

  4. 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

  5. Demographic Trends in Korean Native Cattle Explained Using Bovine SNP50 Beadchip

    PubMed Central

    Sharma, Aditi; Lim, Dajeong; Chai, Han-Ha; Choi, Bong-Hwan; Cho, Yongmin

    2016-01-01

    Linkage disequilibrium (LD) is the non-random association between the loci and it could give us a preliminary insight into the genetic history of the population. In the present study LD patterns and effective population size (Ne) of three Korean cattle breeds along with Chinese, Japanese and Mongolian cattle were compared using the bovine Illumina SNP50 panel. The effective population size (Ne) is the number of breeding individuals in a population and is particularly important as it determines the rate at which genetic variation is lost. The genotype data in our study comprised a total of 129 samples, varying from 4 to 39 samples. After quality control there were ~29,000 single nucleotide polymorphisms (SNPs) for which r2 value was calculated. Average distance between SNP pairs was 1.14 Mb across all breeds. Average r2 between adjacent SNP pairs ranged between was 0.1 for Yanbian to 0.3 for Qinchuan. Effective population size of the breeds based on r2 varied from 16 in Hainan to 226 in Yanbian. Amongst the Korean native breeds effective population size of Brindle Hanwoo was the least with Ne = 59 and Brown Hanwoo was the highest with Ne = 83. The effective population size of the Korean cattle breeds has been decreasing alarmingly over the past generations. We suggest appropriate measures to be taken to prevent these local breeds in their native tracts. PMID:28154516

  6. SNP-based markers for discriminating olive (Olea europaea L.) cultivars.

    PubMed

    Reale, S; Doveri, S; Díaz, A; Angiolillo, A; Lucentini, L; Pilla, F; Martín, A; Donini, P; Lee, D

    2006-09-01

    A set of 11 polymorphic markers (1 cleaved amplified polymorphic sequence (CAPS), 2 sequence-characterized amplified regions (SCARs), and 8 single-nucleotide polymorphism (SNP)-derived markers) was obtained for olive cultivar identification by comparing DNA sequences from different accessions. Marker development was more efficient, using sequences from the database rather than cloning arbitrary DNA fragments. Analyses of the sequences of 3 genes from 11 diverse cultivars revealed an SNP frequency of 1 per 190 base pairs in exons and 1 per 149 base pairs in introns. Most mutations were silent or had little perceptible effect on the polypeptide encoded. The higher incidence of transversions (55%) suggests that methylation is not the major driving force for DNA base changes. Evidence of linkage disequilibrium in 2 pairs of markers has been detected. The set of predominantly SNP-based markers was used to genotype 65 olive samples obtained from Europe and Australia, and was able clearly to discriminate 77% of the cultivars. Samples, putatively of the same cultivar but derived from different sources, were revealed as identical, demonstrating the utility of these markers as tools for resolving nomenclature issues. Genotyping data were used for constructing a dendrogram by UPGMA cluster analysis using the simple matching similarity coefficient. Relationships between cultivars are discussed in relation to the route of olive's spread.

  7. 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

  8. High-throughput SNP-genotyping analysis of the relationships among Ponto-Caspian sturgeon species.

    PubMed

    Rastorguev, Sergey M; Nedoluzhko, Artem V; Mazur, Alexander M; Gruzdeva, Natalia M; Volkov, Alexander A; Barmintseva, Anna E; Mugue, Nikolai S; Prokhortchouk, Egor B

    2013-08-01

    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.

  9. 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.

  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. 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

  12. Triallelic SNP-mediated genotyping of regenerated protoplasts of the heterokaryotic fungus Rhizoctonia solani.

    PubMed

    Thomas, Elizabeth; Pakala, Suman; Fedorova, Natalie D; Nierman, William C; Cubeta, Marc A

    2012-04-15

    The aneuploid and heterokaryotic nuclear condition of the soil fungus Rhizoctonia solani have provided challenges in obtaining a complete genome sequence. To better aid in the assembly and annotation process, a protoplast and single nucleotide polymorphism (SNP)-based method was developed to identify regenerated protoplasts with a reduced nuclear genome. Protocol optimization experiments showed that enzymatic digestion of mycelium from a 24 h culture of R. solani increased the proportion of protoplasts with a diameter of ≤7.5 μm and 1-4 nuclei. To determine whether strains regenerated from protoplasts with a reduced number of nuclei were genetically different from the parental strain, triallelic SNPs identified from variance records of the genomic DNA sequence reads of R. solani were used in PCR-based genotyping assays. Results from 16 of the 24 SNP-based PCR assays provided evidence that one of the three alleles was missing in the 11 regenerated protoplast strains, suggesting that these strains represent a reduced genomic complement of the parental strain. The protoplast and triallelic SNP-based method used in this study may be useful in strain development and analysis of other basidiomycete fungi with complex nuclear genomes.

  13. 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.

  14. 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

  15. Quadruplex-single nucleotide polymorphisms (Quad-SNP) influence gene expression difference among individuals.

    PubMed

    Baral, Aradhita; Kumar, Pankaj; Halder, Rashi; Mani, Prithvi; Yadav, Vinod Kumar; Singh, Ankita; Das, Swapan K; Chowdhury, Shantanu

    2012-05-01

    Non-canonical guanine quadruplex structures are not only predominant but also conserved among bacterial and mammalian promoters. Moreover recent findings directly implicate quadruplex structures in transcription. These argue for an intrinsic role of the structural motif and thereby posit that single nucleotide polymorphisms (SNP) that compromise the quadruplex architecture could influence function. To test this, we analysed SNPs within quadruplex motifs (Quad-SNP) and gene expression in 270 individuals across four populations (HapMap) representing more than 14,500 genotypes. Findings reveal significant association between quadruplex-SNPs and expression of the corresponding gene in individuals (P < 0.0001). Furthermore, analysis of Quad-SNPs obtained from population-scale sequencing of 1000 human genomes showed relative selection bias against alteration of the structural motif. To directly test the quadruplex-SNP-transcription connection, we constructed a reporter system using the RPS3 promoter-remarkable difference in promoter activity in the 'quadruplex-destabilized' versus 'quadruplex-intact' promoter was noticed. As a further test, we incorporated a quadruplex motif or its disrupted counterpart within a synthetic promoter reporter construct. The quadruplex motif, and not the disrupted-motif, enhanced transcription in human cell lines of different origin. Together, these findings build direct support for quadruplex-mediated transcription and suggest quadruplex-SNPs may play significant role in mechanistically understanding variations in gene expression among individuals.

  16. Demographic Trends in Korean Native Cattle Explained Using Bovine SNP50 Beadchip.

    PubMed

    Sharma, Aditi; Lim, Dajeong; Chai, Han-Ha; Choi, Bong-Hwan; Cho, Yongmin

    2016-12-01

    Linkage disequilibrium (LD) is the non-random association between the loci and it could give us a preliminary insight into the genetic history of the population. In the present study LD patterns and effective population size (Ne) of three Korean cattle breeds along with Chinese, Japanese and Mongolian cattle were compared using the bovine Illumina SNP50 panel. The effective population size (Ne) is the number of breeding individuals in a population and is particularly important as it determines the rate at which genetic variation is lost. The genotype data in our study comprised a total of 129 samples, varying from 4 to 39 samples. After quality control there were ~29,000 single nucleotide polymorphisms (SNPs) for which r(2) value was calculated. Average distance between SNP pairs was 1.14 Mb across all breeds. Average r(2) between adjacent SNP pairs ranged between was 0.1 for Yanbian to 0.3 for Qinchuan. Effective population size of the breeds based on r(2) varied from 16 in Hainan to 226 in Yanbian. Amongst the Korean native breeds effective population size of Brindle Hanwoo was the least with Ne = 59 and Brown Hanwoo was the highest with Ne = 83. The effective population size of the Korean cattle breeds has been decreasing alarmingly over the past generations. We suggest appropriate measures to be taken to prevent these local breeds in their native tracts.

  17. FASTSNP: an always up-to-date and extendable service for SNP function analysis and prioritization

    PubMed Central

    Yuan, Hsiang-Yu; Chiou, Jen-Jie; Tseng, Wen-Hsien; Liu, Chia-Hung; Liu, Chuan-Kun; Lin, Yi-Jung; Wang, Hui-Hung; Yao, Adam; Chen, Yuan-Tsong; Hsu, Chun-Nan

    2006-01-01

    Single nucleotide polymorphism (SNP) prioritization based on the phenotypic risk is essential for association studies. Assessment of the risk requires access to a variety of heterogeneous biological databases and analytical tools. FASTSNP (function analysis and selection tool for single nucleotide polymorphisms) is a web server that allows users to efficiently identify and prioritize high-risk SNPs according to their phenotypic risks and putative functional effects. A unique feature of FASTSNP is that the functional effect information used for SNP prioritization is always up-to-date, because FASTSNP extracts the information from 11 external web servers at query time using a team of web wrapper agents. Moreover, FASTSNP is extendable by simply deploying more Web wrapper agents. To validate the results of our prioritization, we analyzed 1569 SNPs from the SNP500Cancer database. The results show that SNPs with a high predicted risk exhibit low allele frequencies for the minor alleles, consistent with a well-known finding that a strong selective pressure exists for functional polymorphisms. We have been using FASTSNP for 2 years and FASTSNP enables us to discover a novel promoter polymorphism. FASTSNP is available at . PMID:16845089

  18. Rapid Detection of Rare Deleterious Variants by Next Generation Sequencing with Optional Microarray SNP Genotype Data.

    PubMed

    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; Carr, Ian M

    2015-09-01

    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.

  19. SNP discovery and development of a high-density genotyping array for sunflower.

    PubMed

    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.

  20. 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

  1. Citrus (Rutaceae) SNP markers based on Competitive Allele-Specific PCR; transferability across the Aurantioideae subfamily1

    PubMed Central

    Garcia-Lor, Andres; Ancillo, Gema; Navarro, Luis; Ollitrault, Patrick

    2013-01-01

    • Premise of the study: Single nucleotide polymorphism (SNP) markers based on Competitive Allele-Specific PCR (KASPar) were developed from sequences of three Citrus species. Their transferability was tested in 63 Citrus genotypes and 19 relative genera of the subfamily Aurantioideae to estimate the potential of SNP markers, selected from a limited intrageneric discovery panel, for ongoing broader diversity analysis at the intra- and intergeneric levels and systematic germplasm bank characterization. • Methods and Results: Forty-two SNP markers were developed using KASPar technology. Forty-one were successfully genotyped in all of the Citrus germplasm, where intra- and interspecific polymorphisms were observed. The transferability and diversity decreased with increasing taxonomic distance. • Conclusions: SNP markers based on the KASPar method developed from sequence data of a limited intrageneric discovery panel provide a valuable molecular resource for genetic diversity analysis of germplasm within a genus and should be useful for germplasm fingerprinting at a much broader diversity level. PMID:25202535

  2. 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...

  3. [Novel mechanism of 3' exonuclease of polymerase in maintenance of DNA replication fidelity and its application in SNP assay].

    PubMed

    Chen, Lin-Ling; Zhang, Jia; Peng, Cui-Ying; Liao, Duan-Fang; Li, Hong-Jian; Gao, Han-Lin; Li, Kai

    2005-03-01

    Polymerase with 3' to 5'exonulcease plays an important role in the maintenance of in vivo DNA replication fidelity. In order to develop more reliable SNP assays, we revisit the underlying molecular mechanisms by which DNA polymerases with 3' exonucleases maintain high fidelity of DNA replication. In addition to mismatch removal by proofreading, we recently discovered a premature termination of polymerization by a new mechanism of OFF-switch. This novel ON/OFF switch turns off DNA polymerization from mismatched primers and turns on DNA polymerization from matched primers. Two SNP assays were developed based on the proofreading and the newly identified OFF-switch respectively: terminal labeled primer extension and the ON/OFF switch operated SNP assay. These two new methods are well adapted to conventional techniques such as electrophoresis, real time PCR, microplates, and microarray. Application of these reliable SNP assays will greatly facilitate genetic and biomedical studies in the post-genome era.

  4. A Multiple-SNP Approach for Genome-Wide Association Study of Milk Production Traits in Chinese Holstein Cattle

    PubMed Central

    Fang, Ming; Fu, Weixuan; Jiang, Dan; Zhang, Qin; Sun, Dongxiao; Ding, Xiangdong; Liu, Jianfeng

    2014-01-01

    The multiple-SNP analysis has been studied by many researchers, in which the effects of multiple SNPs are simultaneously estimated and tested in a multiple linear regression. The multiple-SNP association analysis usually has higher power and lower false-positive rate for detecting causative SNP(s) than single marker analysis (SMA). Several methods have been proposed to simultaneously estimate and test multiple SNP effects. In this research, a fast method called MEML (Mixed model based Expectation-Maximization Lasso algorithm) was developed for simultaneously estimate of multiple SNP effects. An improved Lasso prior was assigned to SNP effects which were estimated by searching the maximum joint posterior mode. The residual polygenic effect was included in the model to absorb many tiny SNP effects, which is treated as missing data in our EM algorithm. A series of simulation experiments were conducted to validate the proposed method, and the results showed that compared with SMMA, the new method can dramatically decrease the false-positive rate. The new method was also applied to the 50k SNP-panel dataset for genome-wide association study of milk production traits in Chinese Holstein cattle. Totally, 39 significant SNPs and their nearby 25 genes were found. The number of significant SNPs is remarkably fewer than that by SMMA which found 105 significant SNPs. Among 39 significant SNPs, 8 were also found by SMMA and several well-known QTLs or genes were confirmed again; furthermore, we also got some positional candidate gene with potential function of effecting milk production traits. These novel findings in our research should be valuable for further investigation. PMID:25148050

  5. 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

  6. TheSNPpit-A High Performance Database System for Managing Large Scale SNP Data.

    PubMed

    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

  7. 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.

  8. 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

  9. Supplementing High-Density SNP Microarrays for Additional Coverage of Disease-Related Genes: Addiction as a Paradigm

    PubMed Central

    Saccone, Scott F.; Bierut, Laura J.; Chesler, Elissa J.; Kalivas, Peter W.; Lerman, Caryn; Saccone, Nancy L.; Uhl, George R.; Li, Chuan-Yun; Philip, Vivek M.; Edenberg, Howard J.; Sherry, Stephen T.; 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. PMID:19381300

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. A Proposal of a Load/Source Simulator Based on the UPFC (Unified Power Flow Controller) and Operating Performance of a 200-V, 10-kW Laboratory System

    NASA Astrophysics Data System (ADS)

    Taguchi, Yoshiaki; Akagi, Hirofumi

    The main purpose of a load/source simulator is to imitate an actual load/source in terms of power or current. This paper proposes a novel load/source simulator based on the unified power flow controller that is one of FACTS devices. This system takes the following prominent advantage: The converter volt-ampere rating required for the proposed system is much smaller than that for a conventional system based on a BTB (Back-To-Back) converter. Experimental results obtained from a 200-V, 10-kW laboratory system confirm the viability and effectiveness of the system. This paper also discusses the control method theoretically, and analyzes a voltage fluctuation of the dc link, thus leading to system design.

  15. 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

  16. 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.

  17. 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

  18. 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

  19. SNP identification and SNAP marker development for a GmNARK gene controlling supernodulation in soybean.

    PubMed

    Kim, M Y; Van, K; Lestari, P; Moon, J-K; Lee, S-H

    2005-04-01

    Supernodulation in soybean (Glycine max L. Merr.) is an important source of nitrogen supply to subterranean ecological systems. Single nucleotide-amplified polymorphism (SNAP) markers for supernodulation should allow rapid screening of the trait in early growth stages, without the need for inoculation and phenotyping. The gene GmNARK (Glycine max nodule autoregulation receptor kinase), controlling autoregulation of nodulation, was found to have a single nucleotide polymorphism (SNP) between the wild-type cultivar Sinpaldalkong 2 and its supernodulating mutant, SS2-2. Transversion of A to T at the 959-bp position of the GmNARK sequence results in a change of lysine (AAG) to a stop codon (TAG), thus terminating its translation in SS2-2. Based on the identified SNP in GmNARK, five primer pairs specific to each allele were designed using the WebSnaper program to develop a SNAP marker for supernodulation. One A-specific primer pair produced a band present in only Sinpaldalkong 2, while two T-specific pairs showed a band in only SS2-2. Both complementary PCRs, using each allele-specific primer pair were performed to genotype supernodulation against F2 progeny of Sinpaldalkong 2 x SS2-2. Among 28 individuals with the normal phenotype, eight individuals having only the A-allele-specific band were homozygous and normal, while 20 individuals were found to be heterozygous at the SNP having both A and T bands. Twelve supernodulating individuals showed only the band specific to the T allele. This SNAP marker for supernodulation could easily be analyzed through simple PCR and agarose gel electrophoresis. Therefore, use of this SNAP marker might be faster, cheaper, and more reproducible than using other genotyping methods, such as a cleaved amplified polymorphic sequence marker, which demand of restriction enzymes.

  20. Transcriptome-based SNP discovery by GBS and the construction of a genetic map for olive.

    PubMed

    İpek, Ahmet; İpek, Meryem; Ercişli, Sezai; Tangu, Nesrin Aktepe

    2017-02-18

    Molecular markers located in the genic regions of plants are valuable tools for the identification of candidate genes of economically important traits and consequent use in marker-assisted selection (MAS). In the past, simple sequence repeat markers (SSRs) and single-nucleotide polymorphisms (SNPs) located in expressed sequence tags (ESTs) were developed by sequencing RNA derived from different plant tissues, which involves laborious RNA extraction, mRNA isolation, and cDNA synthesis. In order to develop SNP markers located in olive transcriptomes, we used the recently developed genotyping-by-sequencing (GBS) technique. An analysis was done for 125 olive DNA samples (123 DNA samples from a cross-pollinated F1 mapping population, and two samples from parents). From 45 to 66% of Illumina reads from GBS analysis were aligned to the olive transcriptome. A total of 22,033 transcriptome-based SNP markers were identified, and 3384 of these were mapped in the olive genome. The genetic linkage map constructed in this study consists of 1 cleaved amplified polymorphic sequence (CAPS), 19 SSR, and 3384 transcriptome-based SNP markers. The map covers 3340.8 cM of the olive genome in 23 linkage groups, with the length of the linkage groups ranging from 55.6 to 248.7 cM. Average map distance between flanking markers was 0.98 cM. This genetic linkage map is a saturated genetic map and will be a useful tool for the localization of quantitative trait loci (QTLs) and gene(s) of interest and for the identification of candidate genes for economically important traits.

  1. SNP variation in ADRB3 gene reflects the breed difference of sheep populations.

    PubMed

    Wu, Jianliang; Qiao, Liying; Liu, Jianhua; Yuan, Yanan; Liu, Wenzhong

    2012-08-01

    The β3-adrenergic receptor (ADRB3), a G-protein coupled receptor, plays a major role in energy metabolism and regulation of lipolysis and homeostasis. We detect the single nucleotide polymorphism (SNP) variation in full-length sequence of ovine ADRB3 gene in 12 domestic sheep populations within four types by polymerase chain reaction-single strand conformation polymorphism and sequencing to reveal the breed difference. Twenty-two SNPs, 12 of which in the exon 1 and ten in the intron, were detected, and 12 new exonic and four new intronic SNPs were found. Most SNPs presented in Shanxi Dam Line and least ones in Dorset. The average SNP number in both meat and dual purpose for meat and wool breeds was significantly higher than general and dual purpose breeds for wool and meat. Frequency of each SNP in studied breeds or types was different. The 18C Del and 1617T Ins majorly existed in dual purpose breeds for wool and meat. The 25A Del, 119C>G and 130C>T were mostly found in the meat and dual purpose for meat and wool breeds. The 1764C>A more frequently presented in meat than in other types. The majority of variations came from within the populations as suggested by analysis of molecular variance. Close relationship presented among the Chinese and western breeds, respectively. In conclusion, SNPs of ovine ADRB3 gene can reflect the breed difference and within- and between-population variations, and to a great extent, the breed relationship.

  2. Validation of a Cost-Efficient Multi-Purpose SNP Panel for Disease Based Research

    PubMed Central

    Hou, Liping; Phillips, Christopher; Azaro, Marco; Brzustowicz, Linda M.; Bartlett, Christopher W.

    2011-01-01

    Background Here we present convergent methodologies using theoretical calculations, empirical assessment on in-house and publicly available datasets as well as in silico simulations, that validate a panel of SNPs for a variety of necessary tasks in human genetics disease research before resources are committed to larger-scale genotyping studies on those samples. While large-scale well-funded human genetic studies routinely have up to a million SNP genotypes, samples in a human genetics laboratory that are not yet part of such studies may be productively utilized in pilot projects or as part of targeted follow-up work though such smaller scale applications require at least some genome-wide genotype data for quality control purposes such as DNA “barcoding” to detect swaps or contamination issues, determining familial relationships between samples and correcting biases due to population effects such as population stratification in pilot studies. Principal Findings Empirical performance in classification of relative types for any two given DNA samples (e.g., full siblings, parental, etc) indicated that for outbred populations the panel performs sufficiently to classify relationship in extended families and therefore also for smaller structures such as trios and for twin zygosity testing. Additionally, familial relationships do not significantly diminish the (mean match) probability of sharing SNP genotypes in pedigrees, further indicating the uniqueness of the “barcode.” Simulation using these SNPs for an African American case-control disease association study demonstrated that population stratification, even in complex admixed samples, can be adequately corrected under a range of disease models using the SNP panel. Conclusion The panel has been validated for use in a variety of human disease genetics research tasks including sample barcoding, relationship verification, population substructure detection and statistical correction. Given the ease of genotyping

  3. 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.

  4. A Whole Methylome CpG-SNP Association Study of Psychosis in Blood and Brain Tissue.

    PubMed

    van den Oord, Edwin J C G; Clark, Shaunna L; Xie, Lin Ying; Shabalin, Andrey A; Dozmorov, Mikhail G; Kumar, Gaurav; Vladimirov, Vladimir I; Magnusson, Patrik K E; Aberg, Karolina A

    2016-07-01

    Mutated CpG sites (CpG-SNPs) are potential hotspots for human diseases because in addition to the sequence variation they may show individual differences in DNA methylation. We performed methylome-wide association studies (MWAS) to test whether methylation differences at those sites were associated with schizophrenia. We assayed all common CpG-SNPs with methyl-CpG binding domain protein-enriched genome sequencing (MBD-seq) using DNA extracted from 1408 blood samples and 66 postmortem brain samples (BA10) of schizophrenia cases and controls. Seven CpG-SNPs passed our FDR threshold of 0.1 in the blood MWAS. Of the CpG-SNPs methylated in brain, 94% were also methylated in blood. This significantly exceeded the 46.2% overlap expected by chance (P-value < 1.0×10(-8)) and justified replicating findings from blood in brain tissue. CpG-SNP rs3796293 in IL1RAP replicated (P-value = .003) with the same direction of effects. This site was further validated through targeted bisulfite pyrosequencing in 736 independent case-control blood samples (P-value < 9.5×10(-4)). Our top result in the brain MWAS (P-value = 8.8×10(-7)) was CpG-SNP rs16872141 located in the potential promoter of ENC1. Overall, our results suggested that CpG-SNP methylation may reflect effects of environmental insults and can provide biomarkers in blood that could potentially improve disease management.

  5. Solar Radiation-Associated Adaptive SNP Genetic Differentiation in Wild Emmer Wheat, Triticum dicoccoides

    PubMed Central

    Ren, Jing; Chen, Liang; Jin, Xiaoli; Zhang, Miaomiao; You, Frank M.; Wang, Jirui; Frenkel, Vladimir; Yin, Xuegui; Nevo, Eviatar; Sun, Dongfa; Luo, Ming-Cheng; Peng, Junhua

    2017-01-01

    Whole-genome scans with large number of genetic markers provide the opportunity to investigate local adaptation in natural populations and identify candidate genes under positive selection. In the present study, adaptation genetic differentiation associated with solar radiation was investigated using 695 polymorphic SNP markers in wild emmer wheat originated in a micro-site at Yehudiyya, Israel. The test involved two solar radiation niches: (1) sun, in-between trees; and (2) shade, under tree canopy, separated apart by a distance of 2–4 m. Analysis of molecular variance showed a small (0.53%) but significant portion of overall variation between the sun and shade micro-niches, indicating a non-ignorable genetic differentiation between sun and shade habitats. Fifty SNP markers showed a medium (0.05 ≤ FST ≤ 0.15) or high genetic differentiation (FST > 0.15). A total of 21 outlier loci under positive selection were identified by using four different FST-outlier testing algorithms. The markers and genome locations under positive selection are consistent with the known patterns of selection. These results suggested that genetic differentiation between sun and shade habitats is substantial, radiation-associated, and therefore ecologically determined. Hence, the results of this study reflected effects of natural selection through solar radiation on EST-related SNP genetic diversity, resulting presumably in different adaptive complexes at a micro-scale divergence. The present work highlights the evolutionary theory and application significance of solar radiation-driven natural selection in wheat improvement. PMID:28352272

  6. 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.

  7. 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.

  8. Estimation of effective population size using single-nucleotide polymorphism (SNP) data in Jeju horse.

    PubMed

    Do, Kyoung-Tag; Lee, Joon-Ho; Lee, Hak-Kyo; Kim, Jun; Park, Kyung-Do

    2014-01-01

    This study was conducted to estimate the effective population size using SNPs data of 240 Jeju horses that had raced at the Jeju racing park. Of the total 61,746 genotyped autosomal SNPs, 17,320 (28.1%) SNPs (missing genotype rate of >10%, minor allele frequency of <0.05 and Hardy-Weinberg equilibrium test P-value of <10(-6)) were excluded after quality control processes. SNPs on the X and Y chromosomes and genotyped individuals with missing genotype rate over 10% were also excluded, and finally, 44,426 (71.9%) SNPs were selected and used for the analysis. The measures of the LD, square of correlation coefficient (r(2)) between SNP pairs, were calculated for each allele and the effective population size was determined based on r(2) measures. The polymorphism information contents (PIC) and expected heterozygosity (HE) were 0.27 and 0.34, respectively. In LD, the most rapid decline was observed over the first 1 Mb. But r(2) decreased more slowly with increasing distance and was constant after 2 Mb of distance and the decline was almost linear with log-transformed distance. The average r(2) between adjacent SNP pairs ranged from 0.20 to 0.31 in each chromosome and whole average was 0.26, while the whole average r(2) between all SNP pairs was 0.02. We observed an initial pattern of decreasing Ne and estimated values were closer to 41 at 1 ~ 5 generations ago. The effective population size (41 heads) estimated in this study seems to be large considering Jeju horse's population size (about 2,000 heads), but it should be interpreted with caution because of the technical limitations of the methods and sample size.

  9. High-Throughput SNP Allele-Frequency Determination in Pooled DNA Samples by Kinetic PCR

    PubMed Central

    Germer, Søren; Holland, Michael J.; Higuchi, Russell

    2000-01-01

    We have developed an accurate, yet inexpensive and high-throughput, method for determining the allele frequency of biallelic polymorphisms in pools of DNA samples. The assay combines kinetic (real-time quantitative) PCR with allele-specific amplification and requires no post-PCR processing. The relative amounts of each allele in a sample are quantified. This is performed by dividing equal aliquots of the pooled DNA between two separate PCR reactions, each of which contains a primer pair specific to one or the other allelic SNP variant. For pools with equal amounts of the two alleles, the two amplifications should reach a detectable level of fluorescence at the same cycle number. For pools that contain unequal ratios of the two alleles, the difference in cycle number between the two amplification reactions can be used to calculate the relative allele amounts. We demonstrate the accuracy and reliability of the assay on samples with known predetermined SNP allele frequencies from 5% to 95%, including pools of both human and mouse DNAs using eight different SNPs altogether. The accuracy of measuring known allele frequencies is very high, with the strength of correlation between measured and known frequencies having an r2 = 0.997. The loss of sensitivity as a result of measurement error is typically minimal, compared with that due to sampling error alone, for population samples up to 1000. We believe that by providing a means for SNP genotyping up to thousands of samples simultaneously, inexpensively, and reproducibly, this method is a powerful strategy for detecting meaningful polymorphic differences in candidate gene association studies and genome-wide linkage disequilibrium scans. PMID:10673283

  10. 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.

  11. mrsFAST-Ultra: a compact, SNP-aware mapper for high performance sequencing applications.

    PubMed

    Hach, Faraz; Sarrafi, Iman; Hormozdiari, Farhad; Alkan, Can; Eichler, Evan E; Sahinalp, S Cenk

    2014-07-01

    High throughput sequencing (HTS) platforms generate unprecedented amounts of data that introduce challenges for processing and downstream analysis. While tools that report the 'best' mapping location of each read provide a fast way to process HTS data, they are not suitable for many types of downstream analysis such as structural variation detection, where it is important to report multiple mapping loci for each read. For this purpose we introduce mrsFAST-Ultra, a fast, cache oblivious, SNP-aware aligner that can handle the multi-mapping of HTS reads very efficiently. mrsFAST-Ultra improves mrsFAST, our first cache oblivious read aligner capable of handling multi-mapping reads, through new and compact index structures that reduce not only the overall memory usage but also the number of CPU operations per alignment. In fact the size of the index generated by mrsFAST-Ultra is 10 times smaller than that of mrsFAST. As importantly, mrsFAST-Ultra introduces new features such as being able to (i) obtain the best mapping loci for each read, and (ii) return all reads that have at most n mapping loci (within an error threshold), together with these loci, for any user specified n. Furthermore, mrsFAST-Ultra is SNP-aware, i.e. it can map reads to reference genome while discounting the mismatches that occur at common SNP locations provided by db-SNP; this significantly increases the number of reads that can be mapped to the reference genome. Notice that all of the above features are implemented within the index structure and are not simple post-processing steps and thus are performed highly efficiently. Finally, mrsFAST-Ultra utilizes multiple available cores and processors and can be tuned for various memory settings. Our results show that mrsFAST-Ultra is roughly five times faster than its predecessor mrsFAST. In comparison to newly enhanced popular tools such as Bowtie2, it is more sensitive (it can report 10 times or more mappings per read) and much faster (six times or

  12. Single-cell SNP analyses and interpretations based on RNA-Seq data for colon cancer research.

    PubMed

    Chen, Jiahuan; Zhou, Qian; Wang, Yangfan; Ning, Kang

    2016-09-28

    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.

  13. SNP-based discovery of salinity-tolerant QTLs in a bi-parental population of rice (Oryza sativa).

    PubMed

    Gimhani, D R; Gregorio, Glenn B; Kottearachchi, N S; Samarasinghe, W L G

    2016-12-01

    Breeding for salt tolerance is the most promising approach to enhance the productivity of saline prone areas. However, polygenic inheritance of salt tolerance in rice acts as a bottleneck in conventional breeding for salt tolerance. Hence, we set our goals to construct a single nucleotide polymorphism (SNP)-based molecular map employing high-throughput SNP marker technology and to investigate salinity tolerant QTLs with closest flanking markers using an elite rice background. Seedling stage salinity responses were assessed in a population of 281 recombinant inbred lines (RILs) derived from the cross between At354 (salt tolerant) and Bg352 (salt susceptible), by 11 morpho-physiological indices under a hydroponic system. Selected extreme 94 RILs were genotyped using Illumina Infinium rice 6K SNP array and densely saturated molecular map spanning 1460.81 cM of the rice genome with an average interval of 1.29 cM between marker loci was constructed using 1135 polymorphic SNP markers. The results revealed 83 significant QTLs for 11 salt responsive traits explaining 12.5-46.7 % of phenotypic variation in respective traits. Of them, 72 QTLs responsible for 10 traits were co-localized together forming 14 QTL hotspots at 14 different genomic regions. The all QTL hotspots were flanked less than 1 Mb intervals and therefore the SNP loci associated with these QTL hotspots would be important in candidate gene discovery for salt tolerance.

  14. A chromatin-associated and transcriptionally inactive p53-Mdm2 complex occurs in mdm2 SNP309 homozygous cells.

    PubMed

    Arva, Nicoleta C; Gopen, Tamara R; Talbott, Kathryn E; Campbell, Latoya E; Chicas, Agustin; White, David E; Bond, Gareth L; Levine, Arnold J; Bargonetti, Jill

    2005-07-22

    In cancer cells, the function of the tumor suppressor protein p53 is usually blocked. Impairment of the p53 pathway results in tumor cells with endogenous overexpression of Mdm2 via a naturally occurring single nucleotide polymorphism (SNP) in the mdm2 gene at position 309. Here we report that in mdm2 SNP309 cells, inactivation of p53 results in a chromatin-associated Mdm2-p53 complex without clearance of p53 by protein degradation. Nuclear accumulation of p53 protein in mdm2 SNP309 cells results after 6 h of camptothecin, etoposide, or mitomycin C treatment, with the p53 protein phosphorylated at Ser15. Chromatin immunoprecipitation demonstrated p53 and Mdm2 bound to p53 responsive elements. Interestingly, although the p53 protein was able to bind to DNA, quantitative PCR showed compromised transcription of endogenous target genes. Additionally, exogenously introduced p53 was incapable of activating transcription from p53 responsive elements in SNP309 cells, confirming the trans-acting nature of the inhibitor. Inhibition of Mdm2 by siRNA resulted in transcriptional activation of these p53 targets. Our data suggest that overproduction of Mdm2, resulting from a naturally occurring SNP, inhibits chromatin-bound p53 from activating the transcription of its target genes.

  15. IL-32 promoter SNP rs4786370 predisposes to modified lipoprotein profiles in patients with rheumatoid arthritis

    PubMed Central

    Damen, Michelle S. M. A.; Agca, Rabia; Holewijn, Suzanne; de Graaf, Jacqueline; Dos Santos, Jéssica C.; van Riel, Piet L.; Fransen, Jaap; Coenen, Marieke J. H.; Nurmohamed, Mike T.; Netea, Mihai G.; Dinarello, Charles A.; Joosten, Leo A. B.; Heinhuis, Bas; Popa, Calin D.

    2017-01-01

    Patients with rheumatoid arthritis (RA) are at higher risk of developing cardiovascular diseases (CVD). Interleukin (IL)-32 has previously been shown to be involved in the pathogenesis of RA and might be linked to the development of atherosclerosis. However, the exact mechanism linking IL-32 to CVD still needs to be elucidated. The influence of a functional genetic variant of IL-32 on lipid profiles and CVD risk was therefore studied in whole blood from individuals from the NBS cohort and RA patients from 2 independent cohorts. Lipid profiles were matched to the specific IL-32 genotypes. Allelic distribution was similar in all three groups. Interestingly, significantly higher levels of high density lipoprotein cholesterol (HDLc) were observed in individuals from the NBS cohort and RA patients from the Nijmegen cohort homozygous for the C allele (p = 0.0141 and p = 0.0314 respectively). In contrast, the CC-genotype was associated with elevated low density lipoprotein cholesterol (LDLc) and total cholesterol (TC) in individuals at higher risk for CVD (plaque positive) (p = 0.0396; p = 0.0363 respectively). Our study shows a functional effect of a promoter single-nucleotide polymorphism (SNP) in IL32 on lipid profiles in RA patients and individuals, suggesting a possible protective role of this SNP against CVD. PMID:28134327

  16. PrimerMapper: high throughput primer design and graphical assembly for PCR and SNP detection.

    PubMed

    O'Halloran, Damien M

    2016-02-08

    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.

  17. Informatics Enhanced SNP Microarray Analysis of 30 Miscarriage Samples Compared to Routine Cytogenetics

    PubMed Central

    Lathi, Ruth B.; Loring, Megan; Massie, Jamie A. M.; Demko, Zachary P.; Johnson, David; Sigurjonsson, Styrmir; Gemelos, George; Rabinowitz, Matthew

    2012-01-01

    Purpose The metaphase karyotype is often used as a diagnostic tool in the setting of early miscarriage; however this technique has several limitations. We evaluate a new technique for karyotyping that uses single nucleotide polymorphism microarrays (SNP). This technique was compared in a blinded, prospective fashion, to the traditional metaphase karyotype. Methods Patients undergoing dilation and curettage for first trimester miscarriage between February and August 2010 were enrolled. Samples of chorionic villi were equally divided and sent for microarray testing in parallel with routine cytogenetic testing. Results Thirty samples were analyzed, with only four discordant results. Discordant results occurred when the entire genome was duplicated or when a balanced rearrangement was present. Cytogenetic karyotyping took an average of 29 days while microarray-based karytoyping took an average of 12 days. Conclusions Molecular karyotyping of POC after missed abortion using SNP microarray analysis allows for the ability to detect maternal cell contamination and provides rapid results with good concordance to standard cytogenetic analysis. PMID:22403611

  18. Use of Sequenom sample ID Plus® SNP genotyping in identification of FFPE tumor samples.

    PubMed

    Miller, Jessica K; Buchner, Nicholas; Timms, Lee; Tam, Shirley; Luo, Xuemei; Brown, Andrew M K; Pasternack, Danielle; Bristow, Robert G; Fraser, Michael; Boutros, Paul C; McPherson, John D

    2014-01-01

    Short tandem repeat (STR) analysis, such as the AmpFlSTR® Identifiler® Plus kit, is a standard, PCR-based human genotyping method used in the field of forensics. Misidentification of cell line and tissue DNA can be costly if not detected early; therefore it is necessary to have quality control measures such as STR profiling in place. A major issue in large-scale research studies involving archival formalin-fixed paraffin embedded (FFPE) tissues is that varying levels of DNA degradation can result in failure to correctly identify samples using STR genotyping. PCR amplification of STRs of several hundred base pairs is not always possible when DNA is degraded. The Sample ID Plus® panel from Sequenom allows for human DNA identification and authentication using SNP genotyping. In comparison to lengthy STR amplicons, this multiplexing PCR assay requires amplification of only 76-139 base pairs, and utilizes 47 SNPs to discriminate between individual samples. In this study, we evaluated both STR and SNP genotyping methods of sample identification, with a focus on paired FFPE tumor/normal DNA samples intended for next-generation sequencing (NGS). The ability to successfully validate the identity of FFPE samples can enable cost savings by reducing rework.

  19. The use of SNP markers for linkage mapping in diploid and tetraploid peanuts.

    PubMed

    Bertioli, David J; Ozias-Akins, Peggy; Chu, Ye; Dantas, Karinne M; Santos, Silvio P; Gouvea, Ediene; Guimarães, Patricia M; Leal-Bertioli, Soraya C M; Knapp, Steven J; Moretzsohn, Marcio C

    2014-01-10

    Single nucleotide polymorphic markers (SNPs) are attractive for use in genetic mapping and marker-assisted breeding because they can be scored in parallel assays at favorable costs. However, scoring SNP markers in polyploid plants like the peanut is problematic because of interfering signal generated from the DNA bases that are homeologous to those being assayed. The present study used a previously constructed 1536 GoldenGate SNP assay developed using SNPs identified between two A. duranensis accessions. In this study, the performance of this assay was tested on two RIL mapping populations, one diploid (A. duranensis × A. stenosperma) and one tetraploid [A. hypogaea cv. Runner IAC 886 × synthetic tetraploid (A. ipaënsis × A. duranensis)(4×)]. The scoring was performed using the software GenomeStudio version 2011.1. For the diploid, polymorphic markers provided excellent genotyping scores with default software parameters. In the tetraploid, as expected, most of the polymorphic markers provided signal intensity plots that were distorted compared to diploid patterns and that were incorrectly scored using default parameters. However, these scorings were easily corrected using the GenomeStudio software. The degree of distortion was highly variable. Of the polymorphic markers, approximately 10% showed no distortion at all behaving as expected for single-dose markers, and another 30% showed low distortion and could be considered high-quality. The genotyped markers were incorporated into diploid and tetraploid genetic maps of Arachis and, in the latter case, were located almost entirely on A genome linkage groups.

  20. Measuring inbreeding and inbreeding depression on pig growth from pedigree or SNP-derived metrics.

    PubMed

    Silió, L; Rodríguez, M C; Fernández, A; Barragán, C; Benítez, R; Óvilo, C; Fernández, A I

    2013-10-01

    Multilocus homozygosity, measured as the proportion of the autosomal genome in homozygous genotypes or in runs of homozygosity, was compared with the respective pedigree inbreeding coefficients in 64 Iberian pigs genotyped using the Porcine SNP60 Beadchip. Pigs were sampled from a set of experimental animals with a large inbreeding variation born in a closed strain with a completely recorded multi-generation genealogy. Individual inbreeding coefficients calculated from pedigree were strongly correlated with the different SNP-derived metrics of homozygosity (r = 0.814-0.919). However, unequal correlations between molecular and pedigree inbreeding were observed at chromosomal level being mainly dependent on the number of SNPs and on the correlation between heterozygosities measured across different loci. A panel of 192 SNPs of intermediate frequencies was selected for genotyping 322 piglets to test inbreeding depression on postweaning growth performance (daily gain and weight at 90 days). The negative effects on these traits of homozygosities calculated from the genotypes of 168 quality-checked SNPs were similar to those of inbreeding coefficients. The results support that few hundreds of SNPs may be useful for measuring inbreeding and inbreeding depression, when the population structure or the mating system causes a large variance of inbreeding.

  1. Predicting Alzheimer's Disease Using Combined Imaging-Whole Genome SNP Data.

    PubMed

    Kong, Dehan; Giovanello, Kelly S; Wang, Yalin; Lin, Weili; Lee, Eunjee; Fan, Yong; Murali Doraiswamy, P; Zhu, Hongtu

    2015-01-01

    The growing public threat of Alzheimer's disease (AD) has raised the urgency to discover and validate prognostic biomarkers in order to predicting time to onset of AD. It is anticipated that both whole genome single nucleotide polymorphism (SNP) data and high dimensional whole brain imaging data offer predictive values to identify subjects at risk for progressing to AD. The aim of this paper is to test whether both whole genome SNP data and whole brain imaging data offer predictive values to identify subjects at risk for progressing to AD. In 343 subjects with mild cognitive impairment (MCI) enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI-1), we extracted high dimensional MR imaging (volumetric data on 93 brain regions plus a surface fluid registration based hippocampal subregion and surface data), and whole genome data (504,095 SNPs from GWAS), as well as routine neurocognitive and clinical data at baseline. MCI patients were then followed over 48 months, with 150 participants progressing to AD. Combining information from whole brain MR imaging and whole genome data was substantially superior to the standard model for predicting time to onset of AD in a 48-month national study of subjects at risk. Our findings demonstrate the promise of combined imaging-whole genome prognostic markers in people with mild memory impairment.

  2. A Pipeline for Classifying Relationships Using Dense SNP/SNV Data and Putative Pedigree Information.

    PubMed

    Zeng, Zhen; Weeks, Daniel E; Chen, Wei; Mukhopadhyay, Nandita; Feingold, Eleanor

    2016-02-01

    When genome-wide association studies (GWAS) or sequencing studies are performed on family-based datasets, the genotype data can be used to check the structure of putative pedigrees. Even in datasets of putatively unrelated people, close relationships can often be detected using dense single-nucleotide polymorphism/variant (SNP/SNV) data. A number of methods for finding relationships using dense genetic data exist, but they all have certain limitations, including that they typically use average genetic sharing, which is only a subset of the available information. Here, we present a set of approaches for classifying relationships in GWAS datasets or large-scale sequencing datasets. We first propose an empirical method for detecting identity by descent segments in close relative pairs using un-phased dense SNP data and demonstrate how that information can assist in building a relationship classifier. We then develop a strategy to take advantage of putative pedigree information to enhance classification accuracy. Our methods are tested and illustrated with two datasets from two distinct populations. Finally, we propose classification pipelines for checking and identifying relationships in datasets containing a large number of small pedigrees.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. Screening of human SNP database identifies recoding sites of A-to-I RNA editing

    PubMed Central

    Gommans, Willemijn M.; Tatalias, Nicholas E.; Sie, Christina P.; Dupuis, Dylan; Vendetti, Nicholas; Smith, Lauren; Kaushal, Rikhi; Maas, Stefan

    2008-01-01

    Single nucleotide polymorphisms (SNPs) are DNA sequence variations that can affect the expression or function of genes. As a result, they may lead to phenotypic differences between individuals, such as susceptibility to disease, response to medications, and disease progression. Millions of SNPs have been mapped within the human genome providing a rich resource for genetic variation studies. Adenosine-to-inosine RNA editing also leads to the production of RNA and protein sequence variants, but it acts on the level of primary gene transcripts. Sequence variations due to RNA editing may be misannotated as SNPs when relying solely on expressed sequence data instead of genomic material. In this study, we screened the human SNP database for potential cases of A-to-I RNA editing that cause amino acid changes in the encoded protein. Our search strategy applies five molecular features to score candidate sites. It identifies all previously known cases of editing present in the SNP database and successfully uncovers novel, bona fide targets of adenosine deamination editing. Our approach sets the stage for effective and comprehensive genome-wide screens for A-to-I editing targets. PMID:18772245

  9. Genome-wide prediction of cancer driver genes based on SNP and cancer SNV data.

    PubMed

    He, Quanze; He, Quanyuan; Liu, Xiaohui; Wei, Youheng; Shen, Suqin; Hu, Xiaohui; Li, Qiao; Peng, Xiangwen; Wang, Lin; Yu, Long

    2014-01-01

    Identifying cancer driver genes and exploring their functions are essential and the most urgent need in basic cancer research. Developing efficient methods to differentiate between driver and passenger somatic mutations revealed from large-scale cancer genome sequencing data is critical to cancer driver gene discovery. Here, we compared distinct features of SNP with SNV data in detail and found that the weighted ratio of SNV to SNP (termed as WVPR) is an excellent indicator for cancer driver genes. The power of WVPR was validated by accurate predictions of known drivers. We ranked most of human genes by WVPR and did functional analyses on the list. The results demonstrate that driver genes are usually highly enriched in chromatin organization related genes/pathways. And some protein complexes, such as histone acetyltransferase, histone methyltransferase, telomerase, centrosome, sin3 and U12-type spliceosomal complexes, are hot spots of driver mutations. Furthermore, this study identified many new potential driver genes (e.g. NTRK3 and ZIC4) and pathways including oxidative phosphorylation pathway, which were not deemed by previous methods. Taken together, our study not only developed a method to identify cancer driver genes/pathways but also provided new insights into molecular mechanisms of cancer development.

  10. A genome wide survey of SNP variation reveals the genetic structure of sheep breeds.

    PubMed

    Kijas, James W; Townley, David; Dalrymple, Brian P; Heaton, Michael P; Maddox, Jillian F; McGrath, Annette; Wilson, Peter; Ingersoll, Roxann G; McCulloch, Russell; McWilliam, Sean; Tang, Dave; McEwan, John; Cockett, Noelle; Oddy, V Hutton; Nicholas, Frank W; Raadsma, Herman

    2009-01-01

    The genetic structure of sheep reflects their domestication and subsequent formation into discrete breeds. Understanding genetic structure is essential for achieving genetic improvement through genome-wide association studies, genomic selection and the dissection of quantitative traits. After identifying the first genome-wide set of SNP for sheep, we report on levels of genetic variability both within and between a diverse sample of ovine populations. Then, using cluster analysis and the partitioning of genetic variation, we demonstrate sheep are characterised by weak phylogeographic structure, overlapping genetic similarity and generally low differentiation which is consistent with their short evolutionary history. The degree of population substructure was, however, sufficient to cluster individuals based on geographic origin and known breed history. Specifically, African and Asian populations clustered separately from breeds of European origin sampled from Australia, New Zealand, Europe and North America. Furthermore, we demonstrate the presence of stratification within some, but not all, ovine breeds. The results emphasize that careful documentation of genetic structure will be an essential prerequisite when mapping the genetic basis of complex traits. Furthermore, the identification of a subset of SNP able to assign individuals into broad groupings demonstrates even a small panel of markers may be suitable for applications such as traceability.

  11. MultiBLUP: improved SNP-based prediction for complex traits

    PubMed Central

    Balding, David J.

    2014-01-01

    BLUP (best linear unbiased prediction) is widely used to predict complex traits in plant and animal breeding, and increasingly in human genetics. The BLUP mathematical model, which consists of a single random effect term, was adequate when kinships were measured from pedigrees. However, when genome-wide SNPs are used to measure kinships, the BLUP model implicitly assumes that all SNPs have the same effect-size distribution, which is a severe and unnecessary limitation. We propose MultiBLUP, which extends the BLUP model to include multiple random effects, allowing greatly improved prediction when the random effects correspond to classes of SNPs with distinct effect-size variances. The SNP classes can be specified in advance, for example, based on SNP functional annotations, and we also provide an adaptive procedure for determining a suitable partition of SNPs. We apply MultiBLUP to genome-wide association data from the Wellcome Trust Case Control Consortium (seven diseases), and from much larger studies of celiac disease and inflammatory bowel disease, finding that it consistently provides better prediction than alternative methods. Moreover, MultiBLUP is computationally very efficient; for the largest data set, which includes 12,678 individuals and 1.5 M SNPs, the total analysis can be run on a single desktop PC in less than a day and can be parallelized to run even faster. Tools to perform MultiBLUP are freely available in our software LDAK. PMID:24963154

  12. 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.

  13. 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

  14. Forensically relevant SNaPshot(®) assays for human DNA SNP analysis: a review.

    PubMed

    Mehta, Bhavik; Daniel, Runa; Phillips, Chris; McNevin, Dennis

    2017-01-01

    Short tandem repeats are the gold standard for human identification but are not informative for forensic DNA phenotyping (FDP). Single-nucleotide polymorphisms (SNPs) as genetic markers can be applied to both identification and FDP. The concept of DNA intelligence emerged with the potential for SNPs to infer biogeographical ancestry (BGA) and externally visible characteristics (EVCs), which together enable the FDP process. For more than a decade, the SNaPshot(®) technique has been utilised to analyse identity and FDP-associated SNPs in forensic DNA analysis. SNaPshot is a single-base extension (SBE) assay with capillary electrophoresis as its detection system. This multiplexing technique offers the advantage of easy integration into operational forensic laboratories without the requirement for any additional equipment. Further, the SNP panels from SNaPshot(®) assays can be incorporated into customised panels for massively parallel sequencing (MPS). Many SNaPshot(®) assays are available for identity, BGA and EVC profiling with examples including the well-known SNPforID 52-plex identity assay, the SNPforID 34-plex BGA assay and the HIrisPlex EVC assay. This review lists the major forensically relevant SNaPshot(®) assays for human DNA SNP analysis and can be used as a guide for selecting the appropriate assay for specific identity and FDP applications.

  15. 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.

  16. 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.

  17. Y-SNP analysis versus Y-haplogroup predictor in the Slovak population.

    PubMed

    Petrejcíková, Eva; Carnogurská, Jana; Hronská, Danica; Bernasovská, Jarmila; Boronová, Iveta; Gabriková, Dana; Bôziková, Alexandra; Maceková, Sona

    2014-01-01

    Human Y-chromosome haplogroups are important markers used mainly in population genetic studies. The haplogroups are defined by several SNPs according to the phylogeny and international nomenclature. The alternative method to estimate the Y-chromosome haplogroups is to predict Y-chromosome haplotypes from a set of Y-STR markers using software for Y-haplogroup prediction. The purpose of this study was to compare the accuracy of three types of Y-haplogroup prediction software and to determine the structure of Slovak population revealed by the Y-chromosome haplogroups. We used a sample of 166 Slovak males in which 12 Y-STR markers were genotyped in our previous study. These results were analyzed by three different software products that predict Y-haplogroups. To estimate the accuracy of these prediction software, Y-haplogroups were determined in the same sample by genotyping Y-chromosome SNPs. Haplogroups were correctly predicted in 98.80% (Whit Athey's Haplogroup Predictor), 97.59% (Jim Cullen's Haplogroup Predictor) and 98.19% (YPredictor by Vadim Urasin 1.5.0) of individuals. The occurrence of errors in Y-chromosome haplogroup prediction suggests that the validation using SNP analysis is appropriate when high accuracy is required. The results of SNP based haplotype determination indicate that 39.15% of the Slovak population belongs to R1a-M198 lineage, which is one of the main European lineages.

  18. 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.

  19. 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.

  20. SNP-sites: rapid efficient extraction of SNPs from multi-FASTA alignments

    PubMed Central

    Taylor, Ben; Delaney, Aidan J.; Soares, Jorge; Seemann, Torsten; Keane, Jacqueline A.; Harris, Simon R.

    2016-01-01

    Rapidly decreasing genome sequencing costs have led to a proportionate increase in the number of samples used in prokaryotic population studies. Extracting single nucleotide polymorphisms (SNPs) from a large whole genome alignment is now a routine task, but existing tools have failed to scale efficiently with the increased size of studies. These tools are slow, memory inefficient and are installed through non-standard procedures. We present SNP-sites which can rapidly extract SNPs from a multi-FASTA alignment using modest resources and can output results in multiple formats for downstream analysis. SNPs can be extracted from a 8.3 GB alignment file (1842 taxa, 22 618 sites) in 267 seconds using 59 MB of RAM and 1 CPU core, making it feasible to run on modest computers. It is easy to install through the Debian and Homebrew package managers, and has been successfully tested on more than 20 operating systems. SNP-sites is implemented in C and is available under the open source license GNU GPL version 3. PMID:28348851

  1. Linkage Disequilibrium Patterns and tagSNP Transferability among European Populations

    PubMed Central

    Mueller, Jakob C.; Lõhmussaar, Elin; Mägi, Reedik; Remm, Maido; Bettecken, Thomas; Lichtner, Peter; Biskup, Saskia; Illig, Thomas; Pfeufer, Arne; Luedemann, Jan; Schreiber, Stefan; Pramstaller, Peter; Pichler, Irene; Romeo, Giovanni; Gaddi, Anthony; Testa, Alessandra; Wichmann, Heinz-Erich; Metspalu, Andres; Meitinger, Thomas

    2005-01-01

    The pattern of linkage disequilibrium (LD) is critical for association studies, in which disease-causing variants are identified by allelic association with adjacent markers. The aim of this study is to compare the LD patterns in several distinct European populations. We analyzed four genomic regions (in total, 749 kb) containing candidate genes for complex traits. Individuals were genotyped for markers that are evenly distributed at an average spacing of ∼2–4 kb in eight population-based samples from ongoing epidemiological studies across Europe. The Centre d'Etude du Polymorphisme Humain (CEPH) trios of the HapMap project were included and were used as a reference population. In general, we observed a conservation of the LD patterns across European samples. Nevertheless, shifts in the positions of the boundaries of high-LD regions can be demonstrated between populations, when assessed by a novel procedure based on bootstrapping. Transferability of LD information among populations was also tested. In two of the analyzed gene regions, sets of tagging single-nucleotide polymorphisms (tagSNPs) selected from the HapMap CEPH trios performed surprisingly well in all local European samples. However, significant variation in the other two gene regions predicts a restricted applicability of CEPH-derived tagging markers. Simulations based on our data set show the extent to which further gain in tagSNP efficiency and transferability can be achieved by increased SNP density. PMID:15637659

  2. 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

  3. 100 W Kinetically enhanced copper vapor laser at 10 kHz repetition-rate, high (˜1.5%) efficiency with low (˜1.6 kW/l) specific input power and performance of new resonator configurations

    NASA Astrophysics Data System (ADS)

    Singh, Bijendra; Subramaniam, V. V.; Daultabad, S. R.; Chakraborty, Ashim

    2008-09-01

    It is established here that kinetically enhanced copper vapor lasers (KE-CVLs) based on large-bore discharge tubes can provide high (>1.4%) efficiency at ∼9-10 kHz rep-rate with very low (<2 kW/l) specific input power. Comparative performance of various large-bore kinetically enhanced copper vapor lasers in the range 45-70 mm is presented for most suitable discharge tube. Maximum output power of ∼100 W was achieved with efficiency of about 1.55% at 10 kHz rep-rate from the 60 mm bore KE-CVL. The pulse to pulse efficiency of the KE-CVL was ∼2%, tube efficiency ∼2.1%, and laser pulse energy was about ∼10 mJ. These results show significant advancement in the laser system as an elemental high temperature CVL due to volumetric scaling and KE-effects combined with very low specific input power of ∼1.65 kW/l as compared to 8-9 kW/l normally required in other kinetically enhanced copper vapor lasers to generate ∼100 W output power. Performance of the KE-CVL with 3 new cavity configurations namely, (1) CAT-EYE resonator (2) hybrid resonator, and (3) modified diffraction coupled resonator with dot mirrors are presented for the first here. CAT-EYE resonator was demonstrated to achieve high misalignment tolerance without significant loss of power. A typical drift in power of ∼5% was observed with misalignment responsible for 40% decline in power in case of standard plane-plane cavity. Effect of resonator misalignment on amplifier output drift was also investigated using CAT-EYE resonator in oscillator-amplifier configuration. In case of using stable-unstable hybrid resonator, high magnification of M ∼ 1500 was realized resulting in extremely low divergence (∼0.08 mrad) beam with modest (∼20%) loss in average power. In case of modified DCR cavity, record power of about 48 W was achieved with beam divergence of about 0.1 mrad on using intra-cavity 2 × 2 array of 4 dot mirrors.

  4. Population structure of Atlantic mackerel inferred from RAD-seq-derived SNP markers: effects of sequence clustering parameters and hierarchical SNP selection.

    PubMed

    Rodríguez-Ezpeleta, Naiara; Bradbury, Ian R; Mendibil, Iñaki; Álvarez, Paula; Cotano, Unai; Irigoien, Xabier

    2016-07-01

    Restriction-site-associated DNA sequencing (RAD-seq) and related methods are revolutionizing the field of population genomics in nonmodel organisms as they allow generating an unprecedented number of single nucleotide polymorphisms (SNPs) even when no genomic information is available. Yet, RAD-seq data analyses rely on assumptions on nature and number of nucleotide variants present in a single locus, the choice of which may lead to an under- or overestimated number of SNPs and/or to incorrectly called genotypes. Using the Atlantic mackerel (Scomber scombrus L.) and a close relative, the Atlantic chub mackerel (Scomber colias), as case study, here we explore the sensitivity of population structure inferences to two crucial aspects in RAD-seq data analysis: the maximum number of mismatches allowed to merge reads into a locus and the relatedness of the individuals used for genotype calling and SNP selection. Our study resolves the population structure of the Atlantic mackerel, but, most importantly, provides insights into the effects of alternative RAD-seq data analysis strategies on population structure inferences that are directly applicable to other species.

  5. SNP@Domain: a web resource of single nucleotide polymorphisms (SNPs) within protein domain structures and sequences

    PubMed Central

    Han, Areum; Kang, Hyo Jin; Cho, Yoobok; Lee, Sunghoon; Kim, Young Joo; Gong, Sungsam

    2006-01-01

    The single nucleotide polymorphisms (SNPs) in conserved protein regions have been thought to be strong candidates that alter protein functions. Thus, we have developed SNP@Domain, a web resource, to identify SNPs within human protein domains. We annotated SNPs from dbSNP with protein structure-based as well as sequence-based domains: (i) structure-based using SCOP and (ii) sequence-based using Pfam to avoid conflicts from two domain assignment methodologies. Users can investigate SNPs within protein domains with 2D and 3D maps. We expect this visual annotation of SNPs within protein domains will help scientists select and interpret SNPs associated with diseases. A web interface for the SNP@Domain is freely available at and from . PMID:16845090

  6. 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).

  7. SNP@lincTFBS: an integrated database of polymorphisms in human LincRNA transcription factor binding sites.

    PubMed

    Ning, Shangwei; Zhao, Zuxianglan; Ye, Jingrun; Wang, Peng; Zhi, Hui; Li, Ronghong; Wang, Tingting; Wang, Jianjian; Wang, Lihua; Li, Xia

    2014-01-01

    Large intergenic non-coding RNAs (lincRNAs) are a new class of functional transcripts, and aberrant expression of lincRNAs was associated with several human diseases. The genetic variants in lincRNA transcription factor binding sites (TFBSs) can change lincRNA expression, thereby affecting the susceptibility to human diseases. To identify and annotate these functional candidates, we have developed a database SNP@lincTFBS, which is devoted to the exploration and annotation of single nucleotide polymorphisms (SNPs) in potential TFBSs of human lincRNAs. We identified 6,665 SNPs in 6,614 conserved TFBSs of 2,423 human lincRNAs. In addition, with ChIPSeq dataset, we identified 139,576 SNPs in 304,517 transcription factor peaks of 4,813 lincRNAs. We also performed comprehensive annotation for these SNPs using 1000 Genomes Project datasets across 11 populations. Moreover, one of the distinctive features of SNP@lincTFBS is the collection of disease-associated SNPs in the lincRNA TFBSs and SNPs in the TFBSs of disease-associated lincRNAs. The web interface enables both flexible data searches and downloads. Quick search can be query of lincRNA name, SNP identifier, or transcription factor name. SNP@lincTFBS provides significant advances in identification of disease-associated lincRNA variants and improved convenience to interpret the discrepant expression of lincRNAs. The SNP@lincTFBS database is available at http://bioinfo.hrbmu.edu.cn/SNP_lincTFBS.

  8. 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

  9. Combining fMRI and SNP Data to Investigate Connections Between Brain Function and Genetics Using Parallel ICA

    PubMed Central

    Liu, Jingyu; Pearlson, Godfrey; Windemuth, Andreas; Ruano, Gualberto; Perrone-Bizzozero, Nora I.; Calhoun, Vince

    2009-01-01

    There is current interest in understanding genetic influences on both healthy and disordered brain function. We assessed brain function with functional magnetic resonance imaging (fMRI) data collected during an auditory oddball task—detecting an infrequent sound within a series of frequent sounds. Then, task-related imaging findings were utilized as potential intermediate phenotypes (endophenotypes) to investigate genomic factors derived from a single nucleotide polymorphism (SNP) array. Our target is the linkage of these genomic factors to normal/abnormal brain functionality. We explored parallel independent component analysis (paraICA) as a new method for analyzing multimodal data. The method was aimed to identify simultaneously independent components of each modality and the relationships between them. When 43 healthy controls and 20 schizophrenia patients, all Caucasian, were studied, we found a correlation of 0.38 between one fMRI component and one SNP component. This fMRI component consisted mainly of parietal lobe activations. The relevant SNP component was contributed to significantly by 10 SNPs located in genes, including those coding for the nicotinic α-7cholinergic receptor, aromatic amino acid decarboxylase, disrupted in schizophrenia 1, among others. Both fMRI and SNP components showed significant differences in loading parameters between the schizophrenia and control groups (P = 0.0006 for the fMRI component; P = 0.001 for the SNP component). In summary, we constructed a framework to identify interactions between brain functional and genetic information; our findings provide a proof-of-concept that genomic SNP factors can be investigated by using endophenotypic imaging findings in a multivariate format. PMID:18072279

  10. Protective immunity against acute toxoplasmosis in BALB/c mice induced by a DNA vaccine encoding Toxoplasma gondii 10 kDa excretory-secretory antigen (TgESA10).

    PubMed

    Wang, Shuai; Wang, Yujian; Sun, Xiaoni; Zhang, Zhenchao; Liu, Tingqi; Gadahi, Javaid Ali; Xu, Lixin; Yan, Ruofeng; Song, Xiaokai; Li, Xiangrui

    2015-11-30

    Toxoplasma gondii 10 kDa excretory-secretory antigen (TgESA10) is involved in the early stages of host invasion. The aim of this study was to evaluate the immune protective efficacy of a DNA vaccine encoding TgESA10 gene against acute T. gondii infection in mice. The gene sequence encoding TgESA10 was inserted into the eukaryotic expression vector pVAX I, and the efficacy of intramuscular vaccination of BALB/c mice with pVAX-ESA10 was analyzed. Mice immunized with pVAX-ESA10 elicited high titers of total IgG, IgG1, IgG2a, IgA and IgM antibodies, while IgE showed no changes. Analysis of cytokine profiles revealed significant increases of IFN-γ, IL-4 and IL-17, while no significant changes were detected in TGF-β1. Additionally, we found that pVAX-ESA10 enhanced the activation of CD4(+) and CD8(+) T cells and the expression of MHC-I and MHC-II molecules in spleen in mice. Immunization with pVAX-ESA10 significantly prolonged survival time (14.3 ± 1.7 days) after challenge infection with the virulent T. gondii RH strain, compared with the control groups which died within 8 days. These results suggested that TgESA10 DNA vaccine could trigger strong humoral and cellular responses and induce partial protection against acute toxoplasmosis.

  11. A non-synonymous SNP with the allele frequency correlated with the altitude may contribute to the hypoxia adaptation of Tibetan chicken

    PubMed Central

    Wang, Yan; Yin, Huadong; Zhou, Lanyun; Zhong, Chengling

    2017-01-01

    The hypoxia adaptation to high altitudes is of considerable interest in the biological sciences. As a breed with adaptability to highland environments, the Tibetan chicken (Gallus gallus domestics), provides a biological model to search for genetic differences between high and lowland chickens. To address mechanisms of hypoxia adaptability at high altitudes for the Tibetan chicken, we focused on the Endothelial PAS domain protein 1 (EPAS1), a key regulatory factor in hypoxia responses. Detected were polymorphisms of EPAS1 exons in 157 Tibetan chickens from 8 populations and 139 lowland chickens from 7 breeds. We then designed 15 pairs of primers to amplify exon sequences by Sanger sequencing methods. Six single nucleotide polymorphisms (SNPs) were detected, including 2 missense mutations (SNP3 rs316126786 and SNP5 rs740389732) and 4 synonymous mutations (SNP1 rs315040213, SNP4 rs739281102, SNP6 rs739010166, and SNP2 rs14330062). There were negative correlations between altitude and mutant allele frequencies for both SNP6 (rs739010166, r = 0.758, p<0.001) and SNP3 (rs316126786, r = 0.844, P<0.001). We also aligned the EPAS1 protein with ortholog proteins from diverse vertebrates and focused that SNP3 (Y333C) was a conserved site among species. Also, SNP3 (Y333C) occurred in a well-defined protein domain Per-AhR-Arnt-Sim (PAS domain). These results imply that SNP3 (Y333C) is the most likely casual mutation for the high-altitude adaption in Tibetan chicken. These variations of EPAS1 provide new insights into the gene’s function. PMID:28222154

  12. The MDM2 promoter polymorphism SNP309T→G and the risk of uterine leiomyosarcoma, colorectal cancer, and squamous cell carcinoma of the head and neck

    PubMed Central

    Alhopuro, P; Ylisaukko-oja, S; Koskinen, W; Bono, P; Arola, J; Jarvinen, H; Mecklin, J; Atula, T; Kontio, R; Makitie, A; Suominen, S; Leivo, I; Vahteristo, P; Aaltonen, L; Aaltonen, L

    2005-01-01

    Background: MDM2 acts as a principal regulator of the tumour suppressor p53 by targeting its destruction through the ubiquitin pathway. A polymorphism in the MDM2 promoter (SNP309) was recently identified. SNP309 was shown to result, via Sp1, in higher levels of MDM2 RNA and protein, and subsequent attenuation of the p53 pathway. Furthermore, SNP309 was proposed to be associated with accelerated soft tissue sarcoma formation in both hereditary (Li-Fraumeni) and sporadic cases in humans. Methods: We evaluated the possible contribution of SNP309 to three tumour types known to be linked with the MDM2/p53 pathway, using genomic sequencing or restriction fragment length polymorphism as screening methods. Three separate Finnish tumour materials (population based sets of 68 patients with early onset uterine leiomyosarcomas and 1042 patients with colorectal cancer, and a series of 162 patients with squamous cell carcinoma of the head and neck) and a set of 185 healthy Finnish controls were analysed for SNP309. Results: Frequencies of SNP309 were similar in all four cohorts. In the colorectal cancer series, SNP309 was somewhat more frequent in women and in patients with microsatellite stable tumours. Female SNP309 carriers were diagnosed with colorectal cancer approximately 2.7 years earlier than those carrying the wild type gene. However, no statistically significant association of SNP309 with patients' age at disease onset or to any other clinicopathological parameter was found in these three tumour materials. Conclusion: SNP309 had no significant contribution to tumour formation in our materials. Possible associations of SNP309 with microsatellite stable colorectal cancer and with earlier disease onset in female carriers need to be examined in subsequent studies. PMID:16141004

  13. Pacifiplex: an ancestry-informative SNP panel centred on Australia and the Pacific region.

    PubMed

    Santos, Carla; Phillips, Christopher; Fondevila, Manuel; Daniel, Runa; van Oorschot, Roland A H; Burchard, Esteban G; Schanfield, Moses S; Souto, Luis; Uacyisrael, Jolame; Via, Marc; Carracedo, Ángel; Lareu, Maria V

    2016-01-01

    The analysis of human population variation is an area of considerable interest in the forensic, medical genetics and anthropological fields. Several forensic single nucleotide polymorphism (SNP) assays provide ancestry-informative genotypes in sensitive tests designed to work with limited DNA samples, including a 34-SNP multiplex differentiating African, European and East Asian ancestries. Although assays capable of differentiating Oceanian ancestry at a global scale have become available, this study describes markers compiled specifically for differentiation of Oceanian populations. A sensitive multiplex assay, termed Pacifiplex, was developed and optimized in a small-scale test applicable to forensic analyses. The Pacifiplex assay comprises 29 ancestry-informative marker SNPs (AIM-SNPs) selected to complement the 34-plex test, that in a combined set distinguish Africans, Europeans, East Asians and Oceanians. Nine Pacific region study populations were genotyped with both SNP assays, then compared to four reference population groups from the HGDP-CEPH human diversity panel. STRUCTURE analyses estimated population cluster membership proportions that aligned with the patterns of variation suggested for each study population's currently inferred demographic histories. Aboriginal Taiwanese and Philippine samples indicated high East Asian ancestry components, Papua New Guinean and Aboriginal Australians samples were predominantly Oceanian, while other populations displayed cluster patterns explained by the distribution of divergence amongst Melanesians, Polynesians and Micronesians. Genotype data from Pacifiplex and 34-plex tests is particularly well suited to analysis of Australian Aboriginal populations and when combined with Y and mitochondrial DNA variation will provide a powerful set of markers for ancestry inference applied to modern Australian demographic profiles. On a broader geographic scale, Pacifiplex adds highly informative data for inferring the ancestry

  14. 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

  15. Efficient fast heuristic algorithms for minimum error correction haplotyping from SNP fragments.

    PubMed

    Anaraki, Maryam Pourkamali; Sadeghi, Mehdi

    2014-01-01

    Availability of complete human genome is a crucial factor for genetic studies to explore possible association between the genome and complex diseases. Haplotype, as a set of single nucleotide polymorphisms (SNPs) on a single chromosome, is believed to contain promising data for disease association studies, detecting natural positive selection and recombination hotspots. Various computational methods for haplotype reconstruction from aligned fragment of SNPs have already been proposed. This study presents a novel approach to obtain paternal and maternal haplotypes form the SNP fragments on minimum error correction (MEC) model. Reconstructing haplotypes in MEC model is an NP-hard problem. Therefore, our proposed methods employ two fast and accurate clustering techniques as the core of their procedure to efficiently solve this ill-defined problem. The assessment of our approaches, compared to conventional methods, on two real benchmark datasets, i.e., ACE and DALY, proves the efficiency and accuracy.

  16. Cloning, chromosomal localization, SNP detection and association analysis of the porcine IRS-1 gene.

    PubMed

    Niu, P-X; Huang, Z; Li, C-C; Fan, B; Li, K; Liu, B; Yu, M; Zhao, S-H

    2009-11-01

    Insulin receptor substrate-1(IRS-1) gene is one member of the Insulin receptor substrate (IRS) gene family, which plays an important role in mediating the growth of skeletal muscle and the molecular metabolism of type 2 diabetes. Here, we cloned a 3,573 bp fragment of the partial CDS sequence of porcine IRS-1 gene by in silicon cloning strategy and RT-PCR method. The porcine IRS-1 gene was assigned to SSC15q25 by using IMpRH. Sequencing of PCR products from Duroc and Tibetan pig breeds identified one SNP in exon 1 of porcine IRS-1 gene (C3257A polymorphisms). Association analysis of genotypes with the growth traits, anatomy traits, meat quality traits and physiological biochemical indexes traits showed that different genotypes at locus 3,257 of IRS-1 have significant differences in carcass straight length in pigs (P = 0.0102 \\ 0.05).

  17. Syndromic ciliopathies: From single gene to multi gene analysis by SNP arrays and next generation sequencing.

    PubMed

    Knopp, C; Rudnik-Schöneborn, S; Eggermann, T; Bergmann, C; Begemann, M; Schoner, K; Zerres, K; Ortiz Brüchle, N

    2015-10-01

    Joubert syndrome (JS) and related disorders (JSRD), Meckel syndrome (MKS) and Bardet-Biedl syndrome (BBS) are autosomal recessive ciliopathies with a broad clinical and genetic overlap. In our multiethnic cohort of 88 MKS, 61 JS/JSRD and 66 BBS families we performed genetic analyses and were able to determine mutation frequencies and detection rates for the most frequently mutated MKS genes. On the basis of determined mutation frequencies, a next generation gene panel for JS/JSRD and MKS was established. Furthermore 35 patients from 26 unrelated consanguineous families were investigated by SNP array-based homozygosity mapping and subsequent DNA sequencing of known candidate genes according to runs of homozygosity size in descending order. This led to the identification of the causative homozygous mutation in 62% of unrelated index cases. Based on our data we discuss various strategies for diagnostic mutation detection in the syndromic ciliopathies JS/JSRD, MKS and BBS.

  18. A high-performance computing toolset for relatedness and principal component analysis of SNP data.

    PubMed

    Zheng, Xiuwen; Levine, David; Shen, Jess; Gogarten, Stephanie M; Laurie, Cathy; Weir, Bruce S

    2012-12-15

    Genome-wide association studies are widely used to investigate the genetic basis of diseases and traits, but they pose many computational challenges. We developed gdsfmt and SNPRelate (R packages for multi-core symmetric multiprocessing computer architectures) to accelerate two key computations on SNP data: principal component analysis (PCA) and relatedness analysis using identity-by-descent measures. The kernels of our algorithms are written in C/C++ and highly optimized. Benchmarks show the uniprocessor implementations of PCA and identity-by-descent are ∼8-50 times faster than the implementations provided in the popular EIGENSTRAT (v3.0) and PLINK (v1.07) programs, respectively, and can be sped up to 30-300-fold by using eight cores. SNPRelate can analyse tens of thousands of samples with millions of SNPs. For example, our package was used to perform PCA on 55 324 subjects from the 'Gene-Environment Association Studies' consortium studies.

  19. Development of SNP markers identifying European wildcats, domestic cats, and their admixed progeny.

    PubMed

    Nussberger, B; Greminger, M P; Grossen, C; Keller, L F; Wandeler, P

    2013-05-01

    Introgression can be an important evolutionary force but it can also lead to species extinction and as such is a crucial issue for species conservation. However, introgression is difficult to detect, morphologically as well as genetically. Hybridization with domestic cats (Felis silvestris catus) is a major concern for the conservation of European wildcats (Felis s. silvestris). The available morphologic and genetic markers for the two Felis subspecies are not sufficient to reliably detect hybrids beyond first generation. Here we present a single nucleotide polymorphism (SNP) based approach that allows the identification of introgressed individuals. Using high-throughput sequencing of reduced representation libraries we developed a diagnostic marker set containing 48 SNPs (Fst > 0.8) which allows the identification of wildcats, domestic cats, their hybrids and backcrosses. This allows assessing introgression rate in natural wildcat populations and is key for a better understanding of hybridization processes.

  20. Specificity of SNP detection with molecular beacons is improved by stem and loop separation with spacers.

    PubMed

    Farzan, Valentina M; Markelov, Mikhail L; Skoblov, Alexander Yu; Shipulin, German A; Zatsepin, Timofei S

    2017-03-13

    Molecular beacons (MBs) are valuable tools in molecular biology, clinical diagnostics and analytical chemistry. Here we describe a novel approach for the design of MBs with nucleotide or non-nucleotide linkers between the stem and loop regions. Such modified MBs have significantly improved specificity and performance for single nucleotide polymorphism (SNP) detection. These advantages are especially distinct, when compared to the classic MBs, in the case of possible interactions between the stem and loop regions. We demonstrated the applicability of such modified MBs for the discrimination of common Factor V, NOS3 and ADRB2 SNPs in model plasmids and in clinical samples. The developed approach could be applicable not only to fluorescently labeled MBs, but also to other biosensors based on nucleic acids with stem-loop structures.

  1. [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.

  2. 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.

  3. Prediction of a time-to-event trait using genome wide SNP data

    PubMed Central

    2013-01-01

    Background A popular objective of many high-throughput genome projects is to discover various genomic markers associated with traits and develop statistical models to predict traits of future patients based on marker values. Results In this paper, we present a prediction method for time-to-event traits using genome-wide single-nucleotide polymorphisms (SNPs). We also propose a MaxTest associating between a time-to-event trait and a SNP accounting for its possible genetic models. The proposed MaxTest can help screen out nonprognostic SNPs and identify genetic models of prognostic SNPs. The performance of the proposed method is evaluated through simulations. Conclusions In conjunction with the MaxTest, the proposed method provides more parsimonious prediction models but includes more prognostic SNPs than some naive prediction methods. The proposed method is demonstrated with real GWAS data. PMID:23418752

  4. 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).

  5. A Method for Checking Genomic Integrity in Cultured Cell Lines from SNP Genotyping Data.

    PubMed

    Danecek, Petr; McCarthy, Shane A; Durbin, Richard

    2016-01-01

    Genomic screening for chromosomal abnormalities is an important part of quality control when establishing and maintaining stem cell lines. We present a new method for sensitive detection of copy number alterations, aneuploidy, and contamination in cell lines using genome-wide SNP genotyping data. In contrast to other methods designed for identifying copy number variations in a single sample or in a sample composed of a mixture of normal and tumor cells, this new method is tailored for determining differences between cell lines and the starting material from which they were derived, which allows us to distinguish between normal and novel copy number variation. We implemented the method in the freely available BCFtools package and present results based on induced pluripotent stem cell lines obtained in the HipSci project.

  6. A Method for Checking Genomic Integrity in Cultured Cell Lines from SNP Genotyping Data

    PubMed Central

    McCarthy, Shane A.; Durbin, Richard

    2016-01-01

    Genomic screening for chromosomal abnormalities is an important part of quality control when establishing and maintaining stem cell lines. We present a new method for sensitive detection of copy number alterations, aneuploidy, and contamination in cell lines using genome-wide SNP genotyping data. In contrast to other methods designed for identifying copy number variations in a single sample or in a sample composed of a mixture of normal and tumor cells, this new method is tailored for determining differences between cell lines and the starting material from which they were derived, which allows us to distinguish between normal and novel copy number variation. We implemented the method in the freely available BCFtools package and present results based on induced pluripotent stem cell lines obtained in the HipSci project. PMID:27176002

  7. To Cheat or Not To Cheat: Tryptophan Hydroxylase 2 SNP Variants Contribute to Dishonest Behavior.

    PubMed

    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.

  8. 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

  9. Highly effective SNP-based association mapping and management of recessive defects in livestock.

    PubMed

    Charlier, Carole; Coppieters, Wouter; Rollin, Frédéric; Desmecht, Daniel; Agerholm, Jorgen S; Cambisano, Nadine; Carta, Eloisa; Dardano, Sabrina; Dive, Marc; Fasquelle, Corinne; Frennet, Jean-Claude; Hanset, Roger; Hubin, Xa